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

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.

Organocatalytic asymmetric addition of thioglycolates to o-quinone methides: a route to 5-substituted-5H-benzoxathiepine-2(3H)-ones.

Herein we have developed the first enantioselective synthesis of 5-substituted-5H-benzoxathiepine-2(3H)-ones. 2-Sulfonylmethyl phenols and thioglycolates were employed as reaction partners in this method. The desired thia Michael products were obtained via bifunctional squaramide catalyzed conjugate addition reaction to in situ generated o-quinone methides and then basic hydrolysis followed by cyclization led to the formation of 5-substituted-5H-benzoxathiepine-2(3H)-ones. Broad scope and moderate to high enantioselectivities were observed for both products.

Employment of α-nitroketones in organic synthesis.

α-Nitroketones, useful bidentate reagents having nitro and keto functionalities, have been recently employed in a range of metal and organocatalytic domino reactions. In fact, several C-C, C-O, and C-N bond forming reactions were developed including Michael, domino-Michael, denitration, desymmetrisation, Mannich, nucleophilic addition/elimination and cycloaddition pathways. Unlike nitroalkanes, α-nitroketones can generate a range of active 1,3 dipolar intermediates such as nitronates and nitrile oxides which have been engaged in various cycloaddition reactions. Also α-functionalisation reactions such as arylations and halogenations were carried out. A variety of useful organic frameworks such as chromans, dihydrofurans, isoxazoles, pyrazoles etc. have been prepared. This review highlights the recent developments in the utilisation of α-nitroketones in organic synthesis and discusses the progress over the current years.

Chiral phosphoric acid catalyzed enantioselective annulation of acyclic enecarbamates to in situ-generated ortho-quinone methides.

The first organocatalytic asymmetric reaction of acyclic enecarbamates with o-quinone methides is disclosed. BINOL-based phosphoric acid catalysts were found to be suitable for the annulation reaction. With 10 mol% of the TRIP catalyst, high yields as well as excellent diastereo- and enantioselectivities are achieved for a variety of 2,3,4-trisubstituted chroman products.

Organocatalytic Asymmetric Michael/Hemiketalization/Retro-aldol Reaction of α-Nitroketones with Unsaturated Pyrazolones: Synthesis of 3-Acyloxy Pyrazoles.

An organocatalytic asymmetric cascade Michael/hemiketalization/retro-aldol reaction between unsaturated pyrazolones and α-nitroketones is described. A bifunctional thiourea catalyst was found to be efficient for this reaction. With 10 mol % of catalyst, high yields as well as excellent enantioselectivities are attained for a variety of 3-acyloxy pyrazoles under mild reaction conditions.