Enhanced chemoselective aminolysis of epoxides using diethylmethoxyborane

ORGN 145

Michael P Pence, michael.pence@pfizer.com, Hao T. Mee, and George Chang, changg@pfizer.com. Pfizer Global Research and Development, Pfizer Inc, Eastern Point Road, Groton, CT 06340
Ring opening of epoxides by amines is a classical route to b-amino alcohols.  For synthesis involving primary amines, traditionally the reaction is accomplished at room temperature over a period of 48-72 hrs if high ratio of the secondary amine (1) over the tertiary amine (2) is desired.  Recent advances show that using lanthanide catalysts [e.g. Yb(OTf)3] greatly increase the rate of aminolysis.  However for primary amines, the increased rate of reaction results in a decrease in the ratio of secondary to tertiary amine.  In our search for improved chemoselectivity in aminolysis of epoxides, we find the addition of diethylmethoxyborane greatly enhances the ratio of the desired secondary amine.  The scope and limitations of this reaction will be discussed.