Chemoselectivity E2 eliminations

Chemoselective E2 eliminations can be carried out with sterically hindered, sufficiently strong bases. Their bulkiness causes them to react with an H atom at the periphery of the molecule rather than at a C atom deep within the molecule. These bases are therefore called nonnucleo-philic bases. The weaker nonnucleophilic bases include the bicyclic amidines DBN (diazabi-cyclononene) and DBU (diazabicycloundecene). These can be used to carry out chemoselective E2 eliminations even starting from primary and secondary alkyl halides and sulfonates (Figure 4.17). 

Fig. 4.17. Relatively weak nonnucleophilic bases use in a chemoselective E2 elimination from a primary altyl halide.

In principle, the bases Y are also nucleophiles, and, hence, they can react with the same alkyl halides and sulfonates via the SN2 mechanism. The point of reaction is the C atom that bears the leaving group. In order to carry out E2 eliminations chemoselectively, competing Sn2 reactions must be excluded. To understand the outcome of the competition (E2 elimination vs. Sn2 reaction), it is analyzed kinetically with Equations 4.1-4.3. 

Table 4.1 gives the chemoselectivity of E2 eliminations from representative bromides of the type Rprim—Br, Rsec—Br, and Rten—Br. The fraction of E2 product increases in this sequence from 1 to 79 and to 100% and allows for the following generalization E2 eliminations with sterically unhindered bases can be carried out chemoselectively (i.e., without a competing SN2 reaction) only starting from tertiary alkyl halides and sulfonates. To obtain an E2 product from primary alkyl halides and sulfonates at all or to obtain an E2 product from secondary alkyl halides and sulfonates exclusively, one must change the base (see Section 4.4.2). 

Eliminations of epoxides lead to allyl alcohols. For this reaction to take place, the strongly basic bulky lithium dialkylamides LDA (lithium diisopropylamide), LTMP (lithium tetramethylpiperidide) or LiHMDS (lithium hexamethyldisilazide) shown in Figure 4.18 are used. As for the amidine bases shown in Figure 4.17, the hulkiness of these amides guarantees that they are nonnucleophilic. They react, for example, with epoxides in chemoselective E2 reactions even when the epoxide contains a primary C atom that easily reacts with nucleophiles (see, e.g., Figure 4.18). 

Fig. 4.23. <7wt -Selectivity of an E2 elimination as the reason for the chemoselective formation of a 1,3-diene instead of a bromo-olefin.

Tables 4.1 and 4.2 summarize the typical substrate effects on the chemoselectivity of E2 vs. Sn2 reactions. These substrate effects are so pronounced because NaOEt was used as base. As a reasonably strong base and a quite good nucleophile, NaOEt is able to convert a fair portion of many elimination substrates into SN2 products (see Section 4.4.2).

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