JP2008169125A - Method for producing biaryl compound - Google Patents

Abstract

で表されるオキサゾリン化合物を、有機溶媒中、ルテニウム触媒および水素スカベンジャーの存在下にて反応させる工程；を包含する。本発明によって製造されたビアリール化合物は、遷移金属との錯形成を経てあるいはそれ自体として、化学触媒などの多くの化学製品、もしくはその合成中間体として用いることができる。
【選択図】 なしPROBLEM TO BE SOLVED: To provide a method for producing a biaryl compound, which can provide a relatively free functional group and is excellent in reaction efficiency without requiring expensive and complicated production equipment.
A method for producing a biaryl compound is disclosed. The production method of the present invention has the following formula (II):
[Chemical 1]

Reacting the oxazoline compound represented by formula (I) in an organic solvent in the presence of a ruthenium catalyst and a hydrogen scavenger. The biaryl compound produced by the present invention can be used as a chemical intermediate such as a chemical catalyst, or a synthetic intermediate thereof through complex formation with a transition metal or as such.
[Selection figure] None

Description

  The present invention relates to a method for producing a biaryl compound, and more particularly to a method capable of producing a biaryl compound more simply and efficiently.

  Biaryl compounds are important compounds as many chemical products and their synthetic intermediates. Biaryl compounds are sometimes used as chemical catalysts through complex formation with transition metals or as such.

  In the biaryl compound, many compounds have been synthesized from various optical, chemical or medical viewpoints, and various useful compounds have been found. For example, among the compounds included in the biaryl compound, some of the compounds having a biphenyl skeleton are themselves used as liquid crystal materials (see, for example, Non-Patent Document 1).

  Among the compounds included in the biaryl compound, compounds having a binaphthyl skeleton are used as ligands to metals, and some of them form transition metal catalysts useful for asymmetric catalytic reactions. A typical example is a BINAP catalyst. The BINAP catalyst is a complex of a compound having a binaphthyl skeleton and ruthenium, and is used as an asymmetric reduction catalyst useful in various technical fields such as a pharmaceutical field and an electronic material field (see, for example, Non-Patent Document 2).

  Furthermore, in recent years, it has been reported that a specific quaternary ammonium salt having a biaryl skeleton is used for various useful reactions as an asymmetric phase transfer catalyst. By using such a catalyst, amino acid derivatives can be efficiently synthesized (see, for example, Patent Documents 1 and 2 and Non-Patent Documents 3 and 4).

  From the above utility, various synthetic methods have been developed for biaryl compounds. For example, a synthesis method using a coupling reaction using boric acid or grinder can be mentioned. However, this method requires the synthesis and generation of metal species such as boric acid and grinder prior to the coupling reaction. For these syntheses and generations, water-free reactions are often necessary, and it has been pointed out that the production facilities are complicated. Furthermore, it has been pointed out that functional groups on the aryl group are substantially limited, and it is relatively difficult to synthesize a wide range of biaryl compounds depending on the purpose.

  In addition, Ullman coupling using metallic copper has been developed, but problems such as poor reaction efficiency and complicated work process due to the need to activate copper in advance have been pointed out.

  Under such circumstances, development of a synthesis method capable of industrially and efficiently producing various biaryl compounds is desired.

JP 2001-048866 A JP 2002-326992 A "Introduction to Liquid Crystals" 1992, Yuki Shobo, Ichiro Nakata, Bunichi Hori, Akio Mukai Noyori, Earl. (Noyori, R.), et al., Journal of the American Chemical Society, 1980, vol. 102, p. 7932-7934 Maruoka, Kay. (Maruoka, K.) et al., Tetrahedron Letters, 2005, 46, p. 8555-8558 Maruoka, Kay. (Maruoka, K.) et al., Angewante. Chemie International Edition (2005), 44, p. 1549-1551

  An object of the present invention is to solve the above problems, and the object of the present invention is to provide a relatively free functional group without the need for expensive and complicated production equipment, and An object of the present invention is to provide a method for producing a biaryl compound having excellent reaction efficiency.

  The present invention provides the following formula (I):

A method for producing a biaryl compound represented by the formula:
The following formula (II):

A step of reacting an oxazoline compound represented by formula (I) in an organic solvent in the presence of a ruthenium catalyst and a hydrogen scavenger;
Including
Here, in the formulas (I) and (II),
R ¹ , R ² , and R ³ are each independently
(i) a hydrogen atom;
(ii) —NR ³⁰ R ³¹ (wherein R ³⁰ and R ³¹ are each independently a hydrogen atom or a C _{1 to} C ₄ which may be branched and may be substituted with a halogen atom) An alkyl group)
(iii) a cyano group;
(iv) a nitro group;
(v) a carbamoyl group;
_{(vi) N- (C 1 ~C} 4 alkyl) carbamoyl group;
(vii) an N, N-di (C ₁ -C ₄ alkyl) carbamoyl group;
(viii) —NHCOR ¹⁹ (wherein R ¹⁹ is a hydrogen atom or a C ₁ -C ₄ alkyl group which may be branched and may be substituted with a halogen atom);
(ix) may form a branched or cyclic and may be substituted with a halogen atom, an alkyl group of C ₁ -C _6;
(x) may form a branched or cyclic and may be substituted with a halogen atom, an alkenyl group of C ₂ -C _6;
(xi) may form a branched or cyclic and may be substituted with a halogen atom, an alkynyl group of C ₂ -C _6;
(xii) an aralkyl group, wherein the aryl moiety constituting the aralkyl group is
Branched C ₁ may be substituted in good and halogen atoms optionally -C ₄ alkyl group,
Branched C ₁ may be substituted in good and halogen atoms have -C ₅ alkoxy group,
It branched _C 1 may be substituted in good and halogen atoms optionally -C ₄ alkyl group, a cyano ^{group, -NR} 30 ^{R 31 (wherein, R 30} and ^{R 31} each, independently, a hydrogen atom or is or optionally branched C ₁ -C ₄ substituted in well and halogen atoms have an alkyl group), a nitro group, a carbamoyl group, N- (C ₁ ~C ₄ alkyl) carbamoyl group, N, N-di _(C 1 -C ₄ alkyl) carbamoyl group or -NHCOR ^{19 (wherein,} either ^{R 19} is a hydrogen atom, or an optionally substituted branched to be the well and a halogen atom _{C 1} -C ₄ alkyl group is one) may be substituted by an aryl group,
A cyano group,
—NR ³⁰ R ³¹ (wherein R ³⁰ and R ³¹ are each independently a hydrogen atom or a C ₁ -C ₄ alkyl group which may be branched and substituted with a halogen atom) ),
Nitro group,
A carbamoyl group,
An N- (C ₁ -C ₄ alkyl) carbamoyl group,
N, N-di _(C 1 -C ₄ alkyl) carbamoyl group, and -NHCOR ^{19 (wherein,} either ^{R 19} is a hydrogen atom, or an optionally substituted branched to be the well and a halogen atom _{C 1} ~C is ₄ or alkyl group)
An aralkyl group optionally substituted with at least one group selected from the group consisting of:
(xiii) a heteroaralkyl group having a heteroaryl moiety, wherein the heteroaryl moiety is
Branched C ₁ may be substituted in good and halogen atoms optionally -C ₄ alkyl group,
Branched C ₁ may be substituted in good and halogen atoms have -C ₅ alkoxy group,
It branched _C 1 may be substituted in good and halogen atoms optionally -C ₄ alkyl group, a cyano ^{group, -NR} 30 ^{R 31 (wherein, R 30} and ^{R 31} each, independently, a hydrogen atom or is or optionally branched C ₁ -C ₄ substituted in well and halogen atoms have an alkyl group), a nitro group, a carbamoyl group, N- (C ₁ ~C ₄ alkyl) carbamoyl group, N, N-di _(C 1 -C ₄ alkyl) carbamoyl group or -NHCOR ^{19 (wherein,} either ^{R 19} is a hydrogen atom, or an optionally substituted branched to be the well and a halogen atom _{C 1} -C ₄ alkyl group is one) may be substituted by an aryl group,
A cyano group,
—NR ³⁰ R ³¹ (wherein R ³⁰ and R ³¹ are each independently a hydrogen atom or a C ₁ -C ₄ alkyl group which may be branched and substituted with a halogen atom) ),
Nitro group,
A carbamoyl group,
An N- (C ₁ -C ₄ alkyl) carbamoyl group,
N, N-di _(C 1 -C ₄ alkyl) carbamoyl group, and -NHCOR ^{19 (wherein,} either ^{R 19} is a hydrogen atom, or an optionally substituted branched to be the well and a halogen atom _{C 1} ~C is ₄ or alkyl group)
A heteroaralkyl group optionally substituted with at least one group selected from the group consisting of:
(xiv) an aryl group, wherein the aryl group is
Branched C ₁ may be substituted in good and halogen atoms optionally -C ₄ alkyl group,
Branched C ₁ may be substituted in good and halogen atoms have -C ₅ alkoxy group,
It branched _C 1 may be substituted in good and halogen atoms optionally -C ₄ alkyl group, a cyano ^{group, -NR} 30 ^{R 31 (wherein, R 30} and ^{R 31} each, independently, a hydrogen atom or is or optionally branched C ₁ -C ₄ substituted in well and halogen atoms have an alkyl group), a nitro group, a carbamoyl group, N- (C ₁ ~C ₄ alkyl) carbamoyl group, N, N-di _(C 1 -C ₄ alkyl) carbamoyl group or -NHCOR ^{19 (wherein,} either ^{R 19} is a hydrogen atom, or an optionally substituted branched to be the well and a halogen atom _{C 1} -C ₄ alkyl group is one) may be substituted by an aryl group,
A cyano group,
—NR ³⁰ R ³¹ (wherein R ³⁰ and R ³¹ are each independently a hydrogen atom or a C ₁ -C ₄ alkyl group which may be branched and substituted with a halogen atom) ),
Nitro group,
A carbamoyl group,
An N- (C ₁ -C ₄ alkyl) carbamoyl group,
N, N-di _(C 1 -C ₄ alkyl) carbamoyl group, and -NHCOR ^{19 (wherein,} either ^{R 19} is a hydrogen atom, or an optionally substituted branched to be the well and a halogen atom _{C 1} ~C is ₄ or alkyl group)
And may be substituted with at least one group selected from the group consisting of: or —O— (CH ₂ ) _p —O— (where p is 1 or 2) An aryl group optionally substituted with
(xv) heteroaryl group, where the heteroaryl group is branched C ₁ may be substituted in good and halogen atoms optionally -C ₄ alkyl group,
Branched C ₁ may be substituted in good and halogen atoms have -C ₅ alkoxy group,
It branched _C 1 may be substituted in good and halogen atoms optionally -C ₄ alkyl group, a cyano ^{group, -NR} 30 ^{R 31 (wherein, R 30} and ^{R 31} each, independently, a hydrogen atom or is or optionally branched C ₁ -C ₄ substituted in well and halogen atoms have an alkyl group), a nitro group, a carbamoyl group, N- (C ₁ ~C ₄ alkyl) carbamoyl group, N, N-di _(C 1 -C ₄ alkyl) carbamoyl group or -NHCOR ^{19 (wherein,} either ^{R 19} is a hydrogen atom, or an optionally substituted branched to be the well and a halogen atom _{C 1} -C ₄ alkyl group is one) may be substituted by an aryl group,
A cyano group,
—NR ³⁰ R ³¹ (wherein R ³⁰ and R ³¹ are each independently a hydrogen atom or a C ₁ -C ₄ alkyl group which may be branched and substituted with a halogen atom) ),
Nitro group,
A carbamoyl group,
An N- (C ₁ -C ₄ alkyl) carbamoyl group,
N, N-di _(C 1 -C ₄ alkyl) carbamoyl group, and -NHCOR ^{19 (wherein,} either ^{R 19} is a hydrogen atom, or an optionally substituted branched to be the well and a halogen atom _{C 1} ~C is ₄ or alkyl group)
A heteroaryl group optionally substituted with at least one group selected from the group consisting of:
In _{(xvi) -S (O) n} -R 20 ( where, n represents 0, 1 or 2, and ^{R 20} is branched optionally _C 1 may be substituted in good and halogen atom- is a C ₄ alkyl group);
Or, among R ¹ , R ² , and R ³ , R ¹ and R ² , or R ² and R ³ are the following formula (III):

