Sn2 pathway

The SnI mechanism is an ionization mechanism. The nucleophile does not participate until after the rate-deter-rnining step has taken place. Thus, the effects of nucleophile and alkyl halide structure are expected to be different from those observed for reactions proceeding by the Sn2 pathway. Flow the structure of the alkyl halide affects the rate of SnI reactions is the topic of the next section. 

Eigure 8.11 illustrates the close relationship between the E2 and Sn2 pathways for this case, and the results cited in the preceding equation clearly show that E2 is faster than Sn2 when a secondary alkyl halide reacts with a strong base. 

The strength of their- car bon-halogen bonds causes aryl halides to react very slowly in reactions in which carbon-halogen bond cleavage is rate-detenrrining, as in nucleophilic substitution, for example. Later in this chapter we will see exanples of such reactions that do take place at reasonable rates but proceed by mechanisms distinctly different from the classical SnI and Sn2 pathways. 

Stereochemical course of the reaction. This kind of information was critical in the elucidation of the SnI and Sn2 pathways for nucleophilic substitution at saturated carbon. 

It is noteworthy that the corresponding acetate reacts via an anti-SN2 pathway when treated with BuCu BF,11. 

The E2 pathway is expected to provide the major product, because the Sn2 pathway is more sensitive to steric hindrance provided by secondary substrates. 

We begin by analyzing the reagent. The methoxide ion is both a strong base and a strong nucleophile. Next, we move on to Step 2 and we analyze the substrate. In this case, the substrate is secondary, so we would expect E2 and Sn2 pathways to compete with each other ... 

We expect the E2 pathway to predominate, because it is less sensitive to steric hindrance than the Sn2 pathway. Therefore, we would expect the major product(s) to be generated via an E2 process, and the minor product(s) to be generated via an Sn2 process. In order to draw the products, we must complete the third and final step. That is, we must consider the regiochemical and stereochemical outcomes for both the E2 and Sn2 processes. Let s begin with the E2 process. 

A detailed examination of the kinetics of dimethylaminolysis of N3P3C16 by Krishnamurthy and co-workers has revealed that there is a gradual and subtle mechanistic change that occurs as the degree of replacement of chlorines increases (92). While the first chlorine replacement follows an Sn2 pathway involving the formation of a neutral five-coordinate intermediate [Fig. 8(A)], at the second stage the mechanism can be induced to follow a concerted path [Fig. 8(B)] by using acetonitrile as the solvent. The polar transition state of the concerted path reaction pathway is stabilized in acetonitrile. This postulate has sup-... 

In an effort to identify the origin of the formation of the minor diastereomer 19 and understand whether its formation was a function of a breakdown in the SN2 pathway leading to an SN1 pathway, the activation of the chiral imidate 67 was next investigated. In the etherification reaction between 10 and 67, the acid catalyst increases the electrophilicity of imidate 67 through coordination between the acid... 

When the concentration of BF3 increased, competitive deactivation leading to the formation of 97 resulted in unreacted starting material at the end of the etherification reaction. Efforts to break up this coordination and increase the conversion by the addition of certain additives, such as water, NaPlv, KPF6, l.iPF(l, or NasSiF6, either led to no improvement in conversion or to a complete shut down in the SN2 pathway and significant erosion in the diastereoselectivity resulted. 

In solvolytic reactions like those we have just been considering, where the solvent itself is the nucleophile, such mixed kinetics may not be detectable, irrespective of what is actually happening, as both SN1 and Sn2 pathways are likely to follow a rate equation of the form ... 

This is so because in the SN2 pathway the concentration of nucleophile will remain essentially constant throughout the reaction as—being also the solvent—it is present in very large, unchanging... 

In some cases at least it is possible to demonstrate that a mixed Sn1 + Sn2 pathway is not operating. Thus solvolysis of the halide, (+)C6H5CHMeCl, mentioned above, but this time in MeC02H,... 

