Prediction by 13C NMR of regioselectivity in 1,3‐dipolar cycloadditions of acridin‐9‐yl dipolarophiles

Strong correlation was found between ¹³C NMR chemical shifts of dipolarophilic CH?CH carbons and regioselectivity in 1,3‐dipolar cycloadditions of new acridin‐9‐yl dipolarophiles with stable benzonitrile oxides (BNO). Accordingly, two starting dipolarophiles, (acridin‐9‐yl)‐CH?CH‐R (R = COOCH₃ or Ph), reacted with three BNOs (2,4,6‐trimethoxy, 2,4,6‐trimethyl, and 2,6‐dichloro) to give a mixture of two target isoxazoline regioisomers in which the acridine was bound either to isoxazoline C‐4 carbon (4‐Acr) or C‐5 one (5‐Acr). Methyl 3‐(acridin‐9‐yl)propenoate afforded major 4‐(acridin‐9‐yl)‐isoxazoline‐5‐carboxylates (4‐Acr) and minor 5‐(acridin‐9‐yl)‐4‐carboxylates (5‐Acr). 9‐(2‐Styryl)acridine regiospecifically afforded only 4‐Acr cycloadducts. The ratios of regioisomers were compared with analogous reactions of acridin‐4‐yl dipolarophiles. Regioselectivity was dependent on a polarity of the CH?CH bond, donor effects in BNO, and stabilization by stacking of aromatic substituents in the products. Copyright © 2015 John Wiley & Sons, Ltd.