Synthesis of novel 1-phenyl-1H-indole-2-carboxylic Acids. I. Utilization of ullmann and dieckmann reactions for the preparation of 3-hydroxy, 3-alkoxy,and 3-alkyl derivatives

Methods for the synthesis of novel 3-hydroxy, 3-alkoxy, and 3-alkyl indole-2-carboxylic acids and esters are described. Dieckmann cyclization of various 2-[(carboxymethyl)amino]benzoic acid diesters yielded 1-unsubstituted-, 1-methyl-, and 1-phenyl-3-hydroxy-1H-indole-2-carboxylic acid esters. An Ullmann reaction with bromobenzene converted 1H-indoles to 1-phenylindoles.     

A Practical Photochemical Synthesis of 6-AZA-1, 10-Phenanthroic Anhydride

A high yield synthesis of 6-aza-1, 10-phenanthroic anhydride has been developed. The key step is a volume-efficient photochemical cyclization of azastilbene 5 to the photochemically stable dihydroazaphenanthrene 9.     

Solid‐Phase Approach for the Synthesis of 2‐Amido‐1,3,4‐oxadiazoles

A new solid‐phase approach for the synthesis of 2‐amido‐1,3,4‐oxadiazoles has been developed. In this synthesis, hydroxypentyl JandaJel polymer support was treated with excess of oxalyl chloride to give resin‐bound 2‐chloro‐2‐oxoacetate, and this intermediate was then coupled with different hydrazides to give resin‐bound 2‐(N′‐acylhydrazinyl)‐2‐oxoacetate. Intramolecular dehydrative cyclization of resulting resin‐bound linear precursor followed by direct amidation using aluminum amide reagent provided 5‐substituted 1,3,4‐oxadiazoles as 2‐carboxamides. To explore the scope of this reaction sequence, we synthesized a small set of library using a combination of hydrazides and amines, and the desired products were obtained in good to high yields.     

Synthesis of the southern furan segment of furanocembranoids

Abstract

A convergent synthesis of the southern furan segment of novel furanocembranoids from Croton oblongifolius has been accomplished involving silver-catalyzed cyclization of alkynyl diol as the key step towards 2, 5-disubstituted furan ring formation.     

Total synthesis of (+)-blennolide C and (+)-gonytolide C via spirochromanone

We report the asymmetric total synthesis of (+)-blennolide C and (+)-gonytolide C isolated from endophytic fungi. The synthesis involved construction of a spirochromanone with a chiral quaternary carbon by the aldol reaction of o-hydroxyacetophenones and optically active α-oxygenated cyclohexenone, followed by cyclization under acidic conditions. Oxidative cleavage of the alkene moiety of the spirochromanone furnished the chromanone diester. Through treating the diester with a Lewis acid, the first total synthesis of (+)-blennolide C was achieved by deprotecting the oxygen functionality of the diester and simultaneous Dieckmann condensation. Total synthesis of (+)-gonytolide C was also achieved by lactone formation from the deprotected diester.     

A phosgene and peroxide-free one-pot tandem synthesis of isatoic anhydrides involving anthranilic acid,Boc anhydride,and 2-chloro-N-methyl pyridinium iodide

A phosgene and peroxide-free approach for the synthesis of isatoic anhydrides has been described. The synthesis involves the carbamate formation with Boc anhydride followed by in situ cyclization to afford the isatoic anhydride. The importance of this synthetic strategy is in the ease of operation, scalability, and preparation from readily available raw materials.     

Derivatives of the thiazolo[2,3-a]isoquinolinium system

The ketosulfides (IV) formed by the reaction of α-bromoketones with 2α-thiohomo-phthalimide (II) have been cyclized to form hydrogen-bonded, dimeric hemiperchlorates (V). Alternative products from the cyclization, 2-[2′-(carboxymethyl)phenyl]thiazoles (VII), may be cyclized with acetic anhydride to O-betaines (VI). The same betaines are obtained from the hemiperchlorates (V) by deprotonation. The ketosulfide hydrobromides (XIII) from α-bromoketones and 1-thio-3, 4-dihydroisocarbostyril (XII) give 5,6-dihydro-thiazolo[2,3-a]isoquinolinium salts (XV) on cyclization.     

