820-55-3Relevant 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.
THE LONG-RANGE ACTION OF THE POLAR EFFECT OF SUBSTITUENTS ON THE ABSTRACTION OF HYDROGEN IN FREE-RADICAL CHLORINATION PROCESSES
Aver'yanov, V. A.,Ruban, S. G.,Klykova, M. B.,Golubev, V. E.
, p. 435 - 439 (2007/10/02)
The free-radical chlorination of 1-chloroalkanes between C3 and C6 at 263 deg K was studied under conditions with wide variation in the concentrations of the substrates in benzene.By analysis of the products from chlorination of the pure substrates it was shown that the deactivating effect of the polar substituent does not extend beyond the third carbon atom and is mainly determined by the inductive effect.In the transition to an aromatic solvent the deactivating effect on the substituent extends to the fourth carbon atom.The results are substantiated in terms of a contribution from dipole-dipole interaction between the substituent and the polar form of the transition state to the polar effect of the substituents.
Reactions of Carbanions with Carbon Tetrachloride in Two-Phase Systems. Chlorinated Products as Nucleophilic and Electrophilic Intermediates
Makosza, M.,Kwast, A.,Kwast, E.,Jonczyk, A.
, p. 3722 - 3727 (2007/10/02)
A variety of carbanions generated in the catalytic two-phase system (aqueous NaOH or K2CO3 and tetrabutylammonium bromide catalyst) react with CCl4 to form chlorinated products that can react as nucleophiles and electrophiles.Thus, chlorinated intermediates generated from arylacetonitriles and propiophenone in the presence of aldehydes and electrophilic alkenes form oxirane and cyclopropane derivatives, respectively.The chlorinated intermediates act as electrophiles toward Cl3C- giving (trichloromethyl)oxiranes (from aryl alkyl ketones), α-trichloromethyl nitriles (from phenyl(dialkylamino)acetonitriles), and benzoyldichloro enamines (from α-dialkylamino ketones).From secondary nitroalkanes both chloronitroalkanes and dinitro compounds can be produced.
