Metal-Free CH-CH-Type Cross-Coupling of Arenes and Alkynes Directed by a Multifunctional Sulfoxide Group.

A metal-free CH-CH-type coupling of arenes and alkynes, mediated by a multifunctional sulfoxide directing group, exploits nonprefunctionalized coupling partners, proceeds under mild conditions, is operationally simple, and exhibits high functional group tolerance. The products of the CH-CH coupling are highly versatile, and the metal-free process can be used for the construction and late-stage modification of important molecular scaffolds.

Sulfoxide-Directed Metal-Free ortho-Propargylation of Aromatics and Heteroaromatics.

A sulfoxide-directed, metal-free ortho-propargylation of aromatics and heteroaromatics exploits intermolecular delivery of a propargyl nucleophile to sulfur followed by an intramolecular relay to carbon. The operationally simple cross-coupling procedure is general, regiospecific with regard to the propargyl nucleophile, and shows complete selectivity for products of ortho-propargylation over allenylation. The use of secondary propargyl silanes allows metal-free ortho-coupling to form carbon-carbon bonds between aromatic and heteroaromatic rings and secondary propargylic centres. The 'safety-catch' nature of the sulfoxide directing group is illustrated in a selective, iterative double cross-coupling process. The products of propargylation are versatile intermediates and they have been readily converted into substituted benzothiophenes.

Highly chemoselective reduction of amides (primary, secondary, tertiary) to alcohols using SmI2/amine/H2O under mild conditions.

Highly chemoselective direct reduction of primary, secondary, and tertiary amides to alcohols using SmI2/amine/H2O is reported. The reaction proceeds with C-N bond cleavage in the carbinolamine intermediate, shows excellent functional group tolerance, and delivers the alcohol products in very high yields. The expected C-O cleavage products are not formed under the reaction conditions. The observed reactivity is opposite to the electrophilicity of polar carbonyl groups resulting from the n(X) → π*(C═O) (X = O, N) conjugation. Mechanistic studies suggest that coordination of Sm to the carbonyl and then to Lewis basic nitrogen in the tetrahedral intermediate facilitate electron transfer and control the selectivity of the C-N/C-O cleavage. Notably, the method provides direct access to acyl-type radicals from unactivated amides under mild electron transfer conditions.

Mechanism of SmI2/amine/H2O-promoted chemoselective reductions of carboxylic acid derivatives (esters, acids, and amides) to alcohols.

Samarium(II) iodide-water-amine reagents have emerged as some of the most powerful reagents (E° = -2.8 V) for the reduction of unactivated carboxylic acid derivatives to primary alcohols under single electron transfer conditions, a transformation that had been considered to lie outside the scope of the classic SmI2 reductant for more than 30 years. In this article, we present a detailed mechanistic investigation of the reduction of unactivated esters, carboxylic acids, and amides using SmI2-water-amine reagents, in which we compare the reactivity of three functional groups. The mechanism has been studied using the following: (i) kinetic, (ii) reactivity, (iii) radical clock, and (iv) isotopic labeling experiments. The kinetic data indicate that for the three functional groups all reaction components (SmI2, amine, water) are involved in the rate equation and that the rate of electron transfer is facilitated by base assisted deprotonation of water. Notably, the mechanistic details presented herein indicate that complexation between SmI2, water, and amines can result in a new class of structurally diverse, thermodynamically powerful reductants for efficient electron transfer to a variety of carboxylic acid derivatives. These observations will have important implications for the design and optimization of new processes involving Sm(II)-reduction of ketyl radicals.

Sulfoxide-directed metal-free cross-couplings in the expedient synthesis of benzothiophene-based components of materials.

A metal-free approach combining sulfoxide-directed metal-free C-H cross-couplings with tuneable electrophile-mediated heterocyclizations and carbocyclative dimerizations, allows expedient access to benzothiophene-based systems that are components of important materials or are proven organic materials in their own right. As benzothiophene-based materials are typically prepared using Pd-catalyzed cross-coupling processes, our approach allows potential issues of metal cost and supply, and metal-contamination of products, to be avoided.

Nucleophilic ortho-allylation of pyrroles and pyrazoles: an accelerated Pummerer/thio-Claisen rearrangement sequence.

Arylsulfinyl groups direct the metal-free, regiospecific, nucleophilic ortho-allylation of pyrroles and pyrazoles. Mechanistic studies support the intermediacy of allylsulfonium salts that undergo facile thio-Claisen rearrangement onto the heterocyclic ring, giving products of coupling. The strategy has been adapted to allow regiospecific propargylation of the heterocyclic substrates.

Nucleophilic ortho allylation of aryl and heteroaryl sulfoxides.

Aryl and heteroaryl sulfoxides undergo ortho allylation upon treatment with Tf(2)O and allylsilanes. The method complements the use of sulfoxides to direct ortho-metalation and reaction with electrophiles as it allows allylic carbon nucleophiles to be added ortho to the directing group in a metal-free process. The versatile sulfide adducts can be selectively manipulated using various methods including Kumada-Corriu cross-coupling of the organosulfanyl group.