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Reactions >> Protecting Groups >> Stability

9-Fluorenylmethyl carbamates

Fmoc-NR2, , FMOC amino, FMOC amine, FMOC amide

T. W. Green, P. G. M. Wuts,
Protective Groups in Organic Synthesis,
Wiley-Interscience, New York, 1999, 503-507, 736-739.



H2O: pH < 1, 100C pH = 1, RT pH = 4, RT pH = 9, RT pH = 12, RT pH > 12, 100C
Bases: LDA NEt3, Py t-BuOK Others: DCC SOCl2
Nucleophiles: RLi RMgX RCuLi Enolates NH3, RNH2 NaOCH3
Electrophiles: RCOCl RCHO CH3I Others: :CCl2 Bu3SnH
Reduction: H2 / Ni H2 / Rh Zn / HCl Na / NH3 LiAlH4 NaBH4
Oxidation: KMnO4 OsO4 CrO3 / Py RCOOOH I2, Br2, Cl2 MnO2/CH2Cl2

Protection of Amino Groups

New, stable amino-protecting reagents, Boc-DMT and Fmoc-DMT, were prepared, and found to be useful for the introduction of Boc and Fmoc groups into amines. Both the reagents can protect various amines including amino acids in good yield in aqueous media.
K. Hioki, M. Kinugasa, M. Kishimoto, M. Fujiwara, S. Tani, M. Kunishima, Synthesis, 2006, 1931-1933.

Stable Fmoc-, Boc-, and Alloc-benzotriazoles react with various amino acids including unprotected serine and glutamic acid, in the presence of triethylamine at 20˚C to afford Fmoc-, Boc-, and Alloc-protected amino acids in very good yields free of dipeptide and tripeptide impurities. Fmoc-, and Alloc-Gly-Gly-OH dipeptides were prepared in excellent yields by N-acylation of glycylglycine.
T. S. Ibrahima, S. R. Tala, S. A. El-Feky, Z. K. Abdel-Samii, A. R. Katritzky, Synlett, 2011, 2013-2016.

Amino groups are selectively protected in good yields by reaction with O-alkyl S-(pyridin-2-yl)carbonothiolates at room temperature in air. Even substrates with multiple hydroxyl groups such as glucosamine are selectively N-protected.
T. Suzuki, K. Tanaka III, Y. Hashimoto, N. Morita, O. Tamura, Synlett, 2020, 31, 899-902.

A simple and efficient protection procedure is general and regioselective for the preparation of mono-N-Boc, N-Cbz, N-Fmoc or N-Alloc aromatic amines in high yield without affecting aliphatic amino groups and other functionalities.
V. Perron, S. Abbott, N. Moreau, D. Lee, C. Penney, B. Zacharie, Synthesis, 2009, 283-289.

Other Syntheses of Fmoc-Protected Amino Groups

Weakly basic carbon nucleophiles add efficiently to a Fmoc-protected N,O-acetal. The new reactions shows the compatibility of the Fmoc protecting group with moderately basic reaction conditions and should serve as a model for the development of more efficient syntheses of Fmoc-protected amino acids.
A. E. Hartman, C. L. Brophy, J. A. Cupp, D. K. Hodge, T. J. Peelen, J. Org. Chem., 2009, 74, 3952-3954.