Synthesis of novel 1,7-annulated 4,6-dimethoxyindoles

A range of new 1,7-annulated indole derivatives has been prepared via a ring-closing metathesis approach starting from N-allyl-7-formyl indoles.     

Synthesis of a new conformationally constrained glycoamino acid building block

The synthesis of a suitably protected β-d-glucopyranosyl-(S)-α-methylserine derivative—a new conformationally constrained glycosylated quaternary amino acid analogue of β-d-glucopyranosyl-l-serine—is described. This compound can be used as an attractive building block for the synthesis of new, constrained glycopeptides.     

Synthesis of a versatile pentacyclic building block for organic electronics

A new pentacyclic building block, benzodibenzofuranquinone (BDBFQ), is synthesized in a single step from the inexpensive and readily available feedstocks chloranil and 3‐bromophenol. This versatile repeat unit is incorporated into a series of conjugated materials as either the redox active quinone form or as an electron‐rich dialkylated benzodibenzofuran (BDBF) unit. To illustrate the performance that can be obtained from these systems, optical and electrochemical properties were studied via UV–vis–NIR spectroscopy and cyclic voltammetry. Thin‐film morphology was characterized via grazing incidence wide‐angle X‐ray scattering with thin‐film field‐effect transistor measurements further demonstrating the utility of this system. © 2017 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2017 , 55, 2618–2628     

Novel h-shaped persistent architecture based on a dispiro building block system

[structure: see text] A novel dispiro building block, dispiro[fluorene-9,5'(7'H)-diindeno[2,1-b:1',2'-d]thiophene-7',9' '-fluorene], and its two derivatives, TBP-DSFDITF and TDOF-DSFDITF, were designed and synthesized. Because of the rigidity and orthogonality of the spiro structure, TBP-DSFDITF exhibits a well-defined H-shaped architecture, which consists of two ter(biphenyls) as the arms of the H-shape and 3,4-diphenylthiophene as the rung, connecting via completely rigid dispiro linkages with two sp(3) carbon atoms.     

Synthesis and foaming properties of new anionic surfactants based on a renewable building block: sodium dodecyl isosorbide sulfates

Two agro-based anionic surfactants containing an isosorbide moiety have been synthesized and their amphiphilic properties evaluated. Since isosorbide is now considered as an important platform chemical of the starch industry, these compounds could represent bio-sourced alternatives to the alkyl ether sulfates (notably lauryl ether sulfate, LES) that are based on petroleum-derived ethylene oxides. As isosorbide is an asymmetric diol, two isomers can be prepared (2-O-dodecyl isosorbide sulfate and 5-O-dodecyl isosorbide sulfate) that show significantly different aqueous properties as regards to their Krafft temperatures and critical micellar concentrations. 5-O-dodecyl isosorbide sulfate is the most soluble and the most efficient surfactant. It possesses a much lower critical micelle concentration (cmc) than sodium dodecyl sulfate, SDS, leading to comparable foaming properties with a three times lower concentration. Its behavior compares well with the one of pure diethoxylated dodecyl sulfate that has also been prepared and evaluated in this work.     

Synthesis of novel substituted diaryl-1,4-diazepines

In this paper a convenient route to new 2,3-diaryl-substituted 1,4-diazepines is described through cyclization of ethanedione derivatives and 1,3-propanediamine. The ethanedione derivatives required were synthesized by microwave-assisted oxidation from ethanones. Published in Khimiya Geterotsiklicheskikh Soedinenii, No. 7, pp. 1042–1047, July, 2006.     

Synthesis of novel unsymmetrical coumarinyl-1,4-dihydropyridines

The novel unsymmetrical 3,5-dialkoxycarbonyl-2,6-dimethyl-4-(7′,8′-dimethoxycoumarin-4′-yl)-1,4-dihydropyridines and 5-acetyl-3-alkoxycarbonyl-2,6-dimethyl-4-(7′,8′-dimethoxycoumarin-4′-yl)-1,4-dihydropyridines (coumarinyl-1,4-dihydropyridines) have been synthesized by Knoevenagel condensation of 4-formyl-7,8-dimethoxycoumarin with alkyl acetoacetates in the presence of AlCl₃ followed by cyclization of the resulted Knoevenagel product with other alkyl acetoacetate or acetyl acetone and ammonium acetate. The structure of the intermediate Knoevenagel product and the cyclized unsymmetrical coumarinyl-1,4-dihydropyridines has been established on the basis of their spectral data analysis and single-crystal X-ray diffraction analysis. The observed conformation of the coumarinyl-1,4-dihydropyridines holds the key to promising calcium antagonistic activity of the synthesized coumarinyl-1,4-dihydropyridines.     

