The Construction of Quaternary Stereocenters by the Henry Reaction: Circumventing the Usual Reactivity of Substituted Glyoxals

Abstract

The enantioselective Henry reaction between alkyl- and arylglyoxal hydrates and nitromethane catalyzed by Cu(II)-iminopyridine complexes takes place regioselectively on the ketone carbonyl group to give chiral tertiary nitroaldols with high functional group density and enantiomeric excesses of up to 96 %. Both aromatic and aliphatic glyoxals are suitable substrates for this reaction.

Enantioselective copper‐aminopyridine‐catalyzed aza‐Henry reaction with chelating N‐(2‐pyridyl)sulfonyl imines

“…With respect to the stereochemical mechanism, the results indicate a preference for the nitronate to attack from the Si face of the C═N double bond. According to our previous studies on the Henry reaction, we propose a plausible stereochemical model that would account for the observed stereochemistry (Fig. ).…”

“…Our group has developed new iminopyridine and aminopyridine ligands (Fig. ), which in the presence of copper(II) salts catalyzed the Henry reaction with carbonyl compounds very efficiently and with very high enantioselectivity . In this article, we describe the application of these catalysts in the enantioselective aza‐Henry reaction with N ‐(2‐pyridyl)sulfonyl aldimines.…”

The Application of Arylglyoxals in the Synthesis of Pyrrolo[2,3-d]pyrimidines via Multicomponent Reactions

“…1,2-Dicarbonyl compounds are among the most attractive precursors for the design and synthesis of heterocyclic compounds. Arylglyoxals (AG) are aromatic α-keto aldehydes containing both aldehyde and ketone functional groups with different reactivity, and recently there has been a considerable literature on different reactions of AGs and their derivatives, such as allylation [24], arylation [25], reductive amination [23], reductive coupling with dienes [27], Wittig [28], Cannizzaro [29], Mannich [30] and Henry [31] reactions. The main purpose of this short review is to show the application of AGs as precursors in reactions that lead to the synthesis of the pyrrolo [2,3d]pyrimidine derivatives via multicomponent reactions in the period of 2008-2018.…”

Asymmetric Synthesis of Chiral 1,3‐Diaminopropanols: Bisoxazolidine‐Catalyzed CC Bond Formation with α‐Keto Amides

“…We envisioned that the enantioselective synthesis of Nsubstituted 1,3-diaminopropanols could be accomplished in three steps by nitroaldol reaction of a-keto amides, which are unexplored starting materials in asymmetric catalysis, and subsequent reduction of the nitro and amide groups (Scheme 1). The first catalytic asymmetric nitroaldol reaction was developed in 1992 by Shibasaki and coworkers, who used a BINOL-derived rare-earth-metal complex.[3] This reaction has since received considerable attention and its value for the synthesis of important chiral building blocks and complex target compounds has been demonstrated by many research groups.[4] Relatively few examples of asymmetric nitroaldol reactions with ketones [5] are known compared to the wealth of reactions with aldehydes. The use of a-keto amides has not been reported to date, in fact, catalytic asymmetric intermolecular C À C bond formations with a-keto amides have so far been elusive.…”