Synthesis and studies of tris-indolobenzenes and related compounds

The unsymmetrical N,N,N-trimethyl tris-indolobenzene 3 has been synthesized by several routes, including cyclotrimerization of the O-acetate of indoxyl. This condensation involves a 3→2 rearrangement of the precursor formed in situ. Similar Wagner-Meerwein rearrangements were also prevalent in LAH reductions of some 3,3-diindolyl oxindoles.Treatment of the 3,3-diindolyl indolines with strong acid resulted in a cleavage yielding 3,3'-biindolyls.     

A convenient enantioselective synthesis of 3-asymmetrically substituted oxindoles as progesterone receptor antagonists

A convenient enantioselective synthesis of 3-asymmetrically substituted oxindoles is reported. Compound (2) prepared by radical cyclisation of (1) was used for the synthesis of racemic and enantiomerically pure 3-asymmetrically substituted oxindoles. Desulfurisation of (2) using Raney Ni yielded the racemate (5). Addition of (S)-1-phenylethanol to compound (2) yielded the diastereoisomer (21) the structure of which was determined using X-ray crystallography. Using a sequence of steps (21) was converted to the enantiomer (8). The enantiomer (9) was similarly prepared from (2) using (R)-1-phenylethanol.     

Access to the syntheses of sydnonyl-substituted α,β-unsaturated ketones and 1,3-dihydro-indol-2-ones by modified Knoevenagel reaction

A convenient method for the preparation of sydnonyl-substituted α, β-unsaturated ketones, based on Knoevenagel condensation, is presented. Although well known, this reaction has never been utilized in the condensation involving sydnone derivatives. Thus, 3-aryl-4-formylsydnones (1) are reacted with active methylene compounds such as acetylacetone (2a), ethyl acetoacetate (2b), diethyl malonate (2c), malononitrile (4a), ethyl cyanoacetate (4b) and cyanoacetamide (4c) by modified Knoevenagel condensation to afford multifunctional derivatives. Also, sydnonyl-substituted 1,3-dihydro-indol-2-one derivatives 10 were synthesized successfully by condensing 3-aryl-4-formylsydnones (1) with oxindoles 9.     

Rhodium-catalyzed synthesis of a C(3) disubstituted oxindole: an approach to diazonamide A

A two step synthesis of a C(3) disubstituted oxindoles via the rhodium(II)-catalyzed coupling of diazoketone (6) and 3-methyloxindole (9) is reported.     

Asymmetric construction of quaternary stereocenters by direct conjugate addition of oxindoles to enone

Chiral cinchona-based primary amine A was found to catalyze the asymmetric direct conjugate addition of prochiral 3-oxindoles with enones to afford 3,3-disubstituted oxindoles in good yields, moderate to high diastereoselectivities, and excellent enantioselectivities.     

Conversion of 1-Boc-indoles to 1-Boc-oxindoles

A facile synthesis of substituted oxindoles 2 from the corresponding indole is described. The reaction, which proceeds through the 2-(indolyl) borate intermediate, is general and applicable to several indoles.     

Synthesis and characterization of palladium(II) and platinum(II) complexes with ferrocenylimidazole

The synthesis and characterization of ferrocenylimidazole complexes of platinum(II) and palladium(II) are described. Reaction of ferrocenylimidazoles with K₂MCl₄ (M = Pd, Pt) using a biphasic system of dichloromethane and ethanol/water provided the corresponding complexes 2a–2j in good yields. New synthetic routes for the synthesis of ferrocenylbenzylethers 2k–2o, bis(4-ferrocenylbenzyl)carbonate [2p] and 4-ferrocenylbenzylacetate [2q] are also described. These products were obtained by the reaction of 4-ferrocenylbenzyl-1H-imidazole-carboxylate and K₂PtCl₄ under various conditions. Compounds 2k–2o were also obtained by alternative routes which do not involve the use of a platinum salt. The crystal structures of 2b, 2q and plausible mechanisms for the formation of 2k, 2p and 2q are reported.     

The directed metalation connection to aryl-aryl cross coupling.Regiospecific synthesis of phenanthridines,phenanthridinones and the biphenyl alkaloid ismine

Concise general routes to phenanthridines 4 and phenanthridinones 5 based on directed ortho metalation and cross coupling tactics are described; a short synthesis of the Amaryllidaceae alkaloid ismine (8b) is reported.     

Reconstruction of glycan chains of glycoprotein : Branching mannopentaoside and mannohexaoside

Synthetic routes to the branching mannopentaoside 4 and mannohexaoside 5 are described employing properly protected mannobioside 13 as a key intermediate.     

Synthetic studies on cell surface glycans 3: Branching pentasaccharides of glycoprotein

Synthetic routes for the branching pentasaccharides 4 and 5 of glycoproteins are described in a regio- and stereo- controlled way.     

A study on thermal behaviors of mono ethyl ester azocalix[4]arene derivatives

In the present study, thermal stabilities of five new family of azocalix[4]arene mono ethyl ester derivatives, 4a–e, were investigated using thermogravimetry, differential thermogravimetry, and differential thermal analysis methods. It was found that all compounds showed thermal stability up to 236 °C averagely. After this temperature, decomposition of compounds starts gradually. The decomposition routes of 4a–c compounds are similar and occur with two stages. Ester alkyl groups decompose and remove from the structure in the first stage. Second stage corresponds to rest of structure decomposition. The decomposition routes of the 4d–e compounds are different from the decomposition routes of the 4a–c compounds. These compounds include halogen, and decomposition reactions realize with three and four stages respectively.     

