N-acylsulfonamide assisted tandem C-H olefination/annulation: synthesis of isoindolinones

A tandem C-H olefination/annulation sequence directed by N-acylsulfonamides affords a variety of isoindolinones. This transformation is compatible with aliphatic alkenes as well as conjugated alkenes. Notably, molecular oxygen can be used as the sole, eco-friendly oxidant.     

Synthesis of 2-indanones via [4 + 1] annulation reactions of (trialkylsilyl)arylketenes

[reaction: see text] (Trialkylsilyl)arylketenes combine with (trimethylsilyl)diazomethane in a new [4 + 1] annulation process leading to 2-indanone derivatives. The (trialkylsilyl)arylketene annulation substrates are available via the photochemical Wolff rearrangement of alpha-silyl-alpha-diazo ketones, which are themselves prepared by silylation of the corresponding diazo ketones. The mechanism of the annulation reaction is proposed to involve the formation of a 2,3-bis(silyl)cyclopropanone, which is in equilibrium with an oxyallylic cation. Electrocyclic closure of this intermediate forms the new cyclopentenone ring.     

Direct synthesis of 3-arylindoles via annulation of aryl hydroxylamines with alkynes

3-Arylindoles are produced in moderate to excellent yields from the reaction between aryl hydroxylamines and alkynes catalyzed by 10 mol % iron(II) phthalocyanine [Fe(Pc)]. Terminal and internal alkynes afford 3-aryl substituted indoles exclusively. Electron-donating and -withdrawing groups are tolerated on the aryl hydroxylamine. A few bioactive indoles are synthesized as well as several new indoles using this one-step intermolecular annulation procedure.     

Pd-catalyzed aerobic direct olefination of polyfluoroarenes

The first example of Pd-catalyzed aerobic direct olefination of polyfluoroarenes has been developed. The reaction makes use of molecular O₂ as terminal oxidant, and provides a cost-efficient and environmentally benign access to polyfluoroarene–alkene structures that are of interest in life and material sciences.     

A concise synthesis of 2-benzoyl-1-indanones and 1-indanones from 2-aryl-1-tetralones

Abstract

Methyl-2-(3-oxo-3-aryl) benzoates derived from acid catalyzed air oxidative fragmentation of 2-aryl-1-tetralones were efficiently undergone intramolecular-Claisen condensation in the presence of potassium tertiary butoxide. The resulting 2-benzoyl-1-indanones formed in two-step ring contractions were further subjected to indium triflate mediated retro-Claisen condensation to get 1-indanones.     

Efficient synthesis of furoquinolinones using Hendrickson reagent-initiated cascade annulation

A new synthesis of furo[3,4-b]quinolin-3(1H)-one derivatives has been established in straightforward fashion in high overall yields. An efficient Hendrickson reagent-initiated cascade annulation, which is composed of mild conversion of the stable amide precursor to the reactive imido-carbonium intermediate and subsequent intramolecular aza Diels-Alder reaction, successfully serves as the key reaction in the synthesis. Final oxidative cleavage of the carbon-carbon double bond of representative tricyclic precursor 8g led to completion of the synthesis of quinoline-lactone 2g in a high yield.     

Heterocyclic synthesis via thallation and subsequent palladium-promoted olefination

The thallation and subsequent palladium-promoted olefination of p-tolylacetic acid, N-methylbenzamide, benzamide and acetanilide provides a novel new route to a variety of important oxygen and nitrogen heterocycles.     

Pd-catalyzed olefination of furans and thiophenes with allyl esters

A direct Pd(II)-catalyzed olefination of furans and thiophenes with allyl esters is demonstrated. Under the typical conditions, the dehydrogenative Heck coupling reactions of heteroarenes with allylic esters proceeded via a β-H elimination rather than a β-OAc elimination to give the corresponding γ-substituted allylic esters.     

Solid-phase synthesis of heterocycles via palladium-catalyzed annulation

Solid-phase linked o-iodoanilines (4) and o-iodophenol (9) reacted with 1,3- and 1,4-dienes in the presence of palladium acetate to generate highly substituted indolines, tetrahydroquinolines, hydrobenzofurans and hydrobenzopyrans, which provided an efficient way for making heterocyclic molecule libraries.     

Synthesis of meso-5-azaindolyl-appended Zn(II) porphyrins via Pd-catalyzed annulation

Pd-catalyzed annulation reaction of meso-hexynyl Zn(II) porphyrin with 4-amino-3-iodopyridine efficiently provides meso-3-(5-azaindolyl)-substituted Zn(II) porphyrin as a major product, which assembles to form a slipped cofacial dimer by the complementary coordination of the pyridine moiety to the Zn(II) center. 2-iodoaniline and 2-iodophenol also undergo this [3 + 2] annulation with the meso-hexynyl Zn(II) porphyrin to furnish meso-indolyl- and benzofuranyl-substituted Zn(II) porphyrins, respectively.     