Synthesis, resolution, and applications of 1,16-dihydroxytetraphenylene as a novel building block in molecular recognition and assembly

This paper concerns the synthesis of 1,16-dihydroxytetraphenylene (DHTP) (2) by employing a novel NBS bromination route. (+/-)-DHTP 2 was successfully resolved into its optical antipodes and converted to (+/-)-1,16-bis(diphenylphosphino)tetraphenylene (BPTP) (26), whose platinum complex BPTP-PtCl(2) (27) was also obtained. As a hydrogen bond donor, racemic and optically active DHTP 2 was allowed to assemble with 4,4'-bipyridine to form single crystals of good quality. X-ray Diffraction studies of these crystals revealed that the crystallographic packing of the hydrogen bonded complex between (+/-)-2 and 4,4'-bipyridine was different from the one formed from (S)-2 and 4,4'-bipyridine. It was found that an infinite zigzag chain with alternate chirality was formed in the assembly of (+/-)-2 and 4,4'-bipyridine, while (S)-2 and 4,4'-bipyridine failed to show the same assembly pattern. The reason (+/-)-2 formed an alternate and zigzag chain with 4,4'-bipyridine was most likely due to the inherent stability of this supramolecular assembly. The chiral recognition between 2 and optically active BINAP under the direction of platinum(II) has also been examined. (1)H and (31)P NMR spectroscopic studies demonstrated that there was an obvious discrimination of 2 between the enantiomers of BINAP-PtCO(3).     

Synthesis of aryl-containing terpenoids based on 1,4-dihydronaphthalene

Successive transformations including oxidation of 1,4-dihydronaphthalene into 1,2,3,4-tetrahydronaphthalen-2-one, Reformatskii reaction of the latter with methyl bromoacetate, ozonolysis of the Reformatsky reaction product, and Emmons olefination of the aldehyde group in methyl 3-oxo-5-(2-formylphenyl)pentanate thus formed gave analogs of highly active dienoate juvenoids having an aromatic ring in their molecules.     

Synthesis of tetrazolopiperazine building blocks by a novel multi-component reaction

A novel Ugi-five-centre-four-component reaction (U-5C-4CR) of aldehydes, primary amines, trimethylsilylazide and 2-isocyanoethyltosylate yielding tetrazolopiperazine building blocks is described.     

Synthesis of vinyl-substituted alcohols using acetylene as a C2 building block

Vinyl-substituted alcohols represent a highly useful class of molecular skeletons. The current method typically requires either stoichiometric metallic reagents or preformed precursors. Herein, we report a nickel catalysis-enabled synthesis of vinyl-substituted alcohols via a 5-membered oxa-metallacycle. In this protocol, acetylene, the simplest alkyne and abundant feedstock, is employed as an ideal C2 synthon. The reaction features mild conditions, good functional group tolerance and broad substrate scope. Mechanistic exploration implies that the oxa-metallacycle originated from the cyclometallation of aldehyde and acetylene is the key intermediate for this transformation, which is then terminated by a silane-mediated σ-bond metathesis and subsequent reductive elimination.

Acetylene and aldehydes are coupled through cyclometallation and silane-mediated σ-bond metathesis to synthesize various vinyl-substituted alcohols. This reaction features good functional group tolerance using acetylene as a C2 synthon.

