The Engineering of Chemical Synthesis: Humans and Machines Working in Harmony

Words and phrases such as Artificial Intelligence, Machine Learning, Neural Networks, Robotics, the Cloud, Big Data and the Internet of Things are typically associated with many modern technological and scientific developments. Until recently, however, they have not been applied systematically to the chemical assembly of society’s functional molecules. Indeed, due to the lack of suitable tools, chemical synthesis in the past has tended to rely heavily on robust labour intensive batch processes that were often developed decades ago. This situation is changing rapidly owing to many reasons and, in particular, to the continuing need to discover new reactivity and new reactions, especially more sustainable processes. Smart, self-optimising platforms for continuous compound production along with a vast range of new analytical, monitoring and control devices for improved management of research experimentation and for accelerating the synthesis process are now available.support from the Woolf Fisher Trust (DEF), ECH2020 Future and Emerging Technologies (SVL. Sponsor reference 206410) and the Engineering and Physical Sciences Research Council (SVL. Grant codes: EP/K009494/1, EP/M004120/1)

Professor Steven V Ley CBE FRS FMedSci

Professor Steven Ley is currently Professor of Chemistry and Director of Research at at the University of Cambridge. He is also a Fellow of Trinity College and was BP 1702 Professor of Chemistry for 21 years. Steve obtained his PhD from Loughborough University with Professor Harry Heaney and afterwards carried out postdoctoral research with Professor Leo Paquette (Ohio State University) and then Professor Derek Barton (Imperial College). He was appointed as a lecturer at Imperial College in 1975, promoted to Professor in 1983, and became Head of Department there in 1989. In 1990 he was elected to the Royal Society (London) and was President of The Royal Society of Chemistry from 2000-2002. Steve’s research interests are varied and span many disciplines including new synthetic methodologies, the total synthesis of natural products and the development of enabling technologies for chemical synthesis - especially in the area of flow chemistry technologies. Four spin-out companies have emerged from these research interests. Steve has published over 860 papers and has been honoured with 50 major awards including recently (since 2009): the Tetrahedron Prize for Creativity in Organic Chemistry (Elsevier); Heinrich Wieland Prize (Boehringer Ingelheim, Germany); The Paracelsus Prize (Swiss Chemical Society); The Royal Medal (The Royal Society, London); The Longstaff Prize (The Royal Society of Chemistry); the Franco-Britannique Prize (Société Chimique de France); and the IUPAC-Thales Nano Prize in Flow Chemistry. Professor Ley is also recipient of the 2018 Arthur C. Cope Award

Flow chemistry in Europe

This is an editorial for a Special Issu

Studies in the chemistry of benzobicyclo systems

Reactions of tetrahalogenobenzynes with certain tertiary arylamines afford products which are derived by both 1,2- and 1,4-cyclo-addition as well as from a betaine. The tetrahalogenobenzynes and benzyne react with eneamines to give benzocyclobutene-derivatives via betaines; the tetrahalogenobenzyne derivatives are readily hydrolysed to 2-tetrahalogenophenyl cycloalkanones. 1-N-alkylamino derivatives of 5,6,7,8-tetrahalogeno-1,4-dihydronaphthalene also undergo cleavage reactions in protic media. Thus, for example, 1-N, N-dimethylamino-tetrafluorobenzobarrelene gives 2,3,4,5- tetrafluoro-k'-N, N-dimethylaminobiphenyl in high yield and 1,2,3,1- tetrafluoro-5,8-dihydro-5,8-N-(-methyl)-iminonaphthalene affords 2'- (2,3,4,5-tetrafluorophenyl)-N-methyl. pyrrole. Apparent similarities between mass spectral and thermal processes have been investigated in connection with retro-Diels-Alder reactions leading to k, 5,6,7-tetrahalogeno-isobenzofurans and 1,5,6,7-tetrafluoro- 2-methylisoindole. These derivatives are more stable than the nonhalogenated compounds. The rearrangement reactions of 1-methoxybenzobarrelene derivatives in strong acids have been studied. Various possible mechanistic pathways have been investigated by deuterium labelling methods. Benzobicyclo[3.2.1] derivatives arise via a 2-carbonium ion while a 3-carbonium ion leads to benzobicyclo[2.2.2)dien-2-one derivatives. The solvolyses of certain toluene-p-sulphonates have been used to check mechanistic predictions. The position of protonation and the extent of the rearrangement can be controlled by the use of alkyl substituents. Thus 2,6-dimethyl-l-methoxytetrafluorobenzobarrelene affords only derivatives of benzobicyclo[3.2.1]- octadiene while 3,5-dimethyl-l-methoxy-tetrafluorobenzobarrelene gives products derived by rearrangement to the benzobicyclo[2.2.2] system

Total synthesis and biological evaluation of the tetramic acid based natural product harzianic acid and its stereoisomers

Financial support for this project was provided by Cancer Research UK (Grant No. C21383/A6950)The bioactive natural product harzianic acid was prepared for the first time in just six steps (longest linear sequence) with an overall yield of 22%. The identification of conditions to telescope amide bond formation and a Lacey-Dieckmann reaction into one pot proved important. The three stereoisomers of harzianic acid were also prepared, providing material for comparison of their biological activity. While all of the isomers promoted root growth, improved antifungal activity was unexpectedly associated with isomers in the enantiomeric series opposite that of harzianic acid.Publisher PDFPeer reviewe

The Coombs

The Coombs Building at The Australian National University is a Canberra icon. Named after one of Australia’s greatest administrators and public intellectuals—‘Nugget’ Herbert Cole Coombs—for more than forty years the building has housed two of the University’s four foundational Schools: the Research School of Pacific and Asian Studies and the Research School of Social Sciences. This volume of recollections is about the former. It looks at life in the building through the prism of personal experience and happenstance. Part memoir, part biography, and part celebration, this book is about the people of Coombs, past and present. Through evocative and lucid reflections, present and former denizens of the building share their passions and predilections, quietly savour their accomplishments and recall the failings and foibles of the past with a kindly tolerance

The Evolution of Flow Chemistry: An Opinion on Factors Driving Innovation

This article seeks to provide an overview of the environmental factors within the pharmaceutical industry that have contributed to the emergence of flow chemistry over the past two decades. It highlights some of the challenges facing the industry and describes how they are being overcome by the exponential trajectory of scientific progress in the area. We identify current trends and offer a speculative glimpse into the future of drug development and manufacturing with some examples of progress being made at CARBOGEN AMCIS