Stereospecific Synthesis of α‐Hydroxy‐Cyclopropylboronates from Allylic Epoxides

Abstract

Herein, we report a catalytic and stereospecific method for the preparation of enantioenriched a-hydroxy cyclopropylboronates with control in four contiguous stereocenters. The reaction involves the borylation of readily available allylic epoxides using an inexpensive Cu(I) salt and a commercially available phosphine ligand. High diastereocontrol is achieved and different diastereomers can be selectively prepared. Functionalization of the carbon-boron bond provides access to different enantiomerically enriched trisubstituted cyclopropanes from a common intermediate.

Boron Reagents and Catalysts for the Functionalization of Strained Heterocycles

“…The research group of Miura reported an asymmetric aminoboration of oxa‐ and azabicyclic alkenes with diboron reagents [B 2 pin 2 , Bpin‐Bdan (dan=1,8‐diaminonaphthalenyl)] and O ‐benzoyl‐hydroxylamines under copper catalysis while maintaining the bicyclic framework [83] . Very recently, Tortosa and co‐workers reported a couple of striking examples of the potentiality of copper‐boryl complexes in organic synthesis [84,85] . They discovered that aryl substituted vinylepoxides (such as A , Scheme 23) after initial regioselective carboboration to give intermediate B , undergo an intramolecular S N 2 type reaction to afford stereospecifically cyclopropylboronate D [84] .…”

“…Very recently, Tortosa and co‐workers reported a couple of striking examples of the potentiality of copper‐boryl complexes in organic synthesis [84,85] . They discovered that aryl substituted vinylepoxides (such as A , Scheme 23) after initial regioselective carboboration to give intermediate B , undergo an intramolecular S N 2 type reaction to afford stereospecifically cyclopropylboronate D [84] . Alternatively, if intermediate B is intercepted by protonolysis before cyclization, the corresponding epoxy boronate F undergoes base‐promoted β‐oxygen elimination to give a formal reduction product (Scheme 24).…”

Harnessing the Elusive 1,4-Reduction of Vinyl Epoxides through Copper Catalysis

“…Recently, we used vinyl epoxides to prepare cyclopropylboronates B using a readily available copper(I) catalyst. 11 The catalytic cycle involved the formation of organocopper A from a vinyl epoxide and a copper-boryl complex, followed by an intramolecular SN2-type reaction to provide B. We hypothesized that, in the presence of a proton source such as MeOH, 12 intermediate A would be intercepted before cyclization to afford epoxy boronate C. This intermediate could undergo a basepromoted b-oxygen elimination to give the formal reduction product.…”

“…To test our hypothesis, we selected vinyl epoxide 1a, previously used in our cyclopropane synthesis. 11,14 This starting point was of particular interest given that the 1,4-reduction of vinyl epoxides with a simple aryl group in the double bond is virtually unknown in the literature. 15 Gratifyingly, with similar conditions to those used for the cyclopropanes, in the presence of a proton source, we observed the formation of allylic alcohol 2a as a single E-isomer (Table 1, entry 1).…”

“…The catalytically active copper(I)boryl complex is formed first, followed by insertion of the alkene of the vinyl epoxide into the Cu-B bond to form intermediate A. According to our previous observations in the cyclopropane formation, 11 we assumed a syn approach of the copperboryl complex to the vinyl epoxide in an s-trans conformation (as shown in Scheme 6). Protonation of intermediate A prevents cyclization and provides epoxy boronate C. 25 From intermediate C a syn-elimination process would justify the E geometry of the newly formed double bond.…”