Both overt carbanions and organometallic compounds, such as Grignard reagents, are powerful nucleophiles as we have seen in their addition reactions with C=0 (p. 221 et seq.) they tend therefore to promote an SN2 pathway in their displacement reactions. Particularly useful carbanions, in preparative terms, are those derived from CH2(C02Et)2, (3-ketoesters, l,3-( 3-)diketones, e.g. (55), a-cyanoesters, nitroalkanes, etc.—the so-called reactive methylenes ... 

Support for the suggestion that Fig. 13.6 involves a change in actual reaction pathway is provided by acetolysis of the threo diastereoisomer (31) of the brosylate. Acetolysis leads to two different distinguishable, diastereoisomers whose relative proportion will depend on how much of the total reaction proceeds by external nucleophilic attack via the SN2 pathway (erythro product, 32), and how much by internal nucleophilic attack via a cyclic phenonium ion intermediate (threo product, 33) ... 

The key to the success of the vinyl epoxide route would reside in a nucleophilic ring-opening of vinyl epoxide 75. If this ring-opening proceeds regioselectively at C5 via a SN2 pathway, it would have been the most welcome at this stage of our efforts (Scheme 8.21). However, an array of conditions, including Pd(0)-mediated and Lewis acidic conditions, were screened over a period of almost 2 years, but we never observed the desired 1,4-diol 80. Instead, we could at various times see small... 

Further experimental studies involved the determination of the rate constant of the reaction of several alkyl halides with a series of electrochemically generated anion radicals so as to construct activation driving force plots.39,40,179 Such plots were later used to test the theory of dissociative electron transfer (Section 2),22,49 assuming, in view of the stereochemical data,178 that the Sn2 pathway may be neglected before the ET pathway in their competition for controlling the kinetics of the reaction. 

The thermodynamics of the ET reaction, but also of the SN2 reaction, do not vary much upon increasing steric hindrance. The reactions under discussion therefore essentially provide an illustration of the effect of steric hindrance on transition states. It is also worth noting that, although the SN2 product is more stable than the ET product in each case, the difference in stability is not large ( 0.4eV), thus providing a good opportunity for the ET pathway to compete successfully with the Sn2 pathway as steric hindrance increases. In this sense, although not an anion radical, NO- behaves more like an anion... 

Propargylic substitution reaction is one of the most important routes to allenic compounds [1, 2], As shown in Scheme 3.1, replacement of a leaving group at the propargylic position with an incoming nucleophile via an SN2 pathway rearranges the C=C-C skeleton into a C=C=C moiety to give a propadienyl species. With certain... 

The reaction of propargyl chloride 83 and trichlorosilane 84 showed two different regioselectivities depending on the choice of transition metal catalysts [88]. Whereas the Sn2 substitution proceeded to give the propargylsilane 85 with 94% selectivity using a CuCl catalyst, the silylallene 86 was obtained via an SN2 pathway with >97% selectivity with 3mol% of Ni(PhCOCHCOPh)2 (Scheme 3.42). 

Trialkyl- or triarylallenyltin compounds can also be prepared by Sn2 displacement of propargylic mesylates with various stannylcopper reagents in THF (Eq. 9.82) [71]. This reaction is postulated to proceed by an anti Sn2 pathway based on the stereochemical relationship between the enantioenriched mesylate and the allenic product (Eq. 9.83). The allene obtained from the reaction of the mesylate of (R)-3-phenyl-l-propyn-3-ol with Ph3SnCu was assigned the (P) configuration from a consideration of the observed optical rotation and an application of Brewster s rules [71]. 

Evidence for the mainly SN2 pathway for the silyl migration was obtained from reactions of enantioenriched mesylates (Eq. 9.153). The connfigurations of the alle-nylboronate intermediates were deduced from their reactions with cyclohexanecar-boxaldehyde to afford the anti products of known configuration (Eq. 9.154). It is assumed that these reactions proced by way of a cyclic transition state. 

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