Multigram Synthesis and C−C/C−N Couplings of Functionalized 1,2‐Disubstituted Cyclopropyltrifluoroborates

Abstract

A convenient approach to the multigram synthesis of functionalized 1,2‐disubstituted cyclopropyltrifluoroborates was developed, based on Pd(II)‐ or Cu(I)‐catalyzed reaction of vinyltrifluoroborate and diazo compounds. Optimized protocols allowed for the preparation of the target products as pure diastereomers on multigram scale. It was shown that the title compounds were good coupling partners for the Suzuki‐Miyaura and Chan‐Lam reactions, which provide medicinally relevant (het)arylcyclopropanes with high diastereoselectivity.magnified image

Recent Advances in the Synthesis of CF3‐ or HCF2‐Substituted Cyclopropanes

“…The coupling of the borate building block with other partners gave various CF 3 ‐cyclopropanes. Recently, Grygorenko and co‐workers found the cyclopropanation of a vinyltrifluoroborate with CF 3 CHN 2 catalyzed by Pd(OAc) 2 could proceed smoothly to provide 6 on a large scale (Scheme 6b) [34c] . Although only one CF 3 ‐substituted coupling product was shown in the paper, this work still deserves attention because of the successful large‐scale cyclopropanation.…”

Copper(i) and silver(i) chemistry of vinyltrifluoroborate supported by a bis(pyrazolyl)methane ligand

“…2 Molecular structure of (SIPr)Cu(MeCN)(CH 2 vCHBF 3 ) (4). Selected bond distances (Å) and angles (°): C28-C29, 1.3682 (18); Cu-C1, 1.9756(10); Cu-N3, 1.9741(11); Cu-C28, 2.1061 (12); Cu-C29, 2.0936( 13); C28-B, 1.6187( 19); B-C28-Cu, 109.52( 8); C29-C28-B, 122.87 (12); C28-Cu-C29, 38.03( 5); C1-Cu-N3, 112.78(4); and Cu-N3-C32, 174.50 (12).…”

“…We note that coinage metal complexes involving organoborates are also of interest as reaction intermediates and for PET imaging work. 10 Furthermore, reactions involving vinylcuprates with BF 3 additives 11 and copper catalyzed reactions of vinyltrifluoroborates are known, 12 in which the formation of copper vinyltrifluoroborates as intermediates is a possibility. To test this hypothesis, we have also probed the use of pre-formed copper vinyltrifluoroborate as a catalyst for the synthesis of functionalized 1,2-disubstituted cyclopropyltrifluoroborates, and as a stoichiometric reagent to facilitate the ring opening reactions of an unhindered epoxide.…”

Cycloadditions of Alkenylboronic Derivatives

“…Recently, metal-catalyzed reactions of potassium vinyl trifluoroborate with several diazoacetates, 2,2,2-trifluorodiazoethane, and diazoacetonitrile were reported by our group (Scheme 22). 54 For each substrate, careful optimization of the reaction conditions was necessary to ensure the highest yield of the product. Thus, for ethyl, benzyl, and tert-butyl diazoacetates, optimal conditions included using Pd(OAc) 2 in THF at 45 °C.…”