Carbomagnesiation intramolecular

A facile intramolecular carbomagnesiation becomes possible by inserting one more carbon between the reactive magnesium center and the double bond. For example, when a 6-chloro-l-heptene was refluxed with magnesium, 1,2-dimethylcyclopentane (cis/trans = ca 1/4) was obtained in 88% yield after hydrolysis (Scheme 47) °. The cyclization shows a 5-exo-trig selectivity and the product derived from 6-endo-trig cyclization (methylcyclohexane) is not observed. 

Hoffmann and coworkers have further carefully examined the intramolecular carbomagnesiation of a vinylsilane (Scheme 61) °. Both E) and (Z)-isomers of 88 undergo an intramolecnlar carbomagnesiation and a stereospecific (>95%) 5yn-addition of the carbon-magnesinm bond to the donble bond takes place. The resulting a-sUylalkylmag-nesium componnds 89 are not confignrationally stable under the reaction conditions. They epimerize with a half-life of 2.7 days at room temperatnre. 

II. CARBOMAGNESIATION REACTIONS OF ALKYNES A. Intramolecular Addition to Simple Alkynes... 

One of the classical solutions to overcome the low reactivity is to render the carbomagnesiation intramolecular. For example, Utimoto and coworkers reported that the reaction of ( )-6-bromo-3-methyl-l-trimethylsilyl-l-hexene (85) with magnesium produces the corresponding Grignard reagent 86, which intramolecularly adds to the vinylsilane moiety from the less hindered side affording a single stereoisomer of cycUzed product 87 (Scheme 60) °°. 

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). 

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