Backside attack

If the addition of Br to the alkene results in a bromonium ion, the anti stereochemistry can be readily eiqilained. Nucleophilic ring opening by bromide ion would occur by backside attack at carbon, with rupture of one of the C—Br bonds, giving overall anti addition. 

Epoxidation of the A -enol acetate was originally carried out with per-benzoic acid. Monoperphthalic acid has also been used, but is apparently more susceptible to steric and conformational factors. The commercially available peracetic acid is generally most convenient. Based on the expected backside attack, the derived epoxides have the 17a configuration, and hydrolysis always produces the 17a-hydroxy group. 

Although this is a secondary substrate, complete shielding from backside attack by nucleophiles leads to S l solvolysis without solvent participation. The correspond-... 

Backside attack may be favored for electrostatic reasons. Examine electrostatic potential maps fox bromide + methyl bromide frontside attack and bromide + methyl bromide backside attack, transition states involving frontside and backside attack of Br (the nucleophile) onto CHsBr, respectively. Which atoms in the transition states are most electron-rich Which trajectory better minimizes electrostatic repulsion ... 

Backside attack may be favored in order to facilitate transfer of nonbonding electrons from the nucleophile into the electrophile s lowest-unoccupied molecular orbital (LUMO). Efficient electron transfer requires maximal overlap of the LUMO and the donor orbital (usually a nonbonded electron pair on the nucleophile). Examine the LUMO of methyl bromide. How would a nucleophile have to approach in order to obtain the best overlap Is your answer more consistent with preferential backside or frontside attack ... 

Electrostatic potential map for bromide+methyl bromide backside attack shows most negatively-charged regions (in red) and less negatively-charged regions (in blue). 

Examine space-filling models of ethyl bromide and 2-methyl-2-propyl bromide. Given that Sn2 reactions require backside attack, which of these is more likely to react with EtO in an Sn2 fashion What will the product be What E2 products would be obtained from each alkyl bromide ... 

The synchronous bimolecular mechanism for aromatic nucleophilic substitution involves unfavorable geometry (bonds made and broken are both in the plane of the ring and backside attack is not possible) and unfavorable energetics (one high-energy step is required... 

The one general exception to the rule that ethers don t typically undergo Sn2 reactions occurs with epoxides, the three-membered cyclic ethers that we saw in Section 7.8. Epoxides, because of the angle strain in the three-membered ring, are much more reactive than other ethers. They react with aqueous acid to give 1,2-diols, as we saw in Section 7.8, and they react readily with many other nucleophiles as well. Propene oxide, for instance, reacts with HC1 to give l-chloro-2-propanol by Snj2 backside attack on the less hindered primary carbon atom. We ll look at the process in more detail in Section 18.6. 

Epoxides are cleaved by treatment with acid just as other ethers are, but under much milder conditions because of ring strain. As we saw in Section 7.8, dilute aqueous acid at room temperature is sufficient to cause the hydrolysis of epoxides to 1,2-diols, also called vicinal glycols. (The word vicinal means "adjacent/ and a glycol is a diol.) The epoxide cleavage takes place by SK2-like backside attack of a nucleophile on the protonated epoxide, giving a trans- 1,2-dio) as product. 

Evidently, the transition state for acid-catalyzed epoxide opening has an Sn2 -like geometry but also has a large amount of S]v-l-like carbocationic character- Since the positive charge in the protonated epoxide is shared by the more highly substituted carbon atom, backside attack of Br- occurs at the more highly substituted site. 

Identify the substitution pattern of the two epoxide carbon atoms—in this case, one carbon is secondary and one is primary. Then recall the guidelines for epoxide cleavages. An epoxide with only primary and secondary carbons usually undergoes cleavage by SN2-like attack of a nucleophile on the less hindered carbon, but an epoxide with a tertiary carbon atom usually undergoes cleavage by backside attack on the more hindered carbon. In this case, an S]sj2 cleavage of the primary C—O epoxide bond will occur. 

Perhaps the single most important reaction of enolate ions is their alkylation by treatment with an alkyl halide or tosylate, thereby forming a new C-C bond and joining two smaller pieces into one larger molecule. Alkylation occurs when the nucleophilic enolate ion reacts with the electrophilic alkyl halide in an SN2 reaction and displaces the leaving group by backside attack. 

A kinetic evidence for reversibility of bromonium ion formation has been obtained in the reaction of tetraisobutylethylene and its Dg labeled derivative with Br2 in acetic acid (ref. 9). Owing to steric effects, the first formed bromonium ion cannot undergo backside attack to give the dibromide, but looses a proton to yield... 

