Atroposelectivity in the electrophilic substitution reactions of laterally lithiated and silylated tertiary amides

Lateral lithiation–electrophilic quench of 2-alkyl-1-naphthamides and 2,6-dialkylbenzamides yields products containing an atropisomeric Ar–CO axis and a new stereogenic centre with high (generally >95 ∶ 5) diastereoselectivity. With imines as electrophiles, single diastereoisomers containing an atropisomeric axis and two new stereogenic centres are formed. 2,6-Dialkylbenzamides may be functionalised stereoselectively at both the 2- and 6-positions, leading (with imines) to symmetrical compounds bearing 1,7-related stereogenic centres. 2-Alkylbenzamides with only one ortho alkyl group are not atropisomeric at ambient temperature but are functionalised diastereoselectively by lateral lithiation–electrophilic quench at −78 °C. Stabilisation of the atropisomeric products by further lithiation and alkylation proves their diastereoselective formation. The lack of stereospecificity in the fluoride-promoted reaction of a laterally silylated 1-naphthamide with an aldehyde suggests that reported reactions of laterally silylated benzamides may also be controlled by the rotationally restricted amide group.