Chiral guanidine catalyzed cyclization reactions of 1,3-enynes for lactone synthesis: switchable H-bond catalysis

H-bonding catalysis has attracted much attention in asymmetric reactions. Taking advantage of guanidine-amides as bifunctional organocatalysts, we successfully achieved cyclization as well as 1,4-conjugate addition/cyclization of azlactones with acyclic and cyclic alpha-alkynyl-alpha,beta-enones, respectively. The enol-type activation facilitated the generation of lactones via inverse electron-demand hetero-Diels-Alder reactions, diverging from the typical formation of allenes. A diverse array of delta-lactone derivatives were obtained in high yields and with excellent ee (up to >99%) and dr (>19 : 1). DFT calculations elucidate that the switchable hydrogen bonds formed by the positively charged guanidinium and neutral amide with various acceptors impart versatile activity and stereoselectivity.