Enantioselective Synthesis of Polysubstituted Spiro-nitroprolinates Mediated by a (R,R)-Me-DuPhos·AgF-Catalyzed 1,3-Dipolar Cycloaddition

The synthesis of constrained spirocycles is achieved effectively by means of 1,3-dipolar cyclodditions employing α-imino γ-lactones as azomethine ylide precursors and nitroalkenes as dipolarophiles. The complex formed by (R,R)-Me-DuPhos 18 and AgF is the most efficient bifunctional catalyst. Final spiro-nitroprolinates cycloadducts are obtained in good to moderate yields and both high diastereo- and enantioselectivities. Density functional theory (DFT) calculations supported the expected absolute configuration as well as other stereochemical parameters.

Financial support was provided by the Spanish Ministerio de Ciencia e Innovación (MICINN) (Projects CTQ2010-20387, and Consolider Ingenio 2010, CSD2007-00006), the Spanish Ministerio de Economía y Competitividad (MINECO) (Projects CTQ2013-43446-P, and CTQ2014-51912-REDC), FEDER, the Generalitat Valenciana (PROMETEO 2009/039 and PROMETEOII/2014/017), the University of Alicante, the Gobierno Vasco/Eusko Jaurlaritza (Grant IT673-13), and the University of the Basque Country UPV/EHU (UFI11/22 QOSYC). O.L. gratefully acknowledges the UPV/EHU for her postdoctoral grant.