A novel class of tunable cyclopropanation reagents (RXZnCH2Y) and their synthetic applications

Abstract

The Simmons-Smith cyclopropanation is a widely used method to synthesize cyclopropanes from alkenes using methylene iodide and a zinc reagent. A novel class of organozinc species, RXZnCH 2 Y, has been found to efficiently cyclopropanate alkenes, including traditionally unreactive unfunctionalized alkenes. The reactivity and selectivity of this class of organozinc reagents can be regulated by tuning the electronic and/or steric nature of the RX group attached to Zn. During recent years, this class of organozinc reagent has been widely used in organic synthesis as a reagent for cyclopropanation and other useful synthetic transformations. Catalytic, asymmetric versions of this reaction have been developed providing high enantiomeric excess for unfunctionalized olefins. On Lo AndreaWong was born in Hong Kong in 1981. She moved to Honolulu, Hawai'i in 1994 and received her B.Sc. degree in chemistry from the University of Hawai'i at Mānoa in 2003. She completed her doctoral dissertation in 2009 with Professor Yian Shi at Colorado State University. She is currently a postdoctoral fellow in Professor Christopher Ackerson's laboratory working on the synthesis of monodispersed thiolate-protected gold nanoparticles at Colorado State University.

Cyclopropane Pipecolic Acids as Templates for Linear and Cyclic Peptidomimetics: Application in the Synthesis of an Arg‐Gly‐Asp (RGD)‐Containing Peptide as an αvβ3 Integrin Ligand

“…Despite the low yield in compound 22 , we tried, after O ‐deprotection, its cyclopropanation by using the Wittig–Furukawa zinc carbenoid in CH 2 Cl 2 heated under reflux conditions. However, under these conditions, cyclopropanation of 24 occurred only in part accompanied by the complete loss of the Boc group to give an approximately 3:1 mixture of 2 c and 25 after 16 h. This was another unexpected result, since the N ‐Boc does seem perfectly tolerant to the Wittig–Furakawa cyclopropanation conditions,35a, 41 but the higher reaction temperature, longer reaction times, and probably the relative position of the OH group with respect to the N protection,42 could account for our results 43. Even at room temperature, N ‐Boc deprotection was the exclusive pathway.…”

Cyclopropanation of Various Substrates via Simmons-Smith and Michael-Initiated Ring Closure (MIRC) Reactions

“…In the present work, we applied two different types of substrates for subjecting to the cyclopropanation, i.e., electron rich and electron deficient olefins, which are compatible to the nature of the electrophilic active species in the Simmons-Smith reagent (XZnCH 2 Y) and nucleophilic sulfur ylide in the Michael-initiated ring closure reaction [12,13], respectively. These compounds were obtained either from commercial availability (compounds 14, 19 and 20), and by preparation (compounds 16, 18, 25, and 26).…”

“…The cyclopropanation of compound 16 using diethyl zinc and diiodomethane was also investigated. As shown in Table 2, the reaction was not proceed (entry 8 to 10) probably due to the incompatibility between the reagent and the substrate, i.e., the electrophilic nature of the active species EtZnCH 2 I versus the electron deficient olefin of the substrate, even after the application of the more reactive reagent CF 3 CO 2 ZnCH 2 I prepared by the addition of trifluoroacetic acid into the reaction mixture (entry 10) [12]. It is interesting to note that the reaction seemed to undergo in refluxing diethyl ether affording the product in 20.5% yield (entry 11).…”

Asymmetric Cyclopropanation Reactions

“…7 The popularity of the Simmons-Smith reaction arose from the broad substrate generality, the tolerance of a variety of functional groups, the stereospecificity with respect to the alkene geometry and the syn-directing and rate-enhancing effect observed with proximal oxygen atoms. 15 This last feature, in particular, was widely developed for asymmetric cyclopropanation of various enantiopure allylic alcohols. In addition, the Simmons-Smith reaction with a cyclic allylic alcohol takes place in such a manner that the cyclopropane ring is formed on the same side as the hydroxyl group.…”