Transition metal-free ether coupling and hydroamidation enabling the efficient synthesis of congested heterocycles.

In this study, we discovered that α-bromocarboxamides react with alkynols containing tertiary alcohol moieties to produce congested ethers or heterocycles. Here, the etherification and hydroamidation reactions can be controlled by a suitable base. Both C-O and C-N bond formations occurred without a transition-metal catalyst. The stereospecific etherification and cyclization of diastereo-enriched α-bromocarboxamide afforded the corresponding diastereo-enriched ether and heterocyclic compound.

Dipyrrolyldiketone PtII Complexes: Ion-Pairing π-Electronic Systems with Various Anion-Binding Modes.

A variety of π-electronic ion-pairing assemblies can be constructed by combining anion complexes of π-electronic systems and countercations. In this study, a series of anion-responsive π-electronic molecules, dipyrrolyldiketone PtII complexes containing a phenylpyridine ligand, were synthesized. The resulting PtII complexes exhibited phosphorescence emission, with higher emission quantum yields (0.30-0.42) and microsecond-order lifetimes, and solution-state anion binding, as revealed by our spectroscopic analyses. These PtII complexes displayed solid-state ion-pairing assemblies, exhibiting various anion-binding modes, which derived from pyrrole-inverted and pyrrole-non-inverted conformations, and packing structures, with the contribution of charge-by-charge assemblies, which were dependent on the substituents in the PtII complexes and the geometries and electronic states of their countercations.

Direct α-Tertiary Alkylations of Ketones in a Combined Copper-Organocatalyst System.

Herein, we report an efficient method for the tertiary alkylation of a ketone by using an α-bromocarbonyl compound as the tertiary alkyl source in a combined Cu-organocatalyst system. This dual catalyst system enables the addition of a tertiary alkyl radical to an enamine. Mechanistic studies revealed that the catalytically generated enamine is a key intermediate in the catalytic cycle. The developed method can be used to synthesize substituted 1,4-dicarbonyl compounds containing quaternary carbons bearing various alkyl chains.

Chemistry of Tertiary Carbon Center in the Formation of Congested C-O Ether Bonds.

Nucleophilic substitutions, including SN 1 and SN 2, are classical and reliable reactions, but a serious drawback is their intolerance for both bulky nucleophiles and chiral tertiary alkyl electrophiles for the synthesis of a chiral quaternary carbon center. An SRN 1 reaction via a radical species is another conventional method used to carry out substitution reactions of bulky nucleophiles and alkyl halides, but chiral tertiary alkyl electrophiles cannot be used. Therefore, a stereospecific nucleophilic substitution reaction using chiral tertiary alkyl electrophiles and bulky nucleophiles has not yet been well studied. In this paper, we describe the reaction of tertiary alkyl alcohols and non-chiral or chiral α-bromocarboxamides as a tertiary alkyl source for the formation of congested ether compounds possessing two different tertiary alkyl groups on the oxygen atom with stereoretention.

Organo-photoredox-Catalyzed Atom-Transfer Radical Substitution of Alkenes with α-Carbonyl Alkyl Halides.

A light-driven atom-transfer radical substitution (ATRS) and carboesterification reaction of alkenes with alkyl halides has been developed using PTH as the organo-photoredox catalyst. Two types of products were obtained, depending on the additive and solvent used during the reaction. Primary, secondary, and tertiary alkyl halides reacted to give the ATRS products. This protocol has several advantages: it requires mild reaction conditions and a low catalyst loading and exhibits a broad substrate scope and good functional group tolerance. Mechanistic studies indicate that alkyl radicals might be generated as the key intermediates via photocatalysis, providing a new direction for ATRS reactions.

Controlling alkyne reactivity by means of a copper-catalyzed radical reaction system for the synthesis of functionalized quaternary carbons.

