%A Stephanie R McCabe
%T ENANTIOSELECTIVE CYCLOPROPANATIONS OF ALLENES AND THEIR
APPLICATION TO THE TOTAL SYNTHESIS OF CLAVINE ALKALOIDS
%X The first section of this thesis describes the development of an enantioselective synthesis
of terminally unsubstituted methylenecyclopropanes. The key feature of this approach is a Rh2(STBPTTL)
4-mediated catalytic asymmetric cyclopropanation of unsubstituted allene to produce
enantioenriched methylenecyclopropanes bearing alkyl or activated ester functionalities. This
method was successfully applied to the enantioselective total synthesis of cycloclavine.
The second section of this thesis describes the development of an improved 12
steps/5.2% overall yield racemic total synthesis of the clavine alkaloid cycloclavine. The first
enantioselective total syntheses of the unnatural enantiomer (?)-cycloclavine and the natural
enantiomer (+)-cycloclavine were also accomplished in 8 steps/7.1%(brsm) overall yield and 8
steps/4% overall yield, respectively. Noteworthy features of this approach include a strainpromoted
intramolecular Diels-Alder reaction followed by a highly regioselective aerobic ?,?-
dehydrogenation to form a key enone intermediate in >99.5:0.5 er after crystallization.
Additional noteworthy features include the enone 1,2-addition of a novel TEMPO-carbamate
aminomethyl carbanion and an IMDAF reaction to install the indole core. The mechanism of
thermolysis of the new TEMPOC amine protecting-group was investigated. Finally, the natural
and unnatural enantiomers were evaluated for their ability to bind to several neurotransmitter
receptors in radioligand binding assays.
%D 2018
%K total synthesis, cycloclavine, allene
%I University of Pittsburgh
%L pittir34612