Sn2 reactions at silicon

Sn2 reactions can occur at elements other than carbon. Common examples in organic chemistry are silicon, phosphorus, sulfur, and the halogens. The formation of the tosylate above by attack of the alcohol on TsCl is an example of an Sn2 reaction at sulfur. Later in this chapter you will see that alcohols attack phosphorus very easily and that we use the reaction between ROH and PBra to make alkyl bromides. Alcohols also react rapidly with Si-CI compounds such as MegSiCI to give silyl ethers by an Sn2 reaction at silicon. You have already seen several examples of silyl ether formation (p. 240, for example), though up to this point we have not discussed the mechanism. Here it is B represents a base such as triethyl amine. 

The other side of the coin is that the S 2 reaction at carbon is not much affected by partial positive [ charge (5+) on the carbon a tom. The Sn2 reaction at silicon is affected by the charge on silicon. The r most electrophilic silicon compounds are the silyl triflates and it is estimated that they react some 108-109 times faster with oxygen nucleophiles than do silyl chlorides. Trimethylsilyl triflate is, in fact, an excellent Lewis acid and can be used to form acetals or silyl enol ethers from carbonyl compounds, and to react these two together in aldol-style reactions. In all three reactions the triflate attacks an oxygen atom. 

Evidence that the Sn2 reaction at silicon does indeed go through a pentacovalent intermediate comes from the silicon analogue of the migration step in hydroboration-oxidation. Treatment of reactive organosilanes (that is, those with at least one heteroatom—F, OR, NR2—attached to silicon to encourage nucleophilic attack of hydroperoxide at silicon)... 

The potential energy surfaces for the SN2 reactions at carbon, silicon, and phosphorus have been calculated using the Amsterdam Density Functional method with the... 

Other theoretical studies discussed above include investigations of the potential energy profiles of 18 gas-phase identity S 2 reactions of methyl substrates using G2 quantum-chemical calculations," the transition structures, and secondary a-deuterium and solvent KIEs for the S 2 reaction between microsolvated fluoride ion and methyl halides,66 the S 2 reaction between ethylene oxide and guanine,37 the complexes formed between BF3 and MeOH, HOAc, dimethyl ether, diethyl ether, and ethylene oxide,38 the testing of a new nucleophilicity scale,98 the potential energy surfaces for the Sn2 reactions at carbon, silicon, and phosphorus,74 and a natural bond orbital-based CI/MP through-space/bond interaction analysis of the S 2 reaction between allyl bromide and ammonia.17... 

Just as there is no single measure of acidity and basicity, there is no single measure of nucleophilicity and electrophilicity—the rank order of nucleophiles changes when the reference electrophile changes. A hard nucleophile like a fluoride ion reacts fast with a silyl ether in an SN2 reaction at the silicon atom, which is relatively hard, but a soft nucleophile like triethylamine does not. In contrast, triethylamine reacts with methyl iodide in an SN2 reaction at a carbon atom, but fluoride ion does not. These examples, which are all equilibria, are governed by... 

Quantum-mechanical calculations have centered on anionic pentacoordinat, silicon species, mainly as models for the transition states or intermediates in bimolecular SN2 substitution reactions at silicon—a topic of current experimental interest7 9,359. 

We should compare the reaction at silicon with the Sn2 reaction at carbon. There are some iportant differences. Alkyl halides are soft electrophiles but silyl halides are hard electrophiles. iMcyl halides react only very slowly with fluoride ion but silyl halides react more rapidly with fluoride 1 than with any other nucleophile. The best nucleophiles for saturated carbon are neutral and/or based on elements down the periodic table (S, Se, 1). The best nucleophiles for silicon are charged and based on highly electronegative atoms (chiefly F, Cl, and O). A familiar example is the reaction of enolates at carbon with alkyl halides but at oxygen with silyl chlorides (Chapter 21). 

Figure 8 Frontier orbitai interactions at Sn2 reactions of silicon...

The ether-forming step is an S -like reaction of the alkoxide ion on the silicon atom, with concurrent loss of the leaving chloride anion. Unlike most Sn2 reactions, though, this reaction takes place at a tertiary center—a trialJkyl-substituted silicon atom. The reaction occurs because silicon, a third-row atom, is larger than carbon and forms longer bonds. The three methyl substituents attached to silicon thus offer less steric hindrance to reaction than they do in the analogous ferf-butyl chloride. 

Complex 10c, in contrast to its isomer 11c, has a distinct O Si coordination relatively long O-Si and short Cl-Si distances (Table Y). The 29Si NMR spectra of compounds 10 also behave in the expected manner (Table VI) a decrease of temperature is associated with an upfield shift of the 29Si resonance, again in contrast to 11, presumably a manifestation of more intense coordination. The trend in the axial bond lengths (O-Si and Cl-Si) found in Table V may be viewed as a case of progress along the Sn2 reaction coordinate in a hypothetical nucleophilic displacement at silicon 4a M0... 

Scheme 4. Proposed mechanism for the observed stereochemical reaction pathway of (A)-4 with benzyl chloride SN2-reaction with retention at the silicon center.

Only the stereochemical probe at the silicon center permitted us to obtain an insight into the described processes, since the products of both main reaction pathways - SN2-reaction and... 

These epoxides react stereospecifically with nucleophiles to give single diastereoisomers of adducts. If a carbon nucleophile is used (cuprates are best), it is obvious from the structure of the products that nucleophilic attack has occurred at the end of the epoxide next to silicon. This is obviously an Sn2 reaction because it is stereospecific in any case an SnI reaction would have occurred at the other end of the epoxide through the p-silyl cation. 

Salem s frontier-orbital treatment for Walden inversion is consistent with the fact that retention of configuration is a commonly observed stereochemical outcome at silicon (Table 12), whereas there is still no proven example of an Sn2 reaction with retention at carbon (158). Because Si-X bonds are significantly longer than C-X bonds, the unfavorable interaction between X and the nucleophile for front-side RN attack is less for silicon than for carbon (Scheme 28). The valence orbitals also change from 2s and 2p for carbon to 3s and 3p for silicon and therefore become more diffuse and capable of overlap with the nucleophile at longer distances. Consequently, the probability of attack with retention is enhanced. 

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