Neopentyl halides

Primary, secondary, and tertiary alcohols can be converted to any of the four halides by treatment with the appropriate NaX, KX, or NH4X in polyhydrogen fluoride-pyridine solution." This method is even successful for neopentyl halides. Another reagent that converts neopentyl alcohol to neopentyl chloride, in 95% yield, is PPh3-CCl3CN." ... 

A rel = 1.2 x 10 6) (Ingold, 1957). Neopentyl halides are known in fact to be extremely stable towards nucleophilic displacement. There are few examples in the gas phase that allow for a full comparison since alkyl halides with P-hydrogens may be prone to undergo elimination reactions simultaneously with displacement. For example, the reaction of F with C2H5C1 proceeds with a rate constant krel = 0.86, compared to that of CH3C1 (Jose, 1976), whereas (CH3)3CCH2C1 reacts with k[cl = 0.61 (Olmstead and Brauman,... 

The possibility that R-0 fission may occur in advance of attack by halide ion has been demonstrated in the reactions of dineopentyl phenyl phosphite or neopentyl diphenyl phosphite with alkyl halides. In these cases the Michaelis-Arbuzov intermediates cannot be isolated but the neopentyl halides which are formed are contaminated with varying amounts of rearrangement product (t-pentyl halide) (Table IV). These results may explain the formation of mixtures of isomeric halides (9,10,11) in certain applications of Rydon s method for alkyl halide preparation (12). S i fission of the R-0 bond appears to be encouraged by the electron-attracting effect of phenoxy-substituents (Figure 3). 

Primary chlorides reacted predominantly by a direct mechanism (Sn2 or a multicentered process). Isobutyl or neopentyl halides led to contributions from electron transfer (free radicals) and halogen-metal exchange (anionoid) mechanisms. 

The alkyl halides that react by the S l mechanism have a relatively low reactivity toward polar nucleophilic substitution due to steric, electronic or strain factors11, as shown for several bicycloalkyl, cycloalkyl and neopentyl halides and for /-butyl chloride. In the following section the reaction of these alkyl halides with different nucleophiles will be discussed. 

Neopentyl halides are among the most unreactive substrates in polar nucleophilic substitution reactions118. Due to the fact that the halogens are on a primary carbon atom, neopentyl halides seldom react by the S l mechanism. Beacuse of the steric hindrance by the t-butyl group to backside attack, the S 2 reaction in the neopentyl system is notoriously slow. However, with nucleophiles that are good electron donors, the ET reaction competes with the polar mechanism. 

Palladium-catalysed cross-coupling of organomagnesium compounds with alkyl halides is rarely useful (e.g. see [36]), but a satisfactory nickel-catalysed coupling with a neopentyl halide has been reported recently [37] ... 

Problem 3.13 How do you account for the fact that not only bromination but also chlorination is a feasible laboratory route to a neopentyl halide, (CH,) CCH2X ... 

ProUem 146 Neopentyl halides are notoriously slow in nucleophilic substitution, whatever the experimental conditions. How can you account for this ... 

Exceptionally clean cyclization can be accomplished by utilizing conjugated enones as precursors for the Barbier reaction (equation 43). High diastereoselectivity is achieved in these reactions, and under the mild conditions required for cyclization the TMS ether protecting group remains intact. It is also interesting that a neopentyl halide is effective in the cyclization. This result would appear to exclude an 5N2-type displacement of an organic halide by a samarium ketyl as a possible mechanism for the Smh-promoted intramolecular Barbier reaction. 

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