Back-side attack

Neopentyl (2,2-dimethylpropyl) systems are resistant to nucleo diilic substitution reactions. They are primary and do not form caibocation intermediates, but the /-butyl substituent efiTectively hinders back-side attack. The rate of reaction of neopent>i bromide with iodide ion is 470 times slower than that of n-butyl bromide. Usually, tiie ner rentyl system reacts with rearrangement to the /-pentyl system, aldiough use of good nucleophiles in polar aprotic solvents permits direct displacement to occur. Entry 2 shows that such a reaction with azide ion as the nucleophile proceeds with complete inversion of configuration. The primary beiuyl system in entry 3 exhibits high, but not complete, inversiotL This is attributed to racemization of the reactant by ionization and internal return. 

This step is simply an Sn2, and therefore, must be a back-side attack. In other words, the attacking bromide ion must come from behind (from behind the bridge), and therefore, we get an anti addition. There are some alkenes for which a syn addition predominates. Clearly, a different mechanism is operating in those cases. For the alkenes that you will encounter in this course, this reaction will always be an anti ad-dihon, proceeding via the mechaihsm that we showed. 

As C-Br bond formation occurs by back-side attack, inversion of the configuration at carbon is anticipated. However, both racemization and rearrangement are observed as competing processes.10 For example, conversion of 2-butanol to 2-butyl bromide with PBr3 is accompanied by 10-13% racemization and a small... 

According to this mechanism, the first formed ion pair is 19a. Owing to dispersal of charge in the allylic system, the bond between halogen and C(2) is weakened so that an open carbenium ion (19c) readily forms, allowing for the possibility of front-side attack by the anion with the resulting formation of syn 1,2-adducts. This intermediate explains the formation of the cis-],2-adducts by chlorine addition to cyclic systems. However, syn 1,2-dichlorides can also result from linear dienes by rotation around the C(l)—C(2) bond in 19c to produce 19d, followed by back-side attack by the anion with respect to its position in 19d. Syn 1,4-adducts should instead arise by attack of the anion on C(4) in either 19a, 19c or 19d. Formation of anti dichlorides (1,2- or 1,4-) can only occur when there is appreciable translocation in the ion pair 19a to give 19b. Attack by the anion at C(2) in 19b yields anti 1,2-dichloride and attack at C(4) yields anti 1,4-dichloride. 

In order to explain the formation of nortricyclene from 2-ea o-norbornanol, it is necessary to assume a back side attack at the hydrogen attached to carbon 6. The general mechanism here is similar to the trans elimination reaction as discussed under menthol, 1,4-cyclohexanediol, and bornanols. 

As shown in Fig. 1, the big lobes of these hybrids point toward each other. Therefore, if the nucleophile approaches the substrate from the front side, its HOMO overlaps in phase with the big lobe of 0c and out-of-phase with the big lobe of 0x-Numerical calculations show that the unfavourable (nucleophile-leaving group) interaction usually overrides the favourable (nucleophile - reaction center) interaction in this front-side approach, so that back-side attack is finally preferred, leading to inversion of configuration. 

Notice that this back-side attack corresponds to an attack on the small lobe of 0c- It follows that front-side attack may become competitive if it is possible (a) to... 

Substitutive spiroannulation of 1-donor-substituted vinylcyclopropanes initiated by electrophiles gives access to a wide range of spirobicyclic and spirotricyclic systems. Generally, the electrophile undergoes addition from the sterically less demanding face and the rearrangement proceeds through back-side attack. The net result is a turns addition. 

In the least polar solvents, when presumably largely tight ion pairs are present, Aso found for both a-methylstyrene (29) and isobutyl vinyl ether (28), that the degree of isotacticity was a maximum, with monomer attack being via the back side. As the solvent polarity increased and presumably the ion pair tightness decreased, possibly with some dissociation to free ions, back side attack becomes less favourable and isotactidty falls. 

Concerning the reactions occurring with inversion, the stereochemistry requires a back-side attack of the nucleophile opposite the leaving group. The skeleton of intermediate 14 corresponds to apical entry and departure. 

Figure 8-2 Stereochemistry of displacement of 2-chlorobutane with hydroxide by (1) front-side attack (not observed) and (2) back-side attack...

The. S n reactions between HF and protonated methyl, ethyl, isopropyl, and /-butyl fluorides in the gas phase have been examined at the MP2/6-31+- -G(d,p) level of theory.112 113 The reaction of CH3FH+ clearly occurs via back-side attack as the transition state for this process is of lower energy than the transition state for frontside attack. The EtFH+ can react via a more stable back-side. S N2 reaction or an. S n 1 reaction via front-side attack since the. S N 1 pathway is 4.4 kJmol-1 lower in energy. No. S n2 path could be found for i-PrFH+ and the front- and back-side pathways had equal activation energies for /-BuFH+, which effectively reacts by an. S N1 mechanism. The conclusion is that the preference for back-side attack is reduced as the size of... 

The fact that SN2 reactions always occur with inversion of configuration enables us to form a better picture of the transition state. The nucleophile must approach the carbon from the side opposite the leaving group (back-side attack). The structure of the transition state, with partial bonds to the entering hydroxide and the leaving chloride, is shown in the following structure. Figure 8.3 uses orbitals to show how this process occurs. 

Figure 6-6 shows the SN2 reaction of hydroxide ion with ethyl bromide (1°), isopropyl bromide (2°), and ferf-butyl bromide (3°). The nucleophile can easily approach the electrophilic carbon atom of ethyl bromide. In isopropyl bromide, the approach is hindered, but still possible. In contrast, SN2 approach to the tertiary carbon of ferf-butyl bromide is impossible because of the steric hindrance of the three methyl groups. Make models of ethyl bromide, isopropyl bromide, and ferf-butyl bromide, and compare the ease of bringing in an atom for a back-side attack. 

Back-side attack literally turns the tetrahedron of the carbon atom inside out, like an umbrella caught by the wind (Figure 6-7). In the product, the nucleophile assumes a stereochemical position opposite the position the leaving group originally occupied. We call this result an inversion of configuration at the carbon atom. 

Back-side attack inverts the configuration of the carbon atom. 

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