The remainder is the oxazoline ring proximal substituent,
Here, in the formula (III),
R ⁵ , R ⁶ , R ⁷ and R ⁸ are each independently
(i) a hydrogen atom;
(ii) —NR ³⁰ R ³¹ (wherein R ³⁰ and R ³¹ are each independently a hydrogen atom or a C _{1 to} C ₄ which may be branched and may be substituted with a halogen atom) An alkyl group)
(iii) a cyano group;
(iv) a nitro group;
(v) a carbamoyl group;
_{(vi) N- (C 1 ~C} 4 alkyl) carbamoyl group;
(vii) an N, N-di (C ₁ -C ₄ alkyl) carbamoyl group;
(viii) —NHCOR ¹⁹ (wherein R ¹⁹ is a hydrogen atom or a C ₁ -C ₄ alkyl group which may be branched and may be substituted with a halogen atom);
(ix) may form a branched or cyclic and may be substituted with a halogen atom, an alkyl group of C ₁ -C _6;
(x) may form a branched or cyclic and may be substituted with a halogen atom, an alkenyl group of C ₂ -C _6;
(xi) may form a branched or cyclic and may be substituted with a halogen atom, an alkynyl group of C ₂ -C _6;
(xii) an aralkyl group, wherein the aryl moiety constituting the aralkyl group is
Branched C ₁ may be substituted in good and halogen atoms optionally -C ₄ alkyl group,
Branched C ₁ may be substituted in good and halogen atoms have -C ₅ alkoxy group,
It branched _C 1 may be substituted in good and halogen atoms optionally -C ₄ alkyl group, a cyano ^{group, -NR} 30 ^{R 31 (wherein, R 30} and ^{R 31} each, independently, a hydrogen atom or is or optionally branched C ₁ -C ₄ substituted in well and halogen atoms have an alkyl group), a nitro group, a carbamoyl group, N- (C ₁ ~C ₄ alkyl) carbamoyl group, N, N-di _(C 1 -C ₄ alkyl) carbamoyl group or -NHCOR ^{19 (wherein,} either ^{R 19} is a hydrogen atom, or an optionally substituted branched to be the well and a halogen atom _{C 1} -C ₄ alkyl group is one) may be substituted by an aryl group,
A cyano group,
—NR ³⁰ R ³¹ (wherein R ³⁰ and R ³¹ are each independently a hydrogen atom or a C ₁ -C ₄ alkyl group which may be branched and substituted with a halogen atom) ),
Nitro group,
A carbamoyl group,
An N- (C ₁ -C ₄ alkyl) carbamoyl group,
N, N-di _(C 1 -C ₄ alkyl) carbamoyl group, and -NHCOR ^{19 (wherein,} either ^{R 19} is a hydrogen atom, or an optionally substituted branched to be the well and a halogen atom _{C 1} ~C is ₄ or alkyl group)
An aralkyl group optionally substituted with at least one group selected from the group consisting of:
(xiii) a heteroaralkyl group having a heteroaryl moiety, wherein the heteroaryl moiety is
Branched C ₁ may be substituted in good and halogen atoms optionally -C ₄ alkyl group,
Branched C ₁ may be substituted in good and halogen atoms have -C ₅ alkoxy group,
It branched _C 1 may be substituted in good and halogen atoms optionally -C ₄ alkyl group, a cyano ^{group, -NR} 30 ^{R 31 (wherein, R 30} and ^{R 31} each, independently, a hydrogen atom or is or optionally branched C ₁ -C ₄ substituted in well and halogen atoms have an alkyl group), a nitro group, a carbamoyl group, N- (C ₁ ~C ₄ alkyl) carbamoyl group, N, N-di _(C 1 -C ₄ alkyl) carbamoyl group or -NHCOR ^{19 (wherein,} either ^{R 19} is a hydrogen atom, or an optionally substituted branched to be the well and a halogen atom _{C 1} -C ₄ alkyl group is one) may be substituted by an aryl group,
A cyano group,
—NR ³⁰ R ³¹ (wherein R ³⁰ and R ³¹ are each independently a hydrogen atom or a C ₁ -C ₄ alkyl group which may be branched and substituted with a halogen atom) ),
Nitro group,
A carbamoyl group,
An N- (C ₁ -C ₄ alkyl) carbamoyl group,
N, N-di _(C 1 -C ₄ alkyl) carbamoyl group, and -NHCOR ^{19 (wherein,} either ^{R 19} is a hydrogen atom, or an optionally substituted branched to be the well and a halogen atom _{C 1} ~C is ₄ or alkyl group)
A heteroaralkyl group optionally substituted with at least one group selected from the group consisting of:
(xiv) an aryl group, wherein the aryl group is
Branched C ₁ may be substituted in good and halogen atoms optionally -C ₄ alkyl group,
Branched C ₁ may be substituted in good and halogen atoms have -C ₅ alkoxy group,
It branched _C 1 may be substituted in good and halogen atoms optionally -C ₄ alkyl group, a cyano ^{group, -NR} 30 ^{R 31 (wherein, R 30} and ^{R 31} each, independently, a hydrogen atom or is or optionally branched C ₁ -C ₄ substituted in well and halogen atoms have an alkyl group), a nitro group, a carbamoyl group, N- (C ₁ ~C ₄ alkyl) carbamoyl group, N, N-di _(C 1 -C ₄ alkyl) carbamoyl group or -NHCOR ^{19 (wherein,} either ^{R 19} is a hydrogen atom, or an optionally substituted branched to be the well and a halogen atom _{C 1} -C ₄ alkyl group is one) may be substituted by an aryl group,
A cyano group,
—NR ³⁰ R ³¹ (wherein R ³⁰ and R ³¹ are each independently a hydrogen atom or a C ₁ -C ₄ alkyl group which may be branched and substituted with a halogen atom) ),
Nitro group,
A carbamoyl group,
An N- (C ₁ -C ₄ alkyl) carbamoyl group,
N, N-di _(C 1 -C ₄ alkyl) carbamoyl group, and -NHCOR ^{19 (wherein,} either ^{R 19} is a hydrogen atom, or an optionally substituted branched to be the well and a halogen atom _{C 1} ~C is ₄ or alkyl group)
And may be substituted with at least one group selected from the group consisting of: or —O— (CH ₂ ) _p —O— (where p is 1 or 2) An aryl group optionally substituted with
(xv) heteroaryl group, where the heteroaryl group is branched C ₁ may be substituted in good and halogen atoms optionally -C ₄ alkyl group,
Branched C ₁ may be substituted in good and halogen atoms have -C ₅ alkoxy group,
It branched _C 1 may be substituted in good and halogen atoms optionally -C ₄ alkyl group, a cyano ^{group, -NR} 30 ^{R 31 (wherein, R 30} and ^{R 31} each, independently, a hydrogen atom or is or optionally branched C ₁ -C ₄ substituted in well and halogen atoms have an alkyl group), a nitro group, a carbamoyl group, N- (C ₁ ~C ₄ alkyl) carbamoyl group, N, N-di _(C 1 -C ₄ alkyl) carbamoyl group or -NHCOR ^{19 (wherein,} either ^{R 19} is a hydrogen atom, or an optionally substituted branched to be the well and a halogen atom _{C 1} -C ₄ alkyl group is one) may be substituted by an aryl group,
A cyano group,
—NR ³⁰ R ³¹ (wherein R ³⁰ and R ³¹ are each independently a hydrogen atom or a C ₁ -C ₄ alkyl group which may be branched and substituted with a halogen atom) ),
Nitro group,
A carbamoyl group,
An N- (C ₁ -C ₄ alkyl) carbamoyl group,
N, N-di _(C 1 -C ₄ alkyl) carbamoyl group, and -NHCOR ^{19 (wherein,} either ^{R 19} is a hydrogen atom, or an optionally substituted branched to be the well and a halogen atom _{C 1} ~C is ₄ or alkyl group)
A heteroaryl group optionally substituted with at least one group selected from the group consisting of:
In _{(xvi) -S (O) n} -R 20 ( where, n represents 0, 1 or 2, and ^{R 20} is branched optionally _C 1 may be substituted in good and halogen atom- is a C ₄ alkyl group);
An oxazoline ring distal substituent selected from the group consisting of:
R ¹⁴ , R ¹⁵ , R ¹⁶ and R ¹⁷ are each independently a hydrogen atom, or may be branched or formed a ring, and may be substituted with a halogen atom, C ₁ -C _{6 is} an alkyl group, and X is an oxygen atom or a sulfur atom.

