Histidine-Catalyzed Asymmetric Aldol Addition of Enolizable Aldehydes: Insights into its Mechanism

Extensive studies of asymmetric cross-aldol addition between enolizable aldehydes are described and provide a deeper insight into histidine-catalyzed aldol additions. In particular, aspects of enantio- as well as diastereoselectivity of these reactions are discussed. Rules and predictions of configurative outcome are explained by using different transition-state models. These discussions are confirmed by extensive computations

Histidine-Catalyzed Asymmetric Aldol Addition of Enolizable Aldehydes: Insights into its Mechanism

Extensive studies of asymmetric cross-aldol addition between enolizable aldehydes are described and provide a deeper insight into histidine-catalyzed aldol additions. In particular, aspects of enantio- as well as diastereoselectivity of these reactions are discussed. Rules and predictions of configurative outcome are explained by using different transition-state models. These discussions are confirmed by extensive computations

Stereoselectivities of Histidine-Catalyzed Asymmetric Aldol Additions and Contrasts with Proline Catalysis: A Quantum Mechanical Analysis

Quantum mechanical calculations reveal the origin of diastereo- and enantioselectivities of aldol reactions between aldehydes catalyzed by histidine, and differences between related reactions catalyzed by proline. A stereochemical model that explains both the sense and the high levels of the experimentally observed stereoselectivity is proposed. The computations suggest that both the imidazolium and the carboxylic acid functionalities of histidine are viable hydrogen-bond donors that can stabilize the cyclic aldolization transition state. The stereoselectivity is proposed to arise from minimization of gauche interactions around the forming C–C bond

Chemoenzymatic Synthesis of Vitamin B5-Intermediate (<i>R</i>)‑Pantolactone via Combined Asymmetric Organo- and Biocatalysis

The combination of an asymmetric organocatalytic aldol reaction with a subsequent biotransformation toward a “one-pot-like” process for the synthesis of (<i>R</i>)-pantolactone, which to date is industrially produced by a resolution process, is demonstrated. This process consists of an initial aldol reaction catalyzed by readily available l-histidine followed by biotransformation of the aldol adduct by an alcohol dehydrogenase without the need for intermediate isolation. Employing the industrially attractive starting material isobutanal, a chemoenzymatic three-step process without intermediate purification is established allowing the synthesis of (<i>R</i>)-pantolactone in an overall yield of 55% (three steps) and high enantiomeric excess of 95%