Synthesis of Isagarin,a Tetracyclic Naphthoquinone via a Palladium‐Catalyzed Cyclization

Total synthesis of isagarin (2) has been accomplished in five steps with 24.1% overall yield from 2‐bromonaphthoquinone (6). The key step is a palladium‐catalyzed cyclization to form a bicyclic ketal ring.     

Synthesis of (±)-heliannuol C

A synthesis of (±)-heliannuol C is described involving Bargellini condensation, Dieckmann cyclization and ortho-ester Claisen rearrangement followed by a regioselective epoxide reduction. A new CuI-catalyzed [2+2] cycloaddition reaction is also described.     

Polythioamides aliphatiques—I: Synthese des bis(dithioesters)

Bis(n-dodecyl dithioesters) are obtained in two steps from dinitriles with very good yields. These products are solid and stable in the air; their high purity allows them to be used for polycondensation with aliphatic diamines. A degradation in presence of bases, similar to Dieckmann cyclization of diesters, occurs with tetrathioadipates and gives conjugated dithioester; in this last case, bis(dithioester) synthesis had been detailed.     

Facile solid phase synthesis of N-cycloguanidinyl-formyl peptides

A novel strategy of solid phase synthesis of N-cycloguanidinyl-formyl peptides has been established and investigated which involved coupling orthogonal protected diaminoacid with resin bound peptide, α-amino group deprotection, guanidinylation of α-amino group by bis-Cbz-1H-pyrazole-1-carboxamidine followed by cleavage and cyclization in solution, and finally removing Cbz by palladium catalyzed hydrogenation. Through this method, cycloguanidine could be introduced to either N-terminus or sidechain of designated peptides. The reaction conditions were facile, straightforward, and totally adaptive to common solid phase peptide synthesis strategy.     

Enantioselective Total Synthesis of Secalonic Acid E

The first enantioselective synthesis of a secalonic acid containing a dimeric tetrahydroxanthenone skeleton is described, using a Wacker‐type cyclization of a methoxyphenolic compound to form a chiral chroman with a quaternary carbon stereogenic center with >99 % ee. Further steps are a Sharpless dihydroxylation and a Dieckmann condensation to give a tetrahydroxanthenone. A late‐stage one‐pot palladium‐catalyzed Suzuki‐dimerization reaction leads to the 2,2′‐biphenol linkage to complete the enantioselective total synthesis of secalonic acid E in 18 steps with 8 % overall yield.     

Reactivity of Z- and E-isomers of 2-benzamido-3-phenylacrylohydrazide towards some carbon electrophiles. A comparative study

Z- and E-isomers of 2-benzamido-3-phenylacrylohydrazide 2a, 2b have different relative reactivities towards some carbon electrophiles had been discussed.The Z-isomer underwent cyclization to give imidazole derivative 3 and triazine derivative 4, whereas the latter E-isomer does not undergo such cyclization. The reaction of 2a and/or 2b with 1,2-dibenzylidene hydrazine at different reaction conditions afforded the Schiff bases 6, 8 and the triazolidine derivative 9. Reactions of 2a, 2b with formic acid and phthalic anhydride gave the different cyclization products 10–14, respectively. The structures of all the new synthesized compounds were established from their IR, ¹H-NMR and mass spectra as well as elemental analyses.     

A Novel Stereoselective Total Synthesis of (+)‐5‐epi‐Cytoxazone

Abstract

Stereoselective synthesis of a potent cytokine modulator cytoxazone isomer has been achieved from 2,3‐O‐isopropylidene D‐glyceraldehyde involving Grignard reaction, subsequent formation of an azide followed by reduction to the aminodiol, and finally cyclization of the N‐Boc diol.     

