Stereochemistry of SN1 Reactions

What can be said about the stereochemistry of SN1 reactions In the carbenium ion intermediates R1 R2R3C , the positively charged C atom has a trigonal planar geometry (cf. Figure 1.3). These intermediates are therefore achiral, if the substituents R1 themselves do not contain stereogenic centers. 

Figure 5.2 Stereochemistry of Sn1 reactions R V Attack equally likely from both sides R2 R3 More attack from opposite side from leaving group, hence more inversion vicinity or as ion pair...

The mechanism for the addition of the hydrogen halides to alkenes proceeds through a carbocation intermediate. As was the case in the SN1 reaction, the nucleophile can approach the planar carbocation equally well from either side, so we expect that the products should result from a mixture of syn and anti addition. Indeed, this is often the case. Under some conditions, however, the stereochemisty results from predominant syn addition, whereas anti addition is the favored pathway under other conditions. This occurs because these reactions are often conducted in nonpolar solvents in which ion pair formation is favored. The details of how this may affect the stereochemistry of these reactions are complex. Fortunately, stereochemistry is not an issue in most of the reactions in which hydrogen halides add, including all the examples previously presented, because the carbon to which the proton is adding usually has at least one hydrogen already bonded to it. In such situations, syn addition and anti addition give identical products. Stereochemistry will be more important in some of the other reactions that are discussed later in this chapter. 

How- does this reaction take place Although it appears superficially similar to the SN1 and S 2 nucleophilic substitution reactions of alkyl halides discussed in Chapter 11, it must be different because aryl halides are inert to both SN1 and Sj 2 conditions. S l reactions don t occur wdth aryl halides because dissociation of the halide is energetically unfavorable due to tire instability of the potential aryl cation product. S]sj2 reactions don t occur with aryl halides because the halo-substituted carbon of the aromatic ring is sterically shielded from backside approach. For a nucleophile to react with an aryl halide, it would have to approach directly through the aromatic ring and invert the stereochemistry of the aromatic ring carbon—a geometric impossibility. 

To distinguish between SN1 and SN2 mechanisms of solvolysis requires other criteria, notably stereochemistry (Sections 8-5 and 8-6), and the elfect of added nucleophiles on the rate and nature of the reaction products. For example, it often is possible to distinguish between SN1 and SN2 solvolysis by adding to the reaction mixture a relatively small concentration of a substance that is expected to be a more powerful nucleophile than the solvent. If the reaction is strictly SN1, the rate at which RX disappears should remain essentially unchanged because it reacts only as fast as R forms, and the rate of this step is not changed by addition of the nucleophile, even if the nucleophile reacts with R . However, if the reaction is SN2, the rate of disappearance of RX should increase because RX reacts with the nucleophile in an SN2 reaction and now the rate depends on both the nature and the concentration of the nucleophile. (See Exercises 8-5 and 8-6.)... 

Acidic conditions also can be used for the cleavage of oxacyclopropane rings. An oxonium ion is formed first, which subsequently is attacked by the nucleophile in an SN2 displacement or forms a carbocation in an SN1 reaction. Evidence for the SN2 mechanism, which produces inversion, comes not only from the stereochemistry but also from the fact that the rate is dependent on the concentration of the nucleophile. An example is ring opening with hydrogen... 

The only apparent difference between the two mechanisms is the stereochemistry of the product. If the reaction proceeds through an Sn2 mechanism, it gives inversion of configuration conversion of an R starting material into an S product, or vice versa. If the reaction proceeds through a carbocation intermediate via an SN1 mechanism, we get a racemic mixture. 

Fig. 2.13. Stereochemistry of an SN1 reaction that takes place via a contact ion pair.

First, identify the leaving group, the electrophilic carbon, and the nucleophile. Then decide whether the reaction follows the SN1 or SN2 mechanism because this determines the stereochemistry. If the leaving group is bonded to a tertiary carbon, then the reaction must occur by the SN1 mechanism. (Later we will learn other factors that control which substitution mechanism a reaction follows.) For an SNI reaction, replace the leaving group on the electrophilic carbon with the nucleophile with loss of stereochemistry at the reaction center. 

