The Experts below are selected from a list of 84 Experts worldwide ranked by ideXlab platform
Nuria Sotomayor - One of the best experts on this subject based on the ideXlab platform.
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Perturbation-Theory and Machine Learning (PTML) Model for High-Throughput Screening of Parham Reactions: Experimental and Theoretical Studies.
Journal of chemical information and modeling, 2018Co-Authors: Lorena Simon-vidal, Esther Lete, Nuria Sotomayor, Sonia Arrasate, Oihane Garcia-calvo, Uxue Oteo, Humberto González-díazAbstract:Machine learning (ML) algorithms are gaining importance in the processing of chemical information and modeling of chemical reactivity problems. In this work, we have developed a perturbation-theory and machine learning (PTML) model combining perturbation theory (PT) and ML algorithms for predicting the yield of a given reaction. For this purpose, we have selected Parham Cyclization, which is a general and powerful tool for the synthesis of heterocyclic and carbocyclic compounds. This reaction has both structural (substitution pattern on the substrate, internal electrophile, ring size, etc.) and operational variables (organolithium reagent, solvent, temperature, time, etc.), so predicting the effect of changes on substrate design (internal elelctrophile, halide, etc.) or reaction conditions on the yield is an important task that could help to optimize the reaction design. The PTML model developed uses PT operators to account for perturbations under experimental conditions and/or structural variables of all...
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Perturbation-Theory and Machine Learning (PTML) Model for High-Throughput Screening of Parham Reactions: Experimental and Theoretical Studies
2018Co-Authors: Lorena Simón-vidal, Esther Lete, Nuria Sotomayor, Sonia Arrasate, Uxue Oteo, Oihane García-calvo, Humberto González-díazAbstract:Machine learning (ML) algorithms are gaining importance in the processing of chemical information and modeling of chemical reactivity problems. In this work, we have developed a perturbation-theory and machine learning (PTML) model combining perturbation theory (PT) and ML algorithms for predicting the yield of a given reaction. For this purpose, we have selected Parham Cyclization, which is a general and powerful tool for the synthesis of heterocyclic and carbocyclic compounds. This reaction has both structural (substitution pattern on the substrate, internal electrophile, ring size, etc.) and operational variables (organolithium reagent, solvent, temperature, time, etc.), so predicting the effect of changes on substrate design (internal elelctrophile, halide, etc.) or reaction conditions on the yield is an important task that could help to optimize the reaction design. The PTML model developed uses PT operators to account for perturbations under experimental conditions and/or structural variables of all the molecules involved in a query reaction, compared to a reaction of reference. Thus, a dataset of >100 reactions has been collected for different substrates and internal electrophiles, under different reaction conditions, with a wide range of yields (0–98%). The best PTML model found using General Linear Regression (GLR) has R = 0.88 in training and R = 0.83 in external validation series for 10 000 pairs of query and reference reactions. The PTML model has a final R = 0.95 for all reactions using multiple reactions of reference. We also report a comparative study of linear versus nonlinear PTML models based on artificial neural network (ANN) algorithms. PTML-ANN models (LNN, MLP, RBF) with R ≈ 0.1–0.8 do not outperform the first PMTL model. This result confirms the validity of the linearity of the model. Next, we carried out an experimental and theoretical study of nonreported Parham reactions to illustrate the practical use of the PTML model. A 500 000-point simulation and a Hammett analysis of the reactivity space of Parham reactions are also reported
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Brønsted Acid Catalyzed Enantioselective α-Amidoalkylation in the Synthesis of Isoindoloisoquinolines
The Journal of organic chemistry, 2012Co-Authors: Eider Aranzamendi, Nuria Sotomayor, Esther LeteAbstract:The Parham Cyclization–intermolecular α-amidoalkylation sequence results in the facile enantioselective synthesis of 12b-substituted isoindoloisoquinolines (ee up to 95%) using BINOL-derived Bronsted acids. α-Amidoalkylation of indole occurs through the formation of a chiral conjugate base/bicyclic quaternary N-acyliminium ion pair.