In one embodiment, R ¹ , R ² , and R ³ of the oxazoline compound represented by the above formula (II) are each independently the oxazoline ring proximal substituent.

  In one embodiment, the oxazoline compound represented by the above formula (II) has the following formula (II-2):

It is a compound represented by these.

  In one embodiment, the oxazoline compound represented by the above formula (II) has the following formula (II-3):

It is a compound represented by these.

  In one embodiment, the hydrogen scavenger is of the following formula (IV):

(here,
R ¹⁰ is an optionally branched C ₁ -C ₈ alkyl group, and R ¹¹ , R ¹² , and R ¹³ are each independently a hydrogen atom, optionally branched C ₁ -C ₄ alkyl group or aryl group)
It is ester of the allyl alcohol derivative represented by these.

In one embodiment, the ruthenium catalyst is RuCl ₂ (PPh ₃ ) ₃ or a catalyst produced by mixing [RuCl ₂ (cod)] _n with PPh ₃ .

  According to the present invention, a biaryl compound can be produced efficiently and easily without requiring special production equipment. In particular, according to the present invention, it is not necessary to use a metal species having poor reactivity such as copper. In addition, biaryl compounds having functional groups composed of many variations can also be produced.

  Hereinafter, terms used in the present specification are defined.

The term “C ₁ -C _n alkyl group which may form a branch or a ring” (where n is an integer) is any linear alkyl group having 1 to n carbon atoms, 3 to n carbon atoms Any branched alkyl group and any cyclic alkyl group having 3 to n carbon atoms are included. For example, any linear alkyl group having 1 to 6 carbon atoms includes methyl, ethyl, n-propyl, n-butyl, n-pentyl, and n-hexyl, and any branched chain having 3 to 6 carbon atoms. Examples of the chain alkyl group include isopropyl, isobutyl, tert-butyl, and isopentyl, and examples of the cyclic alkyl group having 3 to 6 carbon atoms include cyclobutyl, cyclopentyl, and cyclohexyl. Further, for example, the term “C ₁ -C ₁₂ alkyl group which may form a branch or a ring and / or may be substituted with a halogen atom” is a straight chain having 1 to 12 carbon atoms. Including a chain alkyl group, an arbitrary branched chain alkyl group having 3 to 12 carbon atoms, and an arbitrary cyclic alkyl group having 3 to 12 carbon atoms, wherein a hydrogen atom at any position thereof is substituted with a halogen atom Good. Examples of such an alkyl group include n-heptyl, isoheptyl, n-octyl, isooctyl, n-decyl, n-dodecyl and the like.

In the N- (C ₁ -C ₄ alkyl) carbamoyl group and N, N-di (C ₁ -C ₄ alkyl) carbamoyl, “C ₁ -C ₄ alkyl” is a C ₁ -C ₄ linear alkyl. Means a C ₃ -C ₄ branched alkyl group.

The term "C2-Cn alkenyl group which may form a branch or a ring" (where n is an integer) refers to any straight chain alkenyl group having ₂ to _n carbon atoms, 3 to n carbon atoms It includes any branched alkenyl group and any cyclic alkenyl group having 3 to n carbon atoms. For example, as an arbitrary linear alkenyl group having 2 to 6 carbon atoms, ethenyl, 1-propenyl, 2-propenyl, 1-butenyl, 2-butenyl, 1-pentenyl, 2-pentenyl, 3-pentenyl, 4-pentenyl 1-hexenyl and the like, and as an arbitrary branched chain alkenyl group having 3 to 6 carbon atoms, isopropenyl, 1-methyl-1-propenyl, 1-methyl-2-propenyl, 2-methyl-1-propenyl , 2-methyl-2-propenyl, 1-methyl-2-butenyl, and the like, and arbitrary cyclic alkenyl groups having 3 to 6 carbon atoms include cyclobutenyl, cyclopentenyl, cyclohexenyl, and the like. Further, for example, the term “C ₂ -C ₁₂ alkenyl group which may form a branch or a ring and / or may be substituted with a halogen atom” is a straight chain having 2 to 12 carbon atoms. Including a chain alkenyl group, an arbitrary branched alkenyl group having 3 to 12 carbon atoms, and an arbitrary cyclic alkenyl group having 3 to 12 carbon atoms, wherein a hydrogen atom at any position thereof is substituted with a halogen atom Good. Examples of such alkenyl groups include 1-heptenyl, 2-heptenyl, 1-octenyl, 1-decenyl, 1-dodecenyl and the like.

The term "C2-Cn alkynyl group which may form a branch or a ring" (where n is an integer) refers to any linear alkynyl group having ₂ to _n carbon atoms, 3 to n carbon atoms Any branched alkynyl group and any cyclic alkynyl group having 3 to n carbon atoms are included. For example, arbitrary linear alkynyl groups having 2 to 6 carbon atoms include ethynyl, 1-propynyl, 2-propynyl, 1-butynyl, 2-butynyl, 1-pentynyl, 1-hexynyl, and the like. Arbitrary branched alkynyl groups of ˜6 include 1-methyl-2-propynyl and the like, and arbitrary cyclic alkynyl groups of 3 to 6 carbon atoms include cyclopropylethynyl, cyclobutylethynyl and the like. . Further, for example, the term “a C _{2 to} C ₁₂ alkynyl group which may form a branch or a ring and / or be substituted with a halogen atom” is a straight chain having 1 to 12 carbon atoms. Including a chain alkynyl group, an arbitrary branched alkynyl group having 3 to 12 carbon atoms, and an arbitrary cyclic alkynyl group having 3 to 12 carbon atoms, wherein a hydrogen atom at any position thereof is substituted with a halogen atom Good. Such alkynyl groups include 1-heptynyl, 1-octynyl, 1-decynyl, 1-dodecynyl and the like.

The term “optionally branched C ₁ -C _n alkoxy group” (where n is an integer) means an alkoxy group having an arbitrary linear alkyl group having ₁ to _n carbon atoms and an arbitrary group having 3 to n carbon atoms. And an alkoxy group having a branched alkyl group. For example, methyloxy, ethyloxy, n-propyloxy, isopropyloxy, tert-butyloxy and the like can be mentioned.

  In the present invention, examples of the term “aralkyl group” include benzyl, phenethyl, naphthylmethyl, 3-phenylpropyl, 2-phenylpropyl, 4-phenylbutyl and 2-phenylbutyl.

  Examples of the term “heteroaralkyl group” in the present invention include pyridylmethyl, indolylmethyl, furylmethyl, thienylmethyl, pyrrolylmethyl, 2-pyridylethyl, 1-pyridylethyl and 3-thienylpropyl.

  In the present invention, examples of the term “aryl group” include phenyl, naphthyl, anthryl, phenanthryl and the like.

  Examples of the term “heteroaryl group” in the present invention include pyridyl, pyrrolyl, imidazolyl, furyl, indolyl, benzothiophen-2-yl, thienyl, oxazolyl, thiazolyl, 3,4-methylenedioxyphenyl, 3,4- Examples include ethylenedioxyphenyl and tetrazolyl.

  In the present invention, examples of the term “halogen atom” include chlorine atom, bromine atom, iodine atom and fluorine atom. In the present invention, the term “halide anion” means a halogen ion, and examples include chloride ion, bromide ion, iodide ion, and fluoride ion.

