cis-Fused bicyclic sugar thiocarbamates. Reactivity towards amines

1,2-cis-Fused bicyclic sugar thiocarbamates of gluco and manno configurations have been prepared by treatment of the corresponding O-unprotected amino sugars and glycopyranosyl amines with thiophosgene. The reactivity of these compounds towards amines has been studied in order to determine whether these compounds could act as latent isothiocyanates; it is shown that 1,2-cis-fused bicyclic sugar thiocarbamates are more stable than their trans analogues, and are not transformed into thioureas upon treatment with amines. An unprecedented isomerization of a peracetylated glucopyranoso[2,1-d]oxazolidine-2-thione into a glucopyranoso[2,1-d]thiazolidin-2-one in DMF is also reported. The structure of this thiazolidin-2-one was confirmed by X-ray crystallography.     

A convenient and efficient method for the synthesis of mono- and N,N-disubstituted thioureas

A convenient method for the synthesis of mono- and N,N-disubstituted thioureas by the debenzoylation of N-substituted- and N,N-disubstituted-N′-benzoylthioureas with hydrazine hydrate under solvent-free conditions has been developed. N-Substituted-N′-benzoylthioureas and hydrazine hydrate were mixed, and stirred at room temperature without a solvent to give the corresponding N-substituted thioureas in high yields.     

A General and Scalable Synthesis of Polysubstituted Indoles

A consecutive 2-step synthesis of N-unprotected polysubstituted indoles bearing an electron-withdrawing group at the C-3 position from readily available nitroarenes is reported. The protocol is based on the [3,3]-sigmatropic rearrangement of N-oxyenamines generated by the DABCO-catalyzed reaction of N-arylhydroxylamines and conjugated terminal alkynes, and delivers indoles endowed with a wide array of substitution patterns and topologies.     

Synthesis of O-unprotected glycosyl selenoureas. A new access to bicyclic sugar isoureas

β-d-Gluco and mannopyranosyl selenoureas have been prepared by coupling of the corresponding glycosylamines with phenyl isoselenocyanate in aqueous pyridine. Alkyl and aryl isoselenocyanates, and 1,4-phenylene diisoselenocyanate have been obtained from the corresponding formamides with an excess of triphosgene, black selenium and triethylamine. Treatment of the O-unprotected β-d-glucopyranosyl selenourea with aqueous oxygen peroxide afforded a 1,2-trans-fused bicyclic isourea.     

A Convenient and Facile Hantzsch Synthesis of Aryl Imidazo[1,2‐b]Isoxazolyl‐N‐aryl Thiazol Amines

The Hantzsch synthesis of novel aryl imidazo[1,2‐b]isoxazolyl‐N‐aryl thiazol amines 5 analogues were described. Reaction of 3‐aminoisoxazole 1 with substituted phenacyl bromides 2 in dry ethanol afforded the corresponding 6‐methyl‐3‐arylimidazo[1,2‐b]isoxazoles 3 in good yields. Compounds 3 on reaction with chloroacetyl chloride in 1,4‐dioxane furnished the corresponding 2‐chloro‐1‐(6‐methyl‐3‐arylimidazo[1,2‐b]isoxazol‐2‐yl)ethanones 4 . Compounds 4 on heating with N‐aryl thioureas in an oil bath underwent cyclization to afford the title compounds viz., imidazo[1,2‐b]isoxazolyl‐N‐aryl thiazol amines 5 in moderate to good yields by Hantzsch synthesis.     

Two-pot synthesis of N,N-disubstituted 4H-3,1-benzothiazin-2-amines from aryl(2-isothiocyanatophenyl)methanones and secondary amines

A convenient synthesis of N,N-disubstituted 4H-3,1-benzothiazin-2-amines from aryl(2-isothiocyanatophenyl)methanones using a two-pot procedure has been developed. Thus, treatment of these isothiocyanato ketones with secondary amines gave the corresponding keto thioureas, which were allowed to react with sodium borohydride or methylmagnesium bromide to afford 1,1-dialkyl-3-{2-[aryl(hydroxy)methyl]phenyl}thioureas or 1,1-dialkyl-3-[2-(1-aryl-1-hydroxyethyl)phenyl]thioureas, respectively, in one pot. Hydrobromic acid-mediated cyclization of these hydroxy thiourea precursors provided the desired 4H-3,1-benzothiazin-2-amines.     

A practical synthesis of 2-(N-substituted)-aminobenzimidazoles utilizing CuCl-promoted intramolecular cyclization of N-(2-aminoaryl)thioureas

A practical protocol for synthesis of 2-(N-substituted)-aminobenzimidazoles was developed. N-(2-Aminoaryl)thioureas undergo a CuCl-promoted intramolecular cyclization to give the corresponding 2-(N-substituted amino)benzimidazoles in good to excellent isolated yields.     

