trans-2,5-Disubstituted pyrrolidines: rapid stereocontrolled access from sulfones

Abstract

A direct and versatile route for the reliable synthesis of trans-2,5-disubstituted pyrrolidines from pyroglutamic acid is reported, which can be conducted at scale and without chromatographic purification of key intermediates.

Versatile One‐Pot Reductive Alkylation of Lactams/Amides via Amide Activation: Application to the Concise Syntheses of Bioactive Alkaloids (±)‐Bgugaine, (±)‐Coniine, (+)‐Preussin, and (−)‐Cassine

“…[13a] Other drawbacks associated with some of the methods are low yields, [12b,c] epimerization at a-position, [12j] or use of excess of highly toxic NaBH 3 CN as the reducing agent. [11, 12d,e] As a result, multistep transformations using either thioamides, [14c, 15] lactim ethers, [16] N-tert-butyl formamidines, [17] vinyl triflates, [18] or N-acyl/N-alkoxycarbonyl derivatives [19][20][21] remain the most reliable and widely adapted methods. Moreover, many aamidoalkylation methods are limited to silylated nucleophiles.…”

Rapid diastereocontrolled synthesis of 2,2,5-trisubstituted pyrrolidines

“…Noteworthy is the reduction of the vinyl double bond in the latter case; 21 this borohydride-type reduction of enamines compares very favourably with the diastereoselectivity of our earlier approaches 2,3,22 but is significantly superior in terms Fig. 1 Thermal ellipsoid plots (ORTEP-3 4 ) at 40% probability level for compounds 7a-c.…”

Synthesis and Biological Evaluation of tert-Butyl Ester and Ethyl Ester Prodrugs of L-γ-Methyleneglutamic Acid Amides for Cancer

“…Esterification of 41 with ethanol in the presence of sulfuric acid 18 produced 45 in 60% yield. A Bocprotecting reaction of the amide 11,14,[19][20][21] of 45 gave 46 in 91% yield. Introduction of the methylene group at C4 of compound 46 using a modified αmethylenation method 11,15 produced 35 in 55% yield.…”