Diastereoselectivity Control in Formal Nucleophilic Substitution of Bromocyclopropanes with Oxygen- and Sulfur-Based Nucleophiles

Abstract

A diastereoconvergent formal nucleophilic substitution of bromocyclopropanes with oxygen- and sulfur-based nucleophiles is described. The reaction proceeds via in situ formation of a highly reactive cyclopropene intermediate and subsequent diastereoselective addition of a nucleophile across the strained C═C bond. Three alternative means of controlling the diastereoselectivity of addition have been demonstrated: (1) thermodynamically driven epimerization of enolizable carboxamides, (2) steric control by bulky substituents, and (3) directing effect of carboxamide or carboxylate functions.

Directed nucleophilic addition of phenoxides to cyclopropenes

“…5 However, the reactions of substituted cyclopropenes are typically not diastereoselective, 6 unless the selectivity is enforced by excessive steric hindrance. 7 We have previously reported a formal nucleophilic substitution of bromocyclopropanes operating via dehydrohalogenation/addition of O -based nucleophiles to cyclopropene intermediates, which can be carried out in both inter- 8 or intramolecular fashion. 9 Diastereoselectivity in these reactions is efficiently controlled by steric effects (Scheme 1, eq.…”

“…4). 8 A combination of the above-listed factors was also employed for diastereoselective installation of several contiguous stereogenic centers. 10 While all these transformations are fairly general for alkoxides, aryloxides have been previously engaged only in the reactions with the most electrophilic cyclopropenes activated by a conjugate electron-withdrawing group (i.e.…”

Rearrangements of cyclopropenes into five-membered aromatic heterocycles: mechanistic aspect

“…By taking advantage of the extremely facile nucleophilic addition of alcohols across the cyclopropene double bond [34][35], he succeeded trapping the strained cyclic species 56, obtained under conditions typical for intramolecular cycloisomerization of diazocarbonyl compounds into furans. The only product isolated in high yield corresponded to structure 60.…”

Chiral methyl trans-2,2-dichloro-3-methylcyclopropanecarboxylate upon exposure to thiophenolate nucleophile

“…[16][17][18][19][20] Recently, numerous examples of stereoselective substitution in monobromocyclopropanes with heteroatomic nucleophiles have been described. 21,22 In continuation of our research, 10,11 the substitution of halogens by thiophenoxy groups in the chiral acids 1 has become the object of investigation. The stereochemistry of the dithiocyclopropanes obtained and the process of the cyclopropane ring opening were studied.…”