Stereoselective Synthesis of 3,5‐Dihydroxypyrrolidin‐2‐ones Through a Photoinduced Multicomponent Reaction Followed by Dimerization

Abstract

A photoinduced reaction between diazoketones, isocyanides and silanols, followed by aldol dimerization of the resulting multicomponent adduct, affords polyfunctionalized 3,5‐dihydroxypyrrolidin‐2‐one heterocycles in a straightforward manner. Six new bonds and two quaternary carbons are formed in just two steps with this complexity‐generating methodology. A high degree of stereoselectivity is also observed, as a result of the mild conditions employed. Moreover, the 3,5‐dihydroxypyrrolidin‐2‐one scaffold can be found in two families of biologically relevant natural products, namely anchinopeptolides and eusynstyelamides. The synthetic approach herein described appears to be a very convenient route for the preparation of their analogues.

The 100 facets of the Passerini reaction

“…Compared to α-acyloxyacrylamides 86, silyl enolethers 88 displayed a lower stability, especially during chromatographic purification: the disadvantage in terms of isolated yields turned into an added value in terms of reactivity, as these compounds could be efficiently subjected to the Mannich reaction, Saegusa oxidation, decarboxylative cyclization with α-amino acids, photoredox acetonylation 58 and interestingly to a tandem Michael/aldol dimerization reaction able to afford natural product-like compounds 89 in a very straightforward manner. 59,60 Six new bonds and three stereogenic centres, including two quaternary carbons, could be formed stereoselectively in just two steps, starting from diazoketones, silanols and isocyanides ( Scheme 24 ).…”