Pivotal amine syntheses

It would, in principle, be possible to convert the polyol 115 into the 6"-deoxy sugar 118, a direct precursor of /3-acarbose. However, we decided that it would be better to reassess the whole synthesis and reasoned that a 1,6-epithio sugar such as 119 would be an ideal pivot for a synthesis of acarbose the amine 81 could easily be introduced at C-4, the sulfur at C-1 allows for activation to produce a glycosyl donor ready for attachment to the disaccharide alcohol 113 and, finally, desulfurization at C-6 leads to the necessary methyl group. 

It is possible to speed up aliphatic tertiary amine oxidation by adding tungstate or molybdate catalysts.334 However, for oxidation of aromatic and particularly heterocyclic tertiary nitrogen, a stronger system than hydrogen peroxide alone is required. iV-Oxidation of heterocycles is of pivotal importance in industrial chemical synthesis.335 Catalysed systems have been applied and these are dominated by metal peroxo systems based on molybdenum or tungsten. For example, quinoxaline and pyrazine may be oxidized to mono- or... 

Scheme 98 The pivotal triple reductive amination in Mootoo s synthesis of (+)-casta-nospermine. Reagents and conditions (a) NH4HCO2 (I.Sequiv.), NaBHsCN (1.5 equiv.), 3 A molecular sieves, MeOH, rt, 24 h.

Cu(II)-mediated N-arylation of amines and azoles with aryl boronic acids has been reviewed recently [59]. Pfizer chemists have demonstrated that N-arylpyr-roles can be prepared from aryl boronic adds and dectron-defident pyrroles via Cu(OAc)2 mediated coupling reaction at room temperature in air [60]. These reaction conditions are compatible with a variety of functional groups on boronic adds, but are sensitive to steric hindrance. The method could be successfully applied for the synthesis of compound 93 bearing a 4-cyanoaryl group which is a pivotal intermediate in the synthesis of MMP inhibitor AG3433 (Scheme 3.40). 

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