Nucleophilic substitution chemoselectivities

With higher alkenes, three kinds of products, namely alkenyl acetates, allylic acetates and dioxygenated products are obtained[142]. The reaction of propylene gives two propenyl acetates (119 and 120) and allyl acetate (121) by the nucleophilic substitution and allylic oxidation. The chemoselective formation of allyl acetate takes place by the gas-phase reaction with the supported Pd(II) and Cu(II) catalyst. Allyl acetate (121) is produced commercially by this method[143]. Methallyl acetate (122) and 2-methylene-1,3-diacetoxypropane (123) are obtained in good yields by the gas-phase oxidation of isobutylene with the supported Pd catalyst[144]. 

The domino reaction is initiated by the chemoselective attack of the carbanion 2-458 on the terminal ring carbon atom of epoxyhomoallyl tosylate 2-459 to give the alkoxides 2-460 after a 1,4-carbon-oxygen shift of the silyl group. The final step to give the cyclopentane derivates 2-461 is a nucleophilic substitution. In some cases, using the TBS group and primary tosylates, oxetanes are formed as byproducts. 

There are a number of synthetically important applications, involving these heterocycles, as unstable intermediates, which are reviewed here. These applications feature the ability of selenium to be readily extruded from seleniranes and selenirenes, neighboring group participation by / -Se to control the stereochemistry of nucleophilic substitution reactions, and facile, chemoselective replacement of Se by H in radical-induced reactions. 

The required 5-phenoxypyridazin-3(2/7)-ones 234 and 236 are easily available through a nucleophilic substitution reaction on halopyridazin-3(2TZ)-ones 146 and 239, respectively whereas the required 5-phenylaminopyridazin-3(2//)-one 237 could be synthesized via a chemoselective Buchwald-Hartwig amination reaction on 146 with 2-bromoaniline. 

It is well established that sulfur and oxygen anions behave in an opposite way with electrophilic centres during nucleophilic substitutions. The comparison of the reactivity of 1-octanthiol and 1-octanol with DMC (entries 3 and 4, Table 9) outlines the difference in chemoselectivity of RS and RO anions, due to their diverse hardness. Under all of the investigated conditions, alkoxides show a Bac2 reaction mechanism, differently from thiolates, which react via a B,2 type. 

Dichloro-5-(l-o-carboranylmethyl)-6-methylpyrimidine (674) is said to be a potential synthon for the preparation of 5-(l-o-carboranylmethyl)-6-methylpyrimidines chemoselective nucleophilic substitution of the chlorine atoms can be effected, and the cage can be selectively degraded for the preparation of more water-soluble Wo-undecarborate derivatives. Preparation of the target molecule (674) is effected by the addition of decaborane to an appropriate alkyne (673) as shown in Equation (19) <9lJOC2391>. 

This model study demonstrates the excellent chemoselectivity that the palladium-catalyzed amination reaction provides due to the inability of the catalyst to activate the C-F bond. Furthermore, since nucleophilic substitution is not a viable pathway for the synthesis of these non-flinctionalized substrates, this procedure represents the most general route yet available to simple fluoroanilines. 

Reaction via pyridinium-type salt intermediate Chemoselective deprotection of acetals in the presence of ketals and nucleophilic substitution 13YGK694. 

Chemoselective Cu-catalyzed Nucleophilic Substitution of the alkyl bromide... 

Analogous results were obtained for enol ether bromination. The reaction of ring-substituted a-methoxy-styrenes (ref. 12) and ethoxyvinylethers (ref. 10), for example, leads to solvent-incorporated products in which only methanol attacks the carbon atom bearing the ether substituent. A nice application of these high regio-and chemoselectivities is found in the synthesis of optically active 2-alkylalkanoic acids (ref. 13). The key step of this asymmetric synthesis is the regioselective and chemoselective bromination of the enol ether 4 in which the chiral inductor is tartaric acid, one of the alcohol functions of which acts as an internal nucleophile (eqn. 2). 

Removing the substituted hydrazine (58) leaves acetoacetic ester (57). Phenylhydrazine is available, so it is easier to make (59) and methylate afterwards. This removes the chemoselectivity problem as the more nucleophilic NH group attacks the more electrophilic ketone. 

For the methyl-substituted ethylenes, i.e. in the absence of any steric effects, there is a roughly linear relationship between the chemoselectivity and the 13C nmr chemical shift of the most substituted carbon atom of the bromonium ions (Dubois and Chretien, 1978). This selectivity is therefore discussed in terms of the magnitude of the charge on the carbon atom and the relative hardness of the competing nucleophiles, according to Pearson s theory (Ho, 1977). However, this interpretation does not take into account the substituent dependence of the nucleophilic solvent assistance, which must play a role in determining this chemoselectivity. 

Benzylsilanes are also oxidized under similar conditions with selective cleavage of the C Si bond (Scheme 4) [24,25], Nucleophiles are introduced onto the benzylic carbon exclusively. Nuclear substitution products are not formed. The high chemoselectivity observed for the reaction of p-(trimethylsilyl)benzyltrimethylsilane is interesting. Only the benzyl C-Si bond is cleaved without affecting the aromatic C-Si bond. 

Chemoselective SN reactions of nucleophiles with carboxylic acid derivatives are guaranteed to take place without the risk of an overreaction when the substitution mechanism of Figure 6.4 applies. This is because as long as the nucleophile is present, only one reaction step is possible the formation of the negatively charged tetrahedral intermediate. Figure 6.40 summarizes this addition in the top line as Reaction 1 (— B). 

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