Chemical synthesis generally requires labor-intensive, sometimes tedious trial-and-error optimization of reaction conditions. Here, we describe a plug-and-play, continuous-flow chemical synthesis system that mitigates this challenge with an integrated combination of hardware, software, and analytics. The system software controls the user-selected reagents and unit operations (reactors and separators), processes reaction analytics (high-performance liquid chromatography, mass spectrometry, vibrational spectroscopy), and conducts automated optimizations. The capabilities of this system are demonstrated in high-yielding implementations of C-C and C-N cross-coupling, olefination, reductive amination, nucleophilic aromatic substitution (SNAr), photoredox catalysis, and a multistep sequence. The graphical user interface enables users to initiate optimizations, monitor progress remotely, and analyze results. Subsequent users of an optimized procedure need only download an electronic file, comparable to a smartphone application, to implement the protocol on their own apparatus.

Described herein is a synthetic strategy for the total synthesis of (±)-phomoidride D. This highly efficient and stereoselective approach provides rapid assembly of the carbocyclic core by way of a tandem phenolic oxidation/intramolecular Diels-Alder cycloaddition. A subsequent SmI -mediated cyclization cascade delivers an isotwistane intermediate poised for a Wharton fragmentation that unveils the requisite bicyclo[4.3.1]decene skeleton and sets the stage for synthesis completion.

An enantioselective synthesis of the ABD-ring of (−)-phomactin A is described here. The sequence features Rawal’s asymmetric Diels-Alder cycloaddition. The overall length is significantly reduced from our previous attempt.

An efficient and highly stereoselective approach toward the phomoidride family of natural products is described. The carbocyclic core structure was assembled using a tandem phenolic oxidation/Diels-Alder cycloaddition and a tandem 5-exo-trig/5-exo-trig radical cyclization to deliver an isotwistane intermediate that, upon a late-stage xanthate-initiated Grob fragmentation, furnishes the requisite bicyclo[4.3.1]decene.

Described herein is as ynthetic strategy for the total synthesis of (AE)-phomoidride D. This highly efficient and stereoselective approach provides rapid assembly of the carbocyclic core by wayo fat andem phenolic oxidation/ intramolecular Diels-Alder cycloaddition. Asubsequent SmI 2mediated cyclization cascade delivers an isotwistane intermediate poised for aW harton fragmentation that unveils the requisite bicyclo[4.3.1]decene skeleton and sets the stage for synthesis completion.

The carbocyclic core of the phomoidrides has been synthesized efficiently and in high yield. Key steps include a phenolic oxidation/intramolecular Diels-Alder sequence, tandem radical cyclization, and a late-stage Wharton fragmentation of a densely functionalized isotwistane skeleton.

The use of strong organometallic bases and nucleophiles is commonplace in modern organic synthesis. That they react with a wide range of functional groups requires accurate and precise stoichiometry in reactions that utilize them. For best results, these bases are titrated prior to use, and such titrations can be timeconsuming and variable due to human error near the end point. Herein, we describe an automated method for titrations of multiple commercial organometallic reagents enabled by continuous flow. Through utilizations of continuous monitoring via UV−vis spectroscopy and a feedback loop developed within LabVIEW, titrations with enhanced reproducibility were provided over current batch procedures.