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Density functional theory (DFT) has become a popular method to model transition state (TS) energies to predict enantioselectivity, but the associated errors present challenges. Machine learning has emerged as a powerful tool to model enantioselectivity but generally requires large datasets for training. Herein, we describe the development of a feed forward neural network for predicting enantioselectivity of the Negishi cross-coupling reaction with Boehringer Ingelheim (BI)-type phosphines. The selectivity predicted from DFT TS energies is upgraded through the neural network based on input features including geometries, electron population, and dispersive interactions. This new approach to modeling enantioselectivity is compared to conventional approaches, including exclusive use of DFT energies, and data science approaches using features from ligands or ground states with simple neural network architectures.

Author(s): Goulas, KA; Gunbas, G; Dietrich, PJ; Sreekumar, S; Grippo, A; Chen, JP; Gokhale, AA; Toste, FD | Abstract: Herein, we present work on the catalyst development and the kinetics of acetone-butanol-ethanol (ABE) condensation. After examining multiple combinations of metal and basic catalysts reported in the literature, Cu supported on calcined hydrotalcites (HT) was found to be the optimal catalyst for the ABE condensation. This catalyst gave a six-fold increase in reaction rates over previously reported catalysts. Kinetic analysis of the reaction over CuHT and HT revealed that the rate-determining step is the C−H bond activation of alkoxides that are formed from alcohols on the Cu surface. This step is followed by the addition of the resulting aldehydes to an acetone enolate formed by deprotonation of the acetone over basic sites on the HT surface. The presence of alcohols reduces aldol condensation rates, as a result of the coverage of catalytic sites by alkoxides.

The fermentation of simple sugars to ethanol has been the most successful biofuel process to displace fossil fuel consumption worldwide thus far. However, the physical properties of ethanol and automotive components limit its application in most cases to 10-15 vol% blends with conventional gasoline. Fermentative co-production of ethanol and acetone coupled with a catalytic alkylation reaction could enable the production of gasoline blendstocks enriched in higher-chain oxygenates. Here we demonstrate a synthetic pathway for the production of acetone through the mevalonate precursor hydroxymethylglutaryl-CoA. Expression of this pathway in various strains of Escherichia coli resulted in the co-production of acetone and ethanol. Metabolic engineering and control of the environmental conditions for microbial growth resulted in controllable acetone and ethanol production with ethanol:acetone molar ratios ranging from 0.7:1 to 10.0:1. Specifically, use of gluconic acid as a substrate increased production of acetone and balanced the redox state of the system, predictively reducing the molar ethanol:acetone ratio. Increases in ethanol production and the molar ethanol:acetone ratio were achieved by co-expression of the aldehyde/alcohol dehydrogenase (AdhE) from E. coli MG1655 and by co-expression of pyruvate decarboxylase (Pdc) and alcohol dehydrogenase (AdhB) from Z. mobilis. Controlling the fermentation aeration rate and pH in a bioreactor raised the acetone titer to 5.1 g L(-1) , similar to that obtained with wild-type Clostridium acetobutylicum. Optimizing the metabolic pathway, the selection of host strain, and the physiological conditions employed for host growth together improved acetone titers over 35-fold (0.14-5.1 g/L). Finally, chemical catalysis was used to upgrade the co-produced ethanol and acetone at both low and high molar ratios to higher-chain oxygenates for gasoline and jet fuel applications. Biotechnol. Bioeng. 2016;113: 2079-2087. © 2016 Wiley Periodicals, Inc.

Lignin samples isolated from Miscanthus giganteus using organosolv processes were treated with vanadium catalysts that were previously developed in our group. We demonstrate that the catalyst with high β-O-4' bond-cleaving activity in dimeric lignin models was also effective in depolymerizing actual lignin. Molecular weight-lowering was evidenced by gel permeation chromatography (GPC), whereas 2D NMR experi- ments showed that β-O-4' linkages were selectively cleaved in the degradation process, just as in the case of lignin models. Monophenolic degradation products were also formed, and the individual molecules were identified and quantified by GC/MS.

