Computer-designed repurposing of chemical wastes into drugs.

As the chemical industry continues to produce considerable quantities of waste chemicals, it is essential to devise 'circular chemistry' schemes to productively back-convert at least a portion of these unwanted materials into useful products. Despite substantial progress in the degradation of some classes of harmful chemicals, work on 'closing the circle'-transforming waste substrates into valuable products-remains fragmented and focused on well known areas. Comprehensive analyses of which valuable products are synthesizable from diverse chemical wastes are difficult because even small sets of waste substrates can, within few steps, generate millions of putative products, each synthesizable by multiple routes forming densely connected networks.

A robotic platform for flow synthesis of organic compounds informed by AI planning.

The synthesis of complex organic molecules requires several stages, from ideation to execution, that require time and effort investment from expert chemists. Here, we report a step toward a paradigm of chemical synthesis that relieves chemists from routine tasks, combining artificial intelligence-driven synthesis planning and a robotically controlled experimental platform. Synthetic routes are proposed through generalization of millions of published chemical reactions and validated in silico to maximize their likelihood of success.

Decomposition of Olefin Metathesis Catalysts by Brønsted Base: Metallacyclobutane Deprotonation as a Primary Deactivating Event.

Brønsted bases of widely varying strength are shown to decompose the metathesis-active Ru intermediates formed by the second-generation Hoveyda and Grubbs catalysts. Major products, in addition to propenes, are base·HCl and olefin-bound, cyclometalated dimers [RuCl(κ-HIMes-H)(HC═CHR)] Ru-3. These are generated in ca.

Towards More Efficient, Greener Syntheses through Flow Chemistry.

Technological advances have an important role in the design of greener synthetic processes. In this Personal Account, we describe a wide range of thermal, photochemical, catalytic, and biphasic chemical transformations examined by our group. Each of these demonstrate how the merits of a continuous flow synthesis platform can align with some of the goals put forth by the Twelve Principles of Green Chemistry.

A General Decomposition Pathway for Phosphine-Stabilized Metathesis Catalysts: Lewis Donors Accelerate Methylidene Abstraction.

Sterically accessible Lewis donors are shown to accelerate decomposition during catalysis, for a broad range of Grubbs-class metathesis catalysts. These include benzylidene derivatives RuCl(NHC)(PCy)(═CHPh) (Ru-2: NHC = HIMes, a; IMes, b; HIPr, c; IPr, d; HITol, e) and indenylidene complexes RuCl(NHC)(PCy)(═CH) (NHC = HIMes, Ru-2f; IMes, Ru-2g). All of these precatalysts form methylidene complex RuCl(NHC)(═CH) Ru-3 as the active species in metathesis of terminal olefins, and generate RuCl(NHC)(PCy)(═CH) Ru-4 as the catalyst resting state.

Olefin Metathesis at the Dawn of Implementation in Pharmaceutical and Specialty-Chemicals Manufacturing.

The recent uptake of molecular metathesis catalysts in specialty-chemicals and pharmaceutical manufacturing is reviewed.

The divergent effects of strong NHC donation in catalysis.

Strong σ-donation from NHC ligands (NHC = N-heterocyclic carbene) is shown to have profoundly conflicting consequences for the reactivity of transition-metal catalysts. Such donation is regarded as central to high catalyst activity in many contexts, of which the second-generation Grubbs metathesis catalysts (RuCl(NHC)(PCy)([double bond, length as m-dash]CHPh), ) offer an early, prominent example. Less widely recognized is the dramatically inhibiting impact of NHC ligation on initiation of , and on re-entry into the catalytic cycle from the resting-state methylidene species RuCl(NHC)(PCy)([double bond, length as m-dash]CH), .

Chemical plants: high-value molecules from essential oils.

As society faces a future of dwindling petrochemical supplies at increasing cost, much attention has been focused on methods to degrade biomass into renewable commodity-chemical building blocks. Reported here is a powerful complementary approach that amplifies the complexity of molecular structures present in plant materials. Essential-oil phenylpropenoids are transformed via acrylate cross-metathesis into potent antioxidants that are widely used in perfumery and cosmetics, and in treating disorders associated with oxidative damage.

Ethylene-promoted versus ethylene-free enyne metathesis.

The role of ethylene in promoting metathesis of acetylenic enynes is probed within the context of ring-closing enyne metathesis, using first- and second-generation Grubbs catalysts. Under inert atmosphere, rapid catalyst deactivation is observed by calibrated GC-FID analysis for substrates with minimal propargylic bulk. MALDI-TOF mass spectra reveal a Ru(enyne)(2) derivative that exhibits very low reactivity toward both enyne and ethylene.

Capturing In+ monomers in a neutral weakly coordinating environment.

The application of a new bis(imino)pyridine ligand allowed the isolation and characterization of [{2,4-(t)Bu(2)C(6)H(3)N=CPh}(2)(NC(5)H(3))]In(+)(OTf)(-) as the first low-valent, main-group metal complex of this ligand scaffold. Structural analysis revealed a unique monomeric In(I) species with a surprisingly long metal-ligand bond. In conjunction with a density functional theory investigation, this complex is shown to display only nominal donor-acceptor interactions between the metal and the neutral ligand.