Stereoselective Synthesis of Quaternary Pyrrolidine-2,3-diones and β-Amino Acids

Abstract

A facile, diastereoselective synthesis of highly substituted pyrrolidine-2,3-diones is reported, along with the one-step conversion of these heterocycles to novel β-amino acids and further functionalized derivatives. This method involves an unusually mild, one-pot, three-component cyclization/allylation followed by a Claisen rearrangement to provide unusual pyrrolidinone products that are densely functionalized and contain an all-carbon quaternary stereocenter. The reported reaction sequence is operationally simple, exquisitely diastereoselective, and provides gram-scale access to valuable heterocyclic scaffolds and β-amino acids not readily accessible via existing approaches.

Discovery of 3-hydroxy-3-pyrrolin-2-one-based mPGES-1 inhibitors using a multi-step virtual screening protocol

“…We were intrigued by this result, since this chemical core has shown a wide spectrum of biological activities, such as anticancer and antiviral, and chemical procedures have been reported for its decoration using multi-component reactions, then paving the way for future studies for the identification of chemical analogues. [48][49][50] On the other hand, 5 and 8 showed a modest activity ranging from ∼30 up to ∼40% of mPGES-1 inhibition, suggesting further investigations to identify the minimal pharmacophoric portions in order to obtain more potent analogues. We then investigated the biological activities of compounds 2 and 3 in more detail.…”

[1,3]/[1,4]-Sulfur atom migration in β-hydroxyalkylphosphine sulfides

“…In 29, the signal of the same carbon atom could be found at 133. 6 The shifts indicated the presence of a C-S and not a C-O bond in the carbon skeleton [64,65], and the coupling constant value was typical for an γ-carbon atom present in a phosphine derivative [67][68][69].…”

“…Among all organic reactions, rearrangements are an exciting class of transformations where unusual or even unexpected products can be obtained. Many rearrangements are of practical use in synthetic organic chemistry, including Beckmann [1][2][3][4], Claisen [5][6][7][8], pinacol [9][10][11][12], Wagner-Meerwein [13][14][15][16], Curtius [17][18][19][20], Hofmann [21][22][23][24], Overmann [25][26][27][28] rearrangements, and many others. In organophosphorus chemistry, rearrangements are less developed transformations, however, some examples can be found in the literature (Scheme 1).…”

Pyrrolidine‐2,3‐diones: Synthesis, reactions and biological activity

“…3.16.3. A diastereoselective synthesis of highly substituted pyrrolidine‐2,3‐diones ( 214 ) is reported by Shymanska and Pierce 77 . This method involves an unusually mild, one‐pot, three‐component cyclization/allylation to give 213 , followed by a Claisen rearrangement to provide pyrrolidinone products ( 214 ) (Scheme 72).…”