Rising Stars in Organic Chemistry, Session 4

We recently reported an example of oxidative bicyclo[1.1.0]butane activation for the synthesis of differently-substituted bicyclo[2.1.1]hexanes. In this talk we will explore this unusual reaction, and the divergent mechanisms that we believe are operating depending on the precise nature of the bicyclo[1.1.0]butane and alkene reactants.

Bench-stable and readily accessible carbonyl or 1,2-dicarbonyl compounds are considered ideal candidates for metal carbene precursors. However, this transformation will encounter significant challenges due to the high activation energy required for the cleavage of C=O double bonds and the diverse side reactions plausibly induced by the rich reactivity profiles of carbonyls. Our laboratory has been committed to the development of Mo-catalyzed deoxygenative functionalization reactions of carbonyl compounds, and for the first time the 1,2-dicarbonyl compounds could be directly utilized as metal carbene precursors through the Mo-catalyzed regiospecific deoxygenation. This presentation will be focused on the development of novel Mo-catalyzed deoxygenative functionalization reactions of carbonyl compounds and the design of novel low-valent molybdenum deoxygenation catalysts.

Hypervalent iodine(III) compounds are versatile, highly electrophilic reagents that enable functional group transfer (arylation, amination, fluorination, fluoroalkylation, etc.) under metal-catalysed or metal-free conditions. Alkylation, however, is a challenging transformation for these compounds, as they undergo rapid alpha- and beta-elimination. Our group aims to understand these competing reactions and design stable iodine(III) reagents for (fluoro)alkylation. We have recently reported the hypervalent-iodine mediated 1,1-difluoroethylation of heteroatom nucleophiles, providing access to a variety of pharmaceutically relevant molecules bearing this motif, that can act as a lipophilic hydrogen-bond donor.

Precise modification of a chemical site at the single-atom level is a major challenge for synthetic chemistry. This talk will present on the transfer of a single carbon atom as well as a CN2 fragment in organic synthesis. State-of-the art methods are introduced and a new reagent design strategy for C-atom transfer outlined.

Fuelled by an increasing requirement within the pharmaceutical industry for 3D building blocks, there is significant demand for new synthetic methods targeting chiral molecules with precisely defined stereochemistry. The focus of this talk will be upon C–N atropisomeric amides, which are an underexplored class of stereogenic material whose chirality arises from restricted rotation about a twisted carbon-nitrogen single bond. The talk will explore: (i) development of synthetic methodology to access new atropisomeric scaffolds; (ii) how the presence (or absence!) of atropisomerism in these scaffolds can be probed experimentally; (iii) application of these ideas to design new biologically active molecules.

Nitroxides are organic radicals that are sufficiently stable to be isolable under ambient conditions. Among their many and varied applications, nitroxides can be used as observable probes or polarization agents in magnetic resonance spectroscopy (EPR, NMR) and contrast agents in MRI imaging. To apply these techniques in biological systems, nitroxides with high biological stability and optimal electron spin relaxation properties are needed. We report a range of new nitroxide scaffolds, accessible by scaffold rearrangements, that simultaneously show increased robustness under bio-mimicking reducing conditions and exhibit excellent electron spin relaxation properties. The applicability of these nitroxides as observable probes is demonstrated through spin labelling and EPR investigation of a model protein complex. While we here show that the new nitroxide frameworks are well-suited for use as EPR probes, the reduced reaction rates of these radicals have implications for their other uses across the chemical sciences.