Chemo‐, Regio‐, and Stereoselective Diels–Alder Reaction of Ambident Dienophilic Monothiomaleimide

Both the CS and CC functionalities of N‐arylmonothiomaleimides readily undergo a [4 + 2] cycloaddition reaction at ambient temperatures with both electron‐donating and ‐withdrawing dienes. The CS groups of N‐arylmonothiomaleimides are generally more reactive than the CC groups, especially toward dienes bearing conjugation and electron‐attracting groups, and provide mixtures of ortho,endo products 3 and ortho,exo products 4 with complete regioselectivity (100% ortho) and with high stereoselectivity (more than 86% endo). The CC groups, on the other hand, display a high stereoselectivity (100% endo) but a low regioselectivity, providing ortho,endo adducts 5 and meta,endo adducts 6 in ratios ranging from 1:1 to 6:1. Compared with N‐phenylmonothiomaleimide (1). N‐p‐nitrophenylmonothiomaleimide (11a) is more reactive and displays a higher CS vs. CC chemoselectivity in favor of CS, while N‐p‐anisyl (11b) and N‐benzyl (11c) derivatives display quite the reverse reactivity and selectivity. N‐Phenylmonothiocitraconimide (11d) serves as a CS specific dienophile and reacts with dienes to furnish ortho,endo adducts 12 with excellent regio‐ and stereoselectivities (100% ortho,endo). Both hard (BF3 · OEt2, TiCl4) and soft (CuBr · SMe2) Lewis acids enhance the reaction rate enormously and increase chemoselectivity in favor of CS. The chemo‐ (CS/CC), regio‐ (ortho/meta) and stereochemical outcomes (endo/exo) are rationalized by transition structure analysis based on AM1 calculation.