Functionalized carbomagnesiation

Chromium salts can catalyze the carbomagnesiation reactions of 1,6-enynes with cy-clization (Scheme 12) . This reaction is probably initiated by carbometalation of the alkyne unit. The resultant organomagnesium species 16 undergoes further functionalization upon treatment with various electrophiles (Scheme 12) . ... 

As electrophiles for post-functionalization of awfi-carbomagnesiation, aryl and alkenyl halides can also be used when Pd catalyst is employed. By merging such Pd-catalyzed arylation, tamoxifen can be synthesized in a stereoselective manner (Scheme 36) . ... 

Fleming and coworkers have developed a number of such multicomponent assembling reactions using alkyl halides, aldehydes, ketones and acid chlorides as electrophiles for post-functionalization of carbomagnesiation . The stereoselectivity of the reaction with electrophiles is not only generally high but also highly dependent on the nature of electrophiles. 

The carbomagnesiation of alkenes has been extensively investigated in the last 40 years and several reactions with high synthetic potential have been discovered. The addition of Grignard reagents to non-functionalized alkenes usually requires severe reaction conditions and only the zirconium-catalyzed... 

DFT computations showed that the intramolecular addition of the aryllithium generated from 425 occurs on the central carbon atom of the allenic moiety to yield the intermediate 427 from which lithium ethoxide is eliminated to furnish the benzofuran product 426. Both cyclization processes were found to pass through low-lying transition states, as it would be expected for fast reactions at low temperatures [123]. Further explorations on the anti selectivity in the intramolecular carbolithi-ation by DFT computations revealed additional details regarding the mechanism of this carbocyclization and led the authors to conclude that such a transformation is controlled by the appropriate molecular editing [123]. The synthesis of functionalized heterocycles can be relatively easy to achieve by intramolecular carbometallation reactions. For example, Kunz and Knochel [124] recently reported the preparation of benzothiophene scaffolds 429 by copper-catalyzed carbomagnesiation ofalkynyl thioethers 428 (Scheme 10.148). 

Scheme4.47 Functionalized alkenylmagnesium compounds obtained by carbomagnesiation.

---