In the present invention, the term “C ₃ -C _n allyl group or substituted allyl group which may form a branch or a ring” (where n is an integer) is an allyl group, or 1 and / or 2 and / or Alternatively, it means a substituted allyl group having 4 to n total carbon atoms having a substituent at the 3-position. For example, 2-butenyl, 1-cyclopentenylmethyl, 3-methyl-2-butenyl and the like can be mentioned.

In the present invention, the term “optionally branched C _{3 to} C _n propargyl group or substituted propargyl group” (where n is an integer) has a propargyl group or a substituent at the 1 and / or 3 position. It means any substituted propargyl group having 4 to n total carbon atoms. For example, 2-butynyl, 3-trimethylsilyl-2-propynyl and the like can be mentioned.

  Hereinafter, the present invention will be described in detail.

  In the present invention, first, a specific oxazoline compound is reacted in an organic solvent in the presence of a ruthenium catalyst and a hydrogen scavenger.

  The oxazoline compound used in the present invention has the following formula (II):

(Where R ¹ , R ² , and R ³ are each independently
(i) a hydrogen atom;
(ii) —NR ³⁰ R ³¹ (wherein R ³⁰ and R ³¹ are each independently a hydrogen atom or a C _{1 to} C ₄ which may be branched and may be substituted with a halogen atom) An alkyl group)
(iii) a cyano group;
(iv) a nitro group;
(v) a carbamoyl group;
_{(vi) N- (C 1 ~C} 4 alkyl) carbamoyl group;
(vii) an N, N-di (C ₁ -C ₄ alkyl) carbamoyl group;
(viii) —NHCOR ¹⁹ (wherein R ¹⁹ is a hydrogen atom or a C ₁ -C ₄ alkyl group which may be branched and may be substituted with a halogen atom);
(ix) may form a branched or cyclic and may be substituted with a halogen atom, an alkyl group of C ₁ -C _6;
(x) may form a branched or cyclic and may be substituted with a halogen atom, an alkenyl group of C ₂ -C _6;
(xi) may form a branched or cyclic and may be substituted with a halogen atom, an alkynyl group of C ₂ -C _6;
(xii) an aralkyl group, wherein the aryl moiety constituting the aralkyl group is
Branched C ₁ may be substituted in good and halogen atoms optionally -C ₄ alkyl group,
Branched C ₁ may be substituted in good and halogen atoms have -C ₅ alkoxy group,
It branched _C 1 may be substituted in good and halogen atoms optionally -C ₄ alkyl group, a cyano ^{group, -NR} 30 ^{R 31 (wherein, R 30} and ^{R 31} each, independently, a hydrogen atom or is or optionally branched C ₁ -C ₄ substituted in well and halogen atoms have an alkyl group), a nitro group, a carbamoyl group, N- (C ₁ ~C ₄ alkyl) carbamoyl group, N, N-di _(C 1 -C ₄ alkyl) carbamoyl group or -NHCOR ^{19 (wherein,} either ^{R 19} is a hydrogen atom, or an optionally substituted branched to be the well and a halogen atom _{C 1} -C ₄ alkyl group is one) may be substituted by an aryl group,
A cyano group,
—NR ³⁰ R ³¹ (wherein R ³⁰ and R ³¹ are each independently a hydrogen atom or a C ₁ -C ₄ alkyl group which may be branched and substituted with a halogen atom) ),
Nitro group,
A carbamoyl group,
An N- (C ₁ -C ₄ alkyl) carbamoyl group,
N, N-di _(C 1 -C ₄ alkyl) carbamoyl group, and -NHCOR ^{19 (wherein,} either ^{R 19} is a hydrogen atom, or an optionally substituted branched to be the well and a halogen atom _{C 1} ~C is ₄ or alkyl group)
An aralkyl group optionally substituted with at least one group selected from the group consisting of:
(xiii) a heteroaralkyl group having a heteroaryl moiety, wherein the heteroaryl moiety is
Branched C ₁ may be substituted in good and halogen atoms optionally -C ₄ alkyl group,
Branched C ₁ may be substituted in good and halogen atoms have -C ₅ alkoxy group,
It branched _C 1 may be substituted in good and halogen atoms optionally -C ₄ alkyl group, a cyano ^{group, -NR} 30 ^{R 31 (wherein, R 30} and ^{R 31} each, independently, a hydrogen atom or is or optionally branched C ₁ -C ₄ substituted in well and halogen atoms have an alkyl group), a nitro group, a carbamoyl group, N- (C ₁ ~C ₄ alkyl) carbamoyl group, N, N-di _(C 1 -C ₄ alkyl) carbamoyl group or -NHCOR ^{19 (wherein,} either ^{R 19} is a hydrogen atom, or an optionally substituted branched to be the well and a halogen atom _{C 1} -C ₄ alkyl group is one) may be substituted by an aryl group,
A cyano group,
—NR ³⁰ R ³¹ (wherein R ³⁰ and R ³¹ are each independently a hydrogen atom or a C ₁ -C ₄ alkyl group which may be branched and substituted with a halogen atom) ),
Nitro group,
A carbamoyl group,
An N- (C ₁ -C ₄ alkyl) carbamoyl group,
N, N-di _(C 1 -C ₄ alkyl) carbamoyl group, and -NHCOR ^{19 (wherein,} either ^{R 19} is a hydrogen atom, or an optionally substituted branched to be the well and a halogen atom _{C 1} ~C is ₄ or alkyl group)
A heteroaralkyl group optionally substituted with at least one group selected from the group consisting of:
(xiv) an aryl group, wherein the aryl group is
Branched C ₁ may be substituted in good and halogen atoms optionally -C ₄ alkyl group,
Branched C ₁ may be substituted in good and halogen atoms have -C ₅ alkoxy group,
It branched _C 1 may be substituted in good and halogen atoms optionally -C ₄ alkyl group, a cyano ^{group, -NR} 30 ^{R 31 (wherein, R 30} and ^{R 31} each, independently, a hydrogen atom or is or optionally branched C ₁ -C ₄ substituted in well and halogen atoms have an alkyl group), a nitro group, a carbamoyl group, N- (C ₁ ~C ₄ alkyl) carbamoyl group, N, N-di _(C 1 -C ₄ alkyl) carbamoyl group or -NHCOR ^{19 (wherein,} either ^{R 19} is a hydrogen atom, or an optionally substituted branched to be the well and a halogen atom _{C 1} -C ₄ alkyl group is one) may be substituted by an aryl group,
A cyano group,
—NR ³⁰ R ³¹ (wherein R ³⁰ and R ³¹ are each independently a hydrogen atom or a C ₁ -C ₄ alkyl group which may be branched and substituted with a halogen atom) ),
Nitro group,
A carbamoyl group,
An N- (C ₁ -C ₄ alkyl) carbamoyl group,
N, N-di _(C 1 -C ₄ alkyl) carbamoyl group, and -NHCOR ^{19 (wherein,} either ^{R 19} is a hydrogen atom, or an optionally substituted branched to be the well and a halogen atom _{C 1} ~C is ₄ or alkyl group)
And may be substituted with at least one group selected from the group consisting of: or —O— (CH ₂ ) _p —O— (where p is 1 or 2) An aryl group optionally substituted with
(xv) heteroaryl group, where the heteroaryl group is branched C ₁ may be substituted in good and halogen atoms optionally -C ₄ alkyl group,
Branched C ₁ which may be substituted in good and halogen atoms have -C ₅ alkoxy group,
It branched _C 1 may be substituted in good and halogen atoms optionally -C ₄ alkyl group, a cyano ^{group, -NR} 30 ^{R 31 (wherein, R 30} and ^{R 31} each, independently, a hydrogen atom or is or optionally branched C ₁ -C ₄ substituted in well and halogen atoms have an alkyl group), a nitro group, a carbamoyl group, N- (C ₁ ~C ₄ alkyl) carbamoyl group, N, N-di _(C 1 -C ₄ alkyl) carbamoyl group or -NHCOR ^{19 (wherein,} either ^{R 19} is a hydrogen atom, or an optionally substituted branched to be the well and a halogen atom _{C 1} -C ₄ alkyl group is one) may be substituted by an aryl group,
A cyano group,
—NR ³⁰ R ³¹ (wherein R ³⁰ and R ³¹ are each independently a hydrogen atom or a C ₁ -C ₄ alkyl group which may be branched and substituted with a halogen atom) ),
Nitro group,
A carbamoyl group,
An N- (C ₁ -C ₄ alkyl) carbamoyl group,
N, N-di _(C 1 -C ₄ alkyl) carbamoyl group, and -NHCOR ^{19 (wherein,} either ^{R 19} is a hydrogen atom, or an optionally substituted branched to be the well and a halogen atom _{C 1} ~C is ₄ or alkyl group)
A heteroaryl group optionally substituted with at least one group selected from the group consisting of:
In _{(xvi) -S (O) n} -R 20 ( where, n represents 0, 1 or 2, and ^{R 20} is branched optionally _C 1 may be substituted in good and halogen atom- is a C ₄ alkyl group);
Or, among R ¹ , R ² , and R ³ , R ¹ and R ² , or R ² and R ³ are the following formula (III):

