Page 421 - Advanced Organic Chemistry Part A - Structure and Mechanisms, 5th ed (2007) - Carey _ Sundberg

402 Reactant structure also influences the degree of nucleophilic solvent participation.
Solvation is minimized by steric hindrance and the 2-adamantyl system is regarded as
CHAPTER 4 being a secondary reactant that cannot accommodate significant back-side nucleophilic
Nucleophilic Substitution participation.

H
H
X

The 2-adamantyl system is used as a model reactant for defining the characteristics
of ionization without solvent participation. The degree of nucleophilic participation
in other reactions can then be estimated by comparison with the 2-adamantyl system. 18

4.1.4. Relationship between Stereochemistry and Mechanism of Substitution

Studies of the stereochemistry are a powerful tool for investigation of nucleophilic
substitution reactions. Direct displacement reactions by the S 2(lim) mechanism are
N
expected to result in complete inversion of configuration. The stereochemical outcome
of the ionization mechanism is less predictable, because it depends on whether reaction
occurs via an ion pair intermediate or through a completely dissociated ion. Borderline
mechanisms may also show variable stereochemistry, depending upon the lifetime of
the intermediates and the extent of ion pair recombination.
Scheme 4.2 presents data on some representative nucleophilic substitution
processes. Entry 1 shows the use of 1-butyl-1-d,p-bromobenzenesulfonate (Bs,
brosylate) to demonstrate that primary systems react with inversion, even under
solvolysis conditions in formic acid. The observation of inversion indicates a concerted
mechanism, even in this weakly nucleophilic solvent. The primary benzyl system in

Scheme 4.2. Stereochemistry of Nucleophilic Substitution Reactions

Reactant a Conditions Product Sterechemistry
HCO H CH CH CH CHDO CH
1 b CH CH CH CHDOBs 2 3 2 2 2 99 ± 6% inv.
2
2
3
99° C
CH CO H
2
3
H CHDO CCH
2 c C H CHDOTs 25° C C 6 5 2 3 82 ± 1% inv.
6 5
+
3 c CH CH(CH ) CH 3 Et N – O CCH 3 CH 3 CH(CH ) CH 3 100% inv.
3
2 5
4
2
2 5
acetone, 56° C
OTs
O CCH 3
2
4 d CH CH(CH ) CH 3 75 % aq. dioxane CH 3 CH(CH 2 ) 5 CH 3 77% inv.
3
2 5
65° C
OTs OH
75 % aq. dioxane CH CH(CH ) CH 3 100% inv.
3
2 5
0.06 M NaN , 65° C OH 22%
3
CH CH(CH ) CH 3 100% inv.
2 5
3
N 3 78%
(Continued)
18
F. L. Schadt, T. W. Bentley, and P. v. R. Schleyer, J. Am. Chem. Soc., 98, 7667 (1976).