Facile synthesis of a family of H_8BINOL-amine compounds and catalytic asymmetric arylzinc addition to aldehydes

摘要

A family of optically active H_8BINOL-AM compounds containing 3,3′-bis-tertiary amine substituents are synthesized by using a one-step reaction of H_8BINOL with amino methanols that were in situ generated from various cyclic or acyclic secondary amines and paraformaldehyde. The H _8BINOL-AM compounds are used to catalyze the reaction of functional arylzincs, in situ prepared from the reaction of aryliodides with ZnEt _2, with aldehydes to produce chiral diaryl carbinols and a few arylalkyl carbinols. Through this study, highly enantioselective catalysts were identified. It was found that the H_8BINOL-AM compounds with sterically less congested cyclic or acyclic amino methyl substituents were more enantioselective than those with more bulky substituents. The pyrrolidinyl derivative (S)-12 in most cases showed greater enantioselectivity than other H_8BINOL-AM compounds, especially for the challenging ortho-substituted aromatic aldehydes. A H_8BINOL-AM with 3,3′-bis-sec-amine substituents, prepared by a multistep method, was also used to catalyze the arylzinc addition to aldehydes, but it showed enantioselectivity lower than that of the compounds with tertiary amine groups. It was found for the first time that an aryl bromide, 2-bromothiophene, could be used to prepare an arylzinc reagent by reaction with ZnEt_2. The addition of this heteroarylzinc reagent to an aldehyde in the presence of (S)-12 proceeded with good enantioselectivity.