Highly Stereoselective Halocyclopropanation of α,β‐Unsaturated Amides

Abstract

A convenient highly stereoselective synthesis of chloro-and bromocyclopropanamides from di-tri-or tetrasubstituted (E)-or (Z)-a,b-unsaturated amides with total or high stereoselectivity promoted by chromium dichloride or dibromide is described. The transformation of chlorocyclopropan-A C H T U N G T R E N N U N G amides into the corresponding ketones or amines is also reported. A mechanism to explain these transformations is proposed.

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.…”

“…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. These undesirable results could be explained by assuming that, after iodocyclopropanation, the reaction of the excess of CrCl 2 with the obtained iodocyclopropanamide could afford an organochromium intermediate, which could be hydrolyzed in the same reaction mixture, giving the corresponding cyclopropanamide 3.…”

“…The stereogenic centers generated in the halocyclopropanations (CH À I, CH À Br and CH À Cl) were obtained with the same relative configurations. [4] In all cases, the iodine atom adopted a trans position with respect to the carboxamide.…”

“…These undesirable results could be explained by assuming that, after iodocyclopropanation, the reaction of the excess of CrCl 2 with the obtained iodocyclopropanamide could afford an organochromium intermediate, which could be hydrolyzed in the same reaction mixture, giving the corresponding cyclopropanamide 3. [4] These precedents prompted us to develop a stereoselective iodocyclopropanation of a,b-unsaturated amides using catalytic amounts of CrCl 2 rather than stoichiometric quantities. In addition, this method could overcome the drawback of the high price of CrCl 2 .…”

“…This relative configuration was in agreement to that observed in the previously reported chloro-or bromocyclopropanation of a,b-unsaturated amides. [4] Once compound 2 is generated, the chromiumA C H T U N G T R E N N U N G (III) species are then reduced with iron(0) to produce more chromium(II).…”