Stereospecific Cyclopropanation of Highly Substituted C−C Double Bonds Promoted by CrCl₂. Stereoselective Synthesis of Cyclopropanecarboxamides and Cyclopropyl Ketones

Abstract

We describe herein a CrCl(2)-promoted cyclopropanation of alpha,beta-unsaturated amides. This reaction can be carried out on (E)- or (Z)-alpha,beta-enamides in which the C-C double bond is di-, tri-, or tetrasubstituted. In all cases the process is completely stereospecific and only a single diastereoisomer is obtained. In addition, cyclopropyl ketones were readily prepared by reaction of the cyclopropanecarboxamides (derived from morpholine) obtained with a range of organolithium compounds. A mechanism has been proposed to explain the cyclopropanation reaction.

Highly Stereoselective Halocyclopropanation of α,β‐Unsaturated Amides

“…[29] Thus, treatment of (E)-N,N-diethylcinnamamide with 4 equivalents of CrCl 2 and 2 equivalents of CHCl 3 for 6 h at reflux, gave a 2/1 mixture of the chlorocyclopropanamide I and cyclopropanamide II (Scheme 1). To avoid this C À Cl bond reduction, we tested the reaction conditions shown in Scheme 1 without improving the initial results.…”

Synthesis of Highly Functionalized Enantiopure Halocyclopropanes Derived from Carbohydrates

“…[10] In particular, previous contributions by us (the stereospecific cyclopropanation of α,β-unsaturated amides, [11] the highly stereoselective tert-butyl-and silyl-cyclopropanation, [12] and the chloro-and bromocyclopropanation of α,β-unsaturated amides with total or high stereoselectivity [13] ) and other [14] laboratories, have demonstrated the utility of CrCl 2 for the cyclopropanation of unsaturated compounds. [10] In particular, previous contributions by us (the stereospecific cyclopropanation of α,β-unsaturated amides, [11] the highly stereoselective tert-butyl-and silyl-cyclopropanation, [12] and the chloro-and bromocyclopropanation of α,β-unsaturated amides with total or high stereoselectivity [13] ) and other [14] laboratories, have demonstrated the utility of CrCl 2 for the cyclopropanation of unsaturated compounds.…”

“…Chromium dichloride (CrCl 2 ) has become an important reagent in synthetic organic chemistry because of its versatility in electron transfer reactions, and this reagent has been applied to a multitude of organic transformations, which generally proceeded with high selectivity. [10] In particular, previous contributions by us (the stereospecific cyclopropanation of α,β-unsaturated amides, [11] the highly stereoselective tert-butyl-and silyl-cyclopropanation, [12] and the chloro-and bromocyclopropanation of α,β-unsaturated amides with total or high stereoselectivity [13] ) and other [14] laboratories, have demonstrated the utility of CrCl 2 for the cyclopropanation of unsaturated compounds.…”

An Efficient Catalytic Chromium‐Mediated Iodocyclopropanation Reaction: Stereoselective Synthesis of Iodocyclopropanecarboxamides

“…In particular, previous contributions by us (the stereospecific cyclopropanation of a,b-unsaturated amides, [2] the highly stereoselective tert-butyl-and silylcyclopropanation [3] and the chloro-and bromocyclopropanation of a,b-unsaturated amides with total or high stereoselectivity [4] ) and other [5] laboratories, have demonstrated the utility of CrCl 2 for the cyclopropanation of unsaturated compounds. Unfortunately, when the iodocyclopropanation of a,b-unsaturated amides 1 was attempted under the same conditions described for the halocyclopropanation reaction, [4] a 1:3 mixture of the corresponding iodocyclopropanamide 2 and cyclopropanamide 3, was obtained.…”