A four-step synthesis of cis-3,5-disubstituted morpholines from enantiomerically pure amino alcohols is described. The key step in the synthesis is a Pd-catalyzed carboamination reaction between a substituted ethanolamine derivative and an aryl or alkenyl bromide. The morpholine products are generated as single stereoisomers in moderate to good yield. This strategy also provides access to fused bicyclic morpholines as well as 2,3- and 2,5-disubstituted products.
A four-step synthesis of n class="Chemical">cis-3,5-disubstituted morpholines from enantiomerically pure amino alcohols is described. The key step in the synthesis is a Pd-catalyzed carboamination reaction between a substituted ethanolamine derivative and an aryl or alkenyl bromide. The morpholine products are generated as single stereoisomers in moderate to good yield. This strategy also provides access to fused bicyclic morpholines as well as 2,3- and 2,5-disubstituted products.
Authors: Brett D Allison; Victor K Phuong; Laura C McAtee; Mark Rosen; Magda Morton; Clodagh Prendergast; Terry Barrett; Guy Lagaud; Jamie Freedman; Lina Li; Xiaodong Wu; Hariharan Venkatesan; Marna Pippel; Craig Woods; Michèle C Rizzolio; Michael Hack; Kenway Hoey; Xiaohu Deng; Christopher King; Nigel P Shankley; Michael H Rabinowitz Journal: J Med Chem Date: 2006-10-19 Impact factor: 7.446
Authors: Bryan S Matsuura; Allison G Condie; Ian A McBee; Ryan C Buff; Gregory J Karahalis; Corey R J Stephenson Journal: Org Lett Date: 2011-11-09 Impact factor: 6.005