The remainder is the oxazoline ring proximal substituent,
Here, in the formula (III),
R ⁵ , R ⁶ , R ⁷ and R ⁸ are each independently
(i) a hydrogen atom;
(ii) —NR ³⁰ R ³¹ (wherein R ³⁰ and R ³¹ are each independently a hydrogen atom or a C _{1 to} C ₄ which may be branched and may be substituted with a halogen atom) An alkyl group)
(iii) a cyano group;
(iv) a nitro group;
(v) a carbamoyl group;
_{(vi) N- (C 1 ~C} 4 alkyl) carbamoyl group;
(vii) an N, N-di (C ₁ -C ₄ alkyl) carbamoyl group;
(viii) —NHCOR ¹⁹ (wherein R ¹⁹ is a hydrogen atom or a C ₁ -C ₄ alkyl group which may be branched and may be substituted with a halogen atom);
(ix) may form a branched or cyclic and may be substituted with a halogen atom, an alkyl group of C ₁ -C _6;
(x) may form a branched or cyclic and may be substituted with a halogen atom, an alkenyl group of C ₂ -C _6;
(xi) may form a branched or cyclic and may be substituted with a halogen atom, an alkynyl group of C ₂ -C _6;
(xii) an aralkyl group, wherein the aryl moiety constituting the aralkyl group is
Branched C ₁ may be substituted in good and halogen atoms optionally -C ₄ alkyl group,
Branched C ₁ may be substituted in good and halogen atoms have -C ₅ alkoxy group,
It branched _C 1 may be substituted in good and halogen atoms optionally -C ₄ alkyl group, a cyano ^{group, -NR} 30 ^{R 31 (wherein, R 30} and ^{R 31} each, independently, a hydrogen atom or is or optionally branched C ₁ -C ₄ substituted in well and halogen atoms have an alkyl group), a nitro group, a carbamoyl group, N- (C ₁ ~C ₄ alkyl) carbamoyl group, N, N-di _(C 1 -C ₄ alkyl) carbamoyl group or -NHCOR ^{19 (wherein,} either ^{R 19} is a hydrogen atom, or an optionally substituted branched to be the well and a halogen atom _{C 1} -C ₄ alkyl group is one) may be substituted by an aryl group,
A cyano group,
—NR ³⁰ R ³¹ (wherein R ³⁰ and R ³¹ are each independently a hydrogen atom or a C ₁ -C ₄ alkyl group which may be branched and substituted with a halogen atom) ),
Nitro group,
A carbamoyl group,
An N- (C ₁ -C ₄ alkyl) carbamoyl group,
N, N-di _(C 1 -C ₄ alkyl) carbamoyl group, and -NHCOR ^{19 (wherein,} either ^{R 19} is a hydrogen atom, or an optionally substituted branched to be the well and a halogen atom _{C 1} ~C is ₄ or alkyl group)
An aralkyl group optionally substituted with at least one group selected from the group consisting of:
(xiii) a heteroaralkyl group having a heteroaryl moiety, wherein the heteroaryl moiety is
Branched C ₁ may be substituted in good and halogen atoms optionally -C ₄ alkyl group,
Branched C ₁ may be substituted in good and halogen atoms have -C ₅ alkoxy group,
It branched _C 1 may be substituted in good and halogen atoms optionally -C ₄ alkyl group, a cyano ^{group, -NR} 30 ^{R 31 (wherein, R 30} and ^{R 31} each, independently, a hydrogen atom or is or optionally branched C ₁ -C ₄ substituted in well and halogen atoms have an alkyl group), a nitro group, a carbamoyl group, N- (C ₁ ~C ₄ alkyl) carbamoyl group, N, N-di _(C 1 -C ₄ alkyl) carbamoyl group or -NHCOR ^{19 (wherein,} either ^{R 19} is a hydrogen atom, or an optionally substituted branched to be the well and a halogen atom _{C 1} -C ₄ alkyl group is one) may be substituted by an aryl group,
A cyano group,
—NR ³⁰ R ³¹ (wherein R ³⁰ and R ³¹ are each independently a hydrogen atom or a C ₁ -C ₄ alkyl group which may be branched and substituted with a halogen atom) ),
Nitro group,
A carbamoyl group,
An N- (C ₁ -C ₄ alkyl) carbamoyl group,
N, N-di _(C 1 -C ₄ alkyl) carbamoyl group, and -NHCOR ^{19 (wherein,} either ^{R 19} is a hydrogen atom, or an optionally substituted branched to be the well and a halogen atom _{C 1} ~C is ₄ or alkyl group)
A heteroaralkyl group optionally substituted with at least one group selected from the group consisting of:
(xiv) an aryl group, wherein the aryl group is
Branched C ₁ may be substituted in good and halogen atoms optionally -C ₄ alkyl group,
Branched C ₁ may be substituted in good and halogen atoms have -C ₅ alkoxy group,
It branched _C 1 may be substituted in good and halogen atoms optionally -C ₄ alkyl group, a cyano ^{group, -NR} 30 ^{R 31 (wherein, R 30} and ^{R 31} each, independently, a hydrogen atom or is or optionally branched C ₁ -C ₄ substituted in well and halogen atoms have an alkyl group), a nitro group, a carbamoyl group, N- (C ₁ ~C ₄ alkyl) carbamoyl group, N, N-di _(C 1 -C ₄ alkyl) carbamoyl group or -NHCOR ^{19 (wherein,} either ^{R 19} is a hydrogen atom, or an optionally substituted branched to be the well and a halogen atom _{C 1} -C ₄ alkyl group is one) may be substituted by an aryl group,
A cyano group,
—NR ³⁰ R ³¹ (wherein R ³⁰ and R ³¹ are each independently a hydrogen atom or a C ₁ -C ₄ alkyl group which may be branched and substituted with a halogen atom) ),
Nitro group,
A carbamoyl group,
An N- (C ₁ -C ₄ alkyl) carbamoyl group,
N, N-di _(C 1 -C ₄ alkyl) carbamoyl group, and -NHCOR ^{19 (wherein,} either ^{R 19} is a hydrogen atom, or an optionally substituted branched to be the well and a halogen atom _{C 1} ~C is ₄ or alkyl group)
And may be substituted with at least one group selected from the group consisting of: or —O— (CH ₂ ) _p —O— (where p is 1 or 2) An aryl group optionally substituted with
(xv) heteroaryl group, where the heteroaryl group is branched C ₁ may be substituted in good and halogen atoms optionally -C ₄ alkyl group,
Branched C ₁ may be substituted in good and halogen atoms have -C ₅ alkoxy group,
It branched _C 1 may be substituted in good and halogen atoms optionally -C ₄ alkyl group, a cyano ^{group, -NR} 30 ^{R 31 (wherein, R 30} and ^{R 31} each, independently, a hydrogen atom or is or optionally branched C ₁ -C ₄ substituted in well and halogen atoms have an alkyl group), a nitro group, a carbamoyl group, N- (C ₁ ~C ₄ alkyl) carbamoyl group, N, N-di _(C 1 -C ₄ alkyl) carbamoyl group or -NHCOR ^{19 (wherein,} either ^{R 19} is a hydrogen atom, or an optionally substituted branched to be the well and a halogen atom _{C 1} -C ₄ alkyl group is one) may be substituted by an aryl group,
A cyano group,
—NR ³⁰ R ³¹ (wherein R ³⁰ and R ³¹ are each independently a hydrogen atom or a C ₁ -C ₄ alkyl group which may be branched and substituted with a halogen atom) ),
Nitro group,
A carbamoyl group,
An N- (C ₁ -C ₄ alkyl) carbamoyl group,
N, N-di _(C 1 -C ₄ alkyl) carbamoyl group, and -NHCOR ^{19 (wherein,} either ^{R 19} is a hydrogen atom, or an optionally substituted branched to be the well and a halogen atom _{C 1} ~C is ₄ or alkyl group)
A heteroaryl group optionally substituted with at least one group selected from the group consisting of:
In _{(xvi) -S (O) n} -R 20 ( where, n represents 0, 1 or 2, and ^{R 20} is branched optionally _C 1 may be substituted in good and halogen atom- is a C ₄ alkyl group);
An oxazoline ring distal substituent selected from the group consisting of:
R ¹⁴ , R ¹⁵ , R ¹⁶ and R ¹⁷ are each independently a hydrogen atom, or may be branched or formed a ring, and may be substituted with a halogen atom, C ₁ -C _{6 is} an alkyl group, and X is an oxygen atom or a sulfur atom).

As an oxazoline compound represented by the above formula (II), for example:
(A) the compound wherein R ¹ , R ² and R ³ are each independently the oxazoline ring proximal substituent;
(B) The following formula (II-2):

Wherein R ¹ , R ² , R ³ , R ¹⁴ , R ¹⁵ , R ¹⁶ , R ¹⁷ , and X are the same as the groups defined above; and (C) The following formula (II-3):

Wherein R ¹ , R ² , R ³ , R ¹⁴ , R ¹⁵ , R ¹⁶ , R ¹⁷ , and X are the same as the groups defined above, In particular, it is not limited to these.

  The oxazoline compound represented by the above formula (II) is commercially available and can be obtained, or can be easily synthesized by those skilled in the art.

The ruthenium catalyst used in the present invention is a ruthenium complex in which an organic ligand is coordinated to a ruthenium atom. Examples of ruthenium catalysts that can be used in the present invention include a ruthenium catalyst represented by RuCl ₂ (PPh ₃ ) ₃ ; [RuCl ₂ (cod)] _n (where “cod” represents cyclooctadiene) And a catalyst generated by mixing triphenylphosphine (PPh ₃ ) in a solvent as described later.

