Enantiopure synthesis of dihydrobenzo[1,4]-oxazine-3-carboxylic acids and a route to benzoxazinyl oxazolidinones

Published in: Journal, Article, Research Support, Non-U.S. Gov’t, Volume : 13, Issue : 11, Pages : 3211-3219

DOI : 10.1039/c4ob02475c

Author : Malhotra, Rajesh; Dey, Tushar K.; Basu, Sourav; Hajra, Saumen

Abstract : A two step protocol is developed for the efficient synthesis of enantiopure N-Boc-dihydrobenzo[b]-1,4-oxazine-3-carboxylic acids from serine derived cyclic sulfamidate via intramol. arylamination. The RuPhos Palladacycle along with addnl. RuPhos ligand is an efficient catalyst for the arylamination of β-(2-bromoaryloxy)amino acids 3 to provide easy and direct access to a variety of dihydrobenzo[b]-1,4-oxazine-3-carboxylic acids 4 with complete retention of enantiopurity in moderate to high yields. Dihydrobenzo[b]-1,4-oxazine-3-carboxylic acids are not only important unnatural amino acids, but are key precursors for the synthesis of important compounds such as benzoxazinyl oxazolidinones. A general approach for the synthesis of benzoxazinyl oxazolidinone is presented.