The tert-butyloxycarbonyl protecting group or tert-butoxycarbonyl protecting group [1] (BOC group) is an acid-labile protecting group used in organic synthesis.
The BOC group can be added to amines under aqueous conditions using di-tert-butyl dicarbonate in the presence of a base such as sodium hydroxide:
Protection of amines can also be accomplished in acetonitrile solution using 4-dimethylaminopyridine (DMAP) as the base.
Removal of the BOC group in amino acids can be accomplished with strong acids such as trifluoroacetic acid in dichloromethane, or with HCl in methanol. [2] [3] [4] A complication may be the tendency of the t-butyl cation intermediate to alkylate other nucleophiles; scavengers such as anisole or thioanisole may be used. [5] [6] Selective cleavage of the N-Boc group in the presence of other protecting groups is possible when using AlCl3.
Sequential treatment with trimethylsilyl iodide then methanol can also be used for Boc deprotection, [7] [8] especially where other deprotection methods are too harsh for the substrate. [9] The mechanism involves silylation of the carbonyl oxygen and elimination of tert-butyl iodide ( 1), methanolysis of the silyl ester to the carbamic acid ( 2) and finally decarboxylation to the amine ( 3). [10]
R2NCO2tBu + Me3SiI → R2NCO2SiMe3 + tBuI | (1) |
R2NCO2SiMe3 + MeOH → R2NCO2H + MeOSiMe3 | (2) |
R2NCO2H → R2NH + CO2 | (3) |
The tert-butyloxycarbonyl (Boc) group is used as a protecting group for amines in organic synthesis.
BOC-protected amines are prepared using the reagent
di-tert-butyl-iminodicarboxylate. Upon deprotonation, this reagent affords a doubly BOC-protected source of NH−
2, which can be N-alkylated. The approach is complementary to the
Gabriel synthesis of amines.
The tert-butyloxycarbonyl protecting group or tert-butoxycarbonyl protecting group [1] (BOC group) is an acid-labile protecting group used in organic synthesis.
The BOC group can be added to amines under aqueous conditions using di-tert-butyl dicarbonate in the presence of a base such as sodium hydroxide:
Protection of amines can also be accomplished in acetonitrile solution using 4-dimethylaminopyridine (DMAP) as the base.
Removal of the BOC group in amino acids can be accomplished with strong acids such as trifluoroacetic acid in dichloromethane, or with HCl in methanol. [2] [3] [4] A complication may be the tendency of the t-butyl cation intermediate to alkylate other nucleophiles; scavengers such as anisole or thioanisole may be used. [5] [6] Selective cleavage of the N-Boc group in the presence of other protecting groups is possible when using AlCl3.
Sequential treatment with trimethylsilyl iodide then methanol can also be used for Boc deprotection, [7] [8] especially where other deprotection methods are too harsh for the substrate. [9] The mechanism involves silylation of the carbonyl oxygen and elimination of tert-butyl iodide ( 1), methanolysis of the silyl ester to the carbamic acid ( 2) and finally decarboxylation to the amine ( 3). [10]
R2NCO2tBu + Me3SiI → R2NCO2SiMe3 + tBuI | (1) |
R2NCO2SiMe3 + MeOH → R2NCO2H + MeOSiMe3 | (2) |
R2NCO2H → R2NH + CO2 | (3) |
The tert-butyloxycarbonyl (Boc) group is used as a protecting group for amines in organic synthesis.
BOC-protected amines are prepared using the reagent
di-tert-butyl-iminodicarboxylate. Upon deprotonation, this reagent affords a doubly BOC-protected source of NH−
2, which can be N-alkylated. The approach is complementary to the
Gabriel synthesis of amines.