Further developments of the “computer-aided synthesis planning” software Chematica (bought by Merck and further developed as ‘Synthia’):


  • T. Badowski, K. Molga, and B.A. Grzybowski, "Selection of cost-effective yet chemically diverse pathways from the networks of computer-generated retrosynthetic plans", Chemical Science, vol. 10, pp. 4640-4651, 2019. http://dx.doi.org/10.1039/C8SC05611K
  • [Lilly]


  • G.R. Lambertus, L.P. Webster, T.M. Braden, B.M. Campbell, J. McClary Groh, T.D. Maloney, P. Milenbaugh, R.D. Spencer, W. Sun, and M.D. Johnson, "Development of Universal, Automated Sample Acquisition, Preparation, and Delivery Devices and Methods for Pharmaceutical Applications", Organic Process Research & Development, vol. 23, pp. 189-210, 2018. http://dx.doi.org/10.1021/acs.oprd.8b00280
  • [Prof. Bartosz A. Grzybowski]

  • W. Beker, E.P. Gajewska, T. Badowski, and B.A. Grzybowski, "Prediction of Major Regio-, Site-, and Diastereoisomers in Diels-Alder Reactions by Using Machine-Learning: The Importance of Physically Meaningful Descriptors", Angewandte Chemie International Edition, vol. 58, pp. 4515-4519, 2018. http://dx.doi.org/10.1002/anie.201806920
  • the Jamison group at MIT has published an amazing attempt to create a “plug-and-play, continuous-flow chemical synthesis system” that is able to optimize, in an automated fashion, chemical reactions :

    « Reconfigurable system for automated optimization of diverse chemical reactions » : Bédard, Adamo, Aroh, Russell, Bedermann, Torosian, Yue, Jensen, Jamison, Science 2018, 361(6408), 1220-1225 [10.1126/science.aat0650]

    From a technology point of view, their device comprises “a sort of universal connector bay, and five different modules (so far) that plug into it: a heated reactor (up to 120°C), a cooled reactor (to –20°C), an LED photochemistry reactor, a solid-supported-reagent packed-bed reactor (, a membrane-based liquid-liquid separator (for extraction). There’s also a bypass connector for unused bays, etc…”

    Then they picked 8 different reactions, covering a pretty good range of conceptually different reactions:

    • A Pall-Knorr pyrrole synthesis (amines with 1,4-diketones),
    • a Buchwald-Hartwig coupling system,
    • a Horner-Wadsworth-Emmons olefination,
    • a reductive amination,
    • a Suzuki-Miyaura coupling,
    • a nucleophilic aromatic substitution,
    • photoredox iminium generation/nucleophile trapping,
    • ketene generation from an acid chloride followed by cycloaddition with an alkene


    Their machine is able to automatically vary a number (typically 3 or 4) of variables, generating 30 to 60 reactions on a timescale of hours, and the optimization is controlled by an off-the-shelf MATLAB module called SNOBFIT.

    Compounds could be produced in up to gram quantities once the reactions were optimized on 10mg scale – as with flow systems in general, scaleup can mean just running the system longer.

    Here’s how the group sums up (emphasis added by Derek Lowe, from the In The Pipeline blog):

    This reconfigurable system has changed the way we approach experimentation and optimization in several ways. It accelerates the synthesis of lab-scale quantities of molecules and allows investigators to direct more of their efforts toward the creative aspects of research. The system’s generality and ease of use obviates the need for expertise in flow chemistry to realize its benefits. The system also provides a means to optimize and evaluate the scope of a reaction in a matter of hours or days and do so under identical reaction conditions for each substrate of interest, if desired. Transfer of experimental results is now direct, electronic, and seamless; the time-consuming exercise of reoptimizing literature procedures should thus diminish in its frequency.

  • A. Bédard, A. Adamo, K.C. Aroh, M.G. Russell, A.A. Bedermann, J. Torosian, B. Yue, K.F. Jensen, and T.F. Jamison, "Reconfigurable system for automated optimization of diverse chemical reactions", Science, vol. 361, pp. 1220-1225, 2018. http://dx.doi.org/10.1126/science.aat0650
  • Optimization and robustness assessment of a catalytic coupling (here a C-N coupling) using high-throughput experimentation. Performed at Merck Inc.
    Interesting to note how robust the Cu-based catalysts performed compared to Pd-catalysis:


  • S. Lin, S. Dikler, W.D. Blincoe, R.D. Ferguson, R.P. Sheridan, Z. Peng, D.V. Conway, K. Zawatzky, H. Wang, T. Cernak, I.W. Davies, D.A. DiRocco, H. Sheng, C.J. Welch, and S.D. Dreher, "Mapping the dark space of chemical reactions with extended nanomole synthesis and MALDI-TOF MS", Science, vol. 361, pp. eaar6236, 2018. http://dx.doi.org/10.1126/science.aar6236