α-Alkylation of Chiral Sulfinimines for Constructing Quaternary Chiral Carbons by Introducing Removable Directing Groups

Abstract

This study developed a facile and efficient synthetic strategy to construct quaternary chiral centers at the α-position of imines and ketones. High regioselectivity and diastereoselectivity were achieved through the synergetic effect of electron-withdrawing directing groups and N-tert-butyl sulfinamide as chiral auxiliaries. Either of them could be removed under the optimized conditions without any epimerization.

Transition Metal-Catalyzed α-Position Carbon–Carbon Bond Formations of Carbonyl Derivatives

“…The same group extended their strategy to include various allyl carbonate precursors, and the linear mono-allylated products were obtainable from a range of cyclic chiral sulfinimines [43]. The construction of chiral quaternary carbons at the α-position of chiral sulfinimines was proposed by Yang and coworkers in 2018 (Scheme 30) [44]. In the initial step, chiral sulfinimines 71 and allyl chloroformate give β-amino enoates 75 in the presence of NaHMDS.…”

“…Facilitated by the electron-withdrawing effects of the ester, β-amino enoates 75 undergo NaHMDS-promoted alkylation at the α-position of chiral sulfinimines 71 in a diastereoselective manner. The construction of chiral quaternary carbons at the α-position of chiral sulfinimines was proposed by Yang and coworkers in 2018 (Scheme 30) [44]. In the initial step, chiral sulfinimines 71 and allyl chloroformate give β-amino enoates 75 in the presence of NaHMDS.…”

“…The construction of chiral quaternary carbons at the α-position of chiral sulfinimines was proposed by Yang and coworkers in 2018 (Scheme 30) [44]. In the initial step, chiral sulfinimines 71 and allyl chloroformate give β-amino enoates 75 in the presence of NaHMDS.…”

An Efficient Method for Constructing Cyclic β-Amino Acids Bearing Quaternary Stereocenters

“…[20][21][22][23][24][25][26][27][28] In our previous work, we reported a NaHMDS-promoted asymmetric α-alkylation of chiral sulfimines. 29 Compounds bearing a quaternary stereocenter at the α-position of chiral sulfimines were obtained in high yields and diastereoselectivities, with broad substrate toler-ance. Encouraged by these results, we intended to use the asymmetric alkylation of chiral sulfimines to access cyclic β-amino acids bearing α-quaternary stereocenters.…”

“…Our retrosynthetic analysis, shown in Scheme 1, was based on access to the chiral scaffold 3 from 4 through an asymmetric alkylation reaction. 29 We envisaged that synthesis of the amino acid analogues 2, containing the requisite stereochemical information and substitution pattern for ready transformation into β-amino acids, might be achieved from chiral sulfimines 3 by asymmetric reduction of the imine. The β-amino acids 1 might be accessed from intermediate 2 by sequential removal of the allyl group and the sulfinyl chiral auxiliary.…”