Sn2 stands for substitution nucleophilic bimolecular. The lUPAC designation (p. 384) is AnDn- In this mechanism there is backside attack The nucleophile approaches the substrate from a position 180° away from the leaving group. The reaction is a one-step process with no intermediate (see, however, pp. 392-393 and 400). The C—Y bond is formed as the C—X bond is broken ... 

Furthermore, 48 solvolyzed 350 times faster than its endo isomer 51. Similar high exo/endo rate ratios have been found in many other [2.2.1] systems. These two results—(1) that solvolysis of an optically active exo isomer gave only racemic exo isomers and (2) the high exo/endo rate ratio—were interpreted by Winstein and Trifan as indicating that the 1,6 bond assists in the departure of the leaving group and that a nonclassical intermediate (52) is involved. They reasoned that solvolysis of the endo isomer 51 is not assisted by the 1,6 bond because it is not in a favorable position for backside attack, and that consequently solvolysis of 51 takes... 

C X bond, but not from B because only the has such an orbital. If the intermediate is in conformation B, the OR may leave (if X has a lone-pair orbital in the proper position) rather than X. This factor is called stereoelectwnic control Of course, there is free rotation in acyclic intermediates, and many conformations are possible, but some are preferred, and cleavage reactions may take place faster than rotation, so stereoelectronic control can be a factor in some situations. Much evidence has been presented for this concept. More generally, the term stereoelectronic effects refers to any case in which orbital position requirements affect the course of a reaction. The backside attack in the Sn2 mechanism is an example of a stereoelectronic effect. 

Ideally, Y should measure only the ionizing power of the solvent, and should not reflect any backside attack by a solvent molecule in helping the nucleofuge to leave (nucleophilic assistance k, p. 411). Actually, there is evidence that many solvents... 

When a sulfonate ester possessing this type of chirality was converted to a sulfone with a Grignard reagent (10-129), inversion of configuration was found. This is not incompatible with an intermediate such as 147 but it is also in good accord with an Sn2 like mechanism with backside attack. 

This mechanism, which we call the SeI mechanism (lUPAC designation cyclo-DEAEDnA ),4 also results in retention of configuration. Plainly, where a second-order mechanism involves this kind of internal assistance, backside attack is impossible. 

Ladhams-Zieba (2004) has demonstrated that university students working on reaction mechanisms in organic chemistry also operate on the drawings on the page, rather than on what they represent. She asked 18 second year university students to predict and draw the product species most likely to be produced from the substitution reaction of hydroxide ion into 2 bromobutane, represented as in Fig. 1.13(a). Ten of them drew the inverted substitution product that you might expect from backside attack in an Sn2 reaction (Fig. 1.13(b)). 

Several aluminum biphenolate complexes have been investigated as initiators for the ROP of PO.810,935 Unlike the TPP and salen-based systems, a cis coordination site is realistically accessible and in theory an alternative cis-migratory mechanism to the backside attack pathway might operate. However, NMR analyses on the resultant PPO show that stereochemical inversion still occurs when the biphenolate initiators are used (Scheme 22). It has also been confirmed that the same process occurs with the Union Carbide calcium alkoxide-amide initiator for both PO and CHO.810... 

The above observations with respect to the reactivities of monomers IV-VI can be explained by postulating a direct interaction of the carbonyl and the ether functional groups with the propagating cationic center. This can occur by either an inter- or intramolecular process. As shown in equation 5, intramolecular backside attack by the ester carbonyl group of the d,l-trans IV isomers at either carbon of the protonated or alkylated epoxy group gives rise to bicyclic dioxacarbenium ions IX and X. 

Trigonal-bipyramidal species and nucleophilic displacement reactivity The 3c/4e cu-bonding motif can also be achieved in nonlinear polyatomics by backside attack of a nucleophile X - on a polar Y—Z bond of a conventional Lewis-structure molecule,... 

As described in Section 3.5, any polar M—L bond is susceptible to backside attack by a Lewis base I. to form a linear (or near-linear) 3c/4e /ryperbonded L i- M -i L triad, equivalent to strong resonance mixing of the form... 

Figure 7. Top The formation of heterodimer 6-7 from softballs 6 6 and 7-7. Bottom Two SN2-like window" mechanisms for guest exchange in the softballs. Attack in an approximate 90°C angle between incoming and leaving guest is favored over backside attack energetically - only ten instead of twelve hydrogen bonds are broken - and entropically - statistically, there are four ways to open two vicinal windows, but only two ways to open windows opposite to each other.

Many theories have been put forward to explain the mechanism of inversion. According to the accepted Hugles, Ingold theory aliphatic nucleophilic substitution reactions occur eigher by SN2 or SN1 mechanism. In the SN2 mechanism the backside attack reduces electrostatic repulsion in the transition state to a minimum when the leaving meleophile leaves the asymmetric carbon, naturally an inversion of configuration occurs at the central carbon atom. 

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