A family of 9-amino(9-deoxy) epicinchonine derivatives, possessing a range of mono- and bidentate hydrogen bond donor groups at the 9-position, were synthesised and evaluated for asymmetric organocatalytic activity in the dimethyl malonate Michael addition to beta-nitrostyrene; thiourea derivative was identified as the most effective bifunctional organic catalyst and found to induce high enantioselectivity in the malonate ester Michael addition reaction to a range of nitro olefins.

An efficient enantioselective total synthesis of (R)-rolipram and an efficient enantioselective formal synthesis of (3S,4R)-paroxetine has been achieved using the highly enantioselective Michael addition of malonate nucleophiles as key steps in both cases.

5-Aryl-1,3-dioxolan-4-one heterocycles derived from mandelic acid derivatives and hexafluoroacetone have been identified as new and effective pro-nucleophiles in highly diastereo-and enantioselective Michael addition reactions to nitro olefins catalyzed by bifunctional epi-9-amino-9-deoxy cinchona alkaloid derivatives. Diastereoselectivities up to 98% and enantioselectivities up to 89% for a range of nitro olefins and 5-aryl-1,3-dioxolan-4-ones under mild reaction conditions are reported.Single enantiomer bifunctional organocatalysts derived from cinchona alkaloids or cyclohexane diamine have emerged as powerful tools for the enantioselective formation of carbon-carbon and carbon-heteroatom bonds. 1 Their ready preparation and ability to impart high enantiocontrol in the addition of carbon-and heteroatom-centered nucleophiles to a variety of electrophiles have all contributed to the pace of the field. 2,3 While most efforts have concentrated on the development of the range of electrophilic components, less attention has been devoted to expanding the pool of carboncentered pro-nucleophiles attuned to this type of catalysis.To address this, we have been searching for new and synthetically Versatile pro-nucleophilic entities that would partake in highly stereoselective reactions mediated by metalfree bifunctional catalysts that our group, and others, have developed. One family of heterocycles, the 1,3-dioxolan-4-ones, was particularly attractive owing to the simplicity of their structure combined with their ready synthesis (Scheme 1). We postulated that the tunability arising from possible structural and electronic variations to the group at the 5-position and the acetal function could provide the necessary acidity/nucleophilicity profile for some derivatives to partake in enantioselective Lewis base/Brønsted acid bifunctional organocatalyst mediated additions to electrophiles

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Enantioselective syntheses O 0031Enantioselective Organocatalytic Michael Addition of Malonate Esters to Nitro Olefins Using Bifunctional Cinchonine Derivatives. -A series of 9-amino(9-deoxy) epicinchonine derivatives (I) which possess a range of mono-and bidentate hydrogen bond donor groups at the 9-position is synthesized. They are evaluated for asymmetric organocatalytic activity in the addition of dimethyl malonate to β-nitrostyrene. Thiourea derivative (Ic) is identified as the most effective catalyst and is found to induce high enantioselectivity in the addition of (II) to a range of nitro olefinsV). -(YE, J.; DIXON*, D. J.; HYNES, P. S.; Chem. Commun. (Cambridge) 2005, 35, 4481-4483; Sch. Chem., Univ. Manchester, Manchester M13 9PL, UK; Eng.) -M. Paetzel 04-030

5-Aryl-1,3-dioxolan-4-one heterocycles derived from mandelic acid derivatives and hexafluoroacetone have been identified as new and effective pro-nucleophiles in highly diastereo-and enantioselective Michael addition reactions to nitro olefins catalyzed by bifunctional epi-9-amino-9-deoxy cinchona alkaloid derivatives. Diastereoselectivities up to 98% and enantioselectivities up to 89% for a range of nitro olefins and 5-aryl-1,3-dioxolan-4-ones under mild reaction conditions are reported.Single enantiomer bifunctional organocatalysts derived from cinchona alkaloids or cyclohexane diamine have emerged as powerful tools for the enantioselective formation of carbon-carbon and carbon-heteroatom bonds. 1 Their ready preparation and ability to impart high enantiocontrol in the addition of carbon-and heteroatom-centered nucleophiles to a variety of electrophiles have all contributed to the pace of the field. 2,3 While most efforts have concentrated on the development of the range of electrophilic components, less attention has been devoted to expanding the pool of carboncentered pro-nucleophiles attuned to this type of catalysis.To address this, we have been searching for new and synthetically Versatile pro-nucleophilic entities that would partake in highly stereoselective reactions mediated by metalfree bifunctional catalysts that our group, and others, have developed. One family of heterocycles, the 1,3-dioxolan-4-ones, was particularly attractive owing to the simplicity of their structure combined with their ready synthesis (Scheme 1). We postulated that the tunability arising from possible structural and electronic variations to the group at the 5-position and the acetal function could provide the necessary acidity/nucleophilicity profile for some derivatives to partake in enantioselective Lewis base/Brønsted acid bifunctional organocatalyst mediated additions to electrophiles

Organocatalysts. -The screening of a library of 9-amino(9-deoxy)epicinchonine derivatives (11 examples) presents thiourea CIN as the most reactive and enantioselective catalyst, although a number of the other catalysts are nearly suitable. -(JAKUBEC, P.; COCKFIELD, D. M.; HYNES, P. S.; CLEATOR, E.; DIXON*, D. J.; Tetrahedron: Asymmetry 22 (2011) 11, 1147-1155, http://dx.