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Brønsted Acid Catalyzed Enantioselective α-Amidoalkylation in the Synthesis of Isoindoloisoquinolines
2012Co-Authors: Eider Aranzamendi, Nuria Sotomayor, Esther LeteAbstract:The Parham Cyclization–intermolecular α-amidoalkylation sequence results in the facile enantioselective synthesis of 12b-substituted isoindoloisoquinolines (ee up to 95%) using BINOL-derived Brønsted acids. α-Amidoalkylation of indole occurs through the formation of a chiral conjugate base/bicyclic quaternary N-acyliminium ion pair
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Synthesis of Pyrrolo[1,2-b]isoquinolines through Mesityllithium-Mediated IntramolecularCarbolithiation
Synlett, 2008Co-Authors: Sergio Lage, Nuria Sotomayor, Irune Villaluenga, Esther LeteAbstract:Mesityllithium has proven to be an effective iodine-lithiumexchange reagent. Thus, carbolithiation reactions on 2-alkenyl-substituted N-( O-iodobenzyl)pyrroleshave been accomplished avoiding side reactions to afford pyrroloisoquinolinesin high yields (80-92%), improving the resultsobtained with T-BuLi. The carbolithiationreaction requires the use of electron-deficient alkenes. Mesityllithiumhas also been studied as an alternative to T-BuLiin Parham Cyclization with other internal electrophiles (aldehyde,ketone, ester, amide), proving to be more selective and efficientthan T-BuLi.
Esther Lete - One of the best experts on this subject based on the ideXlab platform.
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Perturbation-Theory and Machine Learning (PTML) Model for High-Throughput Screening of Parham Reactions: Experimental and Theoretical Studies.
Journal of chemical information and modeling, 2018Co-Authors: Lorena Simon-vidal, Esther Lete, Nuria Sotomayor, Sonia Arrasate, Oihane Garcia-calvo, Uxue Oteo, Humberto González-díazAbstract:Machine learning (ML) algorithms are gaining importance in the processing of chemical information and modeling of chemical reactivity problems. In this work, we have developed a perturbation-theory and machine learning (PTML) model combining perturbation theory (PT) and ML algorithms for predicting the yield of a given reaction. For this purpose, we have selected Parham Cyclization, which is a general and powerful tool for the synthesis of heterocyclic and carbocyclic compounds. This reaction has both structural (substitution pattern on the substrate, internal electrophile, ring size, etc.) and operational variables (organolithium reagent, solvent, temperature, time, etc.), so predicting the effect of changes on substrate design (internal elelctrophile, halide, etc.) or reaction conditions on the yield is an important task that could help to optimize the reaction design. The PTML model developed uses PT operators to account for perturbations under experimental conditions and/or structural variables of all...
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Perturbation-Theory and Machine Learning (PTML) Model for High-Throughput Screening of Parham Reactions: Experimental and Theoretical Studies
2018Co-Authors: Lorena Simón-vidal, Esther Lete, Nuria Sotomayor, Sonia Arrasate, Uxue Oteo, Oihane García-calvo, Humberto González-díazAbstract:Machine learning (ML) algorithms are gaining importance in the processing of chemical information and modeling of chemical reactivity problems. In this work, we have developed a perturbation-theory and machine learning (PTML) model combining perturbation theory (PT) and ML algorithms for predicting the yield of a given reaction. For this purpose, we have selected Parham Cyclization, which is a general and powerful tool for the synthesis of heterocyclic and carbocyclic compounds. This reaction has both structural (substitution pattern on the substrate, internal electrophile, ring size, etc.) and operational variables (organolithium reagent, solvent, temperature, time, etc.), so predicting the effect of changes on substrate design (internal elelctrophile, halide, etc.) or reaction conditions on the yield is an important task that could help to optimize the reaction design. The PTML model developed uses PT operators to account for perturbations under experimental conditions and/or structural variables of all the molecules involved in a query reaction, compared to a reaction of reference. Thus, a dataset of >100 reactions has been collected for different substrates and internal electrophiles, under different reaction conditions, with a wide range of yields (0–98%). The best PTML model found using General Linear Regression (GLR) has R = 0.88 in training and R = 0.83 in external validation series for 10 000 pairs of query and reference reactions. The PTML model has a final R = 0.95 for all reactions using multiple reactions of reference. We also report a comparative study of linear versus nonlinear PTML models based on artificial neural network (ANN) algorithms. PTML-ANN models (LNN, MLP, RBF) with R ≈ 0.1–0.8 do not outperform the first PMTL model. This result confirms the validity of the linearity of the model. Next, we carried out an experimental and theoretical study of nonreported Parham reactions to illustrate the practical use of the PTML model. A 500 000-point simulation and a Hammett analysis of the reactivity space of Parham reactions are also reported
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Brønsted Acid Catalyzed Enantioselective α-Amidoalkylation in the Synthesis of Isoindoloisoquinolines
The Journal of organic chemistry, 2012Co-Authors: Eider Aranzamendi, Nuria Sotomayor, Esther LeteAbstract:The Parham Cyclization–intermolecular α-amidoalkylation sequence results in the facile enantioselective synthesis of 12b-substituted isoindoloisoquinolines (ee up to 95%) using BINOL-derived Bronsted acids. α-Amidoalkylation of indole occurs through the formation of a chiral conjugate base/bicyclic quaternary N-acyliminium ion pair.
