9-Fluorenylmethoxycarbonyl group cleavage

The 9-fluorenylmethoxycarbonyl group provides a mode of protection to amines which is stable to acids and catalytic reduction cleavage (Scheme 124) is readily achieved under mild basic, non-hydrolytic conditions, a... 

Scheme 14 shows a typical example in a series of reactions in which a supported amino acid reacted with fluorenylmethoxycarbonyl isothiocyanate to give a supported (on Rink s amide)35 thiourea.36 Removal of the protection followed by 5-alkylation gave supported isothioureas. Reaction of these with amines, then cleavage from the resin, afforded substituted guanidines. For 10 examples the purities were between 40 and 92%. An aryl group separates the resin from the guanidine, just as in the sequences shown in Schemes 11 and 12. 

An efficient procedure for debenzylation of esters under solvent-free conditions has been reported by Varma et al. (Scheme 8.7) [42]. By altering the surface characteristics of the solid support cleavage of the 9-fluorenylmethoxycarbonyl (Fmoc) group and related protected amines can be achieved in a similar fashion. The optimum conditions for cleavage of N-protected moieties are use of basic alumina and an irradiation time of 12-13 min at - 130-140 °C. 

Sieber P (1987) A new acid-labile anchor group for the solid-phase synthesis of C-terminal peptide amides by the Fmoc method. Tetrahedron Lett 28 2107-2110 Mende F, Seitz O (2011) 9-Fluorenylmethoxycarbonyl-based solid-phase synthesis of peptide a-thioesters. Angew Chem Int Ed 50 1232-1240 Giiillier F, Grain D, Bradley M (2000) Linkers and cleavage strategies in solid-phase organic synthesis and combinatorial chemistry. Chem Rev 100 2091-2158... 

---