Grignard reagents, reactions with alkyl halide

B. Grignard Reagents Reaction with Alkyl Halides... 

The 3-pyridyl Grignard reagent has been alkenylated by reaction with allyl halides and the 2-picolyl Grignard reagent homologated with alkyl halides and to-diethoxyalkyl halidesi . Of much greater importance has been the use of picolyl lithium, potassium and sodium compounds in reactions with alkyl and aralkyl halides. 

Strictly speaking the alkyl halides are esters of the halogen acids, but since they enter into many reactions (t.g., formation of Grignard reagents, reaction with potassium cyanide to yield nitriles, etc.) which cannot be brought about by the other eaters, the alkyl halides are usually distinguished from the esters of the other inorganic acids. The preparation of a number of these is described below. 

Some recent studies have underlined the effect that certain physical properties of the reaction medium have in governing the nature and yields of the products obtained when indole Grignard reagents react with alkyl or alkynyl halides. Such factors include the basicity and dielectric constant of the medium and its ability to solvate any of the reacting species. ... 

Unsymmetrically -substituted borazines can be prepared by the reaction of IV-substituted borazines or h-trihalogeno-N-substituted borazines and the appropriate amount of Grignard reagent (94). Borazines unsymmetrically substituted on nitrogen have been prepared by the reaction of Hthium borohydride and ammonium chloride and alkyl ammonium chlorides (105,106), and by Uthiation of B- trime thylb o r azine followed by reaction with alkyl halides (107). 

Cross coii ing of Grignard reagents with 1-alkenyl halides, in marked contrast to alkyl halides, occurs readily with the reduced iron catalyst, as described above. The iron-catalyzed reaction of Grignard reagents with 1-alkenyl halides can, however, be differentiated from the reaction with alkyl halides. Thus, a mixture of propenyl bromide and ethyl bromide on reaction with methylmagnesium bromide afforded butene-2 but no cross-over products such as pentene-2 or propylene. The latter certainly would have resulted if a propenyliron species per se were involved in the catalytic process. Cross coupling under tEese circumstances clearly merits further study. 

The real value of this acid-base reaction is to transform a weak acid into an anion by using a powerful base the organolithium reagent. Such anions behave as nucleophiles in various reactions. In Chapter 11 (Section 11.3.6), alkyne anions underwent Sn2 reactions with alkyl halides. In Chapter 18 (Section 18.3.2), alkyne anions react with aldehydes and ketones. Both Grignard reagents and organolithium reagents react as nucleophiles with aldehydes and ketones (also described in Chapter 18, Section 18.4). Lithium amides such as 45 react as bases with aldehydes or ketones in Chapter 22 (Section 22.3). Many such examples are discussed in this book. 

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