© 2016 American Chemical Society. Condensation reactions such as Guerbet and aldol are important since they allow for C-C bond formation and give higher molecular weight oxygenates. An initial study identified Pd-supported on hydrotalcite as an active catalyst for the transformation, although this catalyst showed extensive undesirable decarbonylation. A catalyst containing Pd and Cu in a 3:1 ratio dramatically decreased decarbonylation, while preserving the high catalytic rates seen with Pd-based catalysts. A combination of XRD, EXAFS, TEM, and CO chemisorption and TPD revealed the formation of CuPd bimetallic nanoparticles with a Cu-enriched surface. Finally, density functional theory studies suggest that the surface segregation of Cu atoms in the bimetallic alloy catalyst produces Cu sites with increased reactivity, while the Pd sites responsible for unselective decarbonylation pathways are selectively poisoned by CO.

The fermentation of simple sugars to ethanol has been the most successful biofuel process to displace fossil fuel consumption worldwide thus far. However, the physical properties of ethanol and automotive components limit its application in most cases to 10-15 vol% blends with conventional gasoline. Fermentative co-production of ethanol and acetone coupled with a catalytic alkylation reaction could enable the production of gasoline blendstocks enriched in higher-chain oxygenates. Here we demonstrate a synthetic pathway for the production of acetone through the mevalonate precursor hydroxymethylglutaryl-CoA. Expression of this pathway in various strains of Escherichia coli resulted in the co-production of acetone and ethanol. Metabolic engineering and control of the environmental conditions for microbial growth resulted in controllable acetone and ethanol production with ethanol:acetone molar ratios ranging from 0.7:1 to 10.0:1. Specifically, use of gluconic acid as a substrate increased production of acetone and balanced the redox state of the system, predictively reducing the molar ethanol:acetone ratio. Increases in ethanol production and the molar ethanol:acetone ratio were achieved by co-expression of the aldehyde/alcohol dehydrogenase (AdhE) from E. coli MG1655 and by co-expression of pyruvate decarboxylase (Pdc) and alcohol dehydrogenase (AdhB) from Z. mobilis. Controlling the fermentation aeration rate and pH in a bioreactor raised the acetone titer to 5.1 g L(-1) , similar to that obtained with wild-type Clostridium acetobutylicum. Optimizing the metabolic pathway, the selection of host strain, and the physiological conditions employed for host growth together improved acetone titers over 35-fold (0.14-5.1 g/L). Finally, chemical catalysis was used to upgrade the co-produced ethanol and acetone at both low and high molar ratios to higher-chain oxygenates for gasoline and jet fuel applications. Biotechnol. Bioeng. 2016;113: 2079-2087. © 2016 Wiley Periodicals, Inc.

© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. Life-cycle analysis (LCA) allows the scientific community to identify the sources of greenhouse gas (GHG) emissions of novel routes to produce renewable fuels. Herein, we integrate LCA into our investigations of a new route to produce drop-in diesel/jet fuel by combining furfural, obtained from the catalytic dehydration of lignocellulosic pentose sugars, with alcohols that can be derived from a variety of bio- or petroleum-based feedstocks. As a key innovation, we developed recyclable transition-metal-free hydrotalcite catalysts to promote the dehydrogenative cross-coupling reaction of furfural and alcohols to give high molecular weight adducts via a transfer hydrogenation-aldol condensation pathway. Subsequent hydrodeoxygenation of adducts over Pt/NbOPO4 yields alkanes. Implemented in a Brazilian sugarcane biorefinery such a process could result in a 53-79% reduction in life-cycle GHG emissions relative to conventional petroleum fuels and provide a sustainable source of low carbon diesel/jet fuel. Drop into renewable diesel: Dehydrogenative cross-condensation of lignocellulosic furfural with a variety of alcohols derived from biological and petrochemical sources provides aldol adducts that are further subjected to hydrodeoxygenation. The alkanes furnished from this process are drop-in components for jet and diesel fuels. The life cycle assessment of this technology shows net reductions in greenhouse gas (GHG) emissions of 57-68% relative to petroleum-derived fuels.

