Sn2 reactions of allyl halides

Relative Sj 2 Rates Like their S l counterparts, Sn2 reactions of allylic halides take place more rapidly than the corresponding reactions of similar alkyl halides. The relative rate profile for a group of alkyl and allylic halides shows two significant trends. 

Sn2 reactions of allylic halides with good nucleophiles (Section 6-8) are faster than those of the corresponding saturated haloalkanes. Two factors contribute to this acceleration. One is that the allylic carbon is attached to a relatively electron-withdrawing sp hybridized carbon (as opposed to sp Section 13-2), making it more electrophilic. The second is that overlap between the double bond and the p orbital in the transition state of the Sn2 displacement (see Figure 6-4) is stabilizing, resulting in a relatively low activation barrier. 

The reaction of allylic halides 1 with the zinc cuprate (R2CuZnCl), prepared by treatment of LiCuR2 with 1 equivalent of anhydrous zinc(II) chloride, affords the SN2 product 2 with 98% regioselectivity, and the diastercoselectivity is nearly 100% am/75. 

Entries 3 to 6 are examples of ester enolate alkylations. These reactions show stereoselectivity consistent with cyclic TSs in which the hydrogen is eclipsed with the enolate and the larger substituent is pseudoequatorial. Entries 4 and 5 involve SN2 substitutions of allylic halides. The formation of the six- and five-membered rings, respectively, is the result of ring size preferences with 5 > 7 and 6 > 8. In Entry 4, reaction occurs through a chairlike TS with the tertiary C(5) substituent controlling the conformation. The cyclic TS results in a trans relationship between the ester and vinylic substituents. 

The second approach for the nucleophilic animation reactions to be considered here will be reactions of allyl halides and allyl acetates leading to allyl amines. Allyl halides are normally very reactive in SN2 reactions, but the direct coupling of allyl halides with nitrogen nucleophiles has been performed with limited success [4], as di- and trialkylated by products often predominate. The application of the Gabriel synthesis can to a certain extent eliminate the problem with polyalkylation of amines using, e.g., the stabilized phthalimide anion 19 as the nucleophile. The allyl amine 20... 

The stereochemistry of the direct substitution reaction has been the subject of some debate. Most recently, it has been reported that reactions of alkylheterocuprates proceed with high syn selectivity, while inversion of allenyl configuration, or anti selectivity, is observ in reactions of phenylcopper reagents. The degree of selectivity is variable and may be a reflection of product isomerization under the reaction conditions. Predominant anti stereoselectivity (anti syn ratios range from 91 9 to >99 1) is observed also in Sn2 reactions of allenyl halides (see Scheme 3), a finding that is consistent with the known preference for anti substitution of allylic substrates (see Section I.5.2.4.5). This method for al-kyne preparation has found application in the leukotriene area, and also for the synthesis of alkoxy al-kynes. ... 

R—Cu—BF3 Conjugate addition including successful reaction with acrylate esters and acrylonitriles. Sn2 displacement of allyl halides. 

The carbon-halogen bonds of allylic halides are especially reactive in both SN1 and Sn2 reactions (Table 14-6). The reasons for the enhanced SN1 reactivity have been discussed previously (Section 8-7B). For example, the ease... 

The high reactivity of allylic halides in SN2 reactions indicates some special stabilization of the transition state ascribable to resonance involving the adjacent tt bond. We can express this in terms of the valence-bond structures, 2a-2c, for the transition state of the reaction of iodide ion with 3-chloropropene (Section 8-7A). The extra stabilization over the corresponding transition state for the reaction of iodide with a saturated chloride (e.g., CH3CH2CH2C1 + 1 ... 

Reactivities comparable to allylic halides are found in the nucleophilic displacement reactions of benzylic halides by SN1 and SN2 mechanisms (Table 14-6). The ability of the benzylic halides to undergo SK1 reactions clearly is related to the stability of the resulting benzylic cations, the electrons of which are extensively delocalized. Thus, for phenylmethyl chloride,... 

Allylic amination of allyl halides can also be achieved using lithium and potassium bis(trimethylsilyl)amides [34] and potassium 1,1,3,3-tetramethyldisilazide [35] as the nucleophiles. It has been found that for the reaction of alkyl-substituted allyl chlorides using lithium bis(trimethylsilyl)amides as the nucleophile the allylic amination proceeds smoothly in a SN2 fashion to give /V,Af-disilylamines in high yields when silver(I) iodide was used as an additive. Other metal complexes such as copper ) iodide and other silver(I) salts can also be used as additives for the reaction. 

Mechanism 6-1 Allylic Bromination 228 Summary Methods for Preparing Alkyl Halides 229 6-7 Reactions of Alkyl Halides Substitution and Elimination 231 6-8 Second-Order Nucleophilic Substitution The Sn2 Reaction 232 Key Mechanism 6-2 The S j2 Reaction 233 6-9 Generality of the SN2 Reaction 234... 

The enhanced reactivity of allylic halides and tosylates makes them particularly attractive as electrophiles for Sn2 reactions. Allylic halides are so reactive that they couple with Grignard and organolithium reagents, a reaction that does not work well with unactivated halides. 

Second-Order Reactions Like allylic halides, benzylic halides are about 100 times more reactive than primary alkyl halides in SN2 displacement reactions. The explanation for this enhanced reactivity is similar to that for the reactivity of allylic halides. 

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