One-pot synthesis of 1-alkyl-1H-indazoles from 1,1-dialkylhydrazones via aryne annulation

The reaction of readily accessible 1,1-dialkylhydrazones with commercially available o-(trimethylsilyl)aryl triflates provides a direct one-step route to pharmaceutically important 1-alkylindazoles. The products are obtained in high yields by one-pot NCS-chlorination/aryne annulation or Ac(2)O-acylation/deprotection/aromatization protocols.     

Stereoselective synthesis of Z alkenyl halides via Julia olefination

Julia olefination between alpha-halomethyl sulfones and a variety of aldehydes afforded alkenyl halides in good to excellent yields with high E/Z stereoselectivities. Sulfones were readily prepared in two or three steps from commercially available reagents in good yields. Optimization revealed that the nature of the solvent, the base, and the additive were crucial to obtain the desired alkenyl halides.     

Straightforward synthesis of fucoxanthin short-chain derivatives via modified-Julia olefination

Fucoxanthin is an essential pigment for the light-harvesting of aquatic algae. It exhibits high energy transfer efficiencies to Chl a (>80%) as well as peridinin (>95%). In order to verify the generality and specificity of the noticeable observation on the ICT excited energy state character, which was found in the study of peridinin, we achieved the straightforward synthesis of a series of fucoxanthin short-chain derivatives via the modified-Julia olefination with the aldehyde half segment possessing a β,γ-epoxyketone function. The established method was successfully applied to the synthesis of the epoxy olefin derivative as an allene modified fucoxanthin analogue.     

Stereoselective total synthesis of aminoiminohexitols via carbamate annulation

New methodology for the preparation of a variety of aminoiminohextitols is described. Key in the synthesis is the application of a diastereoselective Strecker reaction and the extension of our carbamate annulation methodology to protected and functionalized alkenylamines. Insight into the effects that the substitution patterns of the alkenylamines have on the diastereoselectivity of the iodocyclization and carbamate annulation is discussed. An evaluation of the glycosidase inhibitory activity of the aminoiminohexitols and derivatives is also presented, with the previously undisclosed D-talo isomer showing good selective inhibition of β-D-glucosidase.     

Enantioselective synthesis of 1-vinyltetrahydroisoquinolines via Pd-catalyzed intramolecular asymmetric allylic amination reactions

1-Vinyltetrahydroisoquinolines serve as versatile intermediates for the synthesis of a variety of naturally occurring isoquinoline alkaloids. 1-Vinyl-6,8-dimethoxytetrahydroisoquinoline 4 and 1-vinyl-5,6,7-trimethoxytetrahydroisoquinoline 6 with >90% ee by means of Pd-catalyzed intramolecular asymmetric allylic amination reactions, using MPN and BOP ligands, developed in our laboratory. The fine-tuning capability of the MPN and BOP ligands has played a significant role in the optimization of enantioselectivity. Interesting substituent effect as well as solvent effect on the product selectivity and enantioselectivity was observed. Plausible mechanisms are proposed, which can accommodate various findings, including the critical importance of the activation of the trifluoroamide moiety through its coordination to the Lewis acidic Pd²⁺ metal center.     

Mechanistic rationalization of unusual kinetics in Pd-catalyzed C-H olefination

Detailed kinetic studies and novel graphical manipulations of reaction progress data in Pd(II)-catalyzed olefinations in the presence of mono-N-protected amino acid ligands reveal anomalous concentration dependences (zero order in o-CF(3)-phenylacetic acid concentration, zero order in oxygen pressure, and negative orders in both olefin and product concentrations), leaving the catalyst concentration as the sole positive driving force in the reaction. NMR spectroscopic studies support the proposal that rate inhibition by the olefinic substrate and product is caused by formation of reversible off-cycle reservoirs that remove catalyst from the active cycle. NMR studies comparing the interaction between the catalyst and substrate in the presence and absence of the ligand suggest that weak coordination of the ligand to Pd prevents formation of an inactive mixed acetate species. A fuller understanding of these features may lead to the design of more efficient Pd(II) catalysts for this potentially powerful C-H functionalization reaction.     

One-pot synthesis of 2,4-disubstituted quinolines via silver-catalyzed three-component cascade annulation of amines,alkyne esters and terminal alkynes

Described herein is a new and general method for one-pot synthesis of 2,4-disubstituted quinolines via silver-catalyzed [3?+?1?+?2] annulation of simple amines, alkyne esters and terminal alkynes. The versatile transformation might initiate with the facile formation of the enamine species with the feature of good to excellent yields, exclusive regioselectivity, and excellent substrate/functional group tolerance.     

Pd-catalyzed synthesis of beta-biarylacryl ferrocenes via Suzuki cross-coupling

Some novel beta-biarylacryl ferrocene derivatives were synthesized via Pd-catalytic Suzuki cross-coupling reactions of beta-(2-bromophenyl)acrylferrocene and arylboronic acids. The structures were determined with elemental analyses, IR spectra, and (1)H-NMR spectra.