Decarbonizing the transportation sector is critical to achieving global climate change mitigation. Although biofuels will play an important role in conventional gasoline and diesel applications, bioderived solutions are particularly important in jet fuels and lubricants, for which no other viable renewable alternatives exist. Producing compounds for jet fuel and lubricant base oil applications often requires upgrading fermentation products, such as alcohols and ketones, to reach the appropriate molecular-weight range. Ketones possess both electrophilic and nucleophilic functionality, which allows them to be used as building blocks similar to alkenes and aromatics in a petroleum refining complex. Here, we develop a method for selectively upgrading biomass-derived alkyl methyl ketones with95% yields into trimer condensates, which can then be hydrodeoxygenated in near-quantitative yields to give a new class of cycloalkane compounds. The basic chemistry developed here can be tailored for aviation fuels as well as lubricants by changing the production strategy. We also demonstrate that a sugarcane biorefinery could use natural synergies between various routes to produce a mixture of lubricant base oils and jet fuels that achieve net life-cycle greenhouse gas savings of up to 80%.

© 2015, National Academy of Sciences. All rights reserved. Decarbonizing the transportation sector is critical to achieving global climate change mitigation. Although biofuels will play an important role in conventional gasoline and diesel applications, bioderived solutions are particularly important in jet fuels and lubricants, for which no other viable renewable alternatives exist. Producing compounds for jet fuel and lubricant base oil applications often requires upgrading fermentation products, such as alcohols and ketones, to reach the appropriate molecular-weight range. Ketones possess both electrophilic and nucleophilic functionality, which allows them to be used as building blocks similar to alkenes and aromatics in a petroleum refining complex. Here, we develop a method for selectively upgrading biomass-derived alkyl methyl ketones with >95% yields into trimer condensates, which can then be hydrodeoxygenated in near-quantitative yields to give a new class of cycloalkane compounds. The basic chemistry developed here can be tailored for aviation fuels as well as lubricants by changing the production strategy. We also demonstrate that a sugarcane biorefinery could use natural synergies between various routes to produce a mixture of lubricant base oils and jet fuels that achieve net life-cycle greenhouse gas savings of up to 80%.

Clostridium acetobutylicum is a bacterial species that ferments sugar to a mixture of organic solvents (acetone, butanol and ethanol). This protocol delineates a methodology to combine solventogenic clostridial fermentation and chemical catalysis via extractive fermentation for the production of biofuel blendstocks. Extractive fermentation of C. acetobutylicum is operated in fed-batch mode with a concentrated feed solution (500 grams per liter glucose and 50 grams per liter yeast extract) for 60 h, producing in excess of 40 g of solvents (acetone, butanol and ethanol) between the completely immiscible extractant and aqueous phases of the bioreactor. After distillation of the extractant phase, the acetone, butanol and ethanol mixture is upgraded to long-chain ketones over a palladium-hydrotalcite (Pd-HT) catalyst. This reaction is generally carried out in batch with a high-pressure Q-tube for 20 h at 250 °C. Following this protocol enables the production of ∼0.5 g of high-value biofuel precursors from a 1.7-g portion of fermentation solvents.

© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. A highly efficient water-tolerant, solid-base catalyst for the self-condensation of biomass-derived methyl ketones to jet-diesel fuel precursors was developed by grafting site-isolated secondary amines on silica-alumina supports. It is shown that apart from the nature and density of amine groups and the spatial separation of the acidic and basic sites, the acidity of the support material plays a critical role in defining the catalytic activity. It is also found that a combination of weakly acidic silanol/aluminol with secondary amine groups can mimic proline catalysts and are more effective in catalyzing the selective dimerization reaction than the combination of amines with organic acids. In situ FTIR measurements demonstrate that acidic groups activate methyl ketones through their carbonyl groups leading to a favorable C-C bond formation step involving an enamine intermediate. DFT analysis of the reaction pathway confirms that C-C bond formation is the rate-limiting step.

