Aromatic heterocycles are core structural motifs in natural products, pharmaceuticals and biological polymers. Indoles, in particular, represent a significant subclass of aromatic heterocycles, both in terms of sheer numbers, but also in biological and pharmaceutical relevance. As such, new methodologies for the synthesis of indoles represent an important and continually...
The first part of this manuscript is about the total synthesis of the aspidosperma alkaloids leuconoxine, melodinine E and mersicarpine. Our synthetic strategy used a radical translocation-conjugate addition cascade to construct the core of the natural product. Specifically, a vinyl radical was generated from the homolysis of the C–I bond...
The bimolecular reaction of two carbenoid species resulting in the formation of a carbon-carbon double bond (pi-system), referred to herein as carbenoid eliminative cross-coupling (CEXC), involves a series of three fundamental steps: (i) ate-complex formation (transmetalation), (ii) 1,2-metalate rearrangement, and (iii) beta-elimination. All three steps are stereospecific and so the...
State-of-the-art, high-resolution mass spectrometry techniques for acquisition of metabolomic and lipidomic data coupled with advanced computational methods provide new opportunities for interpreting large and complex datasets and comprehending the underlying biological processes of diseases. Both metabolomics and lipidomics strive to obtain comprehensive analyses of small molecules, i.e., metabolites and lipids,...
Iodine-129 is a key risk driver at sites where nuclear materials have been fabricated or processed, and it is a predominant isotope of concern in long-term waste storage strategies. I-129 exists primarily as iodate in the subsurface at the Hanford Site in south-central Washington State. Between 15 and 40% of...
In Part I, (4S,5R)-4,5-dimethyl-4-phenylcyclohex-2-enone (19a) was prepared in 73% yield with high enantio- and diastereo-selectivity (er > 98:2, dr > 20:1) on a multigram scale by a Yamada-Otani condensation between (E)-pent-3-en-2-one and 2-phenylpropanal catalyzed by a sulfonimide derivative of (S)-proline (18, HuaCat®). Synthetically useful transformations of the cyclohexenone product 19a...
Enantioenriched sp³-hybridized carbenoid reagents CR1R2MX (X = nucleofuge, M = electrofuge) of different types were investigated for the synthesis of polysubstituted alkyl chains by iterative stereospecific reagent-controlled homologation (StReCH) and for the stereospecific connective synthesis of alkenes by eliminative cross-coupling.
In the first part, putative enantioenriched α-chloroalkyllithiums (CHRLiCl) were employed...
The stereospecific reagent-controlled homologation (StReCH) of boronic esters with putative lithiooxiranes generated in situ from appropriate precursors via sulfoxide-lithium exchange, tin-lithium exchange, and direct lithiation is described with an emphasis on the first lithiation technique which allows for the regio- and stereo-specific generation of all types of lithiooxirane isomer. Transient...
The stereospecific reagent-controlled homologation (StReCH) of boronic esters with enantioenriched carbenoid species generated in situ by the addition of organolithium initiators to stereodefined α-chloroalkyl aryl sulfoxides was previously reported. The reaction of an organolithium with an α-chloroalkyl aryl sulfoxide ostensibly generates an α-chloroalkyllithium via sulfoxide-lithium exchange; however, the true nature...
Lycopodium alkaloids have generated enormous amounts of interest from the scientific community, both as synthetic targets and for their medicinal properties. Herein is described work towards a unifying approach to large segments of the Lycopodium family. An organocatalyzed intramolecular heteroatom Michael reaction method, for the construction of piperidine and piperizine...