Adrian Maddaford

ASYMMETRIC CATALYSIS OF ACYL TRANSFER BY LEWIS ACIDS AND NUCLEOPHILES. A REVIEW

INTRODUCTION .............................................................................................................................. 333 I. CHIRAL LEWIS ACID CATALYSIS ........................................................................................ 334 11. CHIRAL NUCLEOPHILE CATALYSIS ................................................................................. 338 CONCLUSIONS ................................................................................................................................ 3.56 REFERENCES ................................................................................................................................... 3.57

Atropisomeric α-methyl substituted analogues of 4-(dimethylamino)pyridine: synthesis and evaluation as acyl transfer catalysts

The regioselectivity of α-metalation–methylation of N-BF3 adducts of 4-(dimethylamino)pyridines as a function of β-substitution is examined in attempts to prepare configurationally stable atropisomeric derivatives (I and II) having an α-methyl substituent and a β-biaryl stereogenic axis. The activity of some of these derivatives as catalysts for acyl transfer is examined and the kinetic resolution of 1-(1-naphthyl)ethanol catalysed by α-methyl chiral DMAP (−)-24 is reported. A rationale for the reduced stereoselectivity of this catalyst relative to its non-α-substituted analogue (−)-1 is also proposed.

Synthesis of C2-symmetric analogues of 4-(pyrrolidino)pyridine: new chiral nucleophilic catalysts

The syntheses of a series of enantiomerically pure C2-symmetric 4-(pyrrolidino)pyridine (PPY) derivatives by SNAr of 4-halo-/4-phenoxypyridines and by cyclocondensation from 4-aminopyridine are described. Preliminary results pertaining to their use as catalysts for acylative kinetic resolution of 1-phenylethanol are also presented. A single-crystal X-ray analysis of PPY If is reported.

Synthesis and Biological Evaluation of Acyclic Phosphonic Acid Nucleoside Derivatives

As part of a project to generate a library of nucleosides as potential antiviral agents, a small subset of novel acyclic phosphonic acid nucleosides was prepared. Practical synthetic routes are described for three targets, which were then tested against HIV, hepatitis C virus (HCV), and Dengue virus.