Selective Cleavage of Cbz-Protected Amines

Abstract

Under conditions of catalytic Ni(0) and in most cases just over 1 equiv of Me(2)NH.BH(3)/K(2)CO(3) or Cs(2)CO(3), a Cbz-protected nitrogen, which is part of a heteroaromatic ring, can be chemospecifically cleaved without affecting a Cbz group on an originally basic amine. [reaction: see text]

An Alternative Route for the Synthesis of 2,3,4,5-tetramethoxytoluene

“…2,3,4-Trimethoxyphenol2: Cone.Sulfuricacid (0.5 mL, 6.4 mmol) was added to a stirred solution of the aldehyde 1 (2 g, 10.2 mmol) dissolvedin methanol (20 mL), cooled to lOoC,and then hydrogen peroxide(30%, I mL, 32.6 mmol)was added dropwise.The reaction mixturewas stirredat 10°Cfor 30 min and 24 h at room temperature, diluted with water and extractedwith dichloromethane.The organic extract was washed with brine, then with an aqueous solution of sodium bicarbonate(5%). It was dried and the solvent evaporatedto CHO OH OH 9:0"' (1) A mixture of phenol 2 (1.01 g, 5.4 mmol), anhydrous magnesium chloride (1 g, 10.5 mmol), triethylamine (1.5 mL, 10.8 mmol) and paraformaldehyde (0.5 g, 16.7 mmol) under nitrogen and in dry THF (50 mL) was heated under reflux for 4 h. The reaction mixture was cooled, acidified (5% HCI) and extracted with dicWoromethane. The usual work up yielded an oil (1.03 g) which contained a mixture of phenol 2 (615 mg, 62%) and aldehyde 3 (382 mg, 33%); urn", 1650 (CO) cm-'; 'H NMR: Freshly distilled dimethylsulfate (13 mL, 0.13 mmol) and sodium hydroxide (13 mL 10%) was added to JOURNAL OF CHEMICAL RESEARCH 2009 187 a solution of the phenol 4 (352 mg, 1.77 mmol) in ethanol (100 mL).…”

A Nucleophilic Deprotection of Carbamate Mediated by 2-Mercaptoethanol

“…The Cbz carbamate remains a popular choice among the various readily accessible groups, largely due to the mild Pd-catalyzed hydrogenolysis conditions that are commonly employed for the eventual unmasking of the desired amine. In most instances, these reductive deprotection conditions are compatible with an array of functional groups, although there are examples of interfering reactivity. , In such cases, a nickel catalyst can be employed with the risk of potential dehalogenation if aromatic halogens are present. Another option is to use trimethylsilyl iodide [TMSI] , as a Lewis acid for the deprotection of Cbz groups.…”

“…In most instances, these reductive deprotection conditions are compatible with an array of functional groups, although there are examples of interfering reactivity. 13,14 In such cases, a nickel catalyst 15 can be employed with the risk of potential dehalogenation if aromatic halogens are present. Another option is to use trimethylsilyl iodide [TMSI] 16,17 as a Lewis acid for the deprotection of Cbz groups.…”

Chemoselective Radical Cleavage of Cbz-Protected Nitrogen Compounds

“…The possibility of removal under orthogonal conditions, mainly dissolving metal reductions, catalytic hydrogenation, and acid treatment, , makes this protecting group particularly attractive. However, the majority of protection−deprotection schemes involve N -Cbz derivatives of amines rather than amides 4 or nitrogen heteroaromatic rings, and as far as we know, the available deprotection methods do not discriminate among these different nitrogen functional groups . In this Letter, we describe a novel set of conditions for the removal of the N -Cbz group, which are selective for originally nonbasic nitrogen atoms, both amide and those contained within a heteroaromatic ring (Figure ).…”