A mild and efficient chemoselective protection of amines as N-benzyloxycarbonyl derivatives in the presence of La(NO3)3·6H2O under solvent-free conditions

A facile and versatile method for the chemoselective N-benzyloxycarbonylation of amines has been developed by treatment with benzyloxycarbonyl chloride (Cbz-Cl) in the presence of lanthanum(III) nitrate hexahydrate under solvent-free conditions. The method is general for the preparation of N-Cbz derivatives of aliphatic (acyclic and cyclic) and aromatic amines.     

Regioselective modification of amino groups in aminoglycosides based on cyclic carbamate formation

Conditions for regioselective introduction of cyclic carbamate into per-N-Cbz neamine and per-N-Cbz kanamycin A have been found. The position and number of cyclic carbamate formed in these two aminoglycosides was controllable. On the base of selective cyclic carbamate formation, regioselective modification on N-1, N-6′ or both amino groups in neamine, and on N-6′, N-3″ or both amino groups in kanamycin A was achieved by ring-opening reaction with amines. A new neamine dimer linked at the N-1 was also synthesized with this method.     

Synthesis of l-azaisotryptophan and its analogs: a general access to new 2-substituted azaindoles

l-(N-Cbz)-7-azaisotryptophan, l-(N-Cbz)-1a, a new isostere of tryptophan, was synthesized by reacting Li₂-(N-Boc)-2-amino-3-picoline, Li₂-(N-Boc)-2a, with appropriately protected l-aspartic acid followed by simple functional group manipulation. This synthetic success led us to access a set of analogs of azaisotryptophan (4a–c; 6a–c) as well as a new class of chiral amines (7a–c; 8a–c) for future application in asymmetric synthesis and design of homochiral ligands. Further, we have generalized the method substantiating a variety of new azaindol-2-yl derivatives (10aa–10lc) with functionalized substituents. In a preliminary luminescence characterization, l-(N-Cbz)-1a has exhibited about 30 nm bathochromic shifted fluorescence emission compared to tryptophan and (N-Cbz)-tryptophan.     

Markedly chemoselective hydrogenation with retention of benzyl ester and N-Cbz functions using a heterogeneous Pd-fibroin catalyst

The chemoselective catalytic hydrogenation of acetylene, olefin and azido derivatives bearing benzyl ester and N-Cbz functionalities using a Pd-fibroin (Pd/Fib) catalyst was investigated. Perfect selectivity was accomplished, and the benzyl ester and N-Cbz functionalities are tolerated under the reaction conditions.     

Stereoselective synthesis of α-hydroxy-β-amino acid derivatives from β-hydroxy-γ,δ-unsaturated sulfilimine

The first report on the use of N-sulfinyl benzylcarbamate for the preparation of N-Cbz sulfilimine from the corresponding sulfoxide is reported. The sulfilimine moiety is utilized as an intramolecular nucleophile for the regio- and stereoselective heterofunctionalization of an alkene to furnish a bromo carbamate which is used as a key advanced intermediate in the synthesis of representative α-hydroxy-β-amino acid derivatives.     

Amberlyst-15: a mild, efficient and reusable heterogeneous catalyst for N-tert-butoxycarbonylation of amines

A mild and versatile method has been developed for the chemoselective N-tert-butoxycarbonylation of amines in the presence of Amberlyst-15 under solvent-free condition. The method is general for the preparation of N-Boc derivatives of aliphatic (acyclic and cyclic) and aromatic amines.     

Cp*Co(III) catalyzed annulation of N-Cbz hydrazones for the redox-neutral synthesis of isoquinolines via C–H/N–N bond activation

Abstract

A new cascade oxidative cyclization reaction of N-Cbz hydrazones with internal alkynes has been explored for the preparation of isoquinoline derivatives using Cp*Co^III-catalyst through C–H and N–N bond functionalization. N-Cbz hydrazones are rarely explored as directing group for redox-neutral [4?+?2] cyclization reaction through the cyclometallation and this catalyst system does not require any external oxidizing agent, as well as, silver or antimony salt. The current efficient approach has been utilized for the synthesis of different isoquinoline derivatives with good regioselectivity and yields.     

