Organocatalytic Asymmetric Addition of Aromatic α-Cyanoketones to o-Quinone Methides: Synthesis of 3,4-Dihydrocoumarins and Tetrasubstituted Chromans

Abstract

The first organocatalytic asymmetric addition of aromatic α-cyanoketones to in situ-generated o-quinone methides has been developed. The products 3,4-dihydrocoumarin and tetrasubstituted chroman were obtained via addition of aromatic α-cyanoketones to in situ-generated o-quinone methides followed by treatment with 0.7 N HCl. With 10 mol % catalyst, the desired products were obtained in high enantio- and diastereoselectivities.

Desulfonylative Transformations of Sulfones by Transition-Metal Catalysis, Photocatalysis, and Organocatalysis

“…The reactions are classified according to the types of catalyst employed, including (i) transition-metal catalysts, (ii) photocatalysts, and (iii) organocatalysts. For research into catalytic radical additions of allylic sulfones, the reader is referred to several recent articles. − Examples involving vinylogous imine − or quinodimethane − intermediates generated by elimination of sulfonyl groups are also outside the scope of this Review.…”

Unravelling the Development of Non-Covalent Organocatalysis in India

“…Pan and co-workers reported a novel, organocatalytic, asymmetric synthesis of 3,4-dihydrocoumarins 174 and tetrasubstituted chromans 175 by using aromatic α-cyanoketones 173 and in situ generated o -quinone methides 172 as reacting partners, followed by treatment with 0.7 N HCl (Scheme 58 ). 106 The reaction gave the corresponding products in good yields and high enantio- and diastereoselectivities. The synthetic utility of this protocol was demonstrated by the synthesis of cyano-substituted chromenes, which were obtained after a single synthetic transformation.…”

“…Scheme 57 Asymmetric umpolung addition to allene derivatives using a synergistic combination of a Lewis base and an anion-binding catalyst 105 Pan and co-workers a novel, organocatalytic, asymmetric synthesis of 3,4-dihydrocoumarins 174 and tetrasubstituted chromans 175 by using aromatic -cyanoketones 173 and in situ generated o-quinone methides 172 as reacting partners, followed by treatment with 0.7 N HCl (Scheme 58). 106 The reaction gave the corresponding 3A or 3C (10 mol%) toluene, rt…”

“…The basicity derives from the tertiary nitrogen whereas the functionalities at the C-9 position activate the electrophilic substrate through hydrogen bonding. The orientation of the two rigid rings of the cinchona skeleton, i.e., the quinolone and quinuclidine, effectuates the chiral induction by administering the ap-Scheme 58 Synthesis of 3,4-dihydrocoumarins and tetrasubstituted chromans 106…”

Synthesis of 4-aryl-3,4-dihydrocoumarins and 4-aryl-4H-chromenes via Er(OTf)3-catalyzed cascade reactions of p-quinone methides with 1,3-dicarbonyl compounds

“…5 Due to their wide biological applications, significant efforts have been devoted to the synthesis of 4-aryl-3,4-dihydrocoumarin and 4-aryl-4 H -chromene derivatives. The conventional synthetic methods for 4-aryl-3,4-dihydrocoumarins involve (i) catalytic hydrogenation of 4-aryl-coumarins, 6 (ii) hydroarylation of cinnamic acids with phenols, 7 (iii) annulation reaction of phenols with Meldrum's acid derivatives, 8 (iv) lactonization of 3-aryl-3-(2-hydroxyphenyl)propanoates, 9 (v) asymmetric formal [4 + 2] cyclization of o -quinone methides ( o -QMs) with various two-carbon reaction partners, 10 and (vi) multicomponent reaction between phenols, malonates and aryl aldehydes. 11 Meanwhile, several facile methodologies have been developed for the synthesis of 4-aryl-4 H -chromenes including the electrophilic substitution of aromatic compounds with 4-methylsulfanyl-4 H -chromenes, 12 dehydration of the 1,4-adducts between arylboronic acids and β-(2-hydroxyaryl)-enones, 13 tandem benzylation–cyclization of 2-(hydroxymethyl)phenols with 1,3-dicarbonyl compounds, 14 domino Michael addition–cyclization of 2-hydroxychalcone with indoles, 15 and multicomponent reaction between phenols, aryl aldehydes and malononitrile.…”