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note
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We also prepared pyrrolidines with 2-carboxamide- or 2-methylacetamide- tethered thiourea and thiouronium functionality. Attempted catalysis of the conjugate addition of cyclohexanone to trans-b-nitrostyrene typically resulted in a syn/anti diastereomeric product ratio of >91:9 with carboxamide-tethered catalysts, comparable to that seen with monofunctional catalysis by (2S)-N-benzylpyrrolidine-2-carboxamide. However, poor syn enantioselectivity (<30% ee) resulted and all methylacetamide-tethered examples demonstrated little or no catalytic activity. Similar amide-linked, amine-thiourea catalysts were also reported to give only the racemic product of ketone addition to nitroolefins during the course of our study (ref. 7e), presumably as a result of intramolecular hydrogen bonding between thiourea/uronium functionality and the tethering amide.
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To our knowledge, comparable rates of catalysis for the Michael addition of ketones to nitroalkenes only by diamines have been reported; see references 4e, 6a, and 6b.
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2O at r.t. Typically syn/anti diastereomeric ratios of 1:1 or 2:1 resulted with catalysts 4, 6, 7, 10, 12, or 14; major diastereoisomer ee (%) ranged between 8-77%.
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45
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