Reductive alkylation of thioureas: a highly practical synthesis of unsymmetrical N,N′-disubstituted thioureas

A highly practical synthesis of unsymmetrical N,N′-disubstituted thioureas by the reductive alkylation of N-monosubstituted thioureas with aldehydes is described. N-Monosubstituted thioureas can in turn be synthesized by the reductive amination of thiourea with an appropriate aldehyde. This reductive alkylation methodology was also extended to carbamates.     

Chiral relay in NHC-mediated asymmetric β-lactam synthesis II; asymmetry from NHCs derived from acyclic 1,2-diamines

The synthesis of a range of imidazolinium salts derived from acyclic 1,2-diamines, and an evaluation of the reactivity and asymmetric induction of the corresponding NHCs as catalysts for the asymmetric synthesis of β-lactams, is reported. An N-methyl-substituted NHC derived from (1R,2R)-1,2-diphenylethanediamine shows optimal reactivity and enantioselectivity in this series, in contrast to that observed with NHCs derived from (1R,2R)-cyclohexane-1,2-diamine.     

Synthesis of sugar-derived isoselenocyanates, selenoureas, and selenazoles

Aryl, alkyl, and sugar-derived isoselenocyanates were prepared by a one-pot procedure starting from the corresponding formamides, using triphosgene as a dehydrating agent, triethylamine, and black selenium powder. The preparation of sugar selenoureas by coupling of O-protected sugar-derived isoselenocyanates with different amines, and by coupling of unprotected glycopyranosyl amines with phenyl isoselenocyanate was also accomplished. The synthesis of a glucopyranos-2-yl-selenazole starting from O-protected 2-amino-2-deoxy-d-glucose by coupling with benzoyl isoselenocyanate, Se-alkylation with phenacyl bromide, and acid-catalyzed dehydration is also reported. Unprotected N-(β-d-glucopyranosyl)-N′-phenylselenourea was transformed into a 1,2-trans-fused bicyclic isourea upon treatment with aqueous hydrogen peroxide; the same isourea was prepared by a one-pot three-step procedure from β-d-glycopyranosylamine by thiophosgenation, coupling with aniline, and HgO-mediated desulfurization.     

Regio-controlled synthesis of N-substituted imidazoles

A regio-specific synthesis of N-substituted imidazoles is described. Readily available α-amino acids are converted to α-aminocarbonyl derivatives and reacted with various isothiocyanates to give N-substituted cyclic thioureas. Oxidative or reductive desulfurization of the cyclic thioureas affords structurally diversified imidazoles in good to excellent yields.     

Synthesis of chiral β-3-amino-2-hydroxyalkanoates and 3-alkyl-3-hydroxy-β-lactams by double asymmetric induction

Reactions of chiral (2S)-enolates of dioxolan-4-ones, derived from lactic, mandelic, and phenyllactic acids, with aliphatic (S_S)- and (S_R)-tert-butylsulfinyl aldimines afforded conformationally restrained C2-disubstituted N,O-orthogonally protected 3-amino-2-hydroxyalkanoates in the form of N-sulfinyl protected 1′-aminodioxolan-4-ones. The product distribution showed that there is significant kinetic selectivity, due to the presence of ‘matched’ and ‘mismatched’ components, between the (S)- or (R)-tert-butylsulfinyl aldimines and the (2S)-enolates of the 1,3-dioxolan-4-ones. Selective methoxide-induced removal of the acetal group of the N-sulfinyl-1′-aminodioxolanones yielded the corresponding N-sulfinyl protected methyl alkanoates. In addition, the selective acid-induced removal of the sulfinyl group of the N-sulfinyl-1′-aminodioxolanones provided the corresponding N-unprotected 1′-aminodioxolanones, whose base-induced cyclization afforded the corresponding β-lactams.     

Prearranged Glycosides,Part 10. Intramolecular Glycosylation with Cellobiosyl,Lactosyl, and Maltosyl Donors

ABSTRACT

Acetyl protected 1,2-O-(1-methoxyethylidene)-disaccharides 1 of maltose, cellobiose, and lactose, respectively were converted via the corresponding benzyl protected couterparts 2, the benzyl protected phenyl 2-O-acetyl- 3 and 2-O-unprotected 1-thio-glycoside disaccharides 4 into 2-O-succinoylated disaccharides 5. The latter were esterified with benzyl 2-O-benzoyl-4,6-di-O-benzylidene-α-D-glucopyranoside (6) to afford succinyl linked derivatives 7 the benzylidene groups of which were regioselectively opened to give prearranged glycoside trisaccharides 8. Intramolecular glycosylation of the latter with N-iodosuccinimide resulted in exclusive formation of the corresponding α-(1→4)-linked trisaccharides 9. No influence of the donor moiety on the diastereoselectivity of the intramolecular glycosylation was observed.     

