Di-tert-butyl Dicarbonate Research Articles

An efficient and chemoselective Brønsted acidic ionic liquid-catalyzed N-Boc protection of amines

The first report of a Brønsted acidic ionic liquid, 1-methylimidazolium tetrafluoroborate [(HMIm)BF 4], catalyzed efficient and chemoselective N-Boc protection of various amines using (Boc) 2O is presented. Optically pure amino alcohols and amino acid esters were converted efficiently to their corresponding optically pure N-Boc derivatives. The reported method is mild, solvent-free and has the advantages of both homogeneous and heterogeneous catalysis with high product yields, selectivity and ease of product separation.

Selective acylation of 4,5-diamino-9,9′-dimethylxanthene through an aggregation effect

The proximity of the 4,5-diamino groups in a 9,9′-dimethylxanthene skeleton provides unique reactivity due to aggregation effects. While treatment with 1 equiv of an isocyanate yields the diurea and starting material, under similar conditions, Boc 2O provides essentially only the monocarbamoyl derivative.

Efficient, solventless N-Boc protection of amines carried out at room temperature using sulfamic acid as recyclable catalyst

A simple, rapid, and efficient protocol for the chemoselective N-Boc protection of amines using sulfamic acid as catalyst is described. N-Boc protection of various structurally diverse aliphatic, aromatic, alicyclic, and heterocyclic amines (1°, 2°, 3°) was carried out with (Boc) 2O using sulfamic acid as catalyst (5 mol %) at room temperature under solventless conditions. The advantages of this method are simplicity, shorter reaction times (1–15 min), a cost-effective catalyst, and excellent isolated yields (90–100%); it is also environmentally benign. Moreover, the combined use of ultrasound and sulfamic acid achieves a synergic effect that is especially marked in the N-Boc protection of deactivated (sterically hindered and electron-deficient) amines. The catalyst possesses distinct advantages: ease of handling, cleaner reactions, high activity, and excellent chemoselectivity.

Hyperbranched poly(ether–urea)s using AB2‐type blocked isocyanate monomer and azide monomer: Synthesis, characterization, reactive end functionalization, and copolymerization with AB monomer

Abstract3,5‐bis(4‐aminophenoxy)phenyl phenylcarbamate—a novel AB2‐type blocked isocyanate monomer and 3,5‐bis{ethyleneoxy(4‐aminophenoxy)}phenyl carbonyl azide—a novel AB2‐type azide monomer were synthesized in high yield. Step‐growth polymerization of these monomers were found to give a first example of hyperbranched poly (aryl‐ether‐urea) and poly(aryl‐alkyl‐ether‐urea). Molecular weights (Mw) of the polymer were found to vary from 1,858 to 52,432 depending upon the monomer and experimental conditions used. The polydispersity indexes were relatively narrow due to the controlled regeneration of isocyanate functional groups for the polymerization reaction. The degree of branching (DB) was determined using 1H‐NMR spectroscopy and the values ranged from 87 to 54%. All the polymers underwent two‐stage decomposition and were stable up to 300 °C. Functionalized end‐capping of poly(aryl‐ether‐urea) using phenylchloroformate and di‐t‐butyl dicarbonate (Boc)2O changed the thermal properties and solubility of the polymers. Copolymerization of AB2‐type blocked isocyante monomer with functionally similar AB monomer were also carried out. The molecular weights of copolymers were found to be in the order of 6 × 105 with narrow dispersity. It was found that the Tg's of poly(aryl‐alkyl‐ether‐urea)s were significantly less (46–49 °C) compared to poly(aryl‐ether‐urea)s. Moreover the former showed melting transition at 154 °C, which was not observed in the latter case. © 2007 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 45: 2959–2977, 2007

The synthesis of facial amphiphile 3α,7α-diaminocholestane

The facial amphiphile 3α,7α-diaminocholestane 3 was synthesized from 3β-acetoxy-7-ketocholestane 1 through a stepwise reductive amination. The reductive amination of 1 with NH 4OAc in the presence of NaBH 3CN, and protection with Boc 2O yielded 7α-( tert-butyloxycarbonyl)-aminocholestane 4 in 86% yield. The reductive amination of 6, which was obtained from 4 after hydrolysis and subsequent oxidation, with NH 4OT f in the presence of NaBH(OEh) 3 provided 3 in 75% yield after protection with Boc 2O.

Synthesis and characterization of new amino acyl-4-thiazolidones

A series of heterocyclic compounds with a 4-thiazolidone nucleus and amino acyl moiety were synthesized by protection reaction of thiosemicarbazide using the symmetrical anhydride (Boc)2O and cyclization with chloroacetic acid under mild conditions. Trifluoroacetic acid was used to obtain 4-thiazolidone and the alpha-amino acid condensation reactions were carried out using strategies for peptide synthesis. The characterization of this new class of compounds was performed using IR and ¹H-NMR spectroscopy.

