Leaving groups in Sn2 reactions

Common error alert F, HO, RO (except epoxides), H, and carbanions are almost never leaving groups in Sn2 reactions under basic conditions. 

The reaction is clearly not a simple Sn2 displacement of OH from R by PhC02, because HO is a really awful leaving group in Sn2 reactions and will not leave under these mild conditions, and besides, PI13P and DEAD are required for the reaction. But equally clearly, Sn2 displacement must happen at some point, or clean inversion at R could not occur. 

Q1. Enantiomerically pure 48, prepared from 49, with [a]D20 = -106.1 (neat), underwent reaction with MeS in ethanol to give the starting compound 49, which now had [ct] 20 = -l7.2 (neat). The reaction showed the clean second-order kinetics expected of a bimol-ecular reaction. Explain (I) how 48 might be made from 49 (2) the partial racemization of 49 after reaction of the salt 48 with MeS". A. The salt 48 can be made from 49 by methylation with MeOTs in an SN2 reaction. When partial racemization is involved, an SsJ reaction is suspected. However, this is ruled out by the observation of second-order kinetics with a very strong nucleophile. Lists of leaving groups in SN2 reactions usually include +SMe, however,... 

C to give aldehydes, providing a route from the acid oxidation level. A related phenomenon is the use of imidazylates as excellent leaving groups in Sn2 reactions.They are also useful precursors for the more reactive fluorosulfonates such conversions have been carried out on an 800 kg scale. 

Reactions (109) and (110) as well as nitroalkane deprotonation are all examples of central substitution so that for these reactions a does not measure the earliness or lateness of the transition state. End substitution, such as in the nucleophile or leaving group of SN2 reactions, in which the formal charge does vary between reactants and products generates -values which may be utilized as a relative measure of transition state charge this, provided that the reaction is composed of three configurations. Such applications were discussed in Section 3, p. 152. 

A similar picture holds for other nucleophiles. As a consequence, there might seem little hope for a nucleophile-based reactivity relationship. Indeed this has been implicitly recognized in the popularity of Pearson s concept of hard and soft acids and bases, which provides a qualitative rationalization of, for example, the similar orders of reactivities of halide ions as both nucleophiles and leaving groups in (Sn2) substitution reactions, without attempting a quantitative analysis. Surprisingly, however, despite the failure of rate-equilibrium relationships, correlations between reactivities of nucleophiles, that is, comparisons of rates of reactions for one carbocation with those of another, are strikingly successful. In other words, correlations exist between rate constants and rate constants where correlations between rate and equilibrium constants fail. 

Alkyl halides undergo two kinds of nucleophilic substitution reactions Sn2 and SnI- In both reactions, a nucleophile substitutes for a halogen, which is called a leaving group. An Sn2 reaction is bimolecular— molecules are involved in the rate-limiting step an SnI reaction is unimol-ecular— molecule is involved in the rate-limiting step. 

All these reactions of octadecyl p toluenesulfonate have been reported in the chemical literature and all proceed in synthetically useful yield You should begin by identifying the nucleophile in each of the parts to this problem The nucleophile replaces the p toluenesulfonate leaving group in an Sn2 reaction In part (a) the nucleophile is acetate ion and the product of nucleophilic substitution IS octadecyl acetate... 

The Williamson ether synthesis (Sec tion 16 6) An alkoxide ion displaces a halide or similar leaving group in an Sn2 reaction The alkyl halide cannot be one that is prone to elimination and so this reaction is limited to methyl and primary alkyl halides There is no limitation on the alkoxide ion that can be used... 

The most common example of this process in living organisms is the reaction of the amino acid methionine with adenosine triphosphate (ATP Section 5.8) to give S-adenosylmethionine. The reaction is somewhat unusual in that the biological leaving group in this SN2 process is the triphosphate ion rather than the more frequently seen rliphosphate ion (Section 11.6). 

Table 10.10 lists some leaving groups in approximate order of ability to leave. The order of leaving-group ability is about the same for SnI and Sn2 reactions. 

In Sn2 reactions, substituents at the central atom that can stabilise cationic character will also stabilise the SN2 transition state leading to products. As well as lowering the energy, such stabilisation moves SN2 saddle points in the direction of cationic species resulting in incipient cationic character in the transition structure and longer bonds to both the nucleophile and the leaving group.162 165... 

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