The intermolecular or intramolecular asymmetric benzoin reaction was catalyzed by a small amount of N-heterocyclic carbene (NHC) (0.2-1 mol %) under solvent-free conditions. The solvent-free intramolecular asymmetric Stetter reaction also proceeded efficiently with NHC (0.2-1 mol %). In some cases, even solid-to-solid or solid-to-liquid conversions took place with low catalyst loading (0.2-1 mol %).
Attempts were made to minimize the
amounts of catalyst and solvent in the NHC-catalyzed benzoin reactions
of solid aldehydes. In some case, solid-to-solid conversions proceeded
in the solvent-free NHC-catalyzed benzoin reactions. Even if a mixture
of the substrate, N-heterocyclic carbene (NHC) precursor,
and inorganic base was initially a powdery solid, the reaction did
proceed at reaction temperature lower than the melting points of each
compound. The solid mixture partially melted or became a slurry or
suspension in the meantime. We call this solid/liquid mixture a semisolid
state. The reaction giving an optically active product was faster
than that giving a racemic mixture of the same product. Melting-point
depression was observed for a series of mixtures of the substrate
and product in different substrate/product ratios. Solvent-free solid-to-solid
conversions were accelerated by the formation of a semisolid state
resulting from the melting-point depression of the solid substrate
accompanied by the product formation. In the case of solid substrates
with high melting points, melting-point depression was useless, and
the addition of a small amount of solvent was needed. The first total
synthesis of isodarparvinol B was achieved via the NHC-catalyzed intramolecular
benzoin reaction using a small amount of solvent as an additive.
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