Stereoselective Preparation of Polyfunctional Cyclopentane Derivatives by Radical Nickel‐ or Palladium‐Catalyzed Carbozincations

Abstract

AbstractThe reaction of 5‐hexenyl iodides with diethylzinc (2 equiv) and catalytic amounts of a PdII or NiII complex like PdCl2(dppf), PdCl2(MeCN)2, or Ni(acac)2 results in an efficient ring closure (THF, RT, 2–12 h) affording cyclopentylmethylzinc iodides, which, after transmetalation with CuCN·2LiCl, can be further functionalized by treatment with a range of electrophiles like allylic halides, acyl chlorides, enones, nitroolefins, ethyl propynoate, and alkynyl halides to yield polyfunctional cyclopentane derivatives. The ring closures occur via radical intermediates, and the stereochemistry of the products can be explained according to the rules for radical cyclizations developed by Beckwith. The preparation of several di‐ and trisubstituted cyclopentanes has been achieved with high stereoselectivity. Tandem ring closures can be performed to construct bicyclic or tricyclic ring systems. Cyclizations of iodo‐ethylenic and acetylenic esters and ketones can be accomplished, although the high reactivity of acetylenic ketones leads to unexpected cyclization products. The synthetic utility of this method has been demonstrated by an enantioselective synthesis of (+)‐methyl epijasmonate and (‐)‐methyl cucurbate.