Chemospecific Cyclizations of α‐Carbonyl Sulfoxonium Ylides on Aryls and Heteroaryls

The functionalization of aryl and heteroaryls using α‐carbonyl sulfoxonium ylides without the help of a directing group has remained so far a neglected area, despite the advantageous safety profile of sulfoxonium ylides. Described herein are the cyclizations of α‐carbonyl sulfoxonium ylides onto benzenes, benzofurans and N‐p‐toluenesulfonyl indoles in the presence of a base in HFIP, whereas pyrroles and N‐methyl indoles undergo cyclization in the presence of an iridium catalyst. Significantly, these two sets of conditions are chemospecific for each groups of substrates.     

Transition-metal-free approach to synthesis of indolines from N-(ortho-chloromethyl)aryl amides and iodonium ylides

A transition-metal-free method for the synthesis of indolines has been developed. In the presence of K₂CO₃, the cyclization reaction of N-(ortho-chloromethyl)aryl amides and iodonium ylides proceeded smoothly at room temperature in moderate to good yields.     

A Selective C−H Deprotonation Strategy to Access Functionalized Arynes by Using Hypervalent Iodine

Described here is an efficient method to access highly functionalized arynes from unsymmetrical aryl(mesityl)iodonium tosylate salts. The iodonium salts are prepared in a single pot from either commercially available aryl iodides or arylboronic acids. The aryne intermediates are generated by ortho‐C?H deprotonation of aryl(mesityl)iodonium salt with a commercially available amide base and trapped in a cycloaddition reaction with furan in moderate to good yields. Coupling partners for the aryne intermediates beyond furan are also described, including benzyl azide and alicyclic amine nucleophiles. The regio‐ and chemoselectivity of this reaction is discussed and evidence for the spectator aryl ligand of the iodonium salt as a critical control element in selectivity is presented.     

Cross‐Coupling of α‐Carbonyl Sulfoxonium Ylides with C−H Bonds

The functionalization of carbon–hydrogen bonds in non‐nucleophilic substrates using α‐carbonyl sulfoxonium ylides has not been so far investigated, despite the potential safety advantages that such reagents would provide over either diazo compounds or their in situ precursors. Described herein are the cross‐coupling reactions of sulfoxonium ylides with C(sp²)−H bonds of arenes and heteroarenes in the presence of a rhodium catalyst. The reaction proceeds by a succession of C−H activation, migratory insertion of the ylide into the carbon–metal bond, and protodemetalation, the last step being turnover‐limiting. The method is applied to the synthesis of benz[c]acridines when allied to an iridium‐catalyzed dehydrative cyclization.     

Ruthenium Catalyzed C−H Acylmethylation of N‐Arylphthalazine‐1,4‐diones with α‐Carbonyl Sulfoxonium Ylides: Highway to Diversely Functionalized Phthalazino‐fused Cinnolines

A direct ortho‐Csp²‐H acylmethylation of 2‐aryl‐2,3‐dihydrophthalazine‐1,4‐diones with α‐carbonyl sulfoxonium ylides is achieved through a Ru^II‐catalyzed C?H bond activation process. The protocol featured high functional group tolerance on the two substrates, including aryl‐, heteroaryl‐, and alkyl‐substituted α‐carbonyl sulfoxonium ylides. Thereafter, 2‐(ortho‐acylmethylaryl)‐2,3‐dihydrophthalazine‐1,4‐diones were used as potential starting materials for the expeditious synthesis of 6‐arylphthalazino[2,3‐a]cinnoline‐8,13‐diones and 5‐acyl‐5,6‐dihydrophthalazino[2,3‐a]cinnoline‐8,13‐diones under Lawesson's reagent and BF₃?OEt₂ mediated conditions, respectively. Of these, the BF₃?OEt₂‐mediated cyclization proceeded in DMSO as a solvent and a methylene source via dual C?C and C?N bond formations.     

