syn-Selective asymmetric cross-aldol reactions between aldehydes and glyoxylic acid derivatives catalyzed by an axially chiral amino sulfonamide

Abstract

syn-Selective asymmetric cross-aldol reactions of aldehydes with tert-butyl glyoxylate and glyoxamide were realized by the use of an axially chiral amino sulfonamide (S)-1. The cross-aldol products obtained are densely functionalized and readily converted to synthetically useful and important chiral building blocks such as γ-lactone and γ-lactam.

Unique properties of chiral biaryl-based secondary aminecatalysts for asymmetric enamine catalysis

“…On the other hand, with the binaphthyl-based amino sulfonamide (S)-1 as catalyst, both tertbutyl glyoxylate and glyoxamide 13 were transformed to the corresponding syn-aldol adducts predominantly with excellent enantioselectivity (Scheme 2). 6 The observed switch in diastereoselectivity can be well explained by transition state models as shown in Fig. 4.…”

“…The obtained aldol adducts were versatile intermediates in organic synthesis and were readily converted to important chiral building blocks (Scheme 3). 6 The aldol adduct 12 (syn/anti ¼ 4.7/1) could be converted to g-lactam 15 (anti/syn ¼ 4.0/1) by reductive amination and heating of the resulting amine. When the aldol adduct 14 (syn/anti ¼ 17/1) was treated with 4 M HCl under reux, g-lactone 16 (anti/syn ¼ 17/1) was obtained in good yield with complete retention of the stereochemistry.…”

δ-Valerolactamic Quaternary Amino Acid Derivatives: Enantiodivergent Synthesis and Evidence for Stereodifferentiated β-Turn-Inducing Properties

“…With both N -protected aldehydes 3c and 8b in hand, we next investigated their reductive amination to access pseudoenantiomeric lactamic cDAA precursors (Scheme ). The reaction of 3c with benzylamine using NaBH 3 CN or NaBH­(OAc) 3 in the presence of acetic acid, respectively, without or with preformation of the corresponding imine (Scheme , eq 1), afforded the corresponding secondary amine 9c in good yield (70%). When extended to ( R )-α-methylbenzylamine, the reductive amination was performed in 77% yield ( 10c ).…”

Design of Bifunctional Amino Tf‐Amide Organocatalysts and Application in Various Asymmetric Transformations

“…After evaluation of reaction conditions, we found that sterically bulky tert ‐butyl glyoxylate 21 is effective to improve the stereoselectivity. In the presence of 2 mol% of I , the reaction between propanal and tert ‐butyl glyoxylate 21 produced syn ‐aldol adducts 22 a in moderate yield with high selectivity in acetonitrile at room temperature for 1 hour (Scheme 13a, 61 % yield, syn / anti =5.3/1, 97 % ee) [21] . Under the identical reaction conditions, several aldehydes 1 were employed and the corresponding syn ‐aldol adducts 22 b ‐ e were afforded in high yield with moderate syn ‐selectivity, and excellent enantioselectivity.…”