Stereospecific and Stereoselective Alkyl and Silylcyclopropanation of α,β-Unsaturated Amides

Abstract

A novel chromium-promoted alkyl- and silyl cyclopropanation of (E)- or (Z)-alpha,beta-unsaturated amides in which the C-C double bond is di-, or trisubstituted is described. This process takes place with total stereospecificity, and the new stereogenic center is generated with high or total stereoselectivity. A mechanism is proposed to explain the cyclopropanation reaction.

Highly Stereoselective Halocyclopropanation of α,β‐Unsaturated Amides

“…According to the silylcyclopropanation model, [30] the relative position of the halogen atom in the cyclopropanes obtained from disubstituted (E)-cinnam-A C H T U N G T R E N N U N G amides was opposite with respect to that obtained from the other unsaturated amides, (trans with respect to the carboxamide group). As can be observed in Table 4, the reaction from disubstituted cinnamamides also took place with total stereoselectivity and in high yields.…”

“…Both methods were carried out in the presence of N,N,N',N'-tetraethylethylenediamine (TEEDA). We have also reported the use of CrCl 2 to promote the highly stereoselective cyclopropanation, [29] or alkyl-and silylcyclopropanation [30] of a,b-unsaturated amides with total or high stereoselectivity. Herein we report the valuable, highly stereoselective chloro-and bromocyclopropanations of a,b-unsaturated amides mediated by CrCl 2 ,or CrBr 2 which take place in high yields and with total or high stereoselectivity.…”

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.…”

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.…”

“…This iodocyclopropanation process could be explained assuming the initial formation of a chromium-A C H T U N G T R E N N U N G (III) carbenoid intermediate 4, after the reaction of 2 equivalents of CrCl 2 with 1 equivalent of CHI 3 . This anion could react with a,b-unsaturated amides 1 to give the corresponding iodocyclopropane 2, through a similar mechanism to that proposed by Houk for the addition of carbenoids to olefins.…”