https://pubs.rsc.org/en/content/articlepdf/2019/NP/C8NP00092A

Marine natural products.

Flow chemistry involves the use of channels or tubing to conduct a reaction in a continuous stream rather than in a flask Flow equipment provides chemists with unique control over reaction parameters enhancing reactivity or in some cases enabling new reactions This relatively young technology has received a remarkable amount of attention in the past decade with many reports on what can be done in flow Until recently, however, the question, “Should we do this in flow?” has merely been an afterthought This review introduces readers to the basic principles and fundamentals of flow chemistry and critically discusses recent flow chemistry accounts

The Hitchhiker's Guide to Flow Chemistry

Multicomponent reactions: advanced tools for sustainable organic synthesis

http://pubs.acs.org/doi/pdf/10.1021/acs.oprd.5b00325

Flow Chemistry: Recent Developments in the Synthesis of Pharmaceutical Products

Small-molecule drug discovery can be viewed as a challenging multidimensional problem in which various characteristics of compounds - including efficacy, pharmacokinetics and safety - need to be optimized in parallel to provide drug candidates. Recent advances in areas such as microfluidics-assisted chemical synthesis and biological testing, as well as artificial intelligence systems that improve a design hypothesis through feedback analysis, are now providing a basis for the introduction of greater automation into aspects of this process. This could potentially accelerate time frames for compound discovery and optimization and enable more effective searches of chemical space. However, such approaches also raise considerable conceptual, technical and organizational challenges, as well as scepticism about the current hype around them. This article aims to identify the approaches and technologies that could be implemented robustly by medicinal chemists in the near future and to critically analyse the opportunities and challenges for their more widespread application.

/pdf/automating-drug-discovery-thg349cwp2.pdf

Automating drug discovery

Over the past decade, the integration of synthetic chemistry with flow processing has resulted in a powerful platform for molecular assembly that is making an impact throughout the chemical community. Herein, we demonstrate the extension of these tools to encompass complex natural product synthesis. We have developed a number of novel flow-through processes for reactions commonly encountered in natural product synthesis programs to achieve the first total synthesis of spirodienal A and the preparation of spirangien A methyl ester. Highlights of the synthetic route include an iridium-catalyzed hydrogenation, iterative Roush crotylations, gold-catalyzed spiroketalization and a late-stage cis-selective reduction.

Accelerating Spirocyclic Polyketide Synthesis using Flow Chemistry

Herein, we report a modular synthetic route to linear and branched homoallylic amines that operates through a sequential one-pot Lewis base/transition-metal catalyzed allylic alkylation/Hofmann rearrangement strategy. This protocol is operationally trivial, proceeds from simple and easily prepared substrates and catalysts, and enables all aspects of regio- and stereoselectivity to be controlled through a conserved experimental protocol. Overall, the high levels of enantio-, regio-, and diastereoselectivity obtained, in concert with the ability to access orthogonally protected or free amines, render this a straightforward and effective approach for the preparation of useful enantioenriched homoallylic amines. We have also demonstrated the utility of the products in the context of pharmaceutical synthesis.

A Regio- and Stereodivergent Synthesis of Homoallylic Amines by a One-Pot Cooperative-Catalysis-Based Allylic Alkylation/Hofmann Rearrangement Strategy.

Cooperative catalysis enables the direct enantioselective α-allylation of linear prochiral esters using 2-substituted allyl electrophiles. Critical to the successful development of the method was the recognition that metal-centered reactivity and the source of enantiocontrol are independent. This feature is unique to simultaneous catalysis events and permits logical tuning of the supporting ligands without compromising enantioselectivity.

Traversing Steric Limitations by Cooperative Lewis Base/Palladium Catalysis: An Enantioselective Synthesis of α-Branched Esters Using 2-Substituted Allyl Electrophiles

A lkenes are amongst the most versatile functional groups in synthetic organic chemistry. They can be readily functionalized using a broad toolbox of reagent and catalyst-based methods, which provide more complex molecules for a host of applications. Alkenes are most commonly and conveniently prepared using Wittigand Julia-type reactions of carbonyl electrophiles; however, control over the product alkene geometry can be challenging. Characteristic of these well-established methods is predominant access to one alkene isomer but not the other, whose synthesis might require multi-step preparation via an alternative sequence. Modern recourse to catalysis has provided stereospecific alkyne functionalization reactions, but these often lack the generality and functional group tolerance of the aforementioned reagent-based carbonyl olefination methods. Overall, the preparation of single alkene isomers remains a challenging problem, and it is of continuing interest and importance to develop conceptually innovative methods for their synthesis. In line with this, Gilmour and co-workers have described the riboflavincatalyzed E → Z photo-isomerization of functionalized cinnamonitriles, an approach inspired by ocular retinal isomerization.

Colin M. Pearson

Papers

Accelerating Spirocyclic Polyketide Synthesis using Flow Chemistry

A Regio- and Stereodivergent Synthesis of Homoallylic Amines by a One-Pot Cooperative-Catalysis-Based Allylic Alkylation/Hofmann Rearrangement Strategy.

Traversing Steric Limitations by Cooperative Lewis Base/Palladium Catalysis: An Enantioselective Synthesis of α-Branched Esters Using 2-Substituted Allyl Electrophiles

Alkene Photo-Isomerization Inspired by Vision

Convergent Total Syntheses of Callipeltosides A, B, and C