Chemistry

Carbene

Ketone

Ylide

Electrophile

Organic chemistry

Catalysis

Nucleophile

Intramolecular force

Lewis acids and bases

Enantioselective synthesis

Combinatorial chemistry

Medicinal chemistry

Accounts of Chemical Research

Conspectusα-Diazocarbonyl compounds serve as nucleophiles, dipoles, carbene precursors, and rare electrophiles, enabling a vast array of organic transformations under the influence of metal catalysts. Among them, rearrangement processes are attractive and provide straightforward and efficient accesses to one-carbon extension adducts or heteroatom-containing molecules. The reactions occur upon the release of dinitrogen after nucleophilic addition or before ylide formation. Although significant progress has been made for these two types of rearrangement reactions, the issue of enantiocontrol is challenging because the final optically enriched products are generated via multistep transformations and the inherent spacial arrangement of the intermediates has more or less influence on the regio- and enantioselectivity.In this Account, we collected several rearrangements of α-diazocarbonyl compounds, showcasing the efficient catalysts and tailored strategies for tackling enantioselective varieties of these two types of rearrangement reactions. Our research group initiated the catalytic asymmetric reactions of α-diazocarbonyl compounds during the development of chiral Feng N,N′-dioxide–metal complex catalysts and others. As a kind of useful chiral Lewis acid catalyst chiral N,N′-dioxide–metal complexes are favorable for the activation of various carbonyl compounds, accelerating the diastereo- and enantioselective nucleophilic addition of α-diazoesters and the sequential rearrangements in either an intermolecular or intramolecular manner. Aldehydes, acyclic and cyclic ketone derivatives, and α,β-unsaturated ketones could participate in efficient asymmetric homologation reactions, and an obvious ligand-acceleration effect is observed in these processes. For example, the Roskamp–Feng reaction of aldehydes gives optically active β-ketoesters through a H-shift, overwhelming the aryl group shift or oxygen attack. The shift preference and enantiocontrol in the homologation of acyclic and cyclic ketone derivatives could be under excellent control of the chiral catalysts. An unusual electrophilic α-amination of aryl/alkyl ketones and even a complicated homologation/dyotropic rearrangement/interconversion/[3 + 2] cycloaddition cascade used to construct dimeric polycyclic compounds were discovered as a result of the selection of chiral ligands and additives. On the basis of the understanding of the interaction of the functional group with N,N′-dioxide–metal complexes in catalysis and the key enantio-determining issues in ylide-based rearrangements, we designed new α-diazocarbonyl compounds by introducing a pyrazole-1-carboxyl group as the acceptor unit, which could benefit the formation of both carbenoid species and the chiral catalyst-bound ylides to deliver stereoselectivity. Taking advantage of Ni(II) or Co(II) complexes of Feng N,N′-dioxide ligands, we realized several kinds of enantioselective [2,3]-sigmatropic rearrangements, such as the Doyle–Kirmse reaction with allylic sulfides or selenides, [2,3]-Stevens rearrangements of vinyl-substituted α-diazo pyrazoleamides with thioacetates, Sommelet–Hauser rearrangements of aryl-substituted α-diazo pyrazoleamides with thioamides, and thio-Claisen rearrangements of 2-thio-indoles as well. Moreover, this strategy was shown to be applicable to highly γ-selective and enantioselective insertion into N–H bonds of secondary amines with vinyl-substituted α-diazo pyrazoleamides.

Asymmetric Catalytic Rearrangements with α-Diazocarbonyl Compounds