Clear directions for a robotic platform: The chemistry literature contains more than a century's worth of instructions for making molecules, all written by and for humans. Steiner et al. developed an autonomous compiler and robotic laboratory platform to synthesize organic compounds on the basis of standardized methods descriptions (see the Perspective by Milo). The platform comprises conventional equipment such as round-bottom flasks, separatory funnels, and a rotary evaporator to maximize its compatibility with extant literature. The authors showcase the system with short syntheses of three common pharmaceuticals that proceeded comparably to manual synthesis. Science , this issue p. eaav2211 ; see also p. 122

The oxidation of the C–H and C═C bonds of hydrocarbons with H₂O₂ catalyzed by non-heme iron complexes with pentadentate ligands is widely accepted as involving a reactive Fe^IV═O species such as [(N4Py)Fe^IV═O]²⁺ formed by homolytic cleavage of the O–O bond of an Fe^III–OOH intermediate (where N4Py is 1,1-bis(pyridin-2-yl)-N,N-bis(pyridin-2-ylmethyl)methanamine). We show here that at low H₂O₂ concentrations the Fe^IV═O species formed is detectable in methanol. Furthermore, we show that the decomposition of H₂O₂ to water and O₂ is an important competing pathway that limits efficiency in the terminal oxidant and indeed dominates reactivity except where only sub-/near-stoichiometric amounts of H₂O₂ are present. Although independently prepared [(N4Py)Fe^IV═O]²⁺ oxidizes stoichiometric H₂O₂ rapidly, the rate of formation of Fe^IV═O from the Fe^III–OOH intermediate is too low to account for the rate of H₂O₂ decomposition observed under catalytic conditions. Indeed, with excess H₂O₂, disproportionation to O₂ and H₂O is due to reaction with the Fe^III–OOH intermediate and thereby prevents formation of the Fe^IV═O species. These data rationalize that the activity of these catalysts with respect to hydrocarbon/alkene oxidation is maximized by maintaining sub-/near-stoichiometric steady-state concentrations of H₂O₂, which ensure that the rate of the H₂O₂ oxidation by the Fe^III–OOH intermediate is less than the rate of the O–O bond homolysis and the subsequent reaction of the Fe^IV═O species with a substrate.

A reactive high-valent dinuclear nickel(IV) oxido bridged complex is reported that can be formed at room temperature by reaction of [(L)₂Ni(II)₂(μ-X)₃]X (X = Cl or Br) with NaOCl in methanol or acetonitrile (where L = 1,4,7-trimethyl-1,4,7-triazacyclononane). The unusual Ni(IV) oxido species is stabilized within a dinuclear tris-μ-oxido-bridged structure as [(L)₂Ni(IV)₂(μ-O)₃]²⁺. Its structure and its reactivity with organic substrates are demonstrated through a combination of UV–vis absorption, resonance Raman, ¹H NMR, EPR, and X-ray absorption (near-edge) spectroscopy, ESI mass spectrometry, and DFT methods. The identification of a Ni(IV)-O species opens opportunities to control the reactivity of NaOCl for selective oxidations.

Robotic platforms for chemistry are developing rapidly but most systems are not currently able to adapt to changing circumstances in real-time. We present a dynamically programmable system capable of making, optimizing, and discovering new molecules which utilizes seven sensors that continuously monitor the reaction. By developing a dynamic programming language, we demonstrate the 10-fold scale-up of a highly exothermic oxidation reaction, end point detection, as well as detecting critical hardware failures. We also show how the use of in-line spectroscopy such as HPLC, Raman, and NMR can be used for closed-loop optimization of reactions, exemplified using Van Leusen oxazole synthesis, a four-component Ugi condensation and manganese-catalysed epoxidation reactions, as well as two previously unreported reactions, discovered from a selected chemical space, providing up to 50% yield improvement over 25–50 iterations. Finally, we demonstrate an experimental pipeline to explore a trifluoromethylations reaction space, that discovers new molecules.

Fe^III–hypohalite complexes have been implicated in a wide range of important enzyme-catalyzed halogenation reactions including the biosynthesis of natural products and antibiotics and post-translational modification of proteins. The absence of spectroscopic data on such species precludes their identification. Herein, we report the generation and spectroscopic characterization of nonheme Fe^III–hypohalite intermediates of possible relevance to iron halogenases. We show that Fe^III-OCl polypyridylamine complexes can be sufficiently stable at room temperature to be characterized by UV/Vis absorption, resonance Raman and EPR spectroscopies, and cryo-ESIMS. DFT methods rationalize the pathways to the formation of the Fe^III-OCl, and ultimately Fe^IVO, species and provide indirect evidence for a short-lived Fe^II-OCl intermediate. The species observed and the pathways involved offer insight into and, importantly, a spectroscopic database for the investigation of iron halogenases.