13064-82-9Relevant articles and documents
Site-Selective Aliphatic C-H Chlorination Using N-Chloroamides Enables a Synthesis of Chlorolissoclimide
Quinn, Ryan K.,K?nst, Zef A.,Michalak, Sharon E.,Schmidt, Yvonne,Szklarski, Anne R.,Flores, Alex R.,Nam, Sangkil,Horne, David A.,Vanderwal, Christopher D.,Alexanian, Erik J.
supporting information, p. 696 - 702 (2016/02/03)
Methods for the practical, intermolecular functionalization of aliphatic C-H bonds remain a paramount goal of organic synthesis. Free radical alkane chlorination is an important industrial process for the production of small molecule chloroalkanes from simple hydrocarbons, yet applications to fine chemical synthesis are rare. Herein, we report a site-selective chlorination of aliphatic C-H bonds using readily available N-chloroamides and apply this transformation to a synthesis of chlorolissoclimide, a potently cytotoxic labdane diterpenoid. These reactions deliver alkyl chlorides in useful chemical yields with substrate as the limiting reagent. Notably, this approach tolerates substrate unsaturation that normally poses major challenges in chemoselective, aliphatic C-H functionalization. The sterically and electronically dictated site selectivities of the C-H chlorination are among the most selective alkane functionalizations known, providing a unique tool for chemical synthesis. The short synthesis of chlorolissoclimide features a high yielding, gram-scale radical C-H chlorination of sclareolide and a three-step/two-pot process for the introduction of the β-hydroxysuccinimide that is salient to all the lissoclimides and haterumaimides. Preliminary assays indicate that chlorolissoclimide and analogues are moderately active against aggressive melanoma and prostate cancer cell lines.
Gas-Phase Acid-Induced Nucleophilic Displacement Reactions. Stereochemistry of Inter- and Intramolecular Substitutions at Saturated Carbon
Speranza, Maurizio,Angelini, Giancarlo
, p. 3115 - 3120 (2007/10/02)
The stereochemistry of gas-phase nucleophilic displacement by water on a number of positively charged intermediates was investigated under different experimental conditions.The ionic intermediates were generated in the gas phase at atmospheric pressure by attack of radiolytically formed Broensted (CH5+, C2H5+) and Lewis (C2H5+, CH3FCH3+) acids on selected mono- and bifunctional substrates.Isolation and identification of their neutral substituted products allowed us to demonstrate that, under the used experimental conditions, gas-phase acid-induced inter- and intramolecular nucleophilic displacement reactions occur via predominant (64-98percent) inversion of configuration at the reaction center.The yield and the stereoisomeric distribution of the substituted products were found to depend on either the nature of the gaseous acid used to generate the charged intermediates or the concentration of the added base (NH3 or H2O).Product distribution from bifunctional substrates is characterized by the presence of minor amounts of substituted derivatives retaining the original configuration of their neutral precursors.Their formation is ascribed to the occurence of an extensive neighboring group participation effect (an HO-3 process) on the displacement reaction, resulting in a double inversion of the reaction centers.A mechanistic model is proposed for gas-phase nucleophilic substitutions at atmospheric pressures, and compared with those from the related low-pressure ICR (ion cyclotrone resonance mass spectrometry) and solution-chemistry studies.
