Synthesis of Enantiomerically Pure Cyclopropanes from Cyclopropylboronic Acids

Abstract

A general method for the stereocontrolled synthesis of cyclopropanes is described. Various, highly stable, enantiomerically pure alkenylboronic esters 13 have been conveniently synthesized by the direct hydroboration of alkynes 11 using the new chiral 1,3,2-dioxaborolane 15. The high stability was also demonstrated by the selective deprotection of a tert-butyldimethylsilyl protecting group without hydrolyzing the boronic ester. The diastereoselective cyclopropanation of the olefins was achieved by the palladium(II) acetate catalyzed decomposition of diazomethane. This process was optimized giving cyclopropylboronic esters 20/21 in high yield (89-99%) and with good to excellent diastereomeric ratios (up to 95:5). The diastereomers were separated by means of MPLC and their configurations determined by X-ray crystallography (compound 21c), by transformation to known cyclopropanols, and by correlation of NMR data. Treatment with LiAlH(4) followed by acidic hydrolysis yielded the enantiomerically pure cyclopropylboronic acid 27 for the first time and allowed the nearly quantitative recovery of the chiral auxiliary 3. Different protocols for the Suzuki coupling reaction of compound 27 were investigated.

Recent applications of the Suzuki–Miyaura cross-coupling reaction in organic synthesis

“…247,252,253 During the coupling reaction, the absolute configuration of the cyclopropyl group was retained. Soderquist et al have reported the hydroxy(cyclopropyl)-9-BBN complex 239, which undergoes an efficient crosscoupling reaction under mild conditions to produce a variety of aryl-and vinylcyclopropanes in good to excellent yield (Scheme 109).…”

Suzuki–Miyaura Cross‐Coupling Reactions of Alkylboronic Acid Derivatives or Alkyltrifluoroborates with Aryl, Alkenyl or Alkyl Halides and Triflates

“…[53] Then, using an enantiopure cyclopropylboronic acid in the presence of bromobenzene, iodobenzene or 1-bromonaphthalene, Pietruszka and Luithle were able to obtain enantiopure arylcyclopropanes. [54] They have also reported the coupling of a bicyclopropyl derivative with iodobenzene in good yield (Scheme 30). [55] Finally, in 2003 Pietruszka and co-workers reported the arylation of a functionalised cyclopropylboronic acid.…”

Kinetic Enzymatic Resolution of Cyclopropane Derivatives

“…The cyclopropanation was most conveniently performed by using diazomethane in the presence of catalytic amounts of Pd(OAc) 2 . [64,65] The conversion is usually high, however, in order to obtain pure cyclopropylboronic esters 23, some loss during work-up was acceptable. Oxidation to cyclopropanols 24 and acetylation to 25 using standard conditions was unproblematic (Scheme 7), nevertheless, some loss of material during distillation was observed.…”

“…[59±63] (known compounds: 22b, [65] 22h, [77] and 22i [63] ), cyclopropylboronic esters 23 (known compounds: 23b [65] and 23h [77] ), cyclopropanols 24 (known compounds 24a [70] and 24c [69] ), and vinyl acetate 26.…”