Stereoselective Cyclopropanation as a Way to 1‐Aminocyclopropane‐1‐phosphonic Acids: Rationale for Phosphoryl Group Migration

Abstract

Asymmetric cyclopropanation of vinylphosphonates by using (S)‐dimethylsulfonium(p‐tolylsulfinyl)methylide and subsequent highly stereoselective methylation provided substituted cyclopropylphosphonates, which are useful intermediates in the synthesis of rigid aminophosphonic acids. However, in some examples desulfinylation by iPrMgCl led to 1,2‐migration of the phosphoryl group. The scope of this transformation was investigated by changing the temperature, electronegativity of the substituent α to phosphoryl group, and the configuration of the cyclopropylphosphonates. It was found that a cis relationship between the phosphoryl and sulfinyl groups led exclusively to the product of migration. It was proposed that the rearrangement occurred as an internal process in a concerted manner. The feasibility of an intramolecular mechanism was supported by DFT calculations. The products of desulfinylation with retained structure were used for the synthesis of enantiomerically pure 1‐aminocyclopropane‐1‐phosphonic acids.

Phenylsilane as an effective desulfinylation reagent

“…Our recent investigations were connected with the synthesis and further conversion of multifunctional cyclopropanes, where the carboxylate moiety was present in close proximity to sulfinyl and phosphoryl substituents [18–20]. A selective and effective method of the independent conversion of each of these substituents is therefore a subject of our interest.…”