Game of Aliphatics: A Density Functional Theory Study of Base-Catalyzed Substrate-Controlled Dimerizations of Aliphatic Alkynones.

The present work focuses on a comprehensive density functional theory (DFT) study of newly discovered base-catalyzed substrate-controlled dimerizations of aliphatic alkynones. In order to understand the origin of selectivity of the cascade assemblies of 6-methylene-5-oxaspiro[2.4]heptanones and 2-alkenylfurans, structural and electronic properties of neutral and deprotonated alkynone molecules, thermodynamic and kinetic characteristics of the deprotonation of alkynones having diverse C-H active substituents at the carbonyl function under the action of a base, and thermodynamic and kinetic characteristics of possible mechanisms of the discussed cascade reactions were theoretically assessed. The obtained computational results have confirmed and clarified an early qualitative assumption on the key role of the nature of the aliphatic substituent. Apart from fully rationalizing the experimental results, the theoretical DFT data give valuable details and data for predicting the outcome of related base-catalyzed reactions between various electrophilic substrates and nucleophilic species formed from C-H active aliphatic alkynones.

Diastereoselective synthesis of tetrahydropyrrolo[1,2-d]oxadiazoles from functionalized Δ1-pyrrolines and in situ generated nitrile oxides.

Tetrahydropyrrolo[1,2-d]oxadiazoles have been synthesized in good-to-excellent yields via the cycloaddition of nitrile oxides (in situ generated from aldoximes) to readily accessible functionalized Δ1-pyrrolines. The reaction proceeds smoothly at room temperature in a two-phase system in the presence of sodium hypochloride as an oxidant to diastereoselectively afford pharmaceutically prospective 1,2,4-oxadiazolines fused with a five-membered ring. The reaction tolerates a broad range of substrates, including those with oxidant-sensitive functional groups and competitive reaction sites.

Regio- and stereoselective base-catalyzed assembly of 6-methylene-5-oxaspiro[2.4]heptanones from alkynyl cyclopropyl ketones.

6-Methylene-5-oxaspiro[2.4]heptanones have been synthesized via base-catalyzed dimerization of available alkynyl cyclopropyl ketones. The reaction proceeds effectively in the presence of the t-BuOK/t-BuOH/THF catalytic system at room temperature to afford the desired spirocycles in a regio- and stereoselective manner. A wider synthetic utility of alkynyl cyclopropyl ketones as novel building blocks was demonstrated by the synthesis of diverse spirocyclopropanes.

Synthesis of Pyrrolo[2,1-a]isoquinolinium Salts from 1-Pyrrolines and Alkynes via Rhodium-Catalyzed C-H Functionalization/N-Annulation Tandem Reaction.

A convenient synthesis of pyrrolo[2,1-a]isoquinolinium salts from 1-pyrrolines and alkynes through rhodium-catalyzed C-H functionalization/N-annulation tandem reaction is described. The protocol features a good substrate tolerance, mild reaction conditions, and high yields of target products. Exploration of the alkyne scope unexpectedly revealed a novel labile functional group-promoted rhodium-catalyzed C-H functionalization/C-annulation/elimination cascade reaction of 1-pyrrolines with electron-deficient alkynes.

Recent advances and future challenges in the synthesis of 2,4,6-triarylpyridines.

2,4,6-Triarylpyridines are key building blocks to access functional molecules that are used in the design of advanced materials, metal-organic frameworks, supramolecules, reactive chemical intermediates and drugs. A number of synthetic protocols to construct this heterocyclic scaffold have been developed to date, the most recent of which (2015-present) are included and discussed in the present review. An emphasis has been placed on the utility of each synthetic approach in view of the scope of aryl/hetaryl substituents, limitations and an outlook of each method to be used in applied sciences.

Regiocontrolled synthesis of 2,4,6-triarylpyridines from methyl ketones, electron-deficient acetylenes and ammonium acetate.

A novel one-pot two-step approach for the synthesis of 2,4,6-triarylpyridines via t-BuOK/DMSO-promoted C-vinylation of a variety of methyl ketones with electron-deficient acetylenes (alkynones) followed by a cyclization of the in situ generated unsaturated 1,5-dicarbonyl species with ammonium acetate has been developed. This approach possesses competitive advantages such as high regioselectivity, available starting materials and the absence of transition-metal catalysts, oxidants and undesirable byproducts. A wide synthetic utility of the developed approach was demonstrated by the synthesis of trisubstituted, tetrasubstituted and fused pyridines.

Hydrazides in the reaction with hydroxypyrrolines: less nucleophilicity - more diversity.

Expedient protocols for the synthesis of three types of highly functionalized azaheterocyclic scaffolds (dihydropyridazines, tetrahydropyridazines, and partially saturated tricyclic systems) from readily available hydroxypyrrolines and hydrazides are described. The directions of the transformation of a common initial intermediate, namely a Brønsted acid-activated hydroxypyrroline, depend on the reaction conditions and the structure of the hydrazides.

Retrosynthetic Analysis of α-Alkenyl-ß-Diketones: Regio- and Stereoselective Two-Step Synthesis of Highly Arylated Representatives from Acetylenes, Ketones, and Acyl Chlorides.

Highly arylated α-alkenyl-ß-diketones are synthesized via a two-step sequence consisting of (i) potassium tert-butoxide/DMSO-catalyzed (E)-stereoselective C-H functionalization of ketones with acetylenes followed by (ii) magnesium bromide etherate/DIPEA-soft enolization of the formed ß,γ-unsaturated ketones and regioselective acylation with acyl chlorides. The method is compatible with a broad range of substrates and shown to be applicable as an intermediate stage in the construction of polyarylated heterocycles.

Recent advances in the synthesis of imidazoles.

The review highlights the recent advances (2018-present) in the regiocontrolled synthesis of substituted imidazoles. These heterocycles are key components to functional molecules that are used in a variety of everyday applications. An emphasis has been placed on the bonds constructed during the formation of the imidazole. The utility of these methodologies based around the functional group compatibility of the process and resultant substitution patterns around the ring are described, including discussion of scope and limitations, reaction mechanisms and future challenges.