David M. Lindsay

The brucine N-oxide-promoted asymmetric Pauson–Khand reaction

The brucine N-oxide-mediated asymmetric Pauson–Khand reaction has been further investigated. It was found that the best levels of enantioselection were obtained with substituted propargylic alcohol complexes. The studies also revealed that when acetone or 1,2-dimethoxyethane is used as the reaction solvent, enhanced levels of enantioselectivity, up to an enantiomeric ratio of 11:89, are achieved.

Preparation and reaction of desymmetrised cobalt alkyne complexes

Prochiral alkyne hexacarbonyl dicobalt complexes are desymmetrised directly with brucine N-oxide in the presence of a phosphine or phosphite ligand to produce the corresponding phosphorus-containing pentacarbonyl complex with appreciable enantiomeric excess. In Pauson–Khand reactions, it is found that the enantiomeric integrity of the desymmetrised complex is conserved in the cyclopentenone product. Moreover, the major enantiomer obtained in these reactions is opposite to that from a direct brucine N-oxide promoted Pauson–Khand reaction, allowing the preparation of either enantiomeric cyclopentenone in enriched form from a single source of chirality.

Iridium-Catalysed ortho-Directed Deuterium Labelling of Aromatic Esters—An Experimental and Theoretical Study on Directing Group Chemoselectivity

Herein we report a combined experimental and theoretical study on the deuterium labelling of benzoate ester derivatives, utilizing our developed iridium N-heterocyclic carbene/phosphine catalysts. A range of benzoate esters were screened, including derivatives with electron-donating and -withdrawing groups in the para- position. The substrate scope, in terms of the alkoxy group, was studied and the nature of the catalyst counter-ion was shown to have a profound effect on the efficiency of isotope exchange. Finally, the observed chemoselectivity was rationalized by rate studies and theoretical calculations, and this insight was applied to the selective labelling of benzoate esters bearing a second directing group.

A polymer-supported alkyl methyl sulfide as an efficient promoter of the Khand cyclisation reaction

A readily prepared polymer-supported alkyl methyl sulfide has been shown to be a recyclable, practically convenient, and efficient promoter of the Khand cyclisation reaction, affording good to excellent yields of cyclopentenones.

Preparation of an amine N-oxide on solid phase: an efficient promoter of the Pauson–Khand reaction

A novel, recyclable polymer-supported amine N-oxide has been prepared and shown to be a good promoter of the Pauson–Khand reaction under mild conditions, affording good to excellent yields of cyclopentenones.

Novel octameric structure of the lithium primary amide [{Bu(t)N(H)Li}(8)] and its implication for the directed synthesis of heterometallic imide cages

The crystalline lithium primary amide derived from tert-butylamine, [{ButN(H)Li}n], is structurally characterised by an X-ray diffraction study and shown to be a novel octameric (n= 8) ladder conformation, the cyclic, ‘double-crown’ nature of which implies molecules of this design could direct the synthesis of heterobimetallic (i.e. lithium and another metal) imide cage constructions.

Design, synthesis and antibacterial properties of pyrimido[4,5-b]indol-8-amine inhibitors of DNA gyrase

According to the World Health Organization (WHO), approximately 1.7 million deaths per year are caused by tuberculosis infections. Furthermore, it has been predicted that, by 2050, antibacterial resistance will be the cause of approximately 10 million deaths annually if the issue is not tackled. As a result, novel approaches to treating broad-spectrum bacterial infections are of vital importance. During the course of our wider efforts to discover unique methods of targeting multidrug-resistant (MDR) pathogens, we identified a novel series of amide-linked pyrimido[4,5-b]indol-8-amine inhibitors of bacterial type II topoisomerases. Compounds from the series were highly potent against gram-positive bacteria and mycobacteria, with excellent potency being retained against a panel of relevant Mycobacterium tuberculosis drug-resistant clinical isolates.

A Practical and General Amidation Method from Isocyanates Enabled by Flow Technology

The addition of carbon nucleophiles to isocyanates represents a conceptually flexible and efficient approach to the preparation of amides. This general synthetic strategy has, however, been relatively underutilized owing to narrow substrate tolerance and the requirement for less favourable reaction conditions. Herein, we disclose a high-yielding, mass-efficient, and scalable method with appreciable functional group tolerance for the formation of amides by reaction of Grignard reagents with isocyanates. Through the application of flow chemistry and the use of substoichiometric amounts of CuBr2 , this process has been developed to encompass a broad range of substrates, including reactants found to be incompatible with previously published procedures.

The Synthesis of Cyclic Ether-Containing Natural and Non-natural Products by Metathesis Reactions

This chapter describes recent advances (2005–2015) in the use of metathesis reactions to construct the cyclic ether portions in the total synthesis of natural products. Advances in the synthesis of a range of marine polyether natural products are presented, and various strategic approaches to the bridged pyran-macrocycles neopeltolide and kendomycin are discussed. Finally, the synthesis of a range of biologically active, cyclic ether-based non-natural products is described.