Protecting groups nucleophilic substitution

A somewhat more complex scheme is required for the preparation of benzimidazolones in which one of the nitrogen atoms is substituted by a 4-pi peridyl group. The sequence starts with aromatic nucleophilic substitution on dichlorobenzene by protected amino-piperidine derivative to give Reduction of the... 

Amino groups are often protected as their tert-butoxycarbonvl amide, or Boc, derivatives. The Boc protecting group is introduced by reaction of the amino acid with di-fert-butyl dicarbonate in a nucleophilic acyl substitution reaction and is removed by brief treatment with a strong organic acid such as trifluoro-acetic acid, CF3C02H. 

As an alternative reaction process, nucleophilic substitution reactions of (1,3/2,4,6)-4-bromo-6-(bromomethyl)-l, 2,3-cyclohexanetriol triacetate (51) with benzoate ions furnished 49 in poor yield after exchange of the protective groups. ... 

Methoxyphenyl (PMP) ethers find occasional use as hydroxy protecting groups. Unlike benzylic groups, they cannot be made directly from the alcohol. Instead, the phenoxy group must be introduced by a nucleophilic substitution.185 Mitsunobu conditions are frequently used.186 The PMP group can be cleaved by oxidation with CAN. 

Allyl carbonate esters are also useful hydroxy-protecting groups and are introduced using allyl chloroformate. A number of Pd-based catalysts for allylic deprotection have been developed.209 They are based on a catalytic cycle in which Pd° reacts by oxidative addition and activates the allylic bond to nucleophilic substitution. Various nucleophiles are effective, including dimedone,210 pentane-2,4-dione,211 and amines.212... 

Allyl carbamates also can serve as amino-protecting groups. The allyloxy group is removed by Pd-catalyzed reduction or nucleophilic substitution. These reactions involve formation of the carbamic acid by oxidative addition to the palladium. The allyl-palladium species is reductively cleaved by stannanes,221 phenylsilane,222 formic acid,223 and NaBH4,224 which convert the allyl group to propene. Reagents... 

The ANM group was selected as the nitrogen protecting group for the novel asymmetric nucleophilic substitution providing the optimum enantioselectivity. 

In the initial step, the first BOC-protected amino acid is bound to the polymer, e.g. polystyrene in which a proportion of the phenyl rings have chloromethyl substitution. Attachment to these residues is through the carboxyl via an ester linkage. This involves a simple nucleophilic substitution reaction, with the carboxylate as nucleophile and chloride as leaving group (see Section 6.3.2). After each stage, the insoluble polymer-product combination is washed free of impurities. 

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