Asymmetric Addition Of Pyridyl Aluminum Reagents To Aldehydes Catalyzed By A Titanium（IV） Catalytic System Of（R）-H₈-BINOLate

A series of chiral aryl methanols with pyridyl groups were synthesized through the asymmetric addition of pyridyl aluminum reagent to aldehydes catalyzed by(R)-H8-BINOL/Ti(OiPr)4. The asymmetric 3-pyridyl addition reactions of aldehydes were examined, and results showed that the substrate’s position of aromatic aldehydes had an effect on the enantioselectivity of phenyl transfer to aldehydes. For aromatic aldehydes with either an electron-withdrawing or an electron-donating substituent at the para- or meta-position, 3-pyridyl additions afforded the corresponding alcohols in high yields with excellent enantioselectivities. However, for aromatic aldehydes with either an electron-withdrawing or an electron-donating substituent at the ortho-position, 3-pyridyl additions afforded the corresponding products in low enantioselectivities, except for 2-methylbenzaldehyde. For heteroaromatic aldehydes ?,?-unsaturated aldehydes and aliphatic aldehydes including linear, branched, cyclic aldehydes, reactions afforded the corresponding products in high yields but with low to moderate enantioselectivities. A various of substituted pyridyl aluminum reagents were applied to the asymmetric addition of benzaldehyde. For substituted 3-pyridyl aluminum reagents with an electron-donating group, the reactions provided the corresponding 3-pyridyl methanols in good yields with moderate to good enantioselectivities. Reactions of benzaldehyde with substituted 3-pyridyl aluminum reagents bearing a weak electron-withdrawing group afforded the corresponding products in moderated yields with the low enantioselectivities. However, for 2-pyridyl or 3-pyridyl aluminum reagents bearing a strong electron-withdrawing group, the reaction efficiency was poor probably due to the weak nucleophilicity. The catalytic system could also be suitable for 4-pyridyl aluminums to afford the corresponding products in moderate yields with high enantioselectivities.In summary, the catalytic enantioselective heteroarylation of pyridyl aluminum nucleophile with aldehydes were developed employing the simple titanium catalyst of(R)-H8-BINOL to afford a series of chiral arylmethanols containing pyridyl group in high yields with excellent enantioselectivities.