Carbon nucleophiles amino acid precursors

Treatment of the solid-supported amino acetals (529) with catalytic PTSA, followed by addition of IH-benzotriazole, resulted in the 2-benzotriazole-substituted piperidines (530) as stable N-acyliminium ion precursors, according to Katritzky [392]. A number of different carbon nucleophiles were then added to the N-acyliminium ions, generated under acid catalysis by either boron trifluoride etherate or camphorsulfonic acid (Scheme 107). 

Azomethinium salts are very versatile intermediates since they present an extremely electrophilic carbon for nucleophilic attack. High yields of these salts can be obtained in one step from a-amino acids via their tert-dcsmno derivatives Ethyl N-Benzylidene-glycinate has been used for the synthesis of a-amino acids and as an acyl carbanion equivalent A new reactive formaldehyde anion equivalent is lithium methylthioformaldine, (4,5-dihydro-5-methyl-l,3,5-dithiazin-2-yllithium A convenient synthesis of 2-alkyl- and 2-aryl-l,3-benzo-dithioles, which are precursors of acyl carbanion equivalents, has recently been published . 

The molybdenum and tungsten complexes catalyze reactions of soft nucleophiles, such as malonates, related 1,3-dicarbonyl compoimds, and nitroalkanes. Azlactones are also soft carbanions, and Trost has shown that complexes formed from molybdenum and the bis(pyridine) ligands catalyze enantioselective and diastereoselective allylation of azlactones with allylic phosphates to form quaternary amino acids (Equation 20.40). In these reactions, the nucleophile adds to the more substituted position of the allylic electrophile, and a stereocenter is formed at both the allyl carbon and the azlactone carbon. One route to the protease inhibitor tipranavir by the molybdenum-catalyzed allylation with 1,3-dicarbonyl compounds was demonstrated by Trost (Equation 20.41), and the Merck process group used related allylation chemistry with Trost s bis(pyridine) ligand to prepare the cyclopentanone precursor to various analogs of tipranavir (Equation 20.42). 

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