119206-70-1Relevant 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.
Mechanisms of free-radical reactions. XI. Kinetic investigation of the free-radical chlorination of alkyl aromatic hydrocarbons by phenylchloroiodonium chloride
Dneprovskii, A. S.,Kasatochkin, A. N.
, p. 693 - 699 (2007/10/02)
The free-radical chlorination of meta- and para-substituted toluenes, ethylbenzene, and cumenes by phenylchloroiodonium chloride was investigated by the method of competing reactions.The good correlation between the relative reaction rate constants and the Brown ?+ constants and also the large negative values of ρ indicate separation of charges in the transition state.The values of the primary kinetic isotope effects of hydrogen decrease with increase in the reactivity of the substrate, whereas the values of the reaction parameters vary irregularly.The deviations from the inverse relation between the reactivity and the selectivity are due to the polar character of the transition state.
Selectivity in the Halogenation of Hexane by Tertiary Aminium Radicals from the Photodecomposition of N-Halogenoammonium Perchlorates
Fuller, Steven E.,Smith, John R. Lindsay,Norman, Richard O. C.,Higgins, Raymond
, p. 545 - 552 (2007/10/02)
The photochlorination of hexane with tertiary N-chloroammonium perchlorates in trifluoroacetic acid gives monochlorohexanes in high yield and with a striking preference for the 2-isomer.It is shown that free-radical chains are involved in which hydrogen-atom abstraction is by tertiary aminium radicals.The marked preference for 2- compared with 3-chlorination is attributed mainly to the bulky aminium radical attacking the relatively more accessible 2-position; an alternative explanation involving a reversible hydrogen-atom abstraction is ruled out.The magnitude of the primary deuterium kinetic isotope effect in these photochlorinations gives information about the dependence of the extent of C-H bond breakage in the transition state on the structure of the abstracting aminium radical.