Pd(II)-Catalyzed Addition of Malonates to Dihydroisoquinolines

This is a nice report of the synthesis of C1-chiral tetrahydroisoquinolines (THIQs) from dihydroisoquinolines (DHIQs). DM-SEGPHOS (1) was found to be the best ligand for this reaction and the order of addition of reactants was also found to be important. Interestingly, addition of Boc anhydride to the DHIQ followed by the catalyst and the malonate nucleophile proved the necessary order of addition for any conversion. Isopropyl malonate was found to be the best nucleophile, giving high conversion and high ee values. A variety of substituted DHIQs gave high yields and good enantioselectivities with isopropyl malonate.

A scalable and expedient method of preparing diastereomerically and enantiomerically enriched pseudonorephedrine from norephedrine

Norephedrine has been efficiently converted into the corresponding diastereomer pseudonorephedrine using a three step, one-pot reaction. The three step process involves treatment of norephedrine with di- tert-butyl dicarbonate (Boc 2O); cyclization by way of mesylate formation at the alcohol; and lithium hydroxide mediated hydrolysis of the oxazolidinone. The diastereomeric purity was determined by HPLC and the enantiomeric purity was determined by optical activity measurements and chiral stationary phase HPLC analysis of the pseudonorephedrine oxazolidinone derivatives.

A highly chemoselective Boc protection of amines using sulfonic-acid-functionalized silica as an efficient heterogeneous recyclable catalyst

A facile and versatile method for the chemoselective Boc protection of amines has been developed by a treatment with (Boc)2O in the presence of sulfonic-acid-functionalized silica as a catalyst. The method is general for the preparation of N-Boc derivatives of aliphatic (acyclic and cyclic), aromatic, and heteroaromatic amines; primary and secondary amines; aminols, amino-esters; and sulfonamides. The catalyst works under heterogeneous conditions and can be recycled.

Molecular Iodine-Catalyzed Facile Procedure for N-Boc Protection of Amines

An efficient and practical protocol for the protection of various structurally and electronically divergent aryl and aliphatic amines using (Boc)2O in the presence of a catalytic amount of molecular iodine (10 mol %) under solvent-free conditions at ambient temperature is presented.

A rate enhancement of tert-butoxycarbonylation of aromatic amines with Boc 2O in alcoholic solvents

A rate enhancement of tert-butoxycarbonylation of aromatic amines by Boc 2O in alcohols compared to aprotic solvents was demonstrated. Kinetic analysis by NMR suggested that the reaction in CD 3OD was faster than in CDCl 3 by a factor of 70. Reactions between Boc 2O and various aliphatic and aromatic amines in ethanol provided the N-Boc derivatives in good to excellent yields in short reaction times.

Montmorillonite K 10 and montmorillonite KSF as new and reusable catalysts for conversion of amines to N- tert-butylcarbamates

Montmorillonite K 10 and montmorillonite KSF were found to be new and reusable catalysts for chemoselective conversion of amines to N- t-Boc derivatives at room temperature under solvent-free conditions without competitive formation of isocyanate, urea and N, N-di- t-Boc. Various aromatic, heteroaromatic and aliphatic amines afforded N- t-butylcarbamates in excellent yields on treatment with (Boc) 2O after 5 min–2 h. Chiral amine and esters of α-amino acids afforded optically pure N- t-Boc derivatives in high yields. The catalytic efficiency of montmorillonite KSF was marginally inferior to that of montmorillonite K 10.

A novel 1- tert-butoxy-2- tert-butoxycarbonyl-1,2-dihydroisoquinoline (BBDI)-catalyzed esterification of N-protected amino acids with nearly equimolar amounts of alcohols in the presence of Boc 2O

A very mild, BBDI-catalyzed esterification using approximately equimolar amounts of N-protected amino acids and alcohols, in junction with Boc 2O is described.

Conversion of Five‐, Six‐, and Seven‐Membered Lactams to Racemic or Scalemic 2‐Substituted Heterocycles by Amidoalkylation.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Conversion of Five-, Six-, and Seven-Membered Lactams to Racemic or Scalemic 2-Substituted Heterocycles by Amidoalkylation

An efficient method for the synthesis of 2-alkyl- and 2-aryl pyrrolidines, piperidines, and azepanes from lactams, in either racemic or enantiopure form, is presented. The lactam nitrogens are acylated with either Boc anhydride or trans-cumylcyclohexyl (TCC) chloroformate. Selective reduction of the lactam carbonyl to the carbinolamide is followed by treatment with benzotriazole. Substitution of the benzotriazole is accomplished by treatment with organometallics, yielding the 2-substituted heterocycles. With TCC, up to 90% diastereoselectivity is achieved. After diastereomer purification, reductive removal of the auxiliary affords enantiopure 2-substituted heterocycles. A mechanistic hypothesis is presented that details the conformational equilibria of the key step.

