Unusual structure-energy correlations in intramolecular Diels–Alder reaction transition states

Detailed analysis of calculated data from an experimental/computational study of intramolecular furan Diels–Alder reactions has led to the unusual discovery that the mean contraction of the newly forming C-C σ-bonds from the transition state to the product shows a linear correlation with both reaction Gibbs free energies and reverse energy barriers. There is evidence for a similar correlation in other intramolecular Diels–Alder reactions involving non-aromatic dienes. No such correlation is found for intermolecular Diels–Alder reactions

Halogenation effects in Intramolecular Furan Diels-Alder reactions:broad scope synthetic and computational studies

For the first time a comprehensive synthetic and computational study of the effect of halogen substitution on both furan and dienophile for the intramolecular Furan Diels-Alder (IMDAF) reaction has been undertaken. Contrary to our initial expectations, halogen substitution on the dienophile was found to have a significant effect, making the reactions slower and less thermodynamically favourable. However, careful choice of the site of furan halogenation could be used to overcome dienophile halogen substitution, leading to highly functionalised cycloadducts. These reactions are thought to be controlled by the interplay of three factors: positive charge stabilisation in the transition state and product, steric effects and a dipolar interaction term identified by high level calculations. Frontier orbital effects do not appear to make a major contribution in determining the viability of these reactions, which is consistent with our analysis of calculated transition state structural data

Silver Effect in Regiodivergent Gold-Catalyzed Hydroaminations

We report a silver-induced switching of regioselectivity in gold-catalyzed reactions, and we provide mechanistic evidence to suggest a true “silver effect”: that is, one that is implicated in the catalytic process itself, via σ-gold π-silver acetylides. These results are of significance because they clearly show that the use of silver as halide abstractors in gold-catalyzed reactions may result in “silver effects” when terminal alkyne substrates are involved

Gold(I)-catalysed synthesis of cyclic sulfamidates : current scope, stereochemistry and competing ene-allene cycloisomerisation

AbstractSix-membered cyclic sulfamidates are prepared in high yields by treatment of allenic sulfamates with readily available Ph3PAuNTf2. The reaction enables formation of N-substituted quaternary centres in high yields. The relative stereochemistry has been unambiguously determined. A π-rearrangement is faster than hydroamination in the case of an allyl-substituted sulfamate and a mechanism is proposed for this process

Natural Product Analogues: Towards a Blueprint for Analogue-Focused Synthesis

For the first time a general overview of approaches to the synthesis of natural product analogues is presented. This reflects a process of evolution of natural product synthesis which has accelerated in the years since the implementation of diversity-oriented synthesis, which has emerged in parallel with collective synthesis, diverted total synthesis and the preparation of truncated natural products optimised for biological activity. A method involving computational assessment for the validation of core-modified natural product analogues is discussed

Stabilised Phosphazides

The Staudinger reaction between phosphines and azides provides a straightforward route to azaylides. Until the 1980s, it was thought that the putative intermediates of this reaction, namely phosphazides, were merely transient species that could be detected only by spectroscopic methods. This review summarises the achievements reported over the last 25 years on the preparation, structure and properties of phosphazides stabilised by substitution effects and/or coordination to transition metals or main group elements. Relevant computational studies on the Staudinger reaction are included

Nitrogen-directed free radical rearrangements

This thesis describes efforts to develop new methods for the synthesis of bridged azacycles using nitrogen-directed free radical rearrangements. Free radical addition to 7-azanorbornadienes were carried out to give 7-substituted 2- azanorbornenes (Scheme a.l, X-Y = RS-H or PhSe-H). [illustration in text ...] Scheme a. 1 Nitrogen-directed homoallylic radical rearrangement via intermolecular radical addition. A conceptually novel and theoretically interesting nitrogen-directed neophyl rearrangement (Scheme a.2) was developed into a synthesis of 2- azabenzonorbornanes 2. [illustration in text ...] Scheme a.2 Nitrogen-directed neophyl-like rearrangement to 2-azabenzonorbornanes. In this case the radical 1 was generated by Barton deoxygenation of 7- azabenzonorbornanols. The effect on rearrangement of bicyclic core substitution and of aromatic ring electronics was probed in some detail, and the process was synthetically useful for a wide range of substrates. Variation of the protecting group on nitrogen was investigated and the product profiles from neophyl-like rearrangement were consistent with a process driven by the stability of a radical α to nitrogen as a result of SOMO-lone pair orbital interaction. The kinetics and mechanism of these processes are examined where appropriate, leading to estimates of rate constants for the rearrangements.</p

Gold(I)-catalysed synthesis of cyclic sulfamidates by intramolecular allene hydroamination

Six-membered cyclic sulfamidates are prepared in high yields by treatment of allenic sulfamates with readily available gold(i) complexes. The reaction enables formation of N-substituted quaternary centres and complements existing processes for sulfamidate formation