Access to Aryl‐Naphthaquinone Atropisomers by Phosphine‐Catalyzed Atroposelective (4+2) Annulations of δ‐Acetoxy Allenoates with 2‐Hydroxyquinone Derivatives

Although asymmetric phosphine catalysis is a powerful tool for the construction of various chiral carbon centers, its synthetic potential toward an enantioenriched atropisomer has not been explored yet. Reported herein is a phosphine‐catalyzed atroposelective (4+2) annulation of δ‐acetoxy allenoates and 2‐hydroxyquinone derivatives. The reaction provides expedient access to aryl‐naphthaquinone atropisomers by the de novo construction of a benzene ring. The two functionalities of the catalyst, a tertiary phosphine (Lewis base) and a tertiary amine (Brønsted base), cooperatively enable this process with high regio‐ and enantioselectivities.     

Synthesis of Substituted Pyrido[1,2-a]benzimidazoles by Ruthenium-Catalyzed C−H Bond Activation and Tandem Cyclization of 2-Arylimidazo[1,2-a]pyridines with Iodonium Ylides

Ruthenium-catalyzed C−H bond activation and tandem cyclization of 2-arylimidazo[1,2-a]pyridines with iodonium ylides proceed efficiently. For the first time, the easily available iodonium ylides and inexpensive ruthenium complex were employed to synthesize pyrido[1,2-a]benzimidazole derivatives in good yields under simple and easy-to-operate conditions. Several primary mechanism investigations and synthetic applications involving gram-scale preparation, derivatization reactions and the transformation of iodonium ylide generated in situ have also been conducted.     

Free‐Amine‐Directed Alkenylation of C(sp2)?H and Cycloamination by Palladium Catalysis

A new protocol for the palladium‐catalyzed free‐amine‐directed alkenylation of C(sp²)? H bonds and cycloamination is described. Substituted biaryl‐2‐amines react with various alkenes, including electron‐deficient alkenes, aryl alkenes and alkyl alkenes, to give the corresponding phenanthridines with exclusive regioselectivity. The use of α‐branched styrenes leads to the formation of tricyclic compounds with a seven‐membered amine ring. The method operates through a free‐amine‐directed alkenylation and a subsequent hydroamination cyclization reaction.     

Metal‐free Synthesis of Aryl Amines: Beyond Nucleophilic Aromatic Substitution

A mild and metal‐free approach to C?N coupling is described that employs diaryliodonium salt electrophiles and secondary aliphatic amine nucleophiles. This reaction results in direct ipso‐substitution of the iodonium moiety and unsymmetrical aryl(TMP)iodonium salts are primarily employed. Moreover, arene substituents and substitution patterns that currently pose a challenge to classical metal‐free methods are accommodated and the alicyclic amine nucleophiles used here are unprecedented in other contemporary metal‐free C?N coupling reactions.     

Kinetics and mechanism of tertiary amine‐catalyzed cleavage of N′‐morpholino‐N‐(2′‐methoxyphenyl)phthalamide: Kinetic evidence for the presence of a reactive intermediate on the reaction path

Pseudo‐first‐order rate constants (k_obs) for tertiary amine (DABCO and Me₃N) buffer‐catalyzed cyclization of N′‐morpholino‐N‐(2′‐methoxyphenyl)phthalamide ( 1 ) to N‐(2′‐methoxyphenyl)phthalimide ( 2 ) reveal saturation (nonlinear) plots of k_obs versus [Buf]_T (total tertiary amine buffer concentration) at a constant pH. Such plots at different pH have been attributed to the presence of a reactive intermediate (T^?) formed by tertiary amine buffer‐catalyzed intramolecular nucleophilic addition of the secondary amide nitrogen to the carbonyl carbon of the tertiary amide group of 1 . © 2010 Wiley Periodicals, Inc. Int J Chem Kinet 42: 263–272, 2010     

Benziodoxole Triflate as a Versatile Reagent for Iodo(III)cyclization of Alkynes

The utility of benziodoxole triflate, derived from α,α‐bis(trifluoromethyl)‐2‐iodobenzyl alcohol, as a versatile reagent for iodo(III)cyclization via electrophilic activation of alkyne, is reported herein. The reagent promotes cyclization of alkynes tethered to a variety of nucleophilic moieties, affording benziodoxole‐appended (hetero)arenes such as benzofurans, benzothiophenes, isocoumarins, indoles, and polyaromatics under mild conditions. This unprecedented class of (hetero)aryl‐I^III compounds proved easy to purify, stable, and amenable to various synthetic transformations.     