  The amount of the ruthenium catalyst used in the present invention is not necessarily limited because it varies depending on the reaction conditions, but it is preferably 0.1 mol% to about 0.1 mol% based on the number of moles of the oxazoline compound of the above formula (II) as the substrate. It can be set to 20 mol%, more preferably 1 mol% to 10 mol%, even more preferably 2 mol% to 8 mol%. When the amount of the ruthenium catalyst used is less than 0.1 mol% in the standard, the reaction does not proceed sufficiently, and it may be difficult to produce the target biaryl compound appropriately. On the other hand, even if the amount of the ruthenium catalyst used exceeds 10 mol% on the basis, the yield of the product is not substantially affected, and it may be a cause of poor profitability in industrial use.

  The hydrogen scavenger used in the present invention is a substance that plays a role in efficiently promoting an oxidation reaction in the coupling of the oxazoline compound of the above formula (II). It is a substance that can form As such a hydrogen scavenger, for example, the following formula (IV):

(Where R ¹⁰ is an optionally branched C ₁ -C ₄ alkyl group, and R ¹¹ , R ¹² , and R ¹³ are each independently a hydrogen atom or branched. C ₁ -C ₄ alkyl group or an ester of an allyl alcohol derivative represented by the aryl is group). Or, as a more specific example, the following formula:

The ester represented by these is mentioned.

  The amount of the hydrogen scavenger used in the present invention is not necessarily limited because it varies depending on the reaction conditions, but preferably 0.3 to 50 equivalents based on the number of moles of the oxazoline compound of the above formula (II) as the substrate. More preferably, it can be set to 0.4 to 20 equivalents.

  The organic solvent used in the present invention may include all non-aqueous solvents, and specific examples include xylene, toluene, mesitylene, acetonitrile, dimethylformamide, dimethyl sulfoxide, and N-methylpyrrolidone (NMP). . Xylene and NMP are particularly preferred. The amount of the organic solvent that can be used in the present invention can be appropriately selected by those skilled in the art. It is preferable that a base such as carbonate is added to the organic solvent. More specific examples of such carbonates include alkali metal carbonates such as potassium carbonate and sodium carbonate. Potassium carbonate is preferred.

  In the present invention, the oxazoline compound represented by the formula (II) is charged together with the organic solvent, the ruthenium catalyst and the hydrogen scavenger, and the reaction is preferably carried out under a nitrogen stream. In this reaction, it is preferably heated so that the reaction temperature is, for example, 80 ° C. to 140 ° C., another example is 100 ° C. to 135 ° C., and another example is 110 ° C. to 130 ° C. The reaction time is preferably 5 hours to 30 hours, more preferably 10 hours to 24 hours.

  After completion of the reaction, the precipitate is filtered off by adding ether or the like to the reaction solution. Then, the target biaryl compound can be obtained by purifying the filtrate by means well known to those skilled in the art.

  Biaryl compounds that can be produced in this way have the following formula (I):

Here, R ¹ , R ² , R ³ , R ¹⁴ , R ¹⁵ , R ¹⁶ , R ¹⁷ , and X are the same as the groups defined above.

  The biaryl compound obtained by the present invention is useful as a chemical intermediate such as a chemical catalyst, or a synthetic intermediate thereof, through complex formation with a transition metal or as such.

  Hereinafter, the present invention will be specifically described with reference to Examples, but the present invention is not limited thereto.

  In the following examples, the measurement was performed under the following conditions unless otherwise specified.

  NMR spectra were measured with a Bruker DPX-400 (400 MHz) or DRX-500 (500 MHz) spectrometer. Chemical shifts were measured in ppm using tetramethylsilane as an internal standard. The product was purified by flash column chromatography using spherical silica gel (Kanto Chemical Co., Inc., 40-100 μm).

<Example 1; Coupling of aryloxazoline compound (1)>

A Schlenk flask was charged with [RuCl ₂ (cod)] _n (0.025 mmol based on Ru), triphenylphosphine (0.05 mmol), and anhydrous potassium carbonate (1.0 mmol) and purged with nitrogen. Next, dehydrated xylene (1.0 ml), oxazoline compound (A-1) (0.5 mmol) and allyl acetate (1.5 mmol) were added, and the mixture was heated at 120 ° C. for 20 hours with stirring under a nitrogen stream. After completion of the reaction, 15 ml of diethyl ether was added to the reaction solution, and the deposited precipitate was separated by filtration. Thereafter, the filtrate was collected, concentrated, and purified by silica gel flash chromatography using ethyl acetate / hexane as an eluent to obtain the biaryl compound (B-1) in a yield of 82%.

  The NMR spectrum of the obtained compound (B-1) is shown in Table 1.

<Example 2; Coupling of aryloxazoline compound (2)>

  The reaction was conducted in the same manner as in Example 1 except that the above oxazoline compound (A-2) (0.5 mmol) was used instead of the oxazoline compound (A-1) used in Example 1. Compound (B-2) was obtained with a yield of 31%.

  Table 2 shows the NMR spectrum of the obtained compound (B-2).

<Example 3; Coupling of aryloxazoline compound (3)>

  The reaction was conducted in the same manner as in Example 1 except that the above oxazoline compound (A-3) (0.5 mmol) was used instead of the oxazoline compound (A-1) used in Example 1. Compound (B-3) was obtained with a yield of 44%.

  Table 3 shows the NMR spectrum of the obtained compound (B-3).

<Example 4; Coupling of aryloxazoline compound (4)>

  The reaction was conducted in the same manner as in Example 1 except that the above oxazoline compound (A-4) (0.5 mmol) was used instead of the oxazoline compound (A-1) used in Example 1. Compound (B-4) was obtained with a yield of 52%.

  Table 4 shows the NMR spectrum of the obtained compound (B-4).

<Example 5: Coupling of aryloxazoline compound (5)>

  The reaction was conducted in the same manner as in Example 1 except that the above oxazoline compound (A-5) (0.5 mmol) was used instead of the oxazoline compound (A-1) used in Example 1. Compound (B-5) was obtained with a yield of 58%.

  Table 5 shows the NMR spectrum of the obtained compound (B-5).

<Example 6: Coupling of meta-substituted aryloxazoline compound (1)>

  The reaction was conducted in the same manner as in Example 1 except that the meta-substituted oxazoline compound (C-1) (0.5 mmol) was used instead of the oxazoline compound (A-1) used in Example 1. The biaryl compound (D-1) was obtained in a yield of 12%.

<Example 7: Coupling of meta-substituted aryloxazoline compound (2)>

  The reaction was conducted in the same manner as in Example 1 except that the meta-substituted oxazoline compound (C-2) (0.5 mmol) was used instead of the oxazoline compound (A-1) used in Example 1. The biaryl compound (D-2) was obtained in a yield of 31%.

<Example 8: Coupling of meta-substituted aryloxazoline compound (3)>

  The reaction was conducted in the same manner as in Example 1 except that the meta-substituted oxazoline compound (C-3) (0.5 mmol) was used instead of the oxazoline compound (A-1) used in Example 1. The biaryl compound (D-3) was obtained in a yield of 5%.

Examples 9-12: Coupling of aryloxazoline compounds using various hydrogen scavengers

  The reaction was conducted in the same manner as in Example 1 except that the acetate compound (1.5 mmol) shown in Table 6 was used as a hydrogen scavenger instead of allyl acetate used in Example 1, and the title biaryl compound ( B-1) was obtained. Table 6 shows the yield of the obtained biaryl compound (B-1).

  As shown in Table 6, it can be seen that any of the hydrogen scavengers used in this example can efficiently produce biaryl compounds. In particular, allyl acetate (Example 1) and 2-phenylallyl acetate (Example) It can be seen that the yield of biaryl compounds can be improved when Example 12) is used as a hydrogen scavenger.

<Example 13: Coupling of aryloxazoline compound under various conditions (1)>

A Schlenk flask was charged with RuCl ₂ (PPh ₃ ) ₃ (5.0 mol%, 0.025 mmol based on Ru) and anhydrous potassium carbonate (1.0 mmol) and purged with nitrogen. Next, dehydrated xylene (1.0 ml), oxazoline compound (A-1) (0.5 mmol) and allyl acetate (1.5 mmol) were added, and the mixture was heated at 120 ° C. for 20 hours with stirring under a nitrogen stream. After completion of the reaction, 15 ml of diethyl ether was added to the reaction solution, and the deposited precipitate was separated by filtration. Thereafter, the filtrate was collected, concentrated, and purified by silica gel flash chromatography using ethyl acetate / hexane as an eluent to obtain the biaryl compound (B-1) in a yield of 57%.

<Comparative Example 1; coupling of aryloxazoline compound under various conditions (2)>
Instead of RuCl ₂ (PPh ₃ ) ₃ used in Example 13, [RhCl (cod)] ₂ (0.025 mmol based on Rh) and triphenylphosphine (0.10 mmol) were used as a catalyst. The reaction was performed in the same manner as in Example 1 except that. However, the biaryl compound (B-1) could not be obtained.

