CONSPECTUS Rh-carbenes derived from α-diazocarbonyl compounds have found broad utility across a remarkable range of reactivity, including cyclopropanation, cyclopropenation, C–H insertions, heteroatom–H insertions, and ylide forming reactions. However, in contrast to α-aryl or α-vinyl-α-diazocarbonyl compounds, the utility of α-alkyl-α-diazocarbonyl compounds had been moderated by the propensity of such compounds to undergo intramolecular β-hydride migration to give alkene products. Especially challenging had been intermolecular reactions involving α-alkyl-α-diazocarbonyl compounds.

Enantiomerically enriched cyclobutanes are constructed by a three-component process in which t-butyl (E)-2-diazo-5-arylpent-4-enoates are treated with Rh2(S-NTTL)4 to provide enantiomerically enriched bicyclobutanes, which can subsequently engage in homoconjugate addition/enolate trapping sequence to give densely functionalized cyclobutanes with high diastereoselectivity. This three-component, two-catalyst procedure can be carried out in a single flask. Rh2(S-NTTL)4–catalyzed reaction of t-butyl (Z)-2-diazo-5-phenylpent-4-enoate gives the Buchner cyclization product in excellent enantioselectivity.

A novel, mixed-ligand chiral rhodium(II) catalyst, Rh2(S-NTTL)3(dCPA), has enabled the first enantioselective total synthesis of the natural product piperarborenine B. A crystal structure of Rh2(S-NTTL)3(dCPA) reveals a “chiral crown” conformation with a bulky dicyclohexylphenyl acetate ligand and three N-naphthalimido groups oriented on the same face of the catalyst. The natural product was prepared on large scale using rhodium-catalyzed bicyclobutanation/copper-catalyzed homoconjugate addition chemistry in the key step. The route proceeds in ten steps with an 8% overall yield and 92% ee.

Rh(II)-catalyzed reactions of diazoesters with organozinc reagents are described. Diorganozinc reagents participate in reactions with diazo compounds by two distinct, catalyst-dependent mechanisms. With bulky diisopropylethylacetate ligands, the reaction mechanism is proposed to involve initial formation of a Rh-carbene and subsequent carbozincation to give a zinc enolate. With Rh2(OAc)4, it is proposed that initial formation of an azine precedes 1,2-addition by an organozinc reagent. This straightforward route to the hydrazone products provides a useful method for preparing chiral quaternary α-aminoesters or pyrazoles via the Paul-Knorr condensation with 1,3-diketones. Crossover and deuterium labeling experiments provide evidence for the mechanisms proposed.

A facile, scalable synthesis of previously inaccessible trifluoromethyl and perfluoroalkyl triazoles is disclosed. Mediated by copper, this catalytic protocol enables access to 4-perfluoroalkyl triazoles from commodity chemicals. A catalytic Cu(II) system wherein copper serves two roles (generation of N-tosyl-2vinyldiazenes and N−N bond formation) allows for rapid assembly of 5-carboxyl-4-perfluoroalkyl-triazoles from N-tosylhydrazide and perfluoroalkyl acetoacetates. Ethyl 4,4,4-trifluoro-3-(2-tosylhydrazineylidene)butanoate, a previously unknown air and bench stable reagent for access to CF 3 -triazoles, was developed to enable this chemistry. This led to the identification of a series of crystalline hydrazone reagents that could be used as templates to construct an array of triazoles. Hydrolysis and decarboxylation parlay this approach into a means to access 5-H-4-CF 3 -triazoles. The approach exhibits high functional group tolerance and can be executed on a multigram scale.