The diastereoselective synthesis of cis-1,4-disubstituted morpholines has been accomplished in good to excellent yields via Bi(OTf)3catalyzed ring-closing O-allylation under mild conditions without the need for added base. The bismuth Lewis acid catalyst appeared to play two roles; the mild deprotection of a silyl ether and the Lewis acid activation of an allylic halide for mild nucelophilic cyclization. Substituted morpholines were obtained with diastereoselectivity ranging from 2:1 to >99:1.

het2013-abstract

 

“Bi(OTf)3 as a Dual Role Catalyst. Synthesis of Substituted Morpholine Derivatives via Catalytic O-Alkylation”
Ryuji Hayashi, Jin-A Park, and Gregory R. Cook*
Heterocycles 201488in press
special edition in honor of Prof. Victor Snieckus
DOI: 10.3987/COM-13-S(S)116