Synthesis of novel 2-phenyl-5-substituted dihydropyrimidines using 2-phenyl-1,3-diaza-1,3-butadienes and electron-deficient olefins

A novel synthetic method for 2,5-disubstituted dihydropyrimidines was developed. The cyclization of 1,3-diaza-4-dimethylamino-1,3-butadienes having a N-protecting group (N-Boc, N-Cbz, N-n-C₄H₉, N-Bn or N-Ph) with electron-deficient olefins, such as α,β-unsaturated carbonyl compounds, phenyl vinyl sulfone, and acrylonitrile was studied in detail. The cyclization smoothly proceeded to afford 4-dimethylamino-1,4,5,6-tetrahydropyrimidines or 1,6-dihydropyrimidines in good yields. The isolated 4-dimethylamino-1,4,5,6-tetrahydropyrimidines were converted to 2,5-disubstituted-1,6-dihydropyrimidines through the β-elimination of the dimethylamino group. 2,5-Disubstituted-1,4(6)-dihydropyrimidines were obtained after removal of the N-Boc or N-Cbz group. Independent tautomers of the resulting dihydropyrimidines were observed.     

N-Carbamate α-aminoalkyl-p-tolylsulfones—convenient substrates in the nitro-Mannich synthesis of secondary N-carbamate protected syn-2-amino-1-nitroalkanephosphonates

An efficient one-pot synthesis of secondary N-carbamate protected syn-β-amino-α-nitroalkanephosphonates using diethyl nitromethanephosphonate and N-Boc or N-Cbz imines, generated in situ from stable N-Boc or N-Cbz α-aminoalkyl-p-tolylsulfones has been developed under PTC conditions. A model enantioselective version of this reaction is also described. Enantioselectivity up to 67% ee is achieved using a chiral thiourea catalyst derived from a cinchona alkaloid. Completely stereoselective conversion of the title compounds into partially N-carbamate protected syn-1,2-diaminoalkanephosphonates has also been elaborated.     

Bis-benzyl protected 6-amino cyclitols are poisonous to Pd/C catalysed hydrogenolysis of benzyl ethers

Pd/C and Pd(OH)₂/C catalysts are both poisoned by bis-benzyl protected 6-aminocyclitols thereby inhibiting the hydrogenolysis of benzyl ethers but removing N-Cbz groups chemoselectively. This outcome was unaltered by the use of different hydrogen donors. Replacement of the C-6 nitrogen atom by oxygen resulted in the starting materials being fully deprotected under similar conditions. These findings add cyclitolamines to the list of amines/bases that are poisonous to Pd/C catalysts during hydrogenolysis.     

An efficient synthesis of dehydroamino acids and dehydropeptides from O-Cbz and O-Eoc derivatives of serine and threonine

A simple and efficient method for the synthesis of dehydroamino acids from serine and threonine is reported. Various O-Cbz and O-Eoc derivatives of serine and threonine are prepared using CbzCl and EocCl, respectively, and are subjected to an anti-selective elimination on treatment with K₂CO₃ in DMF at 65 °C to afford dehydroalanine and dehydroamino butyric acid derivatives, respectively, in excellent yields. The high stability of these carbonate derivatives of serine and threonine allows their use in normal peptide synthesis as protected serine and threonine residues. Peptides synthesized by incorporating O-Cbz or O-Eoc derivatives undergo ready elimination under the reported conditions, to give the corresponding dehydropeptides in excellent yields. The reaction conditions are mild enough not to cause the racemization of other stereogenic centers present in the peptide.     

An improved large scale procedure for the preparation of N-Cbz amino acids

A simple and scalable method for the preparation of N-Cbz protected amino acids is presented which uses a mixture of aqueous sodium carbonate and sodium bicarbonate to maintain the appropriate pH during the addition of benzyl chloroformate. The method has been extended to other N-protections and is amenable to large scale preparation of an intermediate toward Zofenopril, an ACE inhibitor.     

An efficient and facile synthesis of N-Cbz-β-aminoalkanesulfonamides

An efficient method for the synthesis of N-Cbz-β-aminoalkanesulfonamides was described.N-Cbz-β-aminoalkanesulfonamides were readily prepared in good yields from a variety of amino alcohols,including optically active ones,via N-Cbz protection with benzyl chloroformate,Mitsunobu esterification reaction with thiolacetic acid,N-chlorosuccinimide oxidation,and ammonolysis process.     

