Diastereoselective synthesis of atropisomers containing two non-biaryl stereogenic axes: stereochemical relay through stereogenic centres in dihydrostilbene-2,2′-dicarboxamides

Abstract

Addition of laterally lithiated tertiary aromatic amides to benzaldimines controls the formation of a new stereogenic centre adjacent to the benzaldimine aromatic ring. Drawing on the fact that such amino-substituted stereogenic centres may themselves control the conformation of amides, with amido-substituted benzaldimines we found it becomes possible to relay stereochemistry from one amide to another via this intervening stereogenic centre. A group of dihydrostilbene-2,2'-dicarboxamide derivatives bearing one or two stereogenic axes are made by this method, which demonstrates the use of combined kinetic and thermodynamic control for the relay of stereochemical information.

Nonbiaryl and Heterobiaryl Atropisomers: Molecular Templates with Promise for Atropselective Chemical Transformations

“…In one of the earliest examples, they were able to show that the silyl substituent in 366 controlled the conformation of the amide that in turn influenced the new chiral center that is being formed in the product 368 resulting in excellent 1,5 diastereoselectivity (Scheme ). , With additional work on these systems, Clayden and co-workers were able to show that the axial chirality can influence the conformations of more than one chiral axis. ,, When a laterally lithiated 369 was added to atropisomeric imine 370 , two diastereomers ( syn - and anti - 371 ) were formed with no kinetic preference leading to a 1:1 mixture. However, due to unequal energies of these isomers, they equilibrate to thermodynamically stable anti - 371 diastereomer as the only product.…”

“…151,226 With additional work on these systems, Clayden and co-workers were able to show that the axial chirality can influence the conformations of more than one chiral axis. 212,227,228 When a laterally lithiated 369 was added to atropisomeric imine 370, two diastereomers (syn-and anti-371) were formed with no kinetic preference leading to a 1:1 mixture. However, due to unequal energies of these isomers, they equilibrate to thermodynamically stable anti-371 diastereomer as the only product.…”

Substituted Functional Olefins Through Lateral Sequential Lithiation/Silylation/Condensation of Tertiary Aromatic Amides: A Ligand for Phosphane‐Free Palladium‐Catalyzed Suzuki Coupling Reactions

“…Inspired by the lithiation method reported by Clayden et al, [4] we investigated the one-pot sequential reactions of amide 1 with a range of carbonyl compounds. Herein, we describe the successful development of lateral sequential lithiation/silylation/condensation of tertiary aromatic amides through key and directed lithiation to generate functional olefins.…”

Conformational preference in aromatic amides bearing chiral ortho substituents: its origin and application to relayed stereocontrol

“…In each case the Ar-CO dihedral § In an accompanying paper (ref. 41) we show how the apparent small size of the NMeR group can be exploited to relay conformational control between remote atropisomeric axes. was constrained to ±90 • .…”