Asymmetric 1,3-dipolar cycloadditions of acrylamides

This critical review, which is relevant to researchers in synthetic organic chemistry, focuses on asymmetric 1,3-dipolar cycloadditions with acrylamides. The use of chiral acrylamides as dipolarophiles leads to high levels of stereocontrol, due to conformational constraint in the acrylamides. Employment of chiral tertiary acrylamides containing nitrogen heterocycles is particularly effective in controlling the stereoselectivity. Following a general overview of 1,3-dipolar cycloadditions, the main body of the review focuses on asymmetric 1,3-dipolar cycloadditions of acrylamides with nitrile oxides, nitrones, diazoalkanes and azomethine ylides, with particular emphasis on the rationale for the observed stereocontrol (215 references)

1,3-Dipolar cycloadditions of 2-thio-3-chloroacrylamides with nitrile oxides and nitrones

1,3-Dipolar cycloadditions of 2-thio-3-chloroacrylamides with nitrile oxides and nitrones is described. A series of novel isoxazolines are isolated from the nitrile oxide cycloadditions, whilst the isoxazolines generated from the nitrone cycloadditions undergo further ring opening to yield piperidines

1,3-Dipolar cycloadditions of 2-thio-3-chloroacrylamides with diazoalkanes

2-Thio-3-chloroacrylamides undergo 1,3-dipolar cycloadditions with diazoalkanes leading to a series of novel pyrazolines and pyrazoles. The mechanistic and synthetic features of the cycloadditions to the 2-thio-3-chloroacrylamides at both the sulfide and sulfoxide levels of oxidation are rationalised on the basis of the nature of the substituents

Diastereoselective sulfur oxidation of 2-thio-3-chloroacrylamides

Diastereoselective sulfur oxidation in 2-thio-3-chloroacrylamides is described. A range of chiral amine auxiliaries were incorporated in the β-chloroacrylamide, and the efficiency with which the stereochemistry was relayed to the sulfur centre during sulfoxidation was investigated. Diastereomeric ratios of up to 3.3:1 were achieved

Synthesis and stereoselective oxidation of α-Thio-β- chloropropenyloxazolidin-2-ones

Investigation of the stereoselective reaction of α-thiopropanoyloxazolidin-2-ones with NCS to yield α-thio-β-chloropropenyloxazolidin-2-ones is described. Diastereoselective sulfur oxidation of the resulting α-thio-β-chloropropenyloxazolidin-2-ones is also discussed, with modest diastereocontrol achieved. However, through a combination of diastereoselective oxidation and subsequent kinetic resolution in the sulfoxide oxidation, diastereoselectivities of up to 94% de are achieved

Investigation of the reaction of α-Thioamides, α-esters and α–nitriles with N-halosuccinimides

Investigation of the reaction of α-thioamides, α-esters and α-nitriles with NBS and NCS is described. The scope of this stereoselective oxidative transformation to the β- haloacrylamides, β-acrylates and β–acrylonitriles has been determined. A mechanistic rationale to explain the observed differences in reactivity between the amide, ester and nitrile series is proposed

Investigation of the chemoselective and enantioselective oxidation of α-thio-β-chloroacrylamides

Investigation of the chemoselective and enantioselective oxidation of α-thio-β-chloroacrylamides is described. The α-thio-β-chloroacrylamides can be selectively oxidized to either the racemic sulfoxide or the sulfone very efficiently. The asymmetric sulfur oxidation of α-thio-β-chloroacrylamides is also discussed, with sulfoxide enantioselectivites of up to 52% ee achieved using the Kagan oxidation, and up to 71% ee when the Bolm oxidation is employed. While the enantioselectivities achieved are modest, these are among the most highly functionalised sulfides investigated in catalytic asymmetric oxidation, and the resulting enantioenriched sulfoxides have significant synthetic potential

The influence of reaction conditions on the Diels-Alder cycloadditions of 2-thio-3-chloroacrylamides; investigation of thermal, catalytic and microwave conditions

The Diels-Alder cycloadditions of cyclopentadiene and 2,3-dimethyl-1,3-butadiene to a range of 2-thio-3-chloroacrylamides under thermal, catalytic and microwave conditions is described. The influence of reaction conditions on the outcome of the cycloadditions, in particular the stereoselectivity and reaction efficiency, is discussed. While the cycloadditions have been attempted at the sulfide, sulfoxide and sulfone levels of oxidation, use of the sulfoxide derivatives is clearly beneficial for stereoselective construction of Diels-Alder cycloadducts

Selective β-oxidation of α-sulfanyl amides

A selective β-oxidation of a series of α-sulfanyl amides to the corresponding β-oxo-α-sulfanyl amides is described. This selective efficient oxidation of an unfunctionalised methyl or methylene group occurs under mild conditions, involving three sequential transformations conducted without isolation of the intermediates. Critically neither the sulfur nor the reactive α-CH bond is affected in the overall process

Addition-substitution reactions of 2-thio-3-chloroacrylamides with carbon, nitrogen, oxygen, sulfur and selenium nucleophiles

Synthetically versatile conjugate addition of a range of carbon, nitrogen, oxygen, sulfur and selenium nucleophiles to the highly functionalised 2-thio-3-chloroacrylamides is described. The stereochemical and synthetic features of this transformation are discussed in detail. In most instances, the nucleophile replaces the chloro substituent with retention of stereochemistry. With the oxygen nucleophiles, a second addition can occur leading to acetals, while with the nitrogen nucleophiles, E-Z isomerism occurs in the resulting enamine derivatives. The ratio of the E/Z isomers can be rationalised on the basis of the substituent and the level of oxidation