Enantioselective Palladium(0)‐Catalyzed Nazarov‐Type Cyclization

A Pd⁰‐catalyzed asymmetric Nazarov‐type cyclization is described. The optimized ligand for the reaction incorporates a weakly coordinating pyridine ring into a TADDOL‐derived phosphoramidite (TADDOL=α,α,α,α‐tetraaryl‐1,3‐dioxolane‐4,5‐dimethanol). The reaction leads to the formation of cyclopentenones as single diastereoisomers that incorporate two contiguous asymmetric centers, one tertiary and one an all‐carbon‐atom quaternary stereocenter, in high yield and optical purity. It is noteworthy that the reaction does not require that substrates should be activated by aryl substituents.     

Synthesis and characterization of bromonium ylides and their unusual ligand transfer reactions with N-heterocycles

Stable aliphatic bromonium ylides (RfSO2)2C--Br+C6H4-p-CF3 (Rf = CF3, CF3(CF2)3) have been synthesized and structurally characterized for the first time. X-ray crystallographic analyses indicated a ylide structure with an sp2 hybridization of the ylide carbanions and with little double-bond character for the ylidic bond. The bromonium ylides selectively undergo transfer of the aryl group to nitrogen heterocycles, such as pyridines, yielding N-arylpyridinium salts. This is in a marked contrast to the reaction of the iodonium ylides, which produces pyridinium ylides through transylidations.     

PdII‐Catalyzed Enantioselective C(sp3)−H Activation/Cross‐Coupling Reactions of Free Carboxylic Acids

Pd^II‐catalyzed enantioselective C(sp³)?H cross‐coupling of free carboxylic acids with organoborons has been realized using either mono‐protected amino acid (MPAA) ligands or mono‐protected aminoethyl amine (MPAAM) ligands. A diverse range of aryl‐ and vinyl‐boron reagents can be used as coupling partners to provide chiral carboxylic acids. This reaction provides an alternative approach to the enantioselective synthesis of cyclopropanecarboxylic acids and cyclobutanecarboxylic acids containing α‐chiral tertiary and quaternary stereocenters. The utility of this reaction was further demonstrated by converting the carboxylic acid into cyclopropyl amine without loss of optical activity.     

Synthesis of Functionalized Monoaryl-λ3-iodanes through Chemo- and Site-Selective ipso-Substitution Reactions

Monoaryl-λ³-iodanes are potentially attractive arylating agents. They are generally synthesized from aryl iodides via oxidation, which can cause functional group incompatibility, especially when polyfunctionalized derivatives are desired. This work describes the direct synthesis of monoaryl-λ³-iodanes through a chemoselective ipso-substitution reaction of arylgermanes and arylstannanes with iodine tris(trifluoroacetate). The generated iodanes were converted to iodonium ylides or used for further transformations in one pot. The presented method enables the preparation of polyfunctionalized monoaryl-λ³-iodanes.     

Efficient Pathway for the Preparation of Aryl(isoquinoline)iodonium(III) Salts and Synthesis of Radiofluorinated Isoquinolines

Iodonium compounds play a pivotal role in ¹⁸F‐fluorination of radiopharmaceuticals containing non‐activated arenes. However, preparation of these species is limited to oxidation conditions or exchange with organometallics that are prepared from aryl halides. Herein we describe a novel “one‐pot” process to assemble aryl(isoquinoline)iodonium salts in 40–94 % yields from mesoionic carbene silver complex and Aryl‐I‐Py₂(OTf)₂. The method is general, practical, and compatible with well‐functionalized molecules as well as useful for the preparation of a wide range of ¹⁸F‐labeled isoquinolines resulting in up to 92 % radiochemical conversion. As proof of concept, a fluorinated isoquinoline alkaloid, ¹⁸F‐aspergillitine is prepared in 10 % isolated radiochemical yield from the corresponding phenyl(aspergillitine)iodonium salt.     

