Diastereoselective Synthesis of 1,2,3-Substituted Potassium Cyclopropyl Trifluoroborates via an Unusual Zinc-Boron Exchange

Abstract

Diastereoselective cyclopropanation of an allylic alcohol with a gem-dizinc carbenoid followed by an unusual zinc-boron exchange and further treatment with excess KHF₂ afforded 1,2,3-syn-cis-substituted cyclopropyl trifluoroborates in 58-63% overall yields. The potassium cyclopropyl trifluoroborates underwent ­Suzuki-Miyaura cross-coupling reactions to give 1,2,3-functionalized cyclopropanes in good yields. Finally, an oxidation-epimerization sequence gave access to 1,2,3-trans-substituted cyclopropyl trifluoroborate.

Key words

carbenoids - zinc - cycloaddition - cross-coupling - dia­stereoselectivity

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10

Undesired cyclopropane 6a was easily separated since only potassium cyclopropyl trifluoroborate precipitated after the KHF₂ treatment.

11

Syn (or anti) stereochemistry relates to the relationship of the methylene group relative to the hydroxyl group, whereas the cis (or trans) stereochemistry relates to the relationship of the zinc (and subsequently the electrophile or boron group) relative to the hydroxymethylene group.

12

According to mechanistic studies: C. Molinaro, unpublished results.

15

We found that Pd(OAc)₂ and 2-biphenyldicyclohexyl-phosphine was optimal in our case.