Optically active substituted 2,3-bisphosphinoquinoxalines and processes for producing the same

A process for preparing a compound represented by formula (1):

• or a stereoisomer thereof,
• wherein:
• each R1 represents alkyl, cycloalkyl, adamantyl, or aryl, wherein each alkyl is branched and has 3 or more carbon atoms, and further wherein each cycloalkyl is optionally substituted with 1 or more substituents independently selected from the group consisting of F, Cl, Br, I, alkyl, NH2, NH(alkyl), NH(aralkyl), NH(acyl), NHC(O)O(alkyl), NH(cycloalkyl), O(alkyl), and cycloalkyl, and each aryl is optionally substituted with 1 or more substituents independently selected from the group consisting of F, Cl, Br, I, alkyl, haloalkyl, NH2, NH(alkyl), N(alkyl)2, O(alkyl), and cycloalkyl, or two vicinal aryl substituents, together with the carbon atoms to which they are attached, form a fused alkylenedioxy moiety;
• R2 represents alkyl, cycloalkyl, or adamantyl, wherein the alkyl is branched and has 3 or more carbon atoms, and further wherein the cycloalkyl is optionally substituted with 1 or more substituents independently selected from the group consisting of F, Cl, Br, I, alkyl, NH2, NH(alkyl), NH(aralkyl), NH(acyl), NHC(O)O(alkyl), NH(cycloalkyl), O(alkyl), and cycloalkyl;
• each R3 independently represents F, Cl, Br, I, C1-5 alkyl, NH2, NO2, OH, or O(alkyl);
• n represents 0, 1, 2, 3, or 4;
• and
• * represents an assymetric center on a phosphorous atom;
• with the provisos that:
• (1) both R1 are identical;
• and
• (2) when R1 is tert-butyl, R1 and R2 are not identical;
• comprising the following steps:
• (1) reacting a compound represented by formula (2):
• wherein:
• each X independently represents Cl, Br, or I;
• each R3 independently represents F, Cl, Br, I, C1-5 alkyl, NH2, NO2, OH, or O(alkyl);
• and
• n represents 0, 1, 2, 3, or 4;
• with a deprotonated form of a compound represented by formula (3):
• wherein:
• each R1 represents alkyl, cycloalkyl, adamantyl, or aryl, wherein each alkyl is branched and has 3 or more carbon atoms, and further wherein each cycloalkyl is optionally substituted with 1 or more substituents independently selected from the group consisting of F, Cl, Br, I, alkyl, NH2, NH(alkyl), NH(aralkyl), NH(acyl), NHC(O)O(alkyl), NH(cycloalkyl), O(alkyl), and cycloalkyl, and each aryl is optionally substituted with 1 or more substituents independently selected from the group consisting of F, Cl, Br, I, alkyl, haloalkyl, NH2, NH(alkyl), N(alkyl)2, O(alkyl), and cycloalkyl, or two vicinal aryl substituents, together with the carbon atoms to which they are attached, form a fused alkylenedioxy moiety;
• with the proviso that both R1 are identical;
• in the presence of a deboranating agent selected from the group consisting of N,N,N′,N′-tetramethylethylenediamine, 1,4-diazabicyclo[2.2.2]octane, triethylamine, tetrafluoroboric acid, and trifluoromethanesulfonic acid, to provide a compound represented by formula (4):
• wherein:
• X represents Cl, Br, or I;
• each R1 represents alkyl, cycloalkyl, adamantyl, or aryl, wherein each alkyl is branched and has 3 or more carbon atoms, and further wherein the cycloalkyl is optionally substituted with 1 or more substituents independently selected from the group consisting of F, Cl, Br, I, alkyl, NH2, NH(alkyl), NH(aralkyl), NH(acyl), NHC(O)O(alkyl), NH(cycloalkyl), O(alkyl), and cycloalkyl, and each aryl is optionally substituted with 1 or more substituents independently selected from the group consisting of F, Cl, Br, I, alkyl, haloalkyl, NH2, NH(alkyl), N(alkyl)2, O(alkyl), and cycloalkyl, or two vicinal aryl substituents, together with the carbon atoms to which they are attached, form a fused alkylenedioxy moiety;
• each R3 independently represents F, Cl, Br, I, C1-5 alkyl, NH2, NO2, OH, or O(alkyl);
• and
• n represents 0, 1, 2, 3, or 4;
• with the proviso that both R1 are identical;
• and
• (2) reacting the compound of formula (4) above with a deprotonated form of a compound represented by formula (5):
• wherein:
• R2 represents alkyl, cycloalkyl, or adamantyl, wherein the alkyl is branched and has 3 or more carbon atoms, and further wherein the cycloalkyl is optionally substituted with 1 or more substituents independently selected from the group consisting of F, Cl, Br, I, alkyl, NH2, NH(alkyl), NH(aralkyl), NH(acyl), NHC(O)O(alkyl), NH(cycloalkyl), O(alkyl), and cycloalkyl;
• and
• * represents an assymetric center on a phosphorous atom;
• in the presence of a deboranating agent selected from the group consisting of N,N,N′,N′-tetramethylethylenediamine, 1,4-diazabicyclo[2.2.2]octane, triethylamine, tetrafluoroboric acid, and trifluoromethanesulfonic acid, to provide the compound represented by formula (1) above.

