Stereoselective α-Hydroxylation of Amides Using Oppolzer’s Sultam as Chiral Auxiliary

Abstract

An Oppolzer's sultam-based highly stereoselective α-hydroxylation of amides was developed to deliver the desired products in good yield and excellent diastereoselectivity (>20/1). The generally crystalline products and the recyclability of the chiral auxiliary illustrate the practicability and scalability of the current approach.

Bifunctional Ammonium Salt Catalyzed Asymmetric α‐Hydroxylation of β‐Ketoesters by Simultaneous Resolution of Oxaziridines

“…The enantioselective construction of α‐hydroxy‐β‐dicarbonyl structures by means of a direct α‐hydroxylation of prochiral 1,3‐dicarbonyl compounds is a very important synthesis strategy, especially when keeping in mind that these motifs are frequently found as such, or in a masked form, in natural products or biologically active pharmaceutical or agrochemical lead structures . Besides the use of chiral auxiliaries, the catalytic enantioselective reaction of 1,3‐dicarbonyl compounds with various electrophilic oxygen‐transfer reagents has turned out to be a very powerful strategy to control the newly formed stereogenic center . We have recently introduced a new class of bifunctional (thio)‐urea‐containing chiral quaternary ammonium salt catalysts 1 , which can be easily obtained in a modular fashion starting from simple trans ‐1,2‐cyclohexanediamine .…”

Synthesis of the Sex Pheromone of the Tea Tussock Moth Based on a Resource Chemistry Strategy

“…As Scheme 2 shows, the synthesis commenced from chiral lactone 2 which was ring-opened [14,15] under basic conditions and subjected to selective benzylation to give compound 4 . In practice it proved laborious to purify the very polar hydroxyacid, so it was used directly without further purification.…”

Use of chiral auxiliaries in the asymmetric synthesis of biologically active compounds: A review

“…Zhang et al reported the synthesis of the side chain of lithospermic acid, a nontoxic anti‐HIV agent. The main objective of their study was to assess the large‐scale viability of the asymmetric α‐hydroxylation methodology using Oppolzer's chiral auxiliary (Scheme ).…”

“…The first step of the strategy, performed on a 5‐g scale, consisted of an α‐hydroxylation from 203 by treatment with oxaziridine ( 204 ) and NaHMDS, leading to the corresponding α‐hydroxyl amide ( 205 ) with high diastereoselectivity (>20:1). Removal of the auxiliary by treatment with MeMgBr and methanol afforded 2.2 g (83%) of the α‐hydroxy ester 206 , an important intermediate of lithospermic acid …”