Facile and Environmentally Benign Zn-Mediated Cyclopropanation of Electron-Deficient 2-Iodoethyl-Substituted Olefins via Radical 3-exo-trigManner

Abstract

An efficient, simple, cheap, and environmentally benign preparation of cyclopropanes via 3-exo-trig manner from various electron-deficient 2-iodoethyl-substituted olefins with zinc powder in a mixture of t-butyl alcohol and water was achieved.The cyclopropane ring is highly strained; nevertheless, a wide variety of naturally occurring cyclopropane derivatives bearing potent utility and biological activity are known. 1 Therefore, synthetic study of the cyclopropane ring is still important. Practical methods for the formation of cyclopropanes with olefinic groups have been carried out with free carbene derived from haloform under basic conditions, 2 diazo-olefins with the Rh-catalyst, 3 the Simmons-Smith reactions 4 and others. 5 These cyclopropanation reactions proceed effectively, especially with the diazo-olefins with the Rh-catalyst and the SimmonsSmith reaction. However, generally electron-rich olefins are required, since these reactions proceed via an electrophilic manner. On the other hand, the formation of cyclopropanes via radical pathways is challenging and interesting, since the cyclopropylmethyl radicals formed via 3-exo-trig manner onto an olefinic group are thermodynamically much disfavored because of their ring strain, 6 and the carbon-centered radicals are generally nucleophilic, and, therefore, electron-deficient olefins are required. 7 Today, to the best of our knowledge, studies on the formation of cyclopropanes via radical 3-exo-trig manner are extremely limited. Thus, for the typical radical reagent system (Bu 3 SnH with AIBN in refluxing benzene), Jung reported an interesting study: the introduction of a gem-dialkoxy group to the 5-position of 6-bromo-2-hexenoate esters dramatically promoted a radical 4-exotrig cyclization to provide the corresponding cyclobutanes (a-cyclobutylacetate esters). 8 Based on this result, methyl 5-bromo-4,4-dimethoxy-2-pentenoate was treated with Bu 3 SnH and AIBN in refluxing benzene. However, the expected cyclopropane derivative was not formed, 9 since ring-opening reaction of the formed cyclopropylmethyl radical occurred rapidly. On the other hand, electrochemical reductive cyclization of ethyl 5-methanesulfonyloxy-4,4-dimethyl-2-pentenoate was effectively carried out to form the corresponding cyclopropane. 10 Photolysis of 2-substituted butyrophenones gave the corresponding cyclopropyl phenyl ketones through a Norrish II-type pathway. 11 A metal-induced radical 3-exo-trig cyclization was reported to occur with chromous acetate, resulting in the formation of 11b-hydroxy-5,9-cyclopregnane-3,20-dione by SET reduction of 9a-bromo-11b-hydroxyprogestrone bearing a d-bromo-a,b-unsaturated ketone group. 12 Treatment of d-iodo-and d-bromo-a,bunsaturated esters with SmI 2 in the presence of t-butyl alcohol in THF gave the corresponding cyclopropanes. 13 The same treatment of g,g-disubstituted d-oxo-a,b-unsaturated esters with SmI 2 in the presence of t-butyl alcohol in THF provided the corresponding cyclopropanols via the ketyl radicals. 14 Among these cyclopropanation...