<Comparative Example 2; coupling of aryloxazoline compound under various conditions (3)>
Implementation was carried out except that PdCl ₂ (cod) (5.0 mol%) and triphenylphosphine (0.10 mmol) were mixed and used instead of RuCl ₂ (PPh ₃ ) ₃ used in Example 13. The reaction was carried out in the same manner as in Example 1. However, the biaryl compound (B-1) could not be obtained.

<Example 14: Coupling of aryloxazoline compound under various conditions (4)>
The reaction was carried out in the same manner as in Example 1 except that N-methylpyrrolidone (1.0 ml) was used as the organic solvent instead of xylene used in Example 13, and the biaryl compound (B-1) was obtained in a yield. Obtained at 46%.

  According to the present invention, a biaryl compound having a relatively free functional group can be easily produced with excellent reaction efficiency without requiring expensive and complicated production equipment. The various biaryl compounds produced in this way are useful as many chemical products such as chemical catalysts or their synthetic intermediates through complex formation with transition metals or as such.

Claims (6)

The following formula (I):

A method for producing a biaryl compound represented by the formula:
The following formula (II):

A step of reacting an oxazoline compound represented by formula (I) in an organic solvent in the presence of a ruthenium catalyst and a hydrogen scavenger;
Including
Here, in the formulas (I) and (II),
R ¹ , R ² , and R ³ are each independently
(i) a hydrogen atom;
(ii) —NR ³⁰ R ³¹ (wherein R ³⁰ and R ³¹ are each independently a hydrogen atom or a C _{1 to} C ₄ which may be branched and may be substituted with a halogen atom) An alkyl group)
(iii) a cyano group;
(iv) a nitro group;
(v) a carbamoyl group;
_{(vi) N- (C 1 ~C} 4 alkyl) carbamoyl group;
(vii) an N, N-di (C ₁ -C ₄ alkyl) carbamoyl group;
(viii) —NHCOR ¹⁹ (wherein R ¹⁹ is a hydrogen atom or a C ₁ -C ₄ alkyl group which may be branched and may be substituted with a halogen atom);
(ix) may form a branched or cyclic and may be substituted with a halogen atom, an alkyl group of C ₁ -C _6;
(x) may form a branched or cyclic and may be substituted with a halogen atom, an alkenyl group of C ₂ -C _6;
(xi) may form a branched or cyclic and may be substituted with a halogen atom, an alkynyl group of C ₂ -C _6;
(xii) an aralkyl group, wherein the aryl moiety constituting the aralkyl group is
Branched C ₁ may be substituted in good and halogen atoms optionally -C ₄ alkyl group,
Branched C ₁ may be substituted in good and halogen atoms have -C ₅ alkoxy group,
It branched _C 1 may be substituted in good and halogen atoms optionally -C ₄ alkyl group, a cyano ^{group, -NR} 30 ^{R 31 (wherein, R 30} and ^{R 31} each, independently, a hydrogen atom or is or optionally branched C ₁ -C ₄ substituted in well and halogen atoms have an alkyl group), a nitro group, a carbamoyl group, N- (C ₁ ~C ₄ alkyl) carbamoyl group, N, N-di _(C 1 -C ₄ alkyl) carbamoyl group or -NHCOR ^{19 (wherein,} either ^{R 19} is a hydrogen atom, or an optionally substituted branched to be the well and a halogen atom _{C 1} -C ₄ alkyl group is one) may be substituted by an aryl group,
A cyano group,
—NR ³⁰ R ³¹ (wherein R ³⁰ and R ³¹ are each independently a hydrogen atom or a C ₁ -C ₄ alkyl group which may be branched and substituted with a halogen atom) ),
Nitro group,
A carbamoyl group,
An N- (C ₁ -C ₄ alkyl) carbamoyl group,
N, N-di _(C 1 -C ₄ alkyl) carbamoyl group, and -NHCOR ^{19 (wherein,} either ^{R 19} is a hydrogen atom, or an optionally substituted branched to be the well and a halogen atom _{C 1} ~C is ₄ or alkyl group)
An aralkyl group optionally substituted with at least one group selected from the group consisting of:
(xiii) a heteroaralkyl group having a heteroaryl moiety, wherein the heteroaryl moiety is
Branched C ₁ may be substituted in good and halogen atoms optionally -C ₄ alkyl group,
Branched C ₁ may be substituted in good and halogen atoms have -C ₅ alkoxy group,
It branched _C 1 may be substituted in good and halogen atoms optionally -C ₄ alkyl group, a cyano ^{group, -NR} 30 ^{R 31 (wherein, R 30} and ^{R 31} each, independently, a hydrogen atom or is or optionally branched C ₁ -C ₄ substituted in well and halogen atoms have an alkyl group), a nitro group, a carbamoyl group, N- (C ₁ ~C ₄ alkyl) carbamoyl group, N, N-di _(C 1 -C ₄ alkyl) carbamoyl group or -NHCOR ^{19 (wherein,} either ^{R 19} is a hydrogen atom, or an optionally substituted branched to be the well and a halogen atom _{C 1} -C ₄ alkyl group is one) may be substituted by an aryl group,
A cyano group,
—NR ³⁰ R ³¹ (wherein R ³⁰ and R ³¹ are each independently a hydrogen atom or a C ₁ -C ₄ alkyl group which may be branched and substituted with a halogen atom) ),
Nitro group,
A carbamoyl group,
An N- (C ₁ -C ₄ alkyl) carbamoyl group,
N, N-di _(C 1 -C ₄ alkyl) carbamoyl group, and -NHCOR ^{19 (wherein,} either ^{R 19} is a hydrogen atom, or an optionally substituted branched to be the well and a halogen atom _{C 1} ~C is ₄ or alkyl group)
A heteroaralkyl group optionally substituted with at least one group selected from the group consisting of:
(xiv) an aryl group, wherein the aryl group is
Branched C ₁ may be substituted in good and halogen atoms optionally -C ₄ alkyl group,
Branched C ₁ may be substituted in good and halogen atoms have -C ₅ alkoxy group,
It branched _C 1 may be substituted in good and halogen atoms optionally -C ₄ alkyl group, a cyano ^{group, -NR} 30 ^{R 31 (wherein, R 30} and ^{R 31} each, independently, a hydrogen atom or is or optionally branched C ₁ -C ₄ substituted in well and halogen atoms have an alkyl group), a nitro group, a carbamoyl group, N- (C ₁ ~C ₄ alkyl) carbamoyl group, N, N-di _(C 1 -C ₄ alkyl) carbamoyl group or -NHCOR ^{19 (wherein,} either ^{R 19} is a hydrogen atom, or an optionally substituted branched to be the well and a halogen atom _{C 1} -C ₄ alkyl group is one) may be substituted by an aryl group,
A cyano group,
—NR ³⁰ R ³¹ (wherein R ³⁰ and R ³¹ are each independently a hydrogen atom or a C ₁ -C ₄ alkyl group which may be branched and substituted with a halogen atom) ),
Nitro group,
A carbamoyl group,
An N- (C ₁ -C ₄ alkyl) carbamoyl group,
N, N-di _(C 1 -C ₄ alkyl) carbamoyl group, and -NHCOR ^{19 (wherein,} either ^{R 19} is a hydrogen atom, or an optionally substituted branched to be the well and a halogen atom _{C 1} ~C is ₄ or alkyl group)
And may be substituted with at least one group selected from the group consisting of: or —O— (CH ₂ ) _p —O— (where p is 1 or 2) An aryl group optionally substituted with
(xv) heteroaryl group, where the heteroaryl group is branched C ₁ may be substituted in good and halogen atoms optionally -C ₄ alkyl group,
Branched C ₁ may be substituted in good and halogen atoms have -C ₅ alkoxy group,
It branched _C 1 may be substituted in good and halogen atoms optionally -C ₄ alkyl group, a cyano ^{group, -NR} 30 ^{R 31 (wherein, R 30} and ^{R 31} each, independently, a hydrogen atom or is or optionally branched C ₁ -C ₄ substituted in well and halogen atoms have an alkyl group), a nitro group, a carbamoyl group, N- (C ₁ ~C ₄ alkyl) carbamoyl group, N, N-di _(C 1 -C ₄ alkyl) carbamoyl group or -NHCOR ^{19 (wherein,} either ^{R 19} is a hydrogen atom, or an optionally substituted branched to be the well and a halogen atom _{C 1} -C ₄ alkyl group is one) may be substituted by an aryl group,
A cyano group,
—NR ³⁰ R ³¹ (wherein R ³⁰ and R ³¹ are each independently a hydrogen atom or a C ₁ -C ₄ alkyl group which may be branched and substituted with a halogen atom) ),
Nitro group,
A carbamoyl group,
An N- (C ₁ -C ₄ alkyl) carbamoyl group,
N, N-di _(C 1 -C ₄ alkyl) carbamoyl group, and -NHCOR ^{19 (wherein,} either ^{R 19} is a hydrogen atom, or an optionally substituted branched to be the well and a halogen atom _{C 1} ~C is ₄ or alkyl group)
A heteroaryl group optionally substituted with at least one group selected from the group consisting of:
In _{(xvi) -S (O) n} -R 20 ( where, n represents 0, 1 or 2, and ^{R 20} is branched optionally _C 1 may be substituted in good and halogen atom- is a C ₄ alkyl group);
Or, among R ¹ , R ² , and R ³ , R ¹ and R ² , or R ² and R ³ are the following formula (III):

