This thesis describes the development of a new enantioselective synthetic method employing chiral cis-2,5-diaminobicyclo[2.2.2]octane-based organometallic catalysts. The significance of this new method to organic synthesis is illustrated with preparation of enantioenriched products that are transformed to important pharmaceutical agents. Chapter 1 provides a brief historical overview of asymmetric catalysis, especially...
The first asymmetric synthesis of (-)-7-epicylindrospermopsin via intramolecular nitrone cycloaddition is described. The synthesis utilized a convergent approach to prepare the cycloaddition precursor 176, which was assembled by condensation of hydroxylamine 175 with aldehyde 145. Hydroxylamine 175 was synthesized from ethylene glycol (166) in seven steps. Aldehyde 145 was completed...
Four strategies which involve synthetic elaboration of
the shikimate nucleus are discussed. Methyl shikimate was
differentially protected as the 3,4-0-cyclopentylidene ketal
and as the 5- 0- tert- butyldiphenylsilyl ether. The methyl
ester was then reduced with diisobutylaluminum hydride and
the resulting allylic alcohol was oxidized to aldehyde 47
with pyridinium...
Irradiation of a tryptamine linked through its side-chain nitrogen to an alkylidene malonate residue results in an intramolecular [2 + 2] cycloaddition to the indole 2,3-double bond. The resultant cyclobutane undergoes spontaneous retro-Mannich fission to produce a spiro[indoline-3,3-pyrrolenine] with relative configuration defined by the orientation of substituents in the transient...
Various hypervalent iodine compounds were evaluated as reagents
for intramolecular phenolic oxidative coupling. It was found that
phenyliodine(III) bis(trifluoroacetate) was effective for the coupling
of the monophenolic substrate 13a to 14a under neutral conditions.
Vanadium oxytrifluoride and hypervalent iodine compounds were compared
as oxidants for the conversion of 32 to...
The mycosporins, formerly called P310's are secondary metabolites
of fungi closely associated with fungal reproductive processes that
require light. The structurally related iminomycosporins are found in
marine plants and animals and may also have functions related to
light. In this study, approaches toward the asymmetric synthesis of
the mycosporins are...
A convergent synthesis of epothilone B that generates all seven of its
asymmetric centers in a completely stereoselective fashion has been
completed. Key reactions include an anti-Felkin aldol condensation to
set the C6 and C7 stereochemistry, a directed α-hydroxylation to install
the C15 (S)-hydroxyl substituent, and a Wittig condensation to...