Enantioselective photocyclization of p-toluidides of α,β-unsaturated carboxylic acids in solution. A mechanistic and preparative study

Abstract

Photolysis of p-toluidides of methacrylic (1a) and cyclohex-2-enecarboxylic (1b) acids in nitrogen-saturated cyclopentane solution yields the corresponding 2-quinolones with over 90% chemoselectivity at almost complete conversion. In the presence of substoichiometric amounts (0.1 equivalents) of chiral inductor, low to moderate enantiomeric excesses (ee) are observed in the photo-product. Ephedrine gave the highest ee (37% ee for the photocyclization of 1a) in a series of 11 chiral inductors including alcohols, amines, aminoalcohols, α-amino and α-hydroxy acids. In the case of the irradiation of 1b in the presence of chiral inductors, both diastereo- and enantioselectivity were observed. A weakly absorbing transient species (λ_max 400 nm) was detected following 308 nm laser excitation and was assigned to the zwitterionic enolate intermediate resulting immediately after the concerted electrocyclic ring closure. The lifetime of this intermediate is unaffected by oxygen but is quenched by trifluoroacetic acid (k_q = 3.76 × 10⁷ M⁻¹ s⁻¹) and ephedrine (k_q = 1.19 × 10⁷ M⁻¹ s⁻¹).