Asymmetric syntheses of three-membered heterocycles using chiral amide-based ammonium ylides

Abstract

Phenylglycinol serves as a powerful chiral auxiliary in ammonium ylide-mediated reactions to obtain chiral epoxides/aziridines with excellent stereoselectivities.

On the origin of the stereoselectivity in chiral amide-based ammonium ylide-mediated epoxidations

“…[8] before). Four conformers are possible, two with a Z -configuration and two with an E -configuration (Fig.…”

“…However, some limitations were observed: While the use of Cinchona alkaloids as chiral amine leaving groups was found to be a very versatile strategy for enantioselective cyclopropanation reactions [14, 15], these simple naturally occurring chiral amines were not suited for epoxidations and aziridinations [6, 11, 13]. Our group has for years been interested in the development of new catalytic [17, 18] and auxiliary-based methods [8, 11] for the synthesis of chiral heterocycles. Based on this general interest, we recently carried out an extensive screening and optimization of different chiral amines for ammonium ylide-mediated epoxidation reactions.…”

“…This allowed us to overcome the above mentioned obstacles when using Cinchona alkaloids and to develop the first highly enantioselective and high yielding ammonium ylide 4 mediated epoxidation protocol (Scheme 1b) [11]. Alternatively, very high stereoselectivities were also obtained by using chiral amide-based ylides 5 , which resulted in complete control of the absolute and relative configuration (Scheme 1c) [8].

…”

“…Impressed by the extraordinarily high stereoselectivities obtained using the chiral phenylglycinol-derived auxiliary-containing ylides 5 [8] and based on our recently gathered mechanistic understanding of the analogous racemic reactions with ylides 1 [11], we have now performed detailed DFT calculations for the reaction of 5 with benzaldehyde ( 2 ) to elucidate the origin of this high stereoselectivity.…”

Asymmetric Synthesis of 2,3‐Dihydrobenzofurans by a [4+1] Annulation Between Ammonium Ylides and In Situ Generated o‐Quinone Methides

“…[7] These versatile reagents have found widespreada pplications in [2+ +1] annulations to access( chiral) epoxides, aziri-dines and cyclopropanes. [7][8][9][10] More recently,t hese compounds were also successfully employed in [4+ +1] annulations [11] by treating them with different vinylogous acceptor molecules. [4-6, 12, 13] One particularly powerful methodology for the generation of carbo-and heterocyclic targets through [4+ +n]a nnulation approaches relies on the use of in situ generated o-quinone methides or analogousa za-o-quinonem ethides.…”