Asymmetric Tandem Conjugate Addition–Aldol Condensation with N-Acryloyloxazolidines Derived from 2-Phenylglycinol

The tandem 1,4-addition–aldol condensation reaction of diethylzinc, α,β-unsaturated chiral enantiopure oxazolidines derived from 2-phenylglycinol, and carbonyl compounds is disclosed. The reaction proceeds through a radical-polar crossover mechanism involving the aldol condensation of a trisubstituted zinc enolate through a Zimmerman–Traxler transition state. Installation of a 2-pyridine moiety at the hemiaminal position of the chiral auxiliary allows obtaining both excellent asymmetric induction and diastereoselectivity (up to >90 % de). The developed protocol is suitable for aromatic and aliphatic aldehydes, as well as ketones.