High regioselectivity in electrochemical α-methoxylation of N-protected cyclic amines

N-Protecting groups of α-substituted cyclic amines strongly affected the regioselectivity in electrochemical methoxylation of these compounds. Namely, N-acyl derivatives were transformed into α′-methoxylated compounds, while N-cyano derivatives changed into α-methoxylated derivatives. Furthermore, Lewis acid catalyzed nucleophilic substitution of the α-methoxylated compounds protected with cyano group afforded α,α-disubstituted cyclic amines.     

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.     

Hydroboration d'amines insaturees: XI. Regio- et stereoselectivite des hydrures du bore vis a vis d'amines propargyliques N-phosphorylees

The regioselectivity and the stereoselectivity of the hydroboration of N-alkylallylphosphoramide was examined. This study shows the preferential formation of γ-boron derivatives (90 to 100%) and the excellent stereospecificity of the reaction (100% (Z) configuration).The P^IV-N bond hinders the nitrogen-boron coordination which is responsible for the anomalous behavior of N-propargylic amines towards hydroboration and allows the same regio- and stereo-selectivity as for alkynes. The iodination of boron derivatives leads, with good yields, to N-phosphoryl-β-ethylenic amines.     

Synthesis of tri-, penta-, and heptasaccharides,functionalized with orthogonally N-protected amino residues at the reducing and non-reducing ends

The synthesis of four bifunctionalized orthogonally N-protected oligosaccharides derived from lactose and mannose, intended as cross-linking derivatives, is described. The aminosugar at the non-reducing end is derivatized with an N-Boc-protected glycine moiety, and further connected to either a mannose (1→6) disaccharide or (1→3) lactose units (one, two or three) resulting in tri-, penta-, or heptasaccharides. All of the synthesized oligosaccharides have an N-benzyloxycarbonyl-aminoethyl residue at the reducing end. The orthogonal N-Boc/N-Cbz protection group pattern enables further conjugation/derivatization and results in a hydrophilic cross-linking molecule. It was found that the order of the final synthetic steps was crucial to avoid acyl migration. A suitable amide coupling protocol has been applied to introduce the N-Boc-protected glycine moiety in alcoholic solvent. The synthesized oligosaccharides will provide a model system to investigate the influence of length, structure and flexibility.     

Easy access to N-alkylation of N-unsubstituted [60]fulleropyrrolidines: reductive amination using sodium triacetoxyborohydride

[60]Fulleropyrrolidines were used as secondary amines to react with aldehydes through reductive aminations to afford N-alkylated derivatives. In spite of the very weak base activity of the nitrogen atom of N-unsubstituted [60]fulleropyrrolidines, this method was found to be efficient at the aid of sodium triacetoxyborohydride. Several N-alkylated derivatives were synthesized and fully characterized.     

High-performance liquid chromatography of 5,7-dinitrobenzofurazan and nitrobenzodifurazan derivatives of aromatic amines

The retention times of 5,7-dinitrobenzofurazan and nitrobenzodifurazan derivatives of aromatic amines in reversed-phase high-performance liquid chromatography on a column filled with Hypersil ODS correlate with the acidity constants of these derivatives in dimethyl sulfoxide (DMSO) and dimethylformamide (DMF) and with the σ constants of substituents in the aromatic nucleus. Procedures were developed for the determination of aniline, N-methylaniline, N,N-dimethylaniline, and N-ethylaniline as their 5,7-dinitrobenzofurazan and nitrobenzodifurazan derivatives with detection limits of 70 μg/mL. The procedures can be used for the analysis of reaction mixtures in the synthesis of these substituted amines.     

Chemical transformations of diazoles in the reactions of carboxylation, N-siloxycarbonylation, and transsilylation

The behavior of 3,5-dimethylpyrazole, 3(5)-methylpyrazole, imidazole and their trimethyl-silyl derivatives in carboxylation, N-siloxycarbonylation, and transsilylation reactions was studied. A new Nsiloxycarbonylation reagent, diazole trimethylsilyl derivative-carbon dioxide, was found. This reagent makes it possible to obtain easily O-silylurethanes starting from primary, secondary amines and hydrazine derivatives, as well as to develop a convenient one pot synthesis method for trimethylsiloxycarbonyldiazoles.