Ruthenium–Porphyrin‐Catalyzed Diastereoselective Intramolecular Alkyl Carbene Insertion into CH Bonds of Alkyl Diazomethanes Generated In Situ from N‐Tosylhydrazones

Abstract

With a ruthenium-porphyrin catalyst, alkyl diazomethanes generated in situ from N-tosylhydrazones efficiently underwent intramolecular C(sp(3))-H insertion of an alkyl carbene to give substituted tetrahydrofurans and pyrrolidines in up to 99% yield and with up to 99:1 cis selectivity. The reaction displays good tolerance of many functionalities, and the procedure is simple without the need for slow addition with a syringe pump. From a synthetic point of view, the C-H insertion of N-tosylhydrazones can be viewed as reductive coupling between a C=O bond and a C-H bond to form a new C-C bond, since N-tosylhydrazones can be readily prepared from carbonyl compounds. This reaction was successfully applied in a concise synthesis of (±)-pseudoheliotridane.

Recent advances in the synthesis of tetrahydrofurans and applications in total synthesis

“…Among them, we can highlight the Hosomi-Sakurai reaction, recently applied by Cox and co-workers to the synthesis of 2,3,4-trisubstituted THF with moderate to good diastereoselectivities. 145 Still starting from an acyclic ether, the C-C bond can also be formed by a domino Heck-Suzuki reaction, as shown by Braun et al, 146 by reaction of a carbene with a benzylic ether, 147 following an indium-catalyzed hydrative cyclization of diyne. 148 Another strategy developed by Rovis and co-workers involves a cyclic acetal, which is activated by a Lewis acid to perform a ring contraction by Mukaiyama-aldol reaction leading M A N U S C R I P T A C C E P T E D ACCEPTED MANUSCRIPT to 2,3,4-trisubstituted THF.…”

Synthesis of Natural Products and Pharmaceuticals via Catalytic CH Functionalization

“…The most recent example of pyrrolidine synthesis by C-H functionalization was illustrated in 2014, when Che and coworkers demonstrated the synthesis of pseudoheliotridane, a simple pyrrolidine alkaloid, by employing a ruthenium-catalyzed C-H insertion reaction (Scheme 16.44) [89]. Although diazocarbonyl compounds are generally required as the precursor of the metal carbenoid intermediate, they utilized an alkyl diazomethane as the carbene source.…”

The chemistry of the carbon-transition metal double and triple bond: Annual survey covering the year 2014

“…709), which undergoes 1,3-dipolar addition with the alkyne to afford the aziridine-ketone after rearrangement. Use of ruthenium porphyrins as catalysts for C-H insertions using diazo compounds generated in situ from tosylhydrazones was also reported [963]. Several examples of Group 8 metal porphyrin complex mediated cyclopropanation reactions were also reported [964].…”