Polymers as Reagents in Organic Synthesis

Polymeric reagents offer a range of unique advantages. Intramolecular reactions, such as the cyclization of peptides or Dieckmann cyclizations, can be brought about by attaching the reactive molecules at remote points along a polymer chain. In contrast, if the reactive molecules are anchored in close proximity on a polymeric support then intermolecular reactions occur, as demonstrated for a ketone synthesis. Apart from such proximity effects, cooperative effects can also be exploited, e.g. in the formation of a 2:1 complex of a crown ether and an alkali metal ion. The hydrolysis of an ester with polyvinylimidazole provides a detailed illustration of hydrophobic interactions. The simple separation of polymer-bound and low-molecular compounds by filtration is another significant advantage.     

Azlactone Synthesis. 2-Phenyl-2-Oxazolin-5-One

Abstract

2-Phenyl-2-oxazolin-5-one (3) has been used as an intermediate in the synthesis of α-amino acids¹, derivatives of α-amino acids,² and peptides.³ Procedures for the dehydration/cyclization of hippuric acid (1) leading to the isolation of azlactone 3, have been reported using acetic anhydride,⁴ phosphorus trihalides⁵, and N, N′-dicyclohexylcarbodiimide.⁶ We report herein an alternative, high yield procedure utilizing a water soluble carbodiimide.     

Solid-phase synthesis of beta-lactams via the ester enolate-imine condensation route

The ester enolate-imine condensation route to beta-lactams via an immobilized ester enolate has been achieved for the first time. The key reaction in the synthesis is the cyclization of the resin bound ester dianion and an imine. Traceless cleavage from the T1-triazene linker system yields the desired beta-lactams.     

An efficient synthesis of a class of novel N‐Alkyl‐N‐aryl‐4‐hydroxy‐1‐methyl‐2‐oxo‐1,2‐dihydro‐3‐quinolinecarbothioamides

The novel title compounds have been prepared in high yield by an optimized amide coupling followed by a Dieckmann cyclization. Additionally, this new route is amenable to preparative scale synthesis.     

Total Synthesis of (±)-Armepavines and (±)-Nuciferines From (2-Nitroethenyl)benzene Derivatives

A concise route to armepavine 1 and nuciferine 2 and 3, which can be isolated from the leaves of Nelumbo nucifera (Nymphaceae), has been achieved in which the longest linear sequence is only six steps from commercially available benzaldehyde in 28%, 21%, and 20% overall yield, respectively. The key transformations in the synthesis are the radical cyclization of aryl bromide with Bu₃SnH and the Pictet–Spengler reaction of N-substituted amine with aldehyde.     

Greener approach: Ionic liquid [Et3NH][HSO4]-catalyzed multicomponent synthesis of 4-arylidene-2-phenyl-5(4H)oxazolones under solvent-free condition

We have developed simple, greener, safer multicomponent synthesis series of 4-arylidene-2-phenyl-5(4H) oxazolones 4(a-r) catalyzed by Bronsted acid ionic liquid as triethylammonium hydrogen sulfate [Et₃NH][HSO₄] and catalytic amount of acetic anhydride and sodium acetate with excellent yields (90–99%). The protocol offers economical, environmentally benign, solvent-free conditions, and recycle–reuse of the catalyst and easily available starting as benzoyl chloride 1, amino acid 2 and a variety of aldehydes 3. The cyclization followed by condensation of benzoyl chloride, amino acid, and a variety of aldehydes catalyzed by ILs [Et₃NH][HSO₄] and catalytic amount of acetic anhydride and sodium acetate. The final products were confirmed by their characterization data such as FTIR, ¹H-NMR, ¹³C-NMR, Mass, high-resolution mass spectra and were compared with its reported method.