Michael A. Bernstein

Preparation of ethyl 5(s),6-epoxy-3(r)-(methoxymethoxy)hexanoate: a key chiral intermediate for mevinolin and compactin.

Abstract The synthesis of Ethyl 5(S),6-Epoxy-3(R)-(methoxymethoxy)hexanoate, a key chiral synthon for the β-hydroxy-δ-lactone portion of Mevinolin and Compactin, via a regiospecific ring opening of a tetrahydrofuran derivative by dimethylboron bromide, is described.

Synthesis of aromatic amines from electron-rich arenes and bis(2,2,2-trichloroethyl) azodicarboxylate

Abstract Electron-rich arenes react with bis(2,2,2-trichloroethyl) azodicarboxylate in 3 M lithium perchlorate-diethylether or acetone solution to produce para-substituted aryl hydrazides in high yields. The corresponding aromatic amines are readily obtained by reducing the hydrazides with zinc in acetic acid.

The unsymmetrical silaketal as a neutral, removable tether for effecting intramolecular diels-alder reactions.

Abstract Silaketals, in which reactive dienes and dienophiles are linked, can participate in intramolecular Diels-Alder reactions to produce products with a high degree of stereocontrol and with regiochemistry opposite to that predicted by bond polarization models.

Ring cleavage of THP and THF ethers using dimethylboron bromide

Abstract The reaction of dimethylboron bromide with THP and THF ethers was studied. Under conditions of kinetic control, these reactions proceed by selective cleavage of the ring carbon—oxygen bond to give acyclic α-bromo ethers. Treatment of these intermediates with a variety of nucleophiles gives ring-opened products.

Conformational analysis of δ-lactams

Abstract δ-lactams substituted at C-5 by an oxygen atom exist, in solution principally, in the axial conformation. This axial preferred form is also present in the solid state.

Dichlorophenylborane a new reagent for the preparation of 2-phenyl-4H-1,3,2-benzodioxaborins

Abstract A novel approach in the preparation of 2-phenyl-4H-1,3,2-benzodioxaborin using dichlorophylborane was developed. The method was applied to the synthesis of cannabinoids via an orthoquinone-methide intermediate generation from the benzodioxaborins.

Polycyclic chromans via novel tricyclic-2-phenyl-4H-1,3,2-benzodioxaborins

Abstract This paper describes a straightforward synthesis of complex polycyclic chromans. They are prepared from novel tricyclic-2-phenyl-4H-1,3,2-benzodioxaborins via a bicyclic orthoquinone-methide intermediate generated in situ under thermolysis or Lewis acid condition. The dioxaborins react with various allyl trimethylsilanes or with ethyl vinyl ether to give polycyclic chromans after acid cyclization or directly.

Unexpected acid-catalysed rearrangement of certain 3-(arylthio)indoles to 2-(2-aminophenyl)benzothiophenes

3-(Arylthio)indoles (1), in which the aryl group is an electron-rich ring system, undergo a novel structural rearrangement to 2-(2-aminophenyl)benzothiophenes (2) upon heating in polyphosphoric acid.

Reaction monitoring using NMR.

There is nothing very new in using various spectroscopies and separation sciences to follow the chemical changes that are associated with chemical reaction progression. Most commonly, when organic chemical reactions are followed, the simplest and sometimes easiest physical methods are chromatography and optical detection, or vibrational spectroscopy. In fact, this is performed almost every day by synthetic organic chemists. The motivation behind these studies can often be to determine the exact reaction mechanism, or to describe the temporal changes in reagent, product, intermediate, and reaction impurities. The most fundamental question is one of quantitation, but more subtle information can add a further dimension of understanding. In this special issue, we consider these issues and approaches under the general name of ‘Reaction Monitoring’. Whilst product formation is a key analytical component of everyday synthetic organic chemistry, a significant change in experiment design occurs when the same reaction is probed at regular and frequent times through the time course of reaction. This technique allows for significantly more information to be extracted, for example as transient species may be formed and consumed, A far more complete picture of the chemistry emerges, bounded by the specific limitations of the analytical method under use. The multiple analytical and spectroscopic approaches that can and are used serve to reinforce the importance of Reaction Monitoring. Motivations for the analyses of this type may be cost, environmental impact, or possibly process control. In the case of pharmaceutical drug production, strict controls are required for the drug compound purity, the impurities that are present, and their concentrations. This assures delivery of materials that have the expected biological efficacy and safety profile.

A general method for determining the anomeric configuration of C-furanoside derivatives: a 1H-nuclear magnetic resonance nuclear overhauser effect study

The nuclear Overhauser effect 1H n.m.r. experiment was found to be an excellent method for a priori determination of the stereochemical configuration of a variety of C-furanoside derivatives. If the stereochemistry at one ring carbon atom is known, the methine proton at this centre may be used to determine the proton stereochemistry at neighbouring carbon centres and this can be repeated until the anomeric proton configuration is determined. Certain protecting groups themselves may be used to report on the C-furanoside anomeric configuration, and this was demonstrated with methoxymethyl and O-isopropylidene derivatives.