Asymmetric Copper‐Catalyzed Carbomagnesiation of Cyclopropenes

Abstract

The highly diastereo- and enantioselective formation of polysubstituted cyclopropanes was easily achieved through the asymmetric copper-catalyzed carbomagnesiation reaction of nonfunctionalized cyclopropene derivatives. The carbometalated species generated in situ readily undergo C-C and C-X bond-forming reactions with various electrophiles with complete retention of configuration.

Pd‐Catalyzed Selective Remote Ring Opening of Polysubstituted Cyclopropanols

“…We initially started our investigation with the racemic diastereomerically pure ω‐ene cyclopropanol 1 a possessing three methylene units between the double bond and the cyclopropyl ring as model substrate and tested the previously reported Heck reaction conditions . We were pleased to observe that the reaction of cyclopropanol 1 a with PhI (1.2 equiv) as a source of the aryl halide, Pd(OAc) 2 (5 mol %), tris (4‐trifluoromethylphenyl)‐phosphine (15 mol %), NaHCO 3 (2.5 equiv) and TBACl (2 equiv) in THF at 70 °C for 24 hours, proceeded successfully to afford the desired aldehyde 2 a as the unique E ‐isomer, accompanied by its Heck‐regioisomer 3 a in a 5.7:1 ratio, in a low combined yield (Table , entry 1).…”

“…It should be emphasized that cyclopropanols 1 are easily accessible through asym-metric catalysis as described in Scheme 1, path ba nd the formation of enantiomerically enriched aldehydes 2 possessinga still challenging acyclicq uaternary carbon stereocenter, present in numerousn atural produts, would in fact result from two catalytic steps (Cu-and Pd-catalyzed) from achiral cyclopropenes. [14] We initially started our investigation with the racemic diastereomerically pure w-ene cyclopropanol 1a possessing three methylene units between the double bond and the cyclopropyl ring as model substrate [14a] and tested the previously reported Heck reactionc onditions. [11a] We were pleased to observe that the reaction of cyclopropanol 1a with PhI (1.2 equiv) as a source of the aryl halide, Pd(OAc) 2 (5 mol %), tris(4-trifluoromethylphenyl)-phosphine (15 mol %), NaHCO 3 (2.5 equiv) and TBACl (2 equiv) in THFa t7 0 8Cf or 24 hours, proceeded successfully to afford the desired aldehyde 2a as the unique Eisomer,a ccompanied by its Heck-regioisomer 3a in a5 .7:1 ratio, in al ow combined yield ( Table 1, entry 1).…”

“…Because enantiomerically enriched w-ene cyclopropanols can easily be preparedb ya symmetric carbometalation of cyclopropenes [14] and because the chiral quaternary center is at no risk of epimerization in the process, the opticalp urity can be assumed to be identical throughout the combined Heck arylation-metal walk-ring fragmentation. Indeed, when enantio- [a] Isolated yields after purification by columnc hromatography.…”

Cobalt‐Catalyzed Reductive Dimethylcyclopropanation of 1,3‐Dienes

“…It is attractive to consider an alternative approach based on the formation of dimethylcyclopropanes, [4] which are themselves common in biologically active compounds [2, 5] but may also be diversified into other frameworks through strain-induced ring-opening reactions. [6] The Simmons–Smith reaction is potentially well-suited to addressing these structures; however, it is known that the efficiency of Zn carbenoid-based cyclopropanations decreases significantly when using disubstituted gem -dihaloalkanes.…”

General Cyclopropane Assembly via Enantioselective Redox-Active Carbene Transfer to Aliphatic Olefins

“…[8] However,common aliphatic alkenes [9] [11g] or alkenyl-methylidenes [11h] are too unstable to engage in cyclopropanation reactions.A s ar esult, the derived cyclopropanes still require long and specific syntheses. [5,6d,e, 11e,12] We conceived au nified strategy [13] to comprehensively address the formal asymmetric transfer of carbenes (6)(7)(8)(9)(10)(11)(12)to alkene feedstocks (5;S cheme 1b)t hrough at wo-stage Scheme 1. State-of-the-art, concept, and challenges towards the unified assemblyo fdiverse chiral cyclopropanes.…”