Processes for the biotechnological production of kerosene and diesel blendstocks are often economically unattractive due to low yields and product titers. Recently, Clostridium acetobutylicum fermentation products acetone, butanol, and ethanol (ABE) were shown to serve as precursors for catalytic upgrading to higher chain-length molecules that can be used as fuel substitutes. To produce suitable kerosene and diesel blendstocks, the butanol:acetone ratio of fermentation products needs to be increased to 2-2.5:1, while ethanol production is minimized. Here we show that the overexpression of selected proteins changes the ratio of ABE products relative to the wild type ATCC 824 strain. Overexpression of the native alcohol/aldehyde dehydrogenase (AAD) has been reported to primarily increase ethanol formation in C. acetobutylicum. We found that overexpression of the AAD(D485G) variant increased ethanol titers by 294%. Catalytic upgrading of the 824(aad(D485G)) ABE products resulted in a blend with nearly 50wt%≤C9 products, which are unsuitable for diesel. To selectively increase butanol production, C. beijerinckii aldehyde dehydrogenase and C. ljungdhalii butanol dehydrogenase were co-expressed (strain designate 824(Cb ald-Cl bdh)), which increased butanol titers by 27% to 16.9gL(-1) while acetone and ethanol titers remained essentially unaffected. The solvent ratio from 824(Cb ald-Cl bdh) resulted in more than 80wt% of catalysis products having a carbon chain length≥C11 which amounts to 9.8gL(-1) of products suitable as kerosene or diesel blendstock based on fermentation volume. To further increase solvent production, we investigated expression of both native and heterologous chaperones in C. acetobutylicum. Expression of a heat shock protein (HSP33) from Bacillus psychrosaccharolyticus increased the total solvent titer by 22%. Co-expression of HSP33 and aldehyde/butanol dehydrogenases further increased ABE formation as well as acetone and butanol yields. HSP33 was identified as the first heterologous chaperone that significantly increases solvent titers above wild type C. acetobutylicum levels, which can be combined with metabolic engineering to further increase solvent production.

Biological and chemocatalytic processes are tailored in order to maximize the production of sustainable biodiesel from lignocellulosic sugar. Thus, the combination of hydrotalcite-supported copper(II) and palladium(0) catalysts with a modification of the fermentation from acetone-butanol-ethanol to isopropanol-butanol-ethanol predictably produces higher concentrations of diesel-range components in the alkylation reaction.

The integration of biological and chemocatalytic routes can be used to convert acetone–butanol–ethanol fermentation products efficiently into ketones by palladium-catalysed alkylation, leading to a renewable method for the alternative production of petrol, jet and diesel blend stocks in high yield. Using a method that combines biological and chemical catalysis, Dean Toste and colleagues demonstrate the efficient conversion of acetone–butanol–ethanol fermentation products into ketones via a palladium-catalysed alkylation. With further improvement, this process could provide a means of selectively manufacturing gasoline, jet and diesel blend stocks from lignocellulosic and cane sugars derived from biomass at yields close to the theoretical maxima. Nearly one hundred years ago, the fermentative production of acetone by Clostridium acetobutylicum provided a crucial alternative source of this solvent for manufacture of the explosive cordite. Today there is a resurgence of interest in solventogenic Clostridium species to produce n-butanol and ethanol for use as renewable alternative transportation fuels1,2,3. Acetone, a product of acetone–n-butanol–ethanol (ABE) fermentation, harbours a nucleophilic α-carbon, which is amenable to C–C bond formation with the electrophilic alcohols produced in ABE fermentation. This functionality can be used to form higher-molecular-mass hydrocarbons similar to those found in current jet and diesel fuels. Here we describe the integration of biological and chemocatalytic routes to convert ABE fermentation products efficiently into ketones by a palladium-catalysed alkylation. Tuning of the reaction conditions permits the production of either petrol or jet and diesel precursors. Glyceryl tributyrate was used for the in situ selective extraction of both acetone and alcohols to enable the simple integration of ABE fermentation and chemical catalysis, while reducing the energy demand of the overall process. This process provides a means to selectively produce petrol, jet and diesel blend stocks from lignocellulosic and cane sugars at yields near their theoretical maxima.