A process for preparing a compound represented by formula (1′):

• or a stereoisomer thereof,
• wherein:
• each R1 represents alkyl, cycloalkyl, adamantyl, or aryl, wherein each alkyl is branched and has 3 or more carbon atoms, and further wherein each cycloalkyl is optionally substituted with 1 or more substituents independently selected from the group consisting of F, Cl, Br, I, alkyl, NH2, NH(alkyl), NH(aralkyl), NH(acyl), NHC(O)O(alkyl), NH(cycloalkyl), O(alkyl), and cycloalkyl, and each aryl is optionally substituted with 1 or more substituents independently selected from the group consisting of F, Cl, Br, I, alkyl, haloalkyl, NH2, NH(alkyl), N(alkyl)2, O(alkyl), and cycloalkyl, or two vicinal aryl substituents, together with the carbon atoms to which they are attached, form a fused alkylenedioxy moiety;
• R2′ represents alkyl, cycloalkyl, or adamantyl, wherein the alkyl is branched and has 3 or more carbon atoms, and further wherein the cycloalkyl is optionally substituted with 1 or more substituents independently selected from the group consisting of F, Cl, Br, I, alkyl, NH2, NH(alkyl), NH(aralkyl), NH(acyl), NHC(O)O(alkyl), NH(cycloalkyl), O(alkyl), and cycloalkyl;
• each R3 independently represents F, Cl, Br, I, C1-5 alkyl, NH2, NO2, OH, or O(alkyl);
• n represents 0, 1, 2, 3, or 4;
• and
• represents an assymetric center on a phosphorous atom;
• with the provisos that:
• (1) both R are identical;
• and
• (2) when R1 is tert-butyl, R and R2′ are not identical;
• comprising the following steps:
• (1) reacting a compound represented by formula (2):
• wherein:
• each X independently represents Cl, Br, or I;
• each R3 independently represents F, Cl, Br, I, C1-5 alkyl, NH2, NO2, OH, or O(alkyl);
• and
• n represents 0, 1, 2, 3, or 4;
• with a deprotonated form of a compound represented by formula (3):
• wherein:
• each R1 represents alkyl, cycloalkyl, adamantyl, or aryl, wherein each alkyl is branched and has 3 or more carbon atoms, and further wherein each cycloalkyl is optionally substituted with 1 or more substituents independently selected from the group consisting of F, Cl, Br, I, alkyl, NH2, NH(alkyl), NH(aralkyl), NH(acyl), NHC(O)O(alkyl), NH(cycloalkyl), O(alkyl), and cycloalkyl, and each aryl is optionally substituted with 1 or more substituents independently selected from the group consisting of F, Cl, Br, I, alkyl, haloalkyl, NH2, NH(alkyl), N(alkyl)2, O(alkyl), and cycloalkyl, or two vicinal aryl substituents, together with the carbon atoms to which they are attached, form a fused alkylenedioxy moiety;
• with the proviso that both R1 are identical;
• in the presence of a deboranating agent selected from the group consisting of N,N,N′,N′-tetramethylethylenediamine, 1,4-diazabicyclo[2.2.2]octane, triethylamine, tetrafluoroboric acid, and trifluoromethanesulfonic acid, to provide a compound represented by formula (4):
• wherein:
• X represents Cl, Br, or I;
• each R1 represents alkyl, cycloalkyl, adamantyl, or aryl, wherein each alkyl is branched and has 3 or more carbon atoms, and further wherein each cycloalkyl is optionally substituted with 1 or more substituents independently selected from the group consisting of F, Cl, Br, I, alkyl, NH2, NH(alkyl), NH(aralkyl), NH(acyl), NHC(O)O(alkyl), NH(cycloalkyl), O(alkyl), and cycloalkyl, and each aryl is optionally substituted with 1 or more substituents independently selected from the group consisting of F, Cl, Br, I, alkyl, haloalkyl, NH2, NH(alkyl), N(alkyl)2, O(alkyl), and cycloalkyl, or two vicinal aryl substituents, together with the carbon atoms to which they are attached, form a fused alkylenedioxy moiety;
• each R3 independently represents F, Cl, Br, I, C1-5 alkyl, NH2, NO2, OH, or O(alkyl);
• and
• n represents 0, 1, 2, 3, or 4;
• with the proviso that both R1 are identical;
• and
• (2) reacting a liquid solvent selected from the group consisting of tetrahydrofuran, N,N-dimethylformamide, cyclopentyl methyl ether, diethyl ether, dibutyl ether, dioxane, hexane, and toluene, or a combination thereof, comprising (a) the compound of formula (4) above, and (b) a compound represented by formula (5′):
• wherein:
• R2′ represents alkyl, cycloalkyl, or adamantyl, wherein the alkyl is branched and has 3 or more carbon atoms, and further wherein the cycloalkyl is optionally substituted with 1 or more substituents independently selected from the group consisting of F, Cl, Br, I, alkyl, NH2, NH(alkyl), NH(aralkyl), NH(acyl), NHC(O)O(alkyl), NH(cycloalkyl), O(alkyl), and cycloalkyl;
• and
• * represents an assymetric center on a phosphorous atom;
• with a base selected from the group consisting of n-butyllithium, sec-butyllithium, lithium diisopropylamide, methylmagnesium bromide, potassium-tert-butoxide, N,N-diisopropylethylamine, potassium hydroxide, and sodium hydroxide, in the presence of a deboranating agent selected from the group consisting of N,N,N′,N′-tetramethylethylenediamine, 1,4-diazabicyclo[2.2.2]octane, triethylamine, tetrafluoroboric acid, and trifluoromethanesulfonic acid, to provide the compound represented by formula (1′) above.