Method for producing optically active naphthalene compound

摘要

The present invention provides an industrially advantageous method for producing an optically active naphthalene compound useful as a therapeutic agent for dermatitis or the like. Specifically, the present invention provides a method for producing an optically active naphthalene compound [I], which comprises: a step of reacting a compound [a-1] and a compound [b-1] with each other in the presence of a base and a catalyst that is composed of a Pd compound and a tertiary phosphine ligand (step a); a step of asymmetrically hydrogenating a compound [c-1] in the presence of a hydrogen donor and a complex that is prepared from a ruthenium compound and a chiral ligand, or alternatively in the presence of an optically active oxazaborolidine compound (a CBS catalyst) and a boron hydride compound (step b); and a step of treating a compound [d-1] with a reducing agent (step c). (In the above formulae, Ra and Rb represent the same or different lower alkyl groups; and X1 represents a halogen atom.).;

主权项

1. A method of producing an optically active naphthalene compound of the following formula [I]: which comprises the following steps of:
(step a) reacting a compound of the following formula [a-1]: wherein Ra and Rb are the same or different and each of them is a lower alkyl group and X1 is a halogen atom with a compound of the following formula [b-1]: in the presence of a catalyst comprising a palladium compound and a tertiary phosphine ligand and a base and in the presence or absence of water or a water-donating substance to produce a compound of the following formula [c-1]: wherein the symbols are the same as defined above, or a solvate thereof,
(step b) subjecting the above compound [c-1] or a solvate thereof to(A) an asymmetric hydrogenation in the presence of a ruthenium complex (a chiral ruthenium catalyst) prepared from a ruthenium compound and a chiral ligand and a hydrogen donor and in the presence or absence of a base, or(B) an asymmetric hydrogenation in the presence of an optically active oxazaborolidine compound (CBS catalyst) of the following formula [R-CBS]: wherein Ph represents a phenyl group and R0 is a lower alkyl group or a phenyl group and a boron hydride compound to produce a compound of the following formula [d-1]: wherein the symbols are the same as defined above, or a solvate thereof, and
(step c) treating the above compound [d-1] or a solvate thereof with a reducing agent.