Show the products, including stereochemistry, of these SN1 reactions ... 

Follow the steps listed in the preceding Visual Summary of Key Reactions section. Identify the leaving group, the electrophilic carbon, and the nucleophile (or base). Then determine which mechanism is favored (see Section 9.7). Watch out for stereochemistry where important, regiochemistry in elimination reactions, and carbocation rearrangements when the mechanism is SN1 or El. 

First-Order Nucleophilic Substitution The S j1 Reaction 246 Key Mechanism 6-4 The Sn1 Reaction 247 6-14 Stereochemistry of the Sn1 Reaction 250 6-15 Rearrangements in the Sn1 Reactions 252... 

Stereochemistry The SnI reaction involves a flat carbocation intermediate that can be attacked from either face. Therefore, the SN1 usually gives a mixture of inversion and retention of configuration. 

CHAPTER 7 Inversion of Configuration in the Sn2 Reaction 244 Racemization in the Sn1 Reaction 252 Hydride Shift in an Sn1 Reaction 253 Methyl Shift in an Sn1 Reaction 254 Rearrangement in an E1 Reaction 261 Dehydrohalogenation by the E2 Mechanism 304 Stereochemistry of the E2 Reaction 306 E2 Debromination of a Vicinal Dibromide 310... 

Overall, we have retention of stereochemistry. As you know, Sn2 reactions go with inversion, and SN1 reactions with loss of stereochemical information—so this result is possible only if we have two sequential Sn2 reactions taking place—in other words neighbouring group participation. 

The differences observed in the regio- and stereochemistry of this ring-opening reaction can be explained according to two different types of reaction mechanism (SN1 or SN2), with the pathway strongly dependent on the substrate structure, as well as on the nature of the fluo-... 

The rate of SE1 reactions is affected by similar considerations as those that affect SN1 reactions. Further, generally any stereochemical information at the carbanion centre is lost, either due to the umbrella effect or due to the formation of a planar intermediate as a result of delocalisation to a -M substituent such as a carbonyl group. However, vinyl carbanions can maintain their configuration, and so retain their stereochemistry. 

Most secondary compounds, such as 11 and 12, will undergo the SN2 reaction (in which the substituents are alkyl groups). When at least one of the groups is aromatic there is some tendency for the group X, the leaving group, to leave of its own accord (this is the basis of the SN1 reaction, Section 7.1.3) rather than to be expelled by the nucleophile in a concerted SN2 reaction. However, the experiments that defined the stereochemistry of the Sn2 reaction were performed on secondary substrates. 

The SN1 reaction is almost always followed by tertiary halides, and also by secondary halides and, for example, tosylates, especially when at least one of the substituents is an aryl group. From this latter case the carbocation is now benzylic. The nature of the intermediate carbocation in an SN1 reaction is illustrated in Figure 7.3, which shows the three substituents in a coplanar arrangement and with an empty p-orbital. This structure provides a clue as to the stereochemistry of the subsequently formed tetrahedral product. 

Stereochemistry SN2 reactions involving optically active halides produce optically active products but with inversion of configuration of the chiral carbon atom bearing the halogen attack by the nucleophile occurs on the opposite side from that the halide is leaving. SN1 reactions proceed by a carbocation intermediate that can be attacked by the nucleophile from either side a racemic mixture results. 

The subject of this chapter is how we can achieve reaction of nucleophiles with vinyl electrophiles such as vinyl halides. We cannot easily make SN1 or SN2 reactions happen at sp2 carbon atoms but we can make the products of those unfavourable reactions by other reactions in which the same bond is formed. We want to be able to use carbon nucleophiles. We also want to control the stereochemistry of the double bond in the product. This is the disconnection we want to achieve 29 ... 

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