As a class of versatile motifs in organic synthesis, vinyl-substituted alcohols (abbreviated as vinyl alcohols) permit a myriad of opportunities for the manipulation and introduction of functional groups as well as construction of complex molecular architectures.¹ Therefore, numerous methods have been established to prepare such significant synthetic building blocks (Scheme 1A).² Among these approaches, alkenylation of aldehydes with vinyl metal is one of the most common strategies to deliver vinyl alcohols (Scheme 1A, path a).³ Despite widespread utilization of this method in organic synthesis, sensitive and stoichiometric organometallic reagents are often required under harsh conditions with poor functional group tolerance. In addition to the alkenylation of aldehydes, direct 1,2-addition of acrolein with organometallic compounds could give the desired vinyl alcohols as well (path b).⁴ However, the competition between 1,2- and 1,4-addition⁵ makes this method useless from a practical point of view. Apart from nucleophilic addition of metallic reagents, transition metal-catalyzed allylic substitution with O-nucleophiles represents another important route to obtain vinyl alcohols (path c),⁶ while it is often plagued with the control of regioselectivities and requirement of pre-synthesized allylic substrates. Taken together, syntheses of vinyl-substituted alcohols via these strategies are limited to either sensitive metallic reagents or allylic precursors. Therefore, developing alternative efficient approaches with easily available reagents to acquire vinyl-substituted alcohols and their derivatives under mild conditions is highly desirable.Open in a separate windowScheme 1Synthetic strategies of vinyl alcohols.As the simplest alkyne, acetylene is an inexpensive and abundant feedstock, which has been used as a raw material for bulk vinyl-containing monomer production in the chemical industry.⁷ While in the fine chemical field, catalytic transformation of this unique C2 unit into high value-added chemicals is underdeveloped.^7e,8,9 Despite great efforts being devoted to the development of reductive coupling of substituted alkynes with aldehydes,¹⁰ incorporation of acetylene with aldehydes still remains unknown (path d). This may be attributed to the unique properties of acetylene.¹¹ Moreover, the gaseous nature and flammable properties of acetylene make chemists stay away from it.¹²Inspired by the fact that substituted allylic alcohols could be provided by reductive coupling of aldehydes with substituted alkynes via an oxa-metallacycle intermediate,^10a,h,j we investigated whether it is feasible to employ acetylene and aldehyde through cyclometallation and subsequent silane-mediated σ-bond metathesis to construct silyl-protected vinyl alcohols (Scheme 1B). However, the cyclometallation of aldehyde with acetylene in the presence of silane to obtain key intermediate oxa-metallacycle is a really big challenge due to the following potential competitions: (1) self-polymerization of acetylene,^11b,13 (2) direct hydrosilation of aldehyde^10c or acetylene and (3) condensation or dimerization of aldehyde (Tischenko reaction and¹⁴ Aldol reaction¹⁵). More importantly, safety issues concerning explosive and flammable acetylene should not be ignored as well.^12b,16Herein, we report the synthesis of vinyl-substituted alcohols enabled by a nickel-catalyzed reductive coupling of aldehyde with acetylene by utilizing hydrosilane as an efficient terminating reductant. Compared with the previously reported reductive coupling method requiring addition of an alkyne utilizing syringe pump, this protocol only needs slow addition of premixed solution of acetylene and aldehyde dropwise. Both aryl and aliphatic aldehydes with diverse functional groups react smoothly under mild conditions. The robustness of this strategy has also been exhibited by gram-scale reactions and further transformations of the resulting vinyl alcohols into diversely functionalized molecules. The mechanistic studies demonstrate that hydrogen comes from silane, which supports the postulation that the oxa-nickelacycle originated from cyclometallation is terminated by silane-mediated σ-bond metathesis.     

2-Chloroquinazoline. Synthesis and reactivity of a versatile heterocyclic building block

Starting from 2,4-dichloroquinazoline, various methods for the selective removal of the 4-chloro substituent were tested, including catalytic hydrogenation, metal-halogen exchange, metal hydride reduction and reduction with tributyltin hydride—the latter both in a radical and in a Stille-type reaction. Amongst these, the most efficient method was found to be the Stille-type coupling. Furthermore, we have studied the reactivity of 2-chloroquinazoline and found it to act as a versatile building block for the direct introduction of the 2-quinazolinyl moiety.     

Synthesis of block copolymers based on polycaprolactam-polybutadiene

Polyamide-polybutadiene segmented block copolymers of well defined structure and composition have been synthesized using α,ω-di-carboxyl-terminated polybutadiene (CTPB) as the initiator for the polymerization of caprolactam (CL) in bulk at 240°C. Both the yield and viscosity increased with the polymerization time and with the CL content in the feed. The segmented copolymers were characterized by i.r. spectra and elemental analysis. The thermal stability of CTPB was also examined using various types of antioxidants in various amounts.     

Synthesis of a thiophene-fused isoindigo derivative: a potential building block for organic semiconductors

Thiophene-fused isoindigo (TII) was synthesized from thieno[2,3-f]indol-6(7H)-one in a one-pot reaction, in which the alkylation, oxidation and condensation were finished in one step. It exhibits better intramolecular charge transfer properties and higher reductive potential compared with isoindigo(II), as evidenced by its optical and electrochemical properties, which shows that it might be used as a building block for n-type or ambipolar OFET materials.     