Synthesis of (-)-fortamine and (+)-2-deoxyfortamine from resolved 3S,4S-N-carbomethoxy-3-aminocyclohexen-4-ol

A three step sequence (Scheme I) starting with racemic 3,4-epoxycyclohexene (5) and (S)-α-methylbenzylamine gave 3S,4S-N-carbomethoxy-3-aminocydohexen-4-ol (10) with chromatographic removal of the undesired 3R,4R byproduct. The absolute configuration of 10 was established by x-ray crystallographic analysis of its precursor, 6 (as the HCl salt). Resolved 10 was converted to the aminocyditols (-)-fortamine (1) and (+)-2-deoxyfortamine (2) by efficient routes which parallel those previously developed in the racemic series.     

One-pot approach for the stereoselective synthesis of spirocyclopropyl oxindoles from isatins and arsonium salts

A one-pot approach for highly stereoselective synthesis of spirocyclopropyl oxindoles 3 with good to excellent yields from the reaction of isatins 1 and arsonium salts 2 in the presence of K₂CO₃ is described. The structure of product 3 was confirmed by ¹H NMR, ¹³C NMR, IR, MS, EA, and X-ray diffraction as well.     

Claisen rearrangements-XII : Synthesis of the coumarins, 5-methoxyseselin,trachyphyllin. coumurrayin and xanthoxyletin

The structure of the natural coumarins, 5-methoxyseselin 7 and trachyphyllin 14 have been confirmed by total syntheses from 7-acetoxy-5-prenyloxycoumarin 1 in good overall yields. Convenient synthetic routes to the natural coumarins, coumurrayin 4 and xanthoxyletin 10 have also been established.     

A Pd[0]-catalyzed Ullmann cross-coupling/reductive cyclization approach to C-3 mono-alkylated oxindoles and related compounds

The Pd[0]-catalyzed Ullmann cross-coupling of o-nitrohaloarenes 1a-e with the brominated heterocycles 2a-f delivers the expected products 3a-j in good to excellent yields. The reductive cyclization of such products, as well as N-acyl derivatives 3k, l, and m, has been investigated and provided the C-3 mono-substituted oxindoles 5a-d, f, g, k, and m, the direct reduction products 4i and j or indole 5l.     

Selenolo [3,4-b]selenophene—The third “Classical” selenophtene

Selenolo[3,4-b]selenophene (3) has been synthesized by two different routes using 2,3-bischloromethyl-5-carbomethoxyselenophene (4) or preferably 4-methylseleno-3-selenophene aldehyde (10) as the starting material. In marked contrast to its thiophene alogue thieno[3,4-b]thiophene 3 was stable. Analysis of the ¹H, ¹³C and, in particular, the ⁷⁷Se N M R gave strong evidence for the more positive nature of the Se-5 than the Se-1 atom of 3.     

Spiro[4H‐2,3‐dihydropyran‐3,3′‐oxindoles] derived from 1,2,3,4‐tetrahydroquinoline

Knoevenagel condensation of 5,6‐dihydro‐4H‐pyrrolo[3,2,1‐ij]quinoline‐1,2‐dione 3 with aryl cyanomethyl ketones 9 generates 3‐(aroyl(cyano)methylidene)oxindoles 10 that react with cyclic 1,3‐diketones 11 to generate polycyclic hemiacetal spiro[4H‐2,3‐dihydropyran‐3,3′‐oxindoles] 13 .     

Spiro[3H‐pyrazole‐3,3′‐oxindoles] Derived from 1,2,3,4‐Tetrahydroquinoline

Aldol condensation of 5,6‐dihydro‐4H‐pyrrolo[3,2,1‐ij ]quinoline‐1,2‐dione with aryl methyl ketones generates 3‐(aroylmethylidene)oxindoles, which react with hydrazine to generate tricyclic spiro[3H‐pyrazole‐3,3′‐oxindoles].     

Studies on organophosphorus compounds: Thiation of 3,1-benzoxathian-4-ones. New routes to 1,2-benzisothiazole-3(2H)-thiones and 3H-1,2-benzodithiol-3-imines

3,1-Benzoxathian-4-ones, 2, when heated with 2,4-bis(4-methoxyphenyl)-1,3,2,4-dithiadiphosphetane-2, 4-disulfide, 1, or with P₄S₁₀ give one or more of the following products 3,1-benzoxathian-4-thione, 3, 1,3-benzodithian-4-one, 4, 1,3-benzodithian-4-thione, 5, and 3H-1,2-benzodithiole-3-thione, 6. Compounds 2, when heated with primary and secondary amines and with hydrazines, give 2-mercaptobenzamides, 7, and 2-mercaptobenzohydrazides, 8, or their corresponding disulfides, 7' and 8'. 3H-1, 2-Benzodithiol-3-immes, which are in equilibrium with 1,2-benzisothiazole-3(2H)-thiones, (9A ? 9B), are prepared by two new routes (a) by allowing 3 or 5 to react with primary amines or hydrazines, (b) by allowing 7, 8, 7' or 8' to react with 1.     

Azaindolines: derisking the indoline structural alert

4-Substitued azaindolines, which are isosteres of indolines, are useful synthetic building blocks that reduce the risk of bioactivation induced idiosyncratic toxicity have been prepared. Multigram routes to 2,3-dihydro-1H-pyrrolo[2,3-c]pyridine-4-triflate 16, 2,3-dihydro-1H-pyrrolo[2,3-b]pyridine-4-carbonitrile 20 and 4-chloro-2,3-dihydro-1H-pyrrolo[2,3-d]pyridazine 30 are outlined.