Atropisomeric benzamides and naphthamides as chiral auxiliaries †

Abstract

Atropisomeric compounds whose chirality resides in a rotationally restricted aryl-CONR 2 bond may be employed as chiral auxiliaries. The electron-withdrawing amide group causes problems in the diastereoselective functionalisation of enolates derived from atropisomeric phenyl esters, but a strategy based on atroposelective nucleophilic addition to a chiral aldehyde followed by stereospecific [3,3] sigmatropic rearrangement allows atropisomeric naphthamides to be used as auxiliaries. The auxiliaries are resolved by dynamic resolution during aminal formation using a prolinederived diamine. Scheme 4 Synthesis of propionate esters of 2-(N,N-dialkyl)carbamoylphenols. Scheme 5 Attempted aldol reactions of propionates 14.

Dynamic resolution of atropisomeric amides using proline-derived imidazolines and ephedrine-derived oxazolidines

“…However, as previously reported, 18,45 diastereoselectivity in the condensation of the peri-substituted naphthamides 1c and 1d was rather poorer, with 20-25% of a minor epimer being evident in the 1 H NMR spectrum of the crude reaction mixture (Scheme 5).…”

“…As with the diamine 9, condensation of a hindered peri-substituted naphthamide with (2)-ephedrine gave much poorer selectivities, and 1c gave a 1:1 mixture of the two diastereoisomers of 16c in 90% yield. 45 …”

Atropisomeric amides: Achiral ligands with chiral conformations

“…Compound 5a has been previously synthesized using the anionic Fries rearrangement. 37 The compound was prepared following the general procedure. The crude product was recrystallized from dichloromethane and hexanes to afford the desired phenol 5a as an off-white powder in 86% yield (1.70 g, 7.22 mol).…”

“…The 1 H NMR and 13 C{ 1 H} NMR spectra are in agreement with those in the literature. 37 N,N-Diphenyl-2-hydroxybenzamide (5b). Compound 5b has been synthesized previously using phenyl salicylate and diphenylamine.…”

First Use of Axially Chiral Thioamides for the Stereocontrol of C−C Bond Formation

“…Introduction of steric hindrance has led to acceptable or significant barriers to rotation along the axis of chirality and opened the way to ™atroposelectivity∫. Reactions that have been stereocontrolled in this fashion include the alkylation and aldol reactions of enolates, [10,11,14,15] nucleophilic addition to carbonyl derivatives [16,17] and iminium salts, [18] addition of electrophiles to ortho or laterally metalated naphthamides, [3, 19±21] Diels ± Alder and dipolar cycloadditions, [12,22] and radical reactions. [6,23] We wished to replace the oxygen atom of amides by a sulfur atom, as there seems to be no precedent for the use of atropisomeric thioamides in asymmetric synthesis, and believe that this will present a number of useful characteristics.…”