Role of Additives to Overcome Limitations of Intermolecular Rhodium-Catalyzed Asymmetric Cyclopropanation

Abstract

This study describes general methods for the enantioselective syntheses of disubstituted cyclopropane carboxylates including substitution patterns or heterocycle functionality previously observed as significant limitations. The key step is the dirhodium tetracarboxylate-catalyzed asymmetric cyclopropanation of vinyl arenes with aryl- or heteroaryldiazoacetates. The reactions are highly diastereoselective and high asymmetric induction could be achieved using either (<i>R</i>)-pantolactone as a chiral auxiliary or chiral dirhodium tetracarboxylate catalysts.

Copper(II) Acetate-Induced Oxidation of Hydrazones to Diazo Compounds under Flow Conditions Followed by Dirhodium-Catalyzed Enantioselective Cyclopropanation Reactions

“…Most of the aryldiazoacetate 2 remained unreacted (Table , entry 1), presumably because the DMAP required for the hydrazone oxidation suppresses the reactivity of the Rh­(II) catalyst in the second step. We have recently shown that HFIP as an additive in rhodium-catalyzed reactions can limit interference by nucleophilic heterocycles . Indeed, this was also the case here, as repeating the reaction with 20 equiv of HFIP generated the cyclopropane 3 in 64% yield with 97% ee (Table , entry 2).…”

“…We have recently shown that HFIP as an additive in rhodium-catalyzed reactions can limit interference by nucleophilic heterocycles. 37 Indeed, this was also the case here, as repeating the reaction with 20 equiv of HFIP generated the cyclopropane 3 in 64% yield with 97% ee (Table 2, entry 2). Insertion of O−H into water was a side product, but this could be eliminated by adding silica to the copper acetate in the first oxidation step (Table 2, entry 3).…”

Effects of Axial Solvent Coordination to Dirhodium Complexes on the Reactivity and Selectivity in C–H Insertion Reactions: A Computational Study

“…The main difficulty in this strategy is to find a suitable concentration of the additive that favors monocoordination over dicoordination since the latter would render the catalytic system inactive (Scheme , center and right). Additives such as tetramethyl urea, Hünig’s base, N , N -diethylaniline, 2,4,6-trimethylpyridine, TfNH 2 , 4-dimethylaminopyridine (DMAP), and 2-chloropyridine also have been used to modulate the reactivity and selectivity of dirhodium tetracarboxylate complexes through axial coordination. − …”