Catalytic, Enantioselective Cyclopropanation of Allylic Alcohols. Substrate Generality

Abstract

Catalytic, enantioselective cyclopropanation of a broad range of allylic alcohols and one homoallylic alcohol was carried out. The cyclopropanation reagent employed was bis(iodomethyl)zinc generated by the method of Furukawa, and the chiral promoter used (10 mol %) was the N,N-bis(methanesulfonyl) derivative of (R,R)-1,2-diaminocyclohexane. Three experimental features were found to be critical for the rapid and selective cyclopropanation: (1) use of the ethylzinc alkoxide of the allylic alcohol as the substrate by prior deprotonation of the allylic alcohols by diethylzinc, (2) the formation of the zinc complex of the promoter by prior deprotonation of the bis-sulfonamide with diethylzinc, and (3) the use of added zinc iodide generated in situ from diethylzinc and iodine. The stereoselectivity of cyclopropanation was found to be independent of olefin geometry and worked well for substrates bearing both aliphatic and aromatic substituents at either or both 3-positions of the allylic alcohol. However, a methyl substituent on the 2-position of the allyl alcohol was not well tolerated and led to slow reactions and poor enantioselectivities. A rationale for the observed selectivities is proposed.

Catalytic Asymmetric Synthesis of all‐Carbon Quaternary Stereocenters

“…High enantioselectivity in type I processes has been achieved with alkenes containing Lewis basic allylic substituents and carbenoids derived from diiodomethane (45). The synthesis of cyclopropyl carbinol 30 by methylene transfer from a zinc carbenoid containing the nonracemic disulfonamide ligand 31 illustrates such a process (46). In type II processes, diazo compounds are commonly used (47)(48)(49).…”

Enantioselective [2+1] Cycloaddition: Cyclopropanation with Zinc Carbenoids

“…3.22) [82]. In this picture, the complex, polymetallic aggregate invoked by Rickborn and later by Kobayashi is featured.…”

“…This high selectivity translates well into a number of allylic alcohols (Table 3.12) [82]. Di-and tri-substituted alkenes perform well under the conditions of protocol V. However, introduction of substituents on the 2 position leads to a considerable decrease in rate and selectivity (Table 3.12, entry 5).…”

Synthesis of a 13C labeled N‐cyclopropylamine tetrahydropyridine derivative

“…Catalysis with ZnEt 2 was shown to be an efficient method to prepare a variety of cyclopropyl derivatives. [38][39][40][41][42] However, using one equivalent of CH 2 I 2 only (instead of the usual 5-10 equivalents relative to the alkene) and an excess of alkene 17 led to modest yields of 18 and therefore this pathway was considered unsuitable for the synthesis of labeled 9.…”