A general approach to homochiral α-amino substituted bromo-heteroaromatics suitable for two-dimensional rapid analogue synthesis

An efficient and general synthesis of homochiral alpha-amino substituted bromo-heteroaromatics B using a diastereoselective 1,2-addition has been developed. The obtained heteroaromatic intermediates allow for a rapid two-dimensional exploration of a new series of histone deacetylase inhibitors, through Suzuki-Miyaura cross-coupling reactions for the introduction of a second aromatic element, followed by global deprotection and derivatization of the amino group. (C) 2009 Published by Elsevier Ltd.