2,2,2-Trichloroethyl Aryldiazoacetates as Robust Reagents for the Enantioselective C–H Functionalization of Methyl Ethers

Abstract

A new class of reagents is described for C-H functionalization by means of C-H insertion using donor/acceptor-substituted rhodium(II) carbene intermediates. The 2,2,2-trichloroethyl aryl and heteroaryl diazoacetates, together with the dirhodium triarylcyclopropane carboxylate catalyst Rh2(R-BPCP)4, enabled the enantioselective intermolecular C-H functionalization of a range of methyl ethers with high levels of site selectivity and enantioselectivity.

Enantioselective dirhodium(II)-catalyzed cyclopropanations with trimethylsilylethyl and trichloroethyl aryldiazoacetates

“…31-33 The TCE aryldiazoacetates have been reported recently as robust reagents and were successfully applied to the selective asymmetric C–H functionalization of methyl ethers by the Davies group. 26 Furthermore, the TCE group can be used with heteroaryldiazoacetates generating heteroaryl-substituted cyclopropanes, further expanding the scope of the reaction. Like TMSE, the TCE ester can be cleaved under mild conditions with Zn/AcOH (see supporting information).…”

“…25 Furthermore, in combination with the more sterically hindered 2,2,2-trichloroethyl aryldiazoacetates, site selective and enantioselective C–H functionalization of methyl ethers was achieved. 26 …”

A Stereoselective [3+1] Ring Expansion for the Synthesis of Highly Substituted Methylene Azetidines

“…Use of a Troc ester in 2j required no slow addition, giving excellent dr in 3aj . 14 The [3+1] reaction was also successful when the aryl of the diazo compound was replaced with a Me in 2ak . Dimerization of the diazoacetate was solved using multiple equivalents of 2k to provide 3ak in good dr .…”

Rhodium‐Catalyzed Enantioselective [4+2] Cycloadditions of Vinylcarbenes with Dienes

“…As the vinylogous reaction would be expected to generate zwitterionic intermediates, we decided to use electron rich 2‐siloxydienes as trapping agents. We have recently found that carbenes substituted with trichloroethyl esters often give a much cleaner reaction than the traditional methyl ester derivatives, and so, we chose the vinyldiazoacetate 21 as the initial carbene precursor. The study was conducted with two catalysts, Du Bois’ Rh 2 (esp) 2 , which is a relatively bulky achiral catalyst and the chiral catalyst Rh 2 ( R ‐ p ‐PhTPCP) 4 , which is one of our recently reported extremely bulky chiral catalysts .…”

“…We have recently found that carbenes substituted with trichloroethyl esters often give a much cleaner reaction than the traditional methyl ester derivatives, and so, we chose the vinyldiazoacetate 21 as the initial carbene precursor. The study was conducted with two catalysts, Du Bois’ Rh 2 (esp) 2 , which is a relatively bulky achiral catalyst and the chiral catalyst Rh 2 ( R ‐ p ‐PhTPCP) 4 , which is one of our recently reported extremely bulky chiral catalysts . The reaction of the vinyldiazoacetate 21 with the first diene examined, 2‐siloxybutadiene 20 , gave the [4+3] cycloadduct 22 with both catalysts.…”