Enantioselective Synthesis of cis- and trans-Borocyclopropylmethanol: Simple Building Blocks To Access Heterocycle-Substituted Cyclopropylmethanols

Abstract

An enantioselective and non-oxidative methodology was developed to obtain enantioenriched cyclopropyl boronates using a diethanolamine-promoted selective decomplexation of dioxaborolane. The non-oxidative decomplexation of the dioxaborolane ligand from the cyclopropylmethoxide species formed in the dioxaborolane-mediated Simmons–Smith cyclopropanation reaction provided the enantio­enriched CIDA-based (CIDA = N-cyclohexyliminodiacetic acid) boro­cyclopropane in 92% yield and 95.6:4.4 er. A robustness screen has shown diethanolamine to be compatible with esters, carbamates and N-heterocycles, providing a tool to access enantioenriched cyclopropanes carrying not only base-sensitive but oxidizable functional groups as well. Diethanolamine was found to be compatible with the modified zinco-cyclopropanation reaction of allyl alcohol to remove residual dioxaborolane from the corresponding cis-N-heterocycle cyclopropylmethanol, thereby leading to improved yields.

Cyclopropanes to Spirocyclic Amine-Boranes: Merging Metal Free C‒H Bond Activation and C‒C Bond Cleavage

“…2b). 35 The spirocyclic boronate 3f represents a unique motif with two different spiroatoms in the form of boron and nitrogen. It must also be noted that based on the 11 B NMR spectrum, SAB 3f exists in equilibrium with the B-N bond dissociated product.…”