Generation of stoichiometric ethylene and isotopic derivatives and application in transition-metal-catalyzed vinylation and enyne metathesis.

Ethylene is one of the most important building blocks in industry for the production of polymers and commodity chemicals. (13)C- and D-isotope-labeled ethylenes are also valuable reagents with applications ranging from polymer-structure determination, reaction-mechanism elucidation to the preparation of more complex isotopically labeled compounds. However, these isotopic derivatives are expensive, and are flammable gases, which are difficult to handle.

Efficient routes to carbon-silicon bond formation for the synthesis of silicon-containing peptides and azasilaheterocycles.

Silasubstitution, where silicon is substituted for carbon at specific sites of the substrate, has become a growing practice in medicinal chemistry. Introducing silicon into bioactive compounds provides slight physical and electronic alterations to the parent compound, which in certain instances could make the substrate a more viable candidate for a drug target. One application is in the field of protease inhibition.

Regioselective Rh(I)-catalyzed sequential hydrosilylation toward the assembly of silicon-based peptidomimetic analogues.

A highly regioselective Rh(I)-catalyzed hydrosilylation of enamides is presented. This mild protocol allows access to a wide variety of different arylsilanes with substitution at the β-position of the enamide and functionalization on the alkyl chain tethered to the silane. This protocol is extended to include a sequential one-pot hydrosilylation.

Enamides accessed from aminothioesters via a Pd(0)-catalyzed decarbonylative/β-hydride elimination sequence.

A facile synthesis of various enamides from aminothioesters via a palladium(0)-catalyzed decarbonylation/β-hydride elimination is reported. This protocol was applied to mercaptopyridyl C-terminal modified peptides for the generation of enamides without epimerization at stereogenic centers.

Enantioselective synthesis of 3,4-chromanediones via asymmetric rearrangement of 3-allyloxyflavones.

Asymmetric scandium(III)-catalyzed rearrangement of 3-allyloxyflavones was utilized to prepare chiral, nonracemic 3,4-chromanediones in high yields and enantioselectivities. These synthetic intermediates have been further elaborated to novel heterocyclic frameworks including angular pyrazines and dihydropyrazines. The absolute configuration of rearrangement products was initially determined by a nonempirical analysis of circular dichroism (CD) using time-dependent density functional theory (TDDFT) calculations and verified by X-ray crystallography of a hydrazone derivative.

An "anti-Baldwin" 3-exo-dig cyclization: preparation of vinylidene cyclopropanes from electron-poor alkenes.

Stabilized carbanions undergo an uncommon 3-exodig cyclization onto propargyl halides through an SN2' substitution. Propargyl iodides as electrophiles are necessary to achieve good yields (36-95%) for most substrates, although the usefulness of chlorides and bromides is documented. A variety of monocyclic and bicyclic vinylidene cyclopropanes can be prepared.

Exploring skeletal diversity via ring contraction of glycal-derived scaffolds.

Aryl ether C-glycoside scaffolds have been prepared from tri-O-acetyl-D-glucal by C-glycosylation followed by allylic substitution with phenols mediated by Pd(0). The aryl ethers were subjected to either [3,3]-sigmatropic rearrangement to produce 3-pyranyl-phenols or Au(III)-mediated ring contraction to create highly substituted tetrahydrofurans. [structure: see text]

Convergent synthesis of a complex oxime library using chemical domain shuffling.

[reaction: see text] The synthesis of a complex hybrid oxime library is reported utilizing convergent ligation of alkoxyamine and carbonyl monomers via "chemical domain shuffling". Initial biological screening of the library against human small cell lung carcinoma (A549) cells led to the identification of a novel hybrid dimer in contrast to the corresponding monomeric compounds which were found to be inactive.