Desulfonylation via Radical Process: Recent Developments in Organic Synthesis.

As the "chemical chameleon", sulfonyl-containing compounds and their variants have been merged with various types of reactions for the efficient construction of diverse molecular architectures by taking advantage of their incredible reactive flexibility. Currently, their involvement in radical transformations, in which the sulfonyl group typically acts as a leaving group via selective C-S, N-S, O-S, S-S, and Se-S bond cleavage/functionalization, has facilitated new bond formation strategies which are complementary to classical two-electron cross-couplings via organometallic or ionic intermediates. Considering the great influence and synthetic potential of these novel avenues, we summarize recent advances in this rapidly expanding area by discussing the reaction designs, substrate scopes, mechanistic studies, and their limitations, outlining the state-of-the-art processes involved in radical-mediated desulfonylation and related transformations. With a specific emphasis on their synthetic applications, we believe this review will be useful for medicinal and synthetic organic chemists who are interested in radical chemistry and radical-mediated desulfonylation in particular.

Three-Component Bisannulation for the Synthesis of Trifluoromethylated Tetracyclic Aza-Aromatics through Six C(sp3)-F Bond Cleavage and Four C-N Bond Formation.

An unprecedented and expeditious tandem bisannulation of polyfluoroalkylated tetralones with benzamidines to access various fluoroalkyl tetracyclic [1,3]-diazepines through multiple C-N bond formation and C(sp3)-F bond cleavage is reported. The process features high regio-/chemoselectivities, broad substrate scope, good functional group tolerance, procedural simplicity, mild reaction conditions, and scale-up synthesis. Mechanistic studies showed that the distinctive fluorine effect of polyfluoroalkyl tetralone plays a vital role for the aza-tetracycle construction.

Copper(II)-Mediated Ring Opening/Alkynylation of Tertiary Cyclopropanols by Using Nonmodified Terminal Alkynes.

The copper(II)-mediated ring opening/alkynylation of cyclopropanol by employing inexpensive and commercially available terminal alkyne is developed. The reactions proceeded efficiently to afford synthetically useful alk-4-yn-1-ones in moderate to good yields with good functional group tolerance. Control experiments showed that the reaction presumably proceeds via the formation of intermediates of copper homoenolate and/or alkynylcopper species.

Clonidine attenuates morphine withdrawal and subsequent drug sensitization in rhesus monkeys.

AIM: Clonidine is an alpha2 adrenoceptor agonist that is frequently used to reduce withdrawal symptoms during opioid detoxification in humans. The long-term effects of clonidine on withdrawal symptoms and its effects on subsequent drug exposure have not been thoroughly documented. The aim of the study was to determine if clonidine administered during morphine withdrawal in rhesus monkeys produces long-lasting effects on withdrawal symptoms and alters the effects of subsequently taken drugs of abuse. METHODS: Adult male rhesus monkeys were treated with increasing doses of morphine for 90 d to induce opiate (narcotic) dependence. The immediate and long-lasting effects of 1 week's administration of clonidine were measured via the recording of morphine withdrawal signs and the subsequent effects of challenge injections of morphine or cocaine. RESULTS: Monkeys chronically treated with morphine displayed withdrawal signs that lasted 2 weeks after cessation of morphine administration and displayed sensitized responses to subsequent morphine and cocaine injections. Clonidine significantly reduced certain morphine withdrawal signs and overall withdrawal score, but these effects did not persist upon cessation of clonidine treatment. Sensitization to the effects of morphine and cocaine were significantly reduced in monkeys previously treated with clonidine. CONCLUSION: Our results suggest that in addition to its short-term alleviating effect on morphine withdrawal signs, clonidine may reduce subsequent effects of drugs of abuse after prolonged abstinence.