Investigations into the partial reduction of substitued pyridines

ORGN 646

Dale J Johnson, dale.johnson@chem.ox.ac.uk1, Timothy J Donohoe, timothy.donohoe@chem.ox.ac.uk1, and Mark J Bamford2. (1) Department of Chemistry, University of Oxford, 12 Mansfield Road, Oxford, OX1 3TA, United Kingdom, (2) Department of Medicinal Chemistry, GlaxoSmithKline Research and Development Ltd, New Frontiers Science Park, Third Avenue, Harlow, CM19 5AW, United Kingdom
The ammonia-free Birch reduction, using lithium and di-tert-butylbiphenyl as a source of electrons, has been applied to the reductive alkylation of 4-methoxypicolinic acid methyl ester pyridinium salt. The nature of the nitrogen substituent was found to be key; acting as both an activating group for the reduction and as a protecting group. The enolate formed during the reduction has been quenched with a range of electrophiles, including acids, alkyl halides and chloroformates to give a variety of dihydropyridones. The dihydropyridone was shown to be a versatile intermediate. Functionalisation at every position around the ring has been achieved, showing compatability with a variety of reaction conditions. The synthetic importance of the dihydropyridone motif has been demonstrated in studies towards the synthesis of the marine alkaloid cylindricine A.

 

Asymmetric Reactions, Heterocycles, Aromatics, Combinatorial, and Physical Organic Chemistry
8:00 PM-10:00 PM, Wednesday, 31 August 2005 Washington DC Convention Center -- Hall A, Poster

Division of Organic Chemistry

The 230th ACS National Meeting, in Washington, DC, Aug 28-Sept 1, 2005