Current progress in the asymmetric aldol addition reaction

Abstract

Control of stereochemistry during aldol addition reactions has attracted considerable interest over the years as the aldol reaction is one of the most fundamental tools for the construction of new carbon-carbon bonds. Several strategies have been implemented whereby eventually any single possible stereoisomeric aldol product can be accessed by choosing the appropriate procedure. With earlier methods, stoichiometric quantities of chiral reagents were required for efficient asymmetric induction, with the auxiliary most often attached covalently to the substrate carbonyl. Lewis acid catalyzed addition reactions of silyl enolates to aldehydes (Mukaiyama reaction) later opened the way for catalytic asymmetric induction. In the last few years, both chiral metal complexes and small chiral organic molecules have been found to catalyse the direct aldol addition of unmodified ketones to aldehydes with relatively high chemical and stereochemical efficiency. These techniques along with the more recent developments in the area are discussed in this tutorial review.

Indução assimétrica 1,5-Anti na adição de enolatos de boro de metilcetonas beta-oxigenadas a aldeídos

“…A reação aldólica é seguramente um dos métodos mais poderosos para a formação de ligações carbono-carbono [1][2][3][4][5][6][7] . Esta reação representa uma ferramenta muito útil na construção de fragmentos com alta complexidade estrutural e com elevados níveis de seletividade, sendo bastante empregada na síntese assimétrica de produtos naturais com atividade farmacológica destacada 8,9 .…”

Stereoselective Synthesis of <i>cis</i>-Substituted-3’-anilino-2’, 3’-dihydro-4-2’-benzo[<i>b</i>]furanylcoumarins via Intramolecular Aldol Reactions

“…The intramolecular reaction of carbon nucleophiles with an electrochemically generated intermediate can provide a unique means for generating new carbon-carbon bonds, and this may also be used to generate a reactive intermediate to construct the dihydrobenzofuran skeletons under mild conditions [19]. Similarly proline catalyzed aldol reaction plays an important role as carbon-carbon bond formation 2 [20][21][22][23] Further mechanistic studies, that is Nitrones undergo deoxygenative reductive coupling and subsequent cyclisation to 3 [24]. Hence carbon nucleophiles are generally unstable under electro-oxidative conditions because most of the nucleophiles possess electron-rich heteroatoms or aromatic rings.…”

Catalytic Asymmetric Synthesis of trans‐Configured β‐Lactones: Cooperation of Lewis Acid and Ion Pair Catalysis

“…[3,5] Accordingly, the development of catalytic, asymmetric [2 + 2] cycloadditions of ketenes [6] and aldehydes [7][8][9] offers the possibility of replacing catalytic asymmetric aldol reactions, which often require the preformation and isolation of enolate equivalents such as silyl ketene acetals. [10] Various bioactive natural and synthetic products possessing a b-lactone structural motif can act as specific enzyme inhibitors. [11,12] Among the derivatives of natural products, tetrahydrolipstatin (orlistat, Xenical) has been identified as an anti-obesity agent and is available as over-the-counter weight-loss medication in a number of countries.…”