Microwave-assisted sequential one-pot protocol to benzothiadiazin-3-one-1,1-dioxides via a copper-catalyzed N-arylation strategy

A microwave-assisted, sequential, one-pot protocol has been developed for the synthesis of a variety of benzothiadiazin-3-one-1,1-dioxides. This protocol utilizes a copper-catalyzed N-arylation of α-bromo-benzenesulfonamides with a number of amines to generate the corresponding 2-aminobenzenesulfonamides, which undergo cyclization to the desired sultams using carbonyl diimidazole (CDI). A range of conditions was evaluated for the key C–N bond formation step with tolerance toward functionalized amines

The UK landscape for robotics and autonomous systems

Robotics and Autonomous Systems Special Interest Group Report: Innovate UK - Technology Strategy Board This landscape collates the output from a series of workshops designed to explore the impact on the UK of advances in Robotics and Autonomous Systems (RAS). In overviewing the resulting landscape it is clear that the RAS opportunity, as perceived by the UK community, is extensive and rich and that the UK has the potential to create a strong RAS market. It is also clear that robotics and autonomous systems will impact on each UK market sector and that the total size of this impact will be significantly greater than the size of the RAS sector itself. Across these sectors strong cross cutting themes exist that can be used to drive synergies to build technical capability and market opportunity. Within those sectors that will benefit the most from robotics and autonomous systems technology the potential for disruptive innovation and the need to respond to change through the development of new business models is now obvious. Robotics and autonomous systems do not work in isolation. They will require testing, regulation, standards, innovation, investment and skills together with technical progress and strong collaborative partnerships in order to fully realise the opportunity. The resulting Landscape carries an essential message; that the UK has a unique opportunity to engage with robotics and autonomous systems, to exploit existing expertise within the UK and explore its potential, but that other nations are similarly engaged and the UK must now be bold and invest to win. 41 Individuals listed as contributor

Reagent based DOS: A "Click, Click, Cyclize" strategy to probe chemical space

The synthesis of small organic molecules as probes for discovering new therapeutic agents has been an important aspect of chemical-biology. Herein we report a reagent-based, diversity-oriented synthetic (DOS) strategy to probe chemical and biological space via a “Click, Click, Cyclize” protocol. In this DOS approach, three sulfonamide linchpins underwent cyclization protocols with a variety of reagents to yield a collection of structurally diverse S-heterocycles. In silico analysis is utilized to evaluate the diversity of the compound collection against chemical space (PC analysis), shape space (PMI) and polar surface area (PSA) calculations

Formal [4+3] Epoxide Cascade Reaction via a Complementary Ambiphilic Pairing Strategy

A formal [4+3] epoxide cascade protocol utilizing ambiphilic sulfonamides and a variety of epoxides (masked ambiphiles) has been developed for the generation of benzothiaoxazepine-1,1′-dioxides and oxathiazepine-1,1′-dioxides. This protocol combines an epoxide ring-opening with either an SNAr or oxa-Michael cyclization pathway

High-Load, Hybrid Si-ROMP Reagents

The combination of norbornenyl-tagged (Nb-tagged) silica particles and functionalized Nb-tagged monomers for the generation of hybrid Si-ROMP reagents and scavengers is reported. Specifically Si-ROMP-derived bis-acid chloride, dichlorotriazine and triphenylphosphine scavenger/reagents have been grafted from the surface of silica particles utilizating surface-initiated, ring-opening metathesis polymerization (ROMP). These hybridpolymeric materials combine the physical properties of current immobilized silica reagents and represent a key advancement in load by merging the inherent tunable properties of the ROMP-derived oligomers with silica supports for application in parallel synthesis

Synthesis of epoxybenzo[d]isothiazole 1,1-dioxides via a reductive-Heck, metathesis-sequestration protocol

An atom-economical purification protocol, using solution phase processing via ring-opening metathesis polymerization (ROMP) has been developed for the synthesis of tricyclic sultams. This chromatography-free method allows for convenient isolation of reductive-Heck products and reclamation of excess starting material via sequestration involving metathesis catalysts and a catalyst-armed Si-surface

Accessing Stereochemically Rich Sultams via Microwave-Assisted, Continuous Flow Organic Synthesis (MACOS) Scale-out

The generation of stereochemically-rich benzothiaoxazepine-1,1′-dioxides for enrichment of high-throughput screening collections is reported. Utilizing a microwave-assisted, continuous flow organic synthesis platform (MACOS), scale-out of core benzothiaoxazepine-1,1′-dioxide scaffolds has been achieved on multi-gram scale using an epoxide opening/SNAr cyclization protocol. Diversification of these sultam scaffolds was attained via a microwave-assisted intermolecular SNAr reaction with a variety of amines. Overall, a facile, 2-step protocol generated a collection of benzothiaoxazepine-1,1′-dioxides possessing stereochemical complexity in rapid fashion, where all 8 stereoisomers were accessed from commercially available starting materials

Metathesis Cascade Strategies (ROM-RCM-CM): A DOS approach to Skeletally Diverse Sultams

The development of a ring-opening metathesis/ring-closing metathesis/cross metathesis (ROM-RCM-CM) cascade strategy to the synthesis of a diverse collection of bi- and tricyclic sultams is reported. In this study, functionalized sultam scaffolds derived from intramolecular Diels-Alder (IMDA) reactions undergo metathesis cascades to yield a collection tricyclic sultams. Additional appendage based diversity was achieved by utilizing a variety of CM partners

Scaling Out by Microwave-Assisted, Continuous Flow Organic Synthesis (MACOS): Multi-Gram Synthesis of Bromo- and Fluoro-benzofused Sultams Benzthiaoxazepine-1,1-dioxides

This is the peer reviewed version of the following article: Ullah, F., Samarakoon, T., Rolfe, A., Kurtz, R. D., Hanson, P. R., & Organ, M. G. (2010). Scaling Out by Microwave-Assisted, Continuous Flow Organic Synthesis (MACOS): Multi-Gram Synthesis of Bromo- and Fluoro-benzofused Sultams Benzthiaoxazepine-1,1-dioxides. Chemistry (Weinheim an Der Bergstrasse, Germany), 16(36), 10959–10962. http://doi.org/10.1002/chem.201001651, which has been published in final form at doi.org/10.1002/chem.201001651. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving

A One-Pot, 3 Component, Domino Heck-aza-Michael Approach to Libraries of Functionalized 1, 1-Dioxido-1, 2-benzisothiazoline-2-acetic acids

This document is the Accepted Manuscript version of a Published Work that appeared in final form in Journal of Combinatorial Chemistry, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see http://doi.org/10.1021/cc900025e.A sequential three-component synthesis of functionalized benzisothiazoline-3-acetic acid 1,1- dioxides utilizing a domino Heck-aza-Michael pathway is reported. This one-pot procedure rapidly assembles functionalized benzylsulfonamides, which undergo a palladium-catalyzed, domino, Heckaza- Michael transformation in an experimentally straightforward manner. This attractive protocol has been utilized to synthesize three combinatorial sub-libraries (I-III) comprising a total of 95 compounds in high purities (≥95% for 75 compounds), yield and quantities