Process for producing enyne derivatives

摘要

A process for producing an enyne derivative of the formula: wherein R<1> is a hydrogen atom, a lower alkyl group, a halo lower alkyl group, a lower alkenyl group, a lower alkynyl group or a cycloalkyl group, R<2> is a hydrogen atom or a group of the formula: wherein each of R<3>, R<3><1> and R<3><2> which may be the same or different, is a hydrogen atom or a lower alkyl group, each of R<4>, R<5>, R<4><1> and R<5><1> which may be the same or different, is a hydrogen atom, a halogen atom, a hydroxyl group, a lower alkyl group or a lower alkoxy group, R<4><2> is a hydroxyl group, a halogen atom, a group of the formula B-O- (wherein B is a protecting group for a hydroxyl group), a hydroxymethyl group, a formyl group, a carboxyl group, a lower alkoxycarbonyl group, a lower alkanoyl group, an amino group, a mercapto group or a group of the formula R<6>-X-Y- (wherein R<6> is a phenyl or thienyl group which may have one or two substituents selected from the group consisting of a halogen atom, a hydroxyl group, a lower alkyl group, a cyano group, a lower alkoxy group and a heterocyclic group, each of X and Y which may be the same or different, is an oxygen atom, a sulfur atom, a carbonyl group, a group of the formula -CHR- (wherein R is a hydrogen atom or a lower alkyl group) or a group of the formula -NR- (wherein R is a hydrogen atom or a lower alkyl group), or X and Y together form a vinylene group or an ethynylene group), provided that when either one of X and Y is an oxygen atom, a sulfur atom or a group of the formula -NR-(wherein R is as defined above), the other is a carbonyl group or a group of the formula -CHR- (wherein R is as defined above), and R<7> is a lower alkyl or cycloalkyl group which may have a hydroxyl group or a lower alkoxy group, a phenyl group or a tri-lower alkylsilyl group, which process comprises reacting a compound of the formula: Z-CH2-CH=CH-W [I] wherein W is a halogen atom, and Z is a leaving group, with an amine of the formula: wherein R<1><1> is a hydrogen atom, a lower alkyl group, a halo lower alkyl group, a lower alkenyl group, a lower alkynyl group or a cycloalkyl group, and R<2><1> is a hydrogen atom or a group of the formula: wherein R<3>, R<4>, R<5>, R<3><1>, R<3><2>, R<4><1>, R<4><2> and R<5><1> are as defined above, if necessary in the presence of a base, to obtain a compound of the formula: wherein R<1><1>, R<2><1> and W are as defined above, then reacting to this compound an acetylene derivative of the formula: HC IDENTICAL C-R<7> [V] wherein R<7> is as defined above, in the presence of a palladium catalyst, to obtain a compound of the formula: wherein R<1><1>, R<2><1> and R<7> are as defined above, and, if necessary, N-alkylating this compound.