Fluorenylmethyl elimination

Many carbamates have been used as protective groups. They are arranged in this chapter in order of increasing complexity of stmcture. The most useful compounds do not necessarily have the simplest stmctures, but are /-butyl (BOC), readily cleaved by acidic hydrolysis benzyl (Cbz or Z), cleaved by catalytic hy-drogenolysis 2,4-dichlorobenzyl, stable to the acid-catalyzed hydrolysis of benzyl and /-butyl carbamates 2-(biphenylyl)isopropyl, cleaved more easily than /-butyl carbamate by dilute acetic acid 9-fluorenylmethyl, cleaved by /3-elimination with base isonicotinyl, cleaved by reduction with zinc in acetic acid 1-adamantyl, readily cleaved by trifluoroacetic acid and ally], readily cleaved by Pd-catalyzed isomerisation. 

Diethylamine (11) is an inexpensive base that removes fluorenylmethyl-based protectors without forming an adduct with the liberated moiety, and it can be eliminated by evaporation. It has been employed as nucleophile for palladium-catalyzed allyl-transfer reactions (see Section 3.13). 

The 9-fluorenylmethyl group, in the guise of the 9-fluorenylmethoxycarbonyl or Fmoc group, is the keystone in modern solid-phase peptide synthesis and we will examine its enormous influence in section 8.3.5. The great virtues of the 9-fluorenylmethyl group have also been adapted to the protection of carboxylic acids as 9-fluorenylmethyl esters (see section 6.5.3). Bodanszky and Bednarek realised the opportunity for extending the principle of 9-fluorenylmethyl activation, the aromaticity of the fluorenyl anion, to the protection of cysteine in peptide synthesis. 9-Fluorenylmethyl thioethers are stable towards iodine and acidic conditions, including HF, but they easily eliminate on treatment with piperidine or DBU. 

The essential shortage of an OPA/SH group reagent (reactive toward primary AAs only) can be eliminated by Shuster s principle - the automatic two-step precolumn derivatization method - by applying the OPA/MPA/fluorenylmethyl-chloroformate... 

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