Automatic generation of 3D-printed reactionware for chemical synthesis digitization using ChemSCAD

We describe a system, ChemSCAD, for the creation of digital reactors based on the chemical operations, physical parameters, and synthetic sequence to produce a given target compound, to show that the system can translate the gram-scale batch synthesis of the antiviral compound Ribavirin (yield 43% over three steps), the narcolepsy drug Modafinil (yield 60% over three steps), and both batch and flow instances of the synthesis of the anticancer agent Lomustine (batch yield 65% over two steps) in purities greater than or equal to 96%. The syntheses of compounds developed using the ChemSCAD system, including reactor designs and analytical data, can be stored in a database repository, with the information necessary to critically evaluate and improve upon reactionware syntheses being easily shared and versioned

Asymmetric Synthesis of Polysubstituted 4-Amino- and 3,4-Diaminochromanes with a Chiral Multifunctional Organocatalyst

A series of multifunctional catalysts with two chiral diaminocyclohexane units were developed and successfully applied in the asymmetric oxa-Michael–aza-Henry cascade reaction of salicylaldimines with nitroolefins. This approach provides a simple and efficient entry to polysubstituted chiral 4-aminobenzopyrans with three consecutive stereocenters and in high yield (up to 97%) with excellent stereoselectivity (up to 98% ee and >99:1 dr). Facile access to the nonsymmetric optically pure 3,4-diaminochromanes was also obtained

Asymmetric Synthesis of Polysubstituted 4-Amino- and 3,4-Diaminochromanes with a Chiral Multifunctional Organocatalyst

A series of multifunctional catalysts with two chiral diaminocyclohexane units were developed and successfully applied in the asymmetric oxa-Michael–aza-Henry cascade reaction of salicylaldimines with nitroolefins. This approach provides a simple and efficient entry to polysubstituted chiral 4-aminobenzopyrans with three consecutive stereocenters and in high yield (up to 97%) with excellent stereoselectivity (up to 98% ee and >99:1 dr). Facile access to the nonsymmetric optically pure 3,4-diaminochromanes was also obtained

An autonomous portable platform for universal chemical synthesis

Robotic systems for synthetic chemistry are becoming more common, but they are expensive, fixed to a narrow set of reactions, and must be used within a complex laboratory environment. A portable system that could synthesize known molecules anywhere, on demand, and in a fully automated way, could revolutionize access to important molecules. Here we present a portable suitcase-sized chemical synthesis platform containing all the modules required for synthesis and purification. The system uses a chemical programming language coupled to a digital reactor generator to produce reactors and executable protocols based on text-based literature syntheses. Simultaneously, the platform generates a reaction pressure fingerprint, used to monitor processes within the reactors and remotely perform a protocol quality control. We demonstrate the system by synthesizing five small organic molecules, four oligopeptides and four oligonucleotides, in good yields and purities, with a total of 24,936 base steps executed over 329 h of platform runtime

Asymmetric Multicomponent Sulfa-Michael/Mannich Cascade Reaction: Synthetic Access to 1,2-Diamino-3-Organosulfur Compounds and 2‑Nitro Allylic Amines

A novel catalytic asymmetric three-component intermolecular sulfa-Michael/Mannich cascade reaction has been developed using a chiral multifunctional catalyst. This reaction provides facile access to 1-amino-2-nitro-3-organosulfur compounds bearing three consecutive stereocenters in high yields (up to 96%) with good diastereo- (up to 91:4:4:1 <i>dr</i>) and excellent enantioselectivities (93–99% <i>ee</i>). Furthermore, the products of this reaction could be facilely transformed into potentially bioactive 1, 2-diamino-3-organosulfur compounds and 2-nitro allylic amines

Automatic Generation of 3D Printed Reactionware for Chemical Synthesis Digitization using ChemSCAD

Digital chemistry aims to define a hard link from the top abstraction layer in chemistry down to the synthesis, but this is difficult in traditional glassware since it is not possible to explicitly link the architecture with the unit operations. By 3D printing the synthesis modules in the precise order to affect the synthesis, it is possible to create digitally encoded reactors for chemical synthesis in ‘reactionware’. However, creation of these devices requires a specific skillset for CAD modelling which few synthetic chemists have. Herein, we describe an intuitive system, ChemSCAD, for the creation of digital reactor models based on the chemical operations, physical parameters and synthetic sequence to produce a given target compound. We demonstrate the ability of the ChemSCAD system to translate the gram-scale batch synthesis of the anti-viral compound Ribavirin (yield 43% over three steps), the narcolepsy drug Modafinil (yield 60% over three steps), and both batch and flow instances of the synthesis of the anti-cancer agent Lomustine (batch yield 65% over two steps) in purities ≥96%. The syntheses of compounds developed using the ChemSCAD system, including reactor designs and analytical data, can be stored in a single database repository where all the information necessary to critically evaluate, and improve upon, reactionware syntheses can be easily shared and versioned.</p

Delocalized, Asynchronous, Closed-Loop Discovery of Organic Laser Emitters

Contemporary materials discovery requires intricate sequences of synthesis, formulation and characterization that often span multiple locations with specialized expertise or instrumentation. To accelerate these workflows, we present a cloud-based strategy that enables delocalized and asynchronous design–make–test–analyze cycles. We showcase this approach through the exploration of molecular gain materials for organic solid-state lasers as a frontier application in molecular optoelectronics. Distributed robotic synthesis and in-line property characterization, orchestrated by a cloud-based AI experiment planner, resulted in the discovery of 21 new state-of-the-art materials. Automated gram-scale synthesis ultimately allowed for the verification of best-in-class stimulated emission in a thin-film device. Demonstrating the asynchronous integration of five laboratories across the globe, this workflow provides a blueprint for delocalizing – and democratizing – scientific discovery