Highly Diastereoselective Strain-Increase Allylborations: Rapid Access to Alkylidenecyclopropanes and Alkylidenecyclobutanes

Allylboration of carbonyl compounds is one of the most widely used methods in the stereoselective synthesis of natural products. However, these powerful transformations are so far limited to allyl- or crotylboron reagents; ring-strained substituents in the alpha-position have not been investigated. Such substrates would lead to an increase in strain energy upon allylboration and as such cause a significant increase in the activation barrier of the reaction. Indeed, no reaction was observed between an alpha-cyclopropyl allylboronic ester and an aldehyde. However, by converting the boronic ester into the much more reactive borinic ester, the allylboration proceeded well giving alkylidenecyclopropanes in high yield. This process was highly diastereoselective and gives rapid access to versatile alkylidenecyclopropanes and alkylidenecyclobutanes. The chemistry shows a broad substrate scope in terms of both the range of vinylcycloalkyl boronic esters and aldehydes that can be employed. The intermediate boronate complexes were also found to be potent nucleophiles, reacting with a range of non-carbonyl-based electrophiles and radicals, leading to an even broader range of alkylidenecyclopropanes and alkylidenecyclobutanes. Using B-11 NMR experiments, we were able to track the intermediates involved, and DFT calculations supported the experimental findings.

Automated summary

The study presents a successful method for the synthesis of alkylidenecyclopropanes using borinic esters, showing high diastereoselectivity and rapid access to versatile alkylidenecyclopropanes and alkylidenecyclobutanes. The chemistry demonstrates a broad substrate scope and reactivity towards a range of electrophiles and radicals, leading to an even broader range of alkylidenecyclopropanes and alkylidenecyclobutanes. The intermediates involved were tracked using B-11 NMR experiments, with DFT calculations supporting the experimental findings.