Chad M. Kormos

Alkoxycarbonylation of aryl iodides using gaseous carbon monoxide and pre-pressurized reaction vessels in conjunction with microwave heating

The microwave-promoted alkoxycarbonylation of aryl iodides using reaction vessels pre-pressurized with carbon monoxide is reported. Reactions are performed using 0.1 mol% palladium acetate as catalyst, DBU as base and are complete within 20-30 min. A range of aryl iodide substrates can be converted to the corresponding esters using this methodology. Primary and secondary alcohols work well whereas a tertiary alcohol substrate proves less reactive. The potential for scale-up of the reaction has also been explored.

Preparation of nonsymmetrically substituted stilbenes in a one-pot two-step heck strategy using ethene as a reagent.

We present here a strategy for the preparation of nonsymmetrically substituted stilbenes using a one-pot two-step double Heck strategy. First a protocol is developed for the selective preparation of a range of styrenes using ethene as the alkene coupling partner. Then conditions are found for the effective coupling of the styrenes with aryl halides using a 1:1 stoichiometric ratio of the two components. The use of the microwave apparatus to perform the reactions offers a convenient method for synthesis as well as for safely, easily, and accurately loading vessels with gaseous reagents.

Flash column chromatograms estimated from thin-layer chromatography data

Given a sample mass and TLC data, a spreadsheet has been developed that provides information on the amount of silica gel needed, the optimal fraction size, and the degree of separation to be expected before flash chromatography is attempted. The spreadsheet is the first utility of its kind to accurately estimate the retention volume and band volume of analytes, as well as the fraction numbers expected to contain each analyte, and the resolution between adjacent peaks. This information allows users to select optimal parameters for preparative-scale separations before the flash column itself is attempted; ensuring a successful first separation.

Microwave Heating in Conjunction with UV Irradiation: a Tool for the Oxidation of 1,4-Dihydropyridines to Pyridines

Microwave heating is used for the preparation of 1,4-dihydropyridines and then, in conjunction with UV irradiation, is used for the efficient oxidation of the 1,4-dihydropyridines to pyridines. The oxidation reactions are performed in a sealed vessel using oxygen as the oxidant and an electrodeless discharge lamp as the irradiation source.

Assessment and use of two silicon carbide multi-well plates for library synthesis and proteolytic digests using microwave heating

The use of two silicon carbide plates is reported for the preparation of three libraries of organic molecules using microwave heating. In addition, a preliminary study has been carried out, showing that one of the plates can also be used in a proteomics setting. Both the 24-position and 48-position plates heated evenly when irradiated with microwave energy. The 48-position plate was used to prepare a library of N-aryl functionalized beta-amino esters via an aza-Michael reaction between anilines and Michael acceptors. The 24-position plate was used to prepare a library of biaryls via a Suzuki coupling methodology and a library of 1,4-dihydropyridines via a Hantzsch synthesis. The 48-position plate was also used to perform the proteolytic digestion of insulin chain B by trypsin.

Simple Tetrahydroisoquinolines Are Potent and Selective Kappa Opioid Receptor Antagonists

Potent and selective κ opioid receptor antagonists have been derived from the N-substituted trans-3,4-dimethyl-4-(3-hydroxyphenyl)piperidine class of pure opioid receptor antagonists. In order to determine if the 3-hydroxyphenyl and/or the piperidine amino groups are required for obtaining the pure opioid antagonists, (3R)-7-hydroxy-N-[(1S)-2-methyl-1-(piperidine-1-ylmethyl)propyl]-1,2,3,4-tetrahydroiosquinoline-3-carboxamide (1), which does not have a 4-(3-hydroxyphenyl) group, and (3R)-N-(1R)-1-(cyclohexylmethyl)-2-methylpropyl]-7-hydroxy-1,2,3,4-tetrahydroisoquinoline-3-carboxamide (2), which does not have a 4-hydroxylphenyl or a piperidine amino group, were synthesized and evaluated for their [35S]GTPγS binding properties at the μ, δ, and κ opioid receptors. Surprisingly compound 1 remained a pure opioid antagonist with a Ke = 6.80 nM at the κ opioid receptor and is 21- and 441-fold selective for the κ receptor relative to the μ and δ opioid receptors, respectively. Even more unexpected and novel is the finding that 2 has a Ke = 0.14 nM at κ and is 1730- and 4570-fold selective for κ relative to the μ and δ opioid receptors, respectively.