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A robust approach allowing for the efficient trifluoroacetylation of a series of highly substituted pyrrolidines in a diastereoselective manner is reported. The transformation is based on a Dakin-West reaction of advanced pyrrolidine 2-carboxylic acid derivatives that can be assembled stereoselectively in four synthetic steps. Importantly, this work demonstrates how the introduction of lateral substituents on the pyrrolidine scaffold enables the generation of the desired trifluoroacetylation products, which was not possible previously due to the exclusive formation of trifluoromethylated oxazoles (vide infra). In the course of this work we succeeded for the first time in isolating and characterizing (HRMS, IR, ¹H, 13C and 19F NMR, X-ray) different intermediates of the Dakin-West reaction allowing us to probe its mechanism. [ABSTRACT FROM AUTHOR]

An efficient reaction cascade delivering a series of pyrrolo[1,2-a]quinolines bearing phosphonate or phosphine oxide moieties is presented. This sequence exploits the in situ transformation of propargylic alcohols into transient allenes by means of a strategic [2,3]-sigmatropic rearrangement followed by trapping of the resulting allenes by an adjacent pyrrole ring. Furthermore, the initial small scale batch process was successfully translated into a continuous flow process allowing efficient preparation of selected pyrrolo[1,2-a]quinolines on multigram scale without any safety concerns due to the reaction's inherent exothermic profile. [ABSTRACT FROM AUTHOR]

Research was conducted to examine a new, extremely mild approach for C-allylation of electron-rich aromatics and heteroaromatics using Mo(II) complexes (Mo(CO4)Br2)2 or Mo(CO)3(MeCN)2(SnCl3)Cl which have not been previously used in catalytic chemistry. Phenol tended to favor ortho-substitution in certain instances while the para-selectivity, observed with anisole and its congeners, was remarkable. Results indicate a Lewis-acid catalysis instead of a metal template-controlled mechanism.

Research was conducted to examine the three variants of molybdenum(II) catalysts, namely, Mo(CO)5(OTf)2, (Mo(CO)4Br2)2, their tungsten(II) congeners and bimetallic complex Mo(CO)3(MeCN)2(SnCl3)Cl. The complexes were found to catalyze the C-C bond-forming allylic substitution with silyl enol ethers obtained from beta-dicarbonyls or from simple ketones, esters and aldehydes as nucleophiles under mild conditions. Results suggest a Lewis-acid catalysis instead of a metal template-controlled approach.

We have prepared a library of functionalized quinolines through the magnesiation of 7-chloroquinolines under mild conditions, employing both batch and continuous flow conditions. The preparation involved the generation of mixed lithium-magnesium intermediates, which were reacted with different electrophiles. Mixed lithium-zinc reagents allowed the synthesis of halogenated and arylated derivatives. Some of the synthesized 4-carbinol quinolines have shown interesting antiproliferative properties, their hydroxyl group being a suitable amino group bioisostere. We also report a two-step approach for optically active derivatives.

A novel rearrangement sequence of 3-hydroxyazetidines via a Ritter initiated cascade provides highly substituted 2-oxazolines in high yields. The reaction conditions and substrate scope of the transformation have been studied demonstrating the generality of the process. The derived products can also be functionalized in order to undergo further intramolecular cyclization leading to a new class of macrocycle. The final cyclization step was shown to be a transformation amenable to continuous flow processing allowing for a dramatic reduction in the reaction time and simple scale-up.