Organic Chemistry Portal
Organic Chemistry Highlights

Monday, April 26, 2004
Douglass Taber
University of Delaware

C-N Ring-forming Reactions by Transition Metal-catalyzed Intramolecular Alkene Hydroamination

Alkene hydroamination has been known for many years, but has been little used as a method in organic synthesis. Tobin Marks of Northwestern recently published a series of three papers that will make this transformation much more readily accessible. In the first (J. Am. Chem. Soc. 2003, 125, 12584. DOI: 10.1021/ja035867m) he describes the use of a family of lanthanide-derived catalysts for intermolecular hydroamination of alkynes (to make imines, not illustrated) and alkenes. With aliphatic amines, the branched (Markownikov) product is observed, 1 -> 2. With styrenes, the linear product is formed. When two alkenes are present, the reaction can proceed (3 -> 4) to form a ring, with impressive regioselectivity.

The products from alkene hydroamination are inherently lightly functionalized. To address this possible deficiency, Professor Marks also reported (J. Am. Chem. Soc. 2003, 125, 15878. DOI: 10.1021/ja036266y) the cyclization of amino dienes such as 5. The cyclizations proceed with high selectivity for the cis-2,6-dialkyl piperidines, and with a little lower selectivity for the trans 2,5-dialkyl pyrrolidine. The product alkenes are ~95% E, the balance being a little Z alkene and the terminal alkene.

More complex substrates can also be cyclized efficiently using these catalysts. Professor Marks and his colleague Frank McDonald, now at Emory University, report (J. Org. Chem. 2004, 69, 1038. DOI: 10.1021/jo035417c) that the amino diene 7 cyclizes to 8 with 81:19 diastereoselectivity. It is particularly noteworthy that with each of these ring-forming reactions, the free amines are employed, avoiding inefficiencies of protection and of protecting group removal

D. F. Taber, Org. Chem. Highlights 2004, April 26.