cis-Selective, Enantiospecific Addition of Donor–Acceptor Cyclopropanes to Activated Alkenes: An Iodination/Michael-Cyclization Cascade

Abstract

We present a versatile method for the enantiospecific, cis-diastereoselective intermolecular and intramolecular cycloaddition of donor−acceptor cyclopropanes to electron-poor alkenes with cyclic acceptor groups to afford highly substituted spirocyclopentanes in good to excellent yields. The reaction can be applied to biologically interesting scaffolds, including barbiturates and isoxazolones. Mechanistic investigations were undertaken to explain the unusual diastereoselectivity and enantiospecificity; these suggest an iodination/Michael-cyclization cascade.

Additive‐Free Synthesis of Trifluoromethylated Spiro Cyclopropanes and Their Transformation into Trifluoromethylated Building Blocks

“…In addition to the inherent potential these spiro TFCps possess, the presence of donor and acceptor groups make them promising candidates for assembling valuable synthetic building blocks either through the ring expansion or ring opening reactions. [12] Drawing inspiration from the well-known annulations of spiro cyclopropanes, [13] we envisioned that an appropriate dipolarophile would take part in the ring expansive annulation reaction under Lewis acid conditions.…”

“…Column chromatography was performed on 100-200 mesh silica gel using the gradient system ethyl acetate-hexane. NMR data were recorded at Bruker AV 400 MHz in CDCl 3 using as internal standards the residual CHCl 3 signal for 1 H NMR (δ = 7.26 ppm) and the deuterated solvent signal for 13 C NMR (δ = 77.16 ppm). Coupling constants are given in Hertz (Hz) and the classical abbreviations are used to describe the signal multiplicities.…”

Exploiting Heavier Organochalcogen Compounds in Donor–Acceptor Cyclopropane Chemistry

“…The situation becomes more difficult when ring-opening reactions install two (maybe even different) substituents at position 1 and 3 and none of them should be hydrogen . (b) Cycloaddition reactions: Because D–A cyclopropanes might be regarded as masked 1,3-zwitterions, the insertion of 1,2-dipoles such as (hetero)­carbonyls and polarized C–C double and triple bonds is possible . Whereas these transformations lead to five-membered rings, six- and seven-membered rings are available by (3 + 3)- and (4 + 3)-cycloaddition approaches using 1,3- and 1,4-dipoles, respectively.…”

Synthesis of (Het)aryl 2-(2-hydroxyaryl)cyclopropyl Ketones

“…During last decades donor-acceptor (D-A) cyclopropanes [1][2][3][4][5][6] attracted a significant attention of organic chemists due to the excellent combination of their availability and high reactivity toward diverse classes of reaction partners: nucleophiles [4,[7][8][9][10], electrophiles [11,12], radicals [13,14], dipolarophiles [15][16][17][18][19][20][21][22], dipoles [23][24][25], 1,3-dienes [26][27][28], etc. (Scheme 1a).…”