Synthesis of 1-C-linked diphosphate analogues of UDP-N-Ac-glucosamine and UDP-N-Ac-muramic acid

UDP-N-acetyl-glucosamine and UDP-N-acetyl-muramic acid are two important cytoplasmic precursors of bacterial peptidoglycan. The convergent synthesis of their analogues is reported. The α-1-C-linked-N-acetyl-glucosamine was synthesized using microwave-assisted Keck radical allylation. Oxidation of alkene derivatives to the corresponding carboxylic acids allowed attachment to O- and N-sulfamoyluridine giving stable diphosphate mimetics.     

New tetrasubstituted thioureas containing the 1-iminoethyl moiety

The reactions of 1,1,3-trisubstituted thioureas with acetonitrile afforded the corresponding tetrasubstituted thioureas containing the N-(1-iminoethyl) moiety.     

Solid-phase synthesis of 2-imidazolidinethiones via Mitsunobu reaction of N-(2-hydroxyethyl)thioureas

This letter reports the solid-phase synthesis of 2-imidazolidinethiones via the N-cyclization of N-(2-hydroxyethyl)thioureas using the Mitsunobu reaction in good yield and purity. This process employed the reductive amination of an ArgoGel-MB-CHO resin to anchor the aminoalcohols, followed by a reaction with isothiocyanates to give the resin-attached N-(2-hydroxyethyl)thioureas. Cleavage of the 2-imidazolidinethiones was performed with trifluoroacetic acid.     

A novel method of synthesis of 1,2-diketones from 1,2-diols using N-bromosuccinimide

A simple and convenient procedure is reported for the synthesis of benzils and aliphatic 1,2-diketones of cyclic and open chain compounds from corresponding hydrobenzoins and 1,2-diols by refluxing with N-bromosuccinimide in carbon tetrachloride in presence or absence of pyridine.     

Synthesis of 3-isothiocyanatopropion-and-butyraldehyde diethyl acetals and their reactions with n-nucleophiles

A one-pot procedure was developed for the synthesis of 3-isothiocyanatopropionaldehyde and 3-isothiocyanatobutyraldehyde diethyl acetals from the corresponding α,β-unsaturated aldehydes. Reactions of 1,1-diethoxy-3-isothiocyanatobutane with aliphatic amines and hydrazines gave, respectively, substituted thioureas and thiosemicarbazides which underwent acid-catalyzed cyclization to form 6-ethoxytetrahydropyrimidine-2(1H)-thiones, 9,10-dimethoxy-2-methyl-1,2,3,6,7,11b-hexahydro-4H-pyrimido[6,1-a]isoquinoline-4-thiones, and 2-methyl-2,3,6,7,12,12b-hexahydropyrimido[1′,6′:1,2]pyrido[3,4-b]indole-4(1H)-thione.     

Native amine-directed site-selective C(sp3)-H arylation of primary aliphatic amines with aryl iodides

Direct C(sp³)-H functionalization of N-unprotected aliphatic amines represents one of the most efficient and straightforward strategies for amine synthesis. Despite some recent progress in this field, the NH₂-directed γ-C(sp³)-H arylation of primary aliphatic amines except α-amino esters remained an unmet challenge. In this report, we established a simple and efficient method for site-selective C(sp³)-H arylation of primary aliphatic amines by aryl iodides. In the presence of only 5 mol% Pd(OAc)₂, a wide range of aliphatic amines including O-benzyl and O-silyl amino alcohols were arylated at γ- or δ-positions by aryl iodides containing a broad scope of functional groups. The synthetic application of this method had also been demonstrated by large-scale synthesis, the synthesis of a fingolimod analogue, and the conjugation with natural d-menthol and fluorescent 1,8-naphthalimide.     

Synthesis and characterization of mercury(II)–sugar thioureas complexes

The synthesis of a novel class of mercury(II) complexes with sugar-derived bidentade isothioureido ligands, by treatment of N-acylated thioureas with an excess of yellow mercury(II) oxide in aqueous acetonitrile is reported. The 1:2 coordination stoichiometry of the complexes were confirmed by elemental analysis, mass spectrometry and NMR spectroscopy, and they were found to be consistent with a four-coordinate geometry.