Enantiomerically Enriched Cyclopropene Derivatives: Versatile Building Blocks in Asymmetric Synthesis

Abstract

Enantiomerically enriched cyclopropene derivatives, the smallest possible unsaturated carbocycles, are of great synthetic interest since they serve as versatile reactive building blocks. Their reactivity results from the relief of the ring strain in the small molecule. They can be transformed into a wide variety of complex chiral structures and a special emphasis will be directed towards the preparation of enantiomerically enriched methylene- and alkylidenecyclopropane derivatives. The ready availability of a wide range of these chiral entities now provides an excellent opportunity to discover new and unique transformations that can further enrich mainstream synthetic methodology.

Recent developments in the reactivity of methylene- and alkylidenecyclopropane derivatives

“…15 As shown in Scheme 6, upon treatment with Pd(PPh 3 ) 4 combined with P(O)n-Bu 3 , a series of aniline-tethered alkylidenecyclopropanes underwent a facile and regioselective cyclisation to provide the corresponding six-membered exomethylene nitrogen heterocycles in high yields. In addition, 1,2-dimethylindolizine could be synthesised in 57% R 1 = R 2 = R 3 = Ph: 42% + 18% R 1 = R 2 = Ph, R 3 = 3,5-Cl 2 C 6 H 3 : 95% + 0% R 1 = R 2 = Ph, R 3 = p-FC 6 H 4 : 65% + 21% R 1 = R 2 = Ph, R 3 = p-EtOC 6 H 4 : 37% + 20% R 1 = R 2 = p-Tol, R 3 = m-CF 3 16 In almost all cases of substrates, the N,N-dialkylated compound was obtained as the major product.…”

“…On the other hand, the synthesis of novel complexes of rhodium and iridium was achieved by Osakada et al based on the reactions of 2,2-bis(2-phenylethyl)-1-methylenecyclopropane with hydride complexes of Rh(I) and Ir(I), respectively. 82 Therefore, the 3-butenyl-rhodium complex, Rh {h 1 :h 2 -CH 2 C(CH 2 CH 2 Ph) 2 CH]CH 2 }(CO)(PPh 3 ) 3 , and the 3-butenyliridium complex, Ir{h 1 :h 2 -CH 2 C(CH 2 CH 2 Ph) 2 CH]CH 2 }(CO)(PPh 3 ) 3 , were obtained from the reactions with RhH(CO)(PPh 3 ) 3 and IrH(CO) (PPh 3 ) 3 at 70 C in 89 and 92% yields, respectively.…”

“…Due to the limited degrees of freedom in the system, these conformationally constrained molecules have very pronounced steric, stereoelectronic and directing effects, which make them versatile probes for the study of regio-, diastereo-and enantioselectivity. 3 Furthermore, a diverse reactivity pattern resulting from the significant strain energy accounts for the use of small carbocycles as convenient models for the investigation of organic and organometallic reaction mechanisms. Among the class of cyclopropanes, methylenecyclopropane and alkylidenecyclopropane derivatives have been well documented as useful synthetic intermediates in organic chemistry over the past few decades.…”

Nickel‐Catalyzed Regioselective Carbomagnesation of Methylenecyclopropanes through a Site‐Selective Carbon–Carbon Bond Cleavage

“…[5,9] To investigate the reaction mechanism, the following labeling experiment was performed. The reaction of an MCP containing deuterium at the terminal vinylic carbon atom ([D 2 ]1 a) with a vinyl Grignard reagent and tributylchlorosilane was conducted in THF at 0 8C for three hours in the presence of [9] In the case of aryl Grignard reagents, the direct oxidative addition of a proximal CÀC bond of the MCP to the nickel catalyst might occur to yield 10.…”

“…[3] We attempted to apply this methodology to methylenecyclopropanes (MCPs), because MCPs are readily accessible [4] and highly reactive unsaturated hydrocarbons which have served as useful building blocks in organic synthesis, especially in transition-metal-catalyzed reactions. [5] We report herein the nickel-catalyzed reaction of MCPs with Grignard reagents, wherein the selective cleavage of the proximal or the distal carbon-carbon bond of the MCPs [6] has been achieved by using Grignard reagents to give the corresponding carbomagnesation products regioselectively [Eq. (1)].…”