Ligand‐Free Copper‐Catalyzed Negishi Coupling of Alkyl‐, Aryl‐, and Alkynylzinc Reagents with Heteroaryl Iodides

Reported herein is an unprecedented ligand‐free copper‐catalyzed cross‐coupling of alkyl‐, aryl‐, and alkynylzinc reagents with heteroaryl iodides. The reaction proceeds at room temperature for the coupling of primary, secondary, and tertiary alkylzinc reagents with heteroaryl iodides without rearrangement. An elevated temperature (100 °C) is required for aryl–heteroaryl and alkynyl–heteroaryl couplings.     

A mechanistic investigation of the three‐component radical photoinitiator system Eosin Y spirit soluble,N‐methyldiethanolamine,and diphenyliodonium chloride

Photo‐DSC and in situ, time‐resolved, laser‐induced, steady‐state fluorescence spectroscopy were used to study the initiation mechanism of the three‐component system: Eosin Y spirit soluble (EYss), N‐methyldiethanolamine, and diphenyliodonium chloride. Kinetic studies based on photo‐DSC revealed that the fastest polymerization occurred when all three components were present (the next fastest was with the dye/amine pair, and the slowest was with the dye/iodonium pair). However, the laser‐induced fluorescence experiments showed that the pairwise reaction between the eosin and iodonium bleaches the dye much more rapidly than does the reaction between the eosin and amine. We concluded that although a direct eosin/amine reaction can produce active radicals in the three‐component system, this reaction is largely overshadowed by the eosin/iodonium reaction, which does not produce active radicals as effectively. We proposed that the amine reduces the oxidized dye radical formed in the eosin/iodonium reaction back to its original state as well as the simultaneous production of an active initiating amine‐based radical. Because of the difference in the pairwise reaction rates for eosin/amine and eosin/iodonium, it is likely that this regeneration reaction was the primary source of active radicals in the three‐component eosin/amine/iodonium system. © 2001 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 39: 715–723, 2001     

Synthesis of 2‐Aryl‐2,3‐dihydro‐1,8‐naphthyridin‐4(1H)‐ones by Deprotective Cyclization of N‐{3‐[(2E)‐3‐Arylprop‐2‐enoyl]pyridin‐2‐yl}‐2,2‐dimethylpropanamides in Water

A new and convenient method for the preparation of 2‐aryl‐2,3‐dihydro‐1,8‐naphthyridin‐4(1H)‐ones 4 has been developed. Thus, N‐{3‐[(2E)‐3‐arylprop‐2‐enoyl]pyridin‐2‐yl}‐2,2‐dimethylpropanamides 3 are synthesized from commercially available pyridin‐2‐amine using an easily performed three‐step sequence and are subjected to cyclization with deprotection under acidic conditions in H₂O to give the desired products. Similarly, 2‐aryl‐2,3‐dihydro‐1,7‐naphthyridin‐4(1H)‐ones 8 and 2‐aryl‐2,3‐dihydro‐1,6‐naphthyridin‐4(1H)‐ones 12 can be prepared from pyridin‐3‐amine and pyridin‐4‐amine, respectively.     

Copper-Catalyzed One-Pot Arylation and Cyclization of Diaryliodonium Salts Derived from o-Iodoanilines for Indolo[2,3-b]indoles Syntheses

One-pot synthesis of various indolo[2,3-b]indoles has been accomplished from a copper-catalyzed transformation of easily accessible 2-(substituted-amino)aryl)(mesityl)iodonium salts and indole derivatives. Reaction offers great functional group toleration, providing a series of indolo[2,3-b]indole derivatives in good yields. Additionally, intramolecular cyclization of 2-(substituted-amino)aryl)(mesityl)iodonium salts in the presence of copper-catalyst provided direct access to benzoxazole derivatives.