Rapid and facile Lewis acid catalysed Boc protection of amines

Efficient Boc protection of amines was carried out using (Boc) 2O in the presence of a catalytic amount of ZrCl 4 (10 mol %) in acetonitrile at room temperature. The reaction times are very short and the yields are generally high.

Chemically Amplified Photosensitive Polybenzoxazoles Based on tert-Butoxycarbonyl Protected Hyperbranched Poly(o-hydroxyamide)s

We describe the synthesis, characterization, and lithographic performance of positive-working chemically amplified photosensitive polybenzoxazoles (PSPBOs) composed of partially tert-butoxycarbonyl (t-BOC) protected hyperbranched poly(o-hydroxyamide)s (HB-tbocPHAs) and diphenyliodonium 9,10-dimethoxyanthracene-2-sulfonate (DIAS) as a photo-acid generator (PAG). The HB-tbocPHAs as precursors of PSPBOs were synthesized from hyperbranched poly(o-hydroxyamide)s (HBPHAs), which were prepared by self-polycondensation of an AB 2 type monomer. A series of HB-tbocPHAs having the t-BOC content of 8-100 mol % were successfully prepared by controlling the feed amount of di-tert-butyl dicarbonate (DTBDC). HB-tbocPHAs had adequate dissolution rate in tetramethylammonium hydroxide (TMAH) aqueous solution as well as excellent solubility in common organic solvents. HB-tbocPHA having 39 mol % t-BOC group showed the optimum dissolution rate in 2.38 wt% TMAH aqueous solution and good adhesion on a silicon wafer. The thermal deprotection of the t-BOC group and conversion to polybenzoxazole (PBO) of HB-tbocPHA in the presence of strong acid such as p-toluenesulfonic acid (p-TsOH) were investigated by using FT-IR, DSC, and TGA to examine the acid effect. Both the deprotection of t-BOC groups and the conversion to PBO were accelerated in the presence of p-TsOH. The photolithographic performance of the resist formulated with HB-tbocPHA and 20 wt % of DIAS was evaluated. The resist showed 115 mJ/cm 2 of sensitivity and 2.2 of contrast with 365 nm light when it was developed in 2.38 wt % TMAH aqueous solution at room temperature. The fine positive pattern was obtained at the 200 mJ/cm 2 of i-line exposure. The patterned film was successfully converted to polybenzoxazole without any distortion by thermal treatment at 300 °C for 1 h.

Preparation of N‐tert‐Butoxycarbonylthiourea Opens the Way to Protected 2‐Aminothiazoles.

AbstractFor Abstract see ChemInform Abstract in Full Text.

New crown-carrier Cα,α-disubstituted glycines derived from α-methyl-( l)-DOPA

The side-chain catechol function of α-methyl-( l)-DOPA was utilized for the synthesis of a new series of crown-carrier C α,α-disubstituted glycines. During N-protection of α-methyl-( l)-DOPA methyl ester (H-Mdp-OMe) with Boc anhydride, the formation of N, O-di-Boc derivatives was observed. Selective aminolysis of the catechol tert-butyl carbonate group was achieved using pyrrolidine as nucleophile. Treatment of the resulting Boc-Mdp-OMe by Cs 2CO 3 in MeOH, followed by bis- O-alkylation with cyclization using various polyethyleneglycol ditosylates or catechol-derived bis-polyethyleneglycol ditosylates in DMF at 60°C, led to the derivatives Boc-[15-C-5]-Mdp-OMe, Boc-[18-C-6]-Mdp-OMe, Boc-[benzo-18-C-6]-Mdp-OMe, Boc-[benzo-24-C-8]-Mdp-OMe and then after saponification, to the corresponding N α-protected amino acids. The tripeptides Fmoc-Ala-[18-C-6]-Mdp-Ala-OMe and Boc-Aib-[18-C-6]-Mdp-Ala-OMe were prepared in solution by using Ala and Aib UNCAs for coupling at the N terminus of the [18-C-6]-Mdp residue and the EDC/HOAt method for coupling Ala at its C terminus.

Activation of carboxylic acids as their active esters by means of tert-butyl 3-(3,4-dihydrobenzotriazine-4-on)yl carbonate

Carboxylic acids were activated in the presence of DMAP with tert-butyl carbonates (BOC-OX) 1 , which were prepared in situ by reaction of X-OH and di- tert-butyl dicarbonate (BOC 2O). The most efficient active carbonate proved to be tert-butyl 3-(3,4-dihydrobenzotriazine-4-on)yl carbonate 1a , leading to efficient formation of benzotriazinonyl esters 3 and 6 , which are intermediates in reactions with primary and secondary amines to afford amides or peptides in good yield. By-products in the formation of 3 or 6 are the environmentally safe tert-BuOH and CO 2. The hindered amino acid AIB also forms a dipeptide in good yield.