A novel building block for the synthesis of isofagomin analogues

The de novo synthesis of the novel potent building blocks phenyl (R)-3-acetoxymethyl-3,6-dihydro-2H-pyridine-1-carboxylate (−)-7 and phenyl (S)-3-butyryl-oxymethyl-3,6-dihydro-2H-pyridine-1-carboxylate (+)-8 starting from commercially available methyl-1-benzyl-4-oxo-3-piperidinecarboxylate is described. The key steps are the enantioselective esterification of the racemic alcohol 6 and the enantioselective hydrolysis of the racemic acetate 5, respectively, using lipase P from Pseudomonas caepacia.     

Synthesis of a core trisaccharide as a versatile building block for N-glycans and glycoconjugates

N-linked oligosaccharides from glycoproteins (N-glycans) can be conveniently assembled with a building block approach. A protected form of the core trisaccharide (beta-mannosyl chitobiose) was identified as a key building block. The chitobiose part of the core trisaccharide was built from a glycosyl fluoride, which served as a precursor for the reducing GlcNAc azide and the inner GlcNAc moiety. Beta-mannosylation was accomplished at the trisaccharide stage by intramolecular inversion of a beta-glucosyl chitobiose. The benzylidene protection of the beta-mannoside and the azido group at the reducing end of the core trisaccharide allow modular synthesis of N-glycans and their glycoconjugates.     

Synthesis of a core trisaccharide building block for the assembly of N-glycan neoconjugates

A short and high yielding synthesis of a core trisaccharide 1 as the key building block in the assembly of a library of N-glycan neoconjugates is presented. The β-d-Manp-(1→4)-d-GlcpNAc linkage was introduced by inversion of the C-2 position of a β-glucoside. The glucosyl donor was efficiently synthesised following a recently published one-pot strategy. 2-Naphthylmethyl and benzylidene-acetal protection in the terminal mannose permitted selective liberation of main branching sites for subsequent glycosylation. A C5 azido linker attached to the anomeric position, which is stable throughout the synthesis, will allow for the posterior immobilisation of deprotected glycans on a microarray surface.     

Synthesis and incorporation of a furan-modified adenosine building block for DNA interstrand crosslinking

2'-O-(3-(Furan-2-yl)propyl)adenosine was synthesized and evaluated for interstrand crosslink (ICL) formation in DNA duplexes. In situ oxidation of the furan moiety with NIS showed rapid crosslink formation to dA and dC, while dT and dG were inactive.     

Synthesis of a novel 8-thia-1,4-diazacycl[3.3.2] azine

A unique covalently hydrated cyclazine adduct, 2-imino-6a-hydroxy-4,5,6,6a-tetrahydro-7H-8-thia-J, 4-diazacycl[3.3.2]azin-5-one hydrochloride was prepared by reacting ethyl 4-chloro-acetoacetate with 4,6-diamino-2-thiopyrimidine in neutral alcohol. Neutralization gave 2-imino-5,6a-dihydroxy-6,6a-dihydro-7H-8-thia-1,4-diazacycl[3.3.2]azine which decomposed to 4,6-diamino-2-acetonylthiopyrimidine upon heating in water. Warming the hydrated hydrochloride in concentrated hydrochloric acid caused dehydration to yield 2-imino-5-hydroxy-6H-8-thia-1,4-diazacycl[3.3.2]azine hydrochloride. Partial isomerization (20%) to 2-imino-5-hydroxy-7H-8-thia-1,4-diazacycl[3.3.2]azine hydrochloride occurred during recrystallization from aqueous acidic methanol. The free base, 2-imino-5-hydroxy-7H-8-thia-1,4-diazacycl[3.3.2]azine was obtained after neutralizing either of the tautomeric hydrochlorides. Treating the free base with trifluoroacetic acid produced a mixture of the trifluoroacetate salts of the two tautomeric bases. Isomerization of one trifluoroacetate salt into the other in trifluoroacetic acid was observed by pmr at room temperature. Both 2-amino-5-hydroxy-7-nitroso-8-thia-1,4-diazacycl[3.3.2]azine and 2-amino-5-hydroxy-6-nitroso-8-thia-1,4-diazacycl[3.3.2]azine were isolated after nitrosation of the hydrochloride mixture.