Date of Award
Doctor of Philosophy
Richard C. Larock
Organopalladium chemistry has found considerable synthetic utility in organic chemistry. Advances in this chemistry led us to develop several efficient new synthetic routes to prostaglandins, hormones which have a host of regulatory functions in the human body. In this dissertation, several prostaglandins were synthesized utilizing organopalladium chemistry in the key step. In addition, a new synthetic approach to allylic aryl ethers was developed during our studies on prostaglandin synthesis;The first chapter of this thesis discusses the formal synthesis of prostaglandin F[subscript]2[alpha] and the total synthesis of 12-epi-PGF[subscript]2[alpha]. An extremely efficient three-component coupling was accomplished with optically active cis-4-t-butyldimethylsilyloxy-2-cyclopenten-1-ol, ethyl vinyl ether and 1-octen-3-one in the presence of Pd(OAc)[subscript]2;The second chapter discusses an efficient synthesis of the PGI[subscript]2 analogue (+)-5,6,7-trinor-4,8-m-phenylene PGI[subscript]2, which is known to have potent inhibitory activity for platelet aggregation. The strategy involves the intramolecular addition of an aryl radical to an olefin bond, followed by trapping of the resulting radical with a tri-n-butylstannyl allylic alcohol in a one-step procedure. The epimer, 12-epi-5,6,7-trinor-4,8-inter-m-phenylene PGI[subscript]2, was also synthesized by a sequence involving a one-step Pd(0)-mediated cyclization and subsequent enone coupling;The third chapter discusses the synthesis of a novel PGI[subscript]2 analogue, 12-epi-carbacyclin. A silyl enol ether prepared through organopalladium chemistry was treated with 1-octen-3-one in the presence of Pd(OAc)[subscript]2 to give an important intermediate in a single step;The last chapter discusses an efficient two-step synthesis of allylic aryl ethers from the corresponding allylic alcohols utilizing a [pi]-allylpalladium intermediate generated from allylic aryl carbonates. Allylic aryl carbonates were prepared either by using phenyl chloroformate or by using triphosgene and functionalized phenols.
Digital Repository @ Iowa State University, http://lib.dr.iastate.edu/
Nam Ho Lee
Lee, Nam Ho, "Organopalladium approaches to prostaglandins " (1991). Retrospective Theses and Dissertations. 9547.