A terminal alkyne is one of the most useful reactants for the synthesis of alkyne and alkene derivatives. Because an alkyne undergoes addition reaction at a C-C triple bond or cross-coupling at a terminal C-H bond. Combining those reaction patterns could realize a new reaction methodology to synthesize complex molecules including C-C multiple bonds. In this report, we found that the reaction of 3 equivalents of terminal alkyne 1 (aryl substituted alkyne) and an α-bromocarbonyl compound 2 (tertiary alkyl radical precursor) undergoes tandem alkyl radical addition/Sonogashira coupling to produce 1,3-enyne compound 3 possessing a quaternary carbon in the presence of a copper catalyst. Moreover, the reaction of α-bromocarbonyl compound 2 and an alkyne 4 possessing a carboxamide moiety undergoes tandem alkyl radical addition/C-H coupling to produce indolinone derivative 5.

Copper-Catalyzed Tertiary Alkylative Cyanation for the Synthesis of Cyanated Peptide Building Blocks.

In this paper, we report efficient cyanation of various peptides containing the α-bromocarbonyl moiety using a Cu-catalyzed radical-based methodology employing zinc cyanide as the cyanide source. Mechanistic studies revealed that in situ formed CuCN was a key intermediate during the catalytic cycle. Our method could be useful for the synthesis of modified peptides containing quaternary carbons.

Hybrid Reaction Systems for the Synthesis of Alkylated Compounds Based upon Cu-Catalyzed Coupling of Radicals and Organometallic Species.

A transition metal catalyzed alkylation with an alkyl halide is one of the most difficult reactions to achieve, because of the difficult oxidative addition of an alkyl-halogen bond to a metal, and the tendency of the resulting alkylmetal intermediate to undergo a ß-hydride elimination reaction to give an olefin. In this review, we discuss hybrid reaction systems involving Cu catalyzed combination of radicals and organometallic species, which enable facile alkylation reactions to construct C-C and C-heteroatom bonds. This paper highlights recent progress in arylation, alkenylation, alkynylation, cyclization, addition and introduction of heteroatoms via these hybrid reaction systems.

Pyrrole-Based π-System-PtII Complexes: Chiroptical Properties and Excited-State Dynamics with Microsecond Triplet Lifetimes.

Heteroleptic PtII complexes comprising π-extended dipyrrins and 2-phenylquinoline were prepared. Single-crystal X-ray analysis disclosed the stepped conformations of two ligand moieties in these PtII complexes. The enantiomers could be separated by HPLC and their configurations were determined from CD spectroscopy results and TD-DFT calculations. Transient absorption measurements revealed excited-state dynamics characterized by fast intersystem crossing and microsecond-order triplet-state lifetimes.

Pyrrole-Based Anion-Responsive π-Electronic Molecules as Hydrogen-Bonding Catalysts.

The abilities of dipyrrolyldiketone boron complexes as hydrogen-bonding donor organocatalysts were examined by the Mannich-type reaction of N-acyl heteroarenium chlorides with 1-methoxy-2-methyl-1-trimethylsiloxy-1-propene, as well as by the classical N-alkylation of amines with trityl chloride under base-free conditions. 1H NMR examinations of the hydrogen-bonding interaction between the pyrrole NH of the catalyst and the Cl- in the N-acyl heteroarenium salt suggested that the activation of N-acyl heteroarenium chlorides occurs through anion binding by the catalyst.

Direct Allylic Amination of Allylic Alcohol Catalyzed by Palladium Complex Bearing Phosphine-Borane Ligand.

The direct electrophilic, nucleophilic, and amphiphilic allylations of allylic alcohol by use of a palladium catalyst and organometallic reagents such as organoborane and organozinc has been developed. The phosphine-borane compound works as the effective ligand for palladium-catalyzed direct allylic amination of allylic alcohol. Thus, with secondary amines, the reaction was completed in only 1 h, even at room temperature.

Palladium-catalyzed [4 + 2] cycloaddition of aldimines and 1,4-dipolar equivalents via amphiphilic allylation.

The combination of Pd catalyst and diethylzinc with triethylborane promotes the amphiphilic allylation of aldimines with 2,3-bismethylenebutane-1,4-diol derivatives to serve as bis-allylic zwitterion species to form 3,4-bismethylenepiperidines via a formal [4 + 2] cycloaddition reaction. 3,4-Bismethylenepiperidine rings are applicable for the synthesis of isoquinoline derivatives via the Diels-Alder reaction followed by an oxidation reaction with DDQ.