Abstract
A simple and efficient asymmetric synthesis of novel sp3 -rich pyrrolidine chemical scaffolds over five steps starting from simple ketones is described. Key steps involve the use of tert-butanesulfinamide as a chiral auxiliary to perform an asymmetric Tsuji-Trost allylation, with subsequent cross-metathesis with an acrylate ester and reduction of the sulfinimine/cyclisation of the resulting amine giving the pyrrolidine scaffolds in high yields and diastereoselectivites. By removing the chiral auxiliary and functionalising the ester group, the resulting scaffold core can be further derivatised.
Highlights
A simple and efficient asymmetric synthesis of novel sp3-rich pyrrolidine chemical scaffolds over five steps starting from simple ketones is described
Prior to applying the optimised reaction conditions of the allylation,[17,18] the focus was turned on the synthesis of required starting N-tert-butanesulfinyl imines 1a-l
The optimised conditions of the Tsuji-Trost allylation were applied on compounds 1a-l affording the corresponding α-allyl N-tert-butanesulfinyl imines 2a-l in good yields (44-83%) with d.r. up to >25:1 (Scheme 2)
Summary
A simple and efficient asymmetric synthesis of novel sp3-rich pyrrolidine chemical scaffolds over five steps starting from simple ketones is described. Key steps involve the use of tert-butanesulfinamide as a chiral auxiliary to perform an asymmetric Tsuji-Trost allylation, with subsequent cross-metathesis with an acrylate ester and reduction of the sulfinimine/cyclisation of the resulting amine giving the pyrrolidine scaffolds in high yields and diastereoselectivites. The α-allylation of chiral N-tert-butanesulfinyl imines derived from symmetric cyclic ketones was reported.[18] we envisioned taking advantage of the Tsuji-Trost allylation of N-tert-butanesulfinyl imines to access, in five steps, pyrrolidine-based chemical scaffolds as outlined in Scheme 1. We aimed to achieve this through cross metathesis of the allylated N-tert-butanesulfinyl imines, followed by reduction and ring cyclisation, using an intramolecular Michael addition
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