The Aldol Addition Reaction: An Old Transformation at Constant Rebirth

Abstract

The main recent conceptual advances in asymmetric aldol reactions are presented. Methods ranging from stoichiometric chiral auxiliary-mediated to direct, catalytic reactions are covered, including the Mukaiyama aldol reactions which use stoichiometric base and silylating reagents, but catalytic (substoichiometric) amounts of the chiral inductor. The salient features of each new development are noted, paying special attention to practical concerns and to the potential implementation for large scale production. After examination of pros and cons of each strategy, gaps and limitations that deserve further investigation are highlighted.

Recent developments in enantioselective lanthanide-catalyzed transformations

“…Whereas many catalytic asymmetric versions of these reactions have been achieved using various types of chiral Lewis acids [42], the first reaction catalyzed by a chiral lanthanide was reported by Shibasaki et al only in 1995, providing moderate enantioselectivity of up to 49% ee [43]. The aqueous asymmetric Mukaiyama-aldol reaction catalyzed by chiral water-compatible lanthanide Lewis acids is one of the most attractive reactions for green chemistry.…”

Multimetallic Bifunctional Asymmetric Catalysis Based on Proximity Effect Control

“…27 On the other hand, the reaction proceeded syn-selectively with Boc-imines (Table 3). 28 syn-Adducts were obtained in good yield (67->99%), diastereomeric ratio (syn/anti = 72: 28-95:5), and enantioselectivity (89->99% ee) using aryl and heteroaryl imines (Entries [1][2][3][4][5][6][7][8][9][10][11][12][13][14]. Diastereoselectivity of alkenyl imine was, however, poor (Entry 15).…”

Solvent free Lewis acid catalyzed vinylogous condensation

“…1,2 In this context, the vinylogous reactions play an important part. 3 More vividly, among vinylogous reactions, the aldol addition reaction has attracted considerable interest over the years as a popular tool for the construction of new carbon-carbon bonds.…”