This talk will summarize some recent results in the development of general methodology for the asymmetric synthesis of a-amino acids (a-AA). We demonstrate that new generation of achiral nucleophilic glycine equivalents 1  can serve as excellent nucleophiles in the reactions with chiral Michael acceptors 2  giving rise to the corresponding b-substituted pyroglutamic acids 3 . The reactions occur at an ambient temperature in the presence of 5-15% of DBU, as a base with complete chemical and stereochemical outcome (>98% yield and >98% de).These, readily available by this method b-substituted pyroglutamic acids 3  can be transformed to various natural or synthetic products. One of the interesting examples is synthesis of trifluoromethyl-containing pyroglutamic acid 3  and its transformation to fluorinated Thalidomide 4  will be discussed in detail.For some published data, please see:1)      Soloshonok, V. A.; Ellis, T. K.; Ueki, H.; Ono, T. J. Am. Chem. Soc. 2009 , 131, 7208-7209.2)      Soloshonok, V. A.; Ueki, H.; Ellis, T. K. Synlett, 2009 , 704-715.3)      Soloshonok, V. A.; Yamada, T.; Sakaguchi, K.; Ohfune Y. Future Medicinal Chem. 2009 , 1, 897-908.4)      Yamada, T.; Okada, T.; Sakaguchi, K.; Ohfune, Y.; Ueki, H.; Soloshonok, V. A. Org. Lett. 2006 , 8, 5625-5628.5)      Ellis, T. K.; Ueki, H.; Yamada, T.; Ohfune, Y.; Soloshonok, V. A. J. Org. Chem. 2006 , 71, 8572-8578.6)      Soloshonok, V. A.; Cai, C.; Yamada, T.; Ueki, H.; Ohfune, Y.; Hruby, V. J. J. Am. Chem. Soc. 2005 , 127, 15296-15303.[Scheme 1]

Michael addition reactions between new generation of achiral nucleophilic glycine equivalents and chiral Michael acceptors: General asymmetric synthesis of fluorine-containing pyroglutamicacids and related compounds

245th National Meeting (2013)

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