The remainder is the oxazoline ring proximal substituent,
Here, in the formula (III),
R ⁵ , R ⁶ , R ⁷ and R ⁸ are each independently
(i) a hydrogen atom;
(ii) —NR ³⁰ R ³¹ (wherein R ³⁰ and R ³¹ are each independently a hydrogen atom or a C _{1 to} C ₄ which may be branched and may be substituted with a halogen atom) An alkyl group)
(iii) a cyano group;
(iv) a nitro group;
(v) a carbamoyl group;
_{(vi) N- (C 1 ~C} 4 alkyl) carbamoyl group;
(vii) an N, N-di (C ₁ -C ₄ alkyl) carbamoyl group;
(viii) —NHCOR ¹⁹ (wherein R ¹⁹ is a hydrogen atom or a C ₁ -C ₄ alkyl group which may be branched and may be substituted with a halogen atom);
(ix) may form a branched or cyclic and may be substituted with a halogen atom, an alkyl group of C ₁ -C _6;
(x) may form a branched or cyclic and may be substituted with a halogen atom, an alkenyl group of C ₂ -C _6;
(xi) may form a branched or cyclic and may be substituted with a halogen atom, an alkynyl group of C ₂ -C _6;
(xii) an aralkyl group, wherein the aryl moiety constituting the aralkyl group is
Branched C ₁ may be substituted in good and halogen atoms optionally -C ₄ alkyl group,
Branched C ₁ may be substituted in good and halogen atoms have -C ₅ alkoxy group,
It branched _C 1 may be substituted in good and halogen atoms optionally -C ₄ alkyl group, a cyano ^{group, -NR} 30 ^{R 31 (wherein, R 30} and ^{R 31} each, independently, a hydrogen atom or is or optionally branched C ₁ -C ₄ substituted in well and halogen atoms have an alkyl group), a nitro group, a carbamoyl group, N- (C ₁ ~C ₄ alkyl) carbamoyl group, N, N-di _(C 1 -C ₄ alkyl) carbamoyl group or -NHCOR ^{19 (wherein,} either ^{R 19} is a hydrogen atom, or an optionally substituted branched to be the well and a halogen atom _{C 1} -C ₄ alkyl group is one) may be substituted by an aryl group,
A cyano group,
—NR ³⁰ R ³¹ (wherein R ³⁰ and R ³¹ are each independently a hydrogen atom or a C ₁ -C ₄ alkyl group which may be branched and substituted with a halogen atom) ),
Nitro group,
A carbamoyl group,
An N- (C ₁ -C ₄ alkyl) carbamoyl group,
N, N-di _(C 1 -C ₄ alkyl) carbamoyl group, and -NHCOR ^{19 (wherein,} either ^{R 19} is a hydrogen atom, or an optionally substituted branched to be the well and a halogen atom _{C 1} ~C is ₄ or alkyl group)
An aralkyl group optionally substituted with at least one group selected from the group consisting of:
(xiii) a heteroaralkyl group having a heteroaryl moiety, wherein the heteroaryl moiety is
Branched C ₁ may be substituted in good and halogen atoms optionally -C ₄ alkyl group,
Branched C ₁ may be substituted in good and halogen atoms have -C ₅ alkoxy group,
It branched _C 1 may be substituted in good and halogen atoms optionally -C ₄ alkyl group, a cyano ^{group, -NR} 30 ^{R 31 (wherein, R 30} and ^{R 31} each, independently, a hydrogen atom or is or optionally branched C ₁ -C ₄ substituted in well and halogen atoms have an alkyl group), a nitro group, a carbamoyl group, N- (C ₁ ~C ₄ alkyl) carbamoyl group, N, N-di _(C 1 -C ₄ alkyl) carbamoyl group or -NHCOR ^{19 (wherein,} either ^{R 19} is a hydrogen atom, or an optionally substituted branched to be the well and a halogen atom _{C 1} -C ₄ alkyl group is one) may be substituted by an aryl group,
A cyano group,
—NR ³⁰ R ³¹ (wherein R ³⁰ and R ³¹ are each independently a hydrogen atom or a C ₁ -C ₄ alkyl group which may be branched and substituted with a halogen atom) ),
Nitro group,
A carbamoyl group,
An N- (C ₁ -C ₄ alkyl) carbamoyl group,
N, N-di _(C 1 -C ₄ alkyl) carbamoyl group, and -NHCOR ^{19 (wherein,} either ^{R 19} is a hydrogen atom, or an optionally substituted branched to be the well and a halogen atom _{C 1} ~C is ₄ or alkyl group)
A heteroaralkyl group optionally substituted with at least one group selected from the group consisting of:
(xiv) an aryl group, wherein the aryl group is
Branched C ₁ may be substituted in good and halogen atoms optionally -C ₄ alkyl group,
Branched C ₁ may be substituted in good and halogen atoms have -C ₅ alkoxy group,
It branched _C 1 may be substituted in good and halogen atoms optionally -C ₄ alkyl group, a cyano ^{group, -NR} 30 ^{R 31 (wherein, R 30} and ^{R 31} each, independently, a hydrogen atom or is or optionally branched C ₁ -C ₄ substituted in well and halogen atoms have an alkyl group), a nitro group, a carbamoyl group, N- (C ₁ ~C ₄ alkyl) carbamoyl group, N, N-di _(C 1 -C ₄ alkyl) carbamoyl group or -NHCOR ^{19 (wherein,} either ^{R 19} is a hydrogen atom, or an optionally substituted branched to be the well and a halogen atom _{C 1} -C ₄ alkyl group is one) may be substituted by an aryl group,
A cyano group,
—NR ³⁰ R ³¹ (wherein R ³⁰ and R ³¹ are each independently a hydrogen atom or a C ₁ -C ₄ alkyl group which may be branched and substituted with a halogen atom) ),
Nitro group,
A carbamoyl group,
An N- (C ₁ -C ₄ alkyl) carbamoyl group,
N, N-di _(C 1 -C ₄ alkyl) carbamoyl group, and -NHCOR ^{19 (wherein,} either ^{R 19} is a hydrogen atom, or an optionally substituted branched to be the well and a halogen atom _{C 1} ~C is ₄ or alkyl group)
And may be substituted with at least one group selected from the group consisting of: or —O— (CH ₂ ) _p —O— (where p is 1 or 2) An aryl group optionally substituted with
(xv) heteroaryl group, where the heteroaryl group is branched C ₁ may be substituted in good and halogen atoms optionally -C ₄ alkyl group,
Branched C ₁ may be substituted in good and halogen atoms have -C ₅ alkoxy group,
It branched _C 1 may be substituted in good and halogen atoms optionally -C ₄ alkyl group, a cyano ^{group, -NR} 30 ^{R 31 (wherein, R 30} and ^{R 31} each, independently, a hydrogen atom or is or optionally branched C ₁ -C ₄ substituted in well and halogen atoms have an alkyl group), a nitro group, a carbamoyl group, N- (C ₁ ~C ₄ alkyl) carbamoyl group, N, N-di _(C 1 -C ₄ alkyl) carbamoyl group or -NHCOR ^{19 (wherein,} either ^{R 19} is a hydrogen atom, or an optionally substituted branched to be the well and a halogen atom _{C 1} -C ₄ alkyl group is one) may be substituted by an aryl group,
A cyano group,
—NR ³⁰ R ³¹ (wherein R ³⁰ and R ³¹ are each independently a hydrogen atom or a C ₁ -C ₄ alkyl group which may be branched and substituted with a halogen atom) ),
Nitro group,
A carbamoyl group,
An N- (C ₁ -C ₄ alkyl) carbamoyl group,
N, N-di _(C 1 -C ₄ alkyl) carbamoyl group, and -NHCOR ^{19 (wherein,} either ^{R 19} is a hydrogen atom, or an optionally substituted branched to be the well and a halogen atom _{C 1} ~C is ₄ or alkyl group)
A heteroaryl group optionally substituted with at least one group selected from the group consisting of:
In _{(xvi) -S (O) n} -R 20 ( where, n represents 0, 1 or 2, and ^{R 20} is branched optionally _C 1 may be substituted in good and halogen atom- is a C ₄ alkyl group);
An oxazoline ring distal substituent selected from the group consisting of:
R ¹⁴ , R ¹⁵ , R ¹⁶ and R ¹⁷ are each independently a hydrogen atom, or may be branched or formed a ring, and may be substituted with a halogen atom, C ₁ -C _6. The method, wherein X is an alkyl group and X is an oxygen atom or a sulfur atom. The method according to claim 1, wherein R ¹ , R ² , and R ³ of the oxazoline compound represented by the formula (II) are each independently the oxazoline ring proximal substituent. The oxazoline compound represented by the formula (II) is represented by the following formula (II-2):

The method of Claim 1 which is a compound represented by these. The oxazoline compound represented by the formula (II) is represented by the following formula (II-3):

The method of Claim 1 which is a compound represented by these. Said hydrogen scavenger has the following formula (IV):

(here,
R ¹⁰ is an optionally branched C ₁ -C ₈ alkyl group, and R ¹¹ , R ¹² , and R ¹³ are each independently a hydrogen atom, optionally branched C ₁ -C ₄ alkyl group or aryl group)
The method in any one of Claim 1 to 4 which is ester of the allyl alcohol derivative represented by these. The ruthenium catalyst is RuCl ₂ (PPh ₃ ) ₃ or a catalyst produced by mixing [RuCl ₂ (cod)] _n and PPh _{3 according} to claim 1. Method.