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Brønsted Acid Catalyzed Enantioselective α-Amidoalkylation in the Synthesis of Isoindoloisoquinolines
2012Co-Authors: Eider Aranzamendi, Nuria Sotomayor, Esther LeteAbstract:The Parham Cyclization–intermolecular α-amidoalkylation sequence results in the facile enantioselective synthesis of 12b-substituted isoindoloisoquinolines (ee up to 95%) using BINOL-derived Brønsted acids. α-Amidoalkylation of indole occurs through the formation of a chiral conjugate base/bicyclic quaternary N-acyliminium ion pair
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Synthesis of Pyrrolo[1,2-b]isoquinolines through Mesityllithium-Mediated IntramolecularCarbolithiation
Synlett, 2008Co-Authors: Sergio Lage, Nuria Sotomayor, Irune Villaluenga, Esther LeteAbstract:Mesityllithium has proven to be an effective iodine-lithiumexchange reagent. Thus, carbolithiation reactions on 2-alkenyl-substituted N-( O-iodobenzyl)pyrroleshave been accomplished avoiding side reactions to afford pyrroloisoquinolinesin high yields (80-92%), improving the resultsobtained with T-BuLi. The carbolithiationreaction requires the use of electron-deficient alkenes. Mesityllithiumhas also been studied as an alternative to T-BuLiin Parham Cyclization with other internal electrophiles (aldehyde,ketone, ester, amide), proving to be more selective and efficientthan T-BuLi.
David A. Hunt - One of the best experts on this subject based on the ideXlab platform.
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A Parham Cyclization route to the 2,3-dihydro-1H-indazole-1,2-dicarboxylate ring systems via condensation of thermolabile aryllithium reagents and azodicarboxylate esters
Tetrahedron Letters, 2017Co-Authors: John Farrokh, Timothy W. Craven, David A. HuntAbstract:The Parham Cyclization reaction of o-lithiobenzyl chlorides (generated by low temperature halogen-metal exchange of the corresponding o-bromobenzyl chlorides with n-butyllithium) with azodicarboxylate esters provides a new entry to the 2,3-dihydro-1H-indazole-1,2-dicarboxylate ring system in moderate to good yield.
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A Parham Cyclization Approach to Diaryl‐Fused Seven‐Membered Ring Heterocyclic Ketones.
ChemInform, 2016Co-Authors: John Farrokh, Catherine A. Campos, David A. HuntAbstract:The novel synthesis of the title compounds involves the generation of functionalized aryllithiums from aryl bromides followed by intramolecular Cyclization onto an electrophilic nitrile functional group.
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a Parham Cyclization approach to diaryl fused seven membered ring heterocyclic ketones
ChemInform, 2016Co-Authors: John Farrokh, Catherine A. Campos, David A. HuntAbstract:The novel synthesis of the title compounds involves the generation of functionalized aryllithiums from aryl bromides followed by intramolecular Cyclization onto an electrophilic nitrile functional group.
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A Parham Cyclization approach to diaryl-fused seven-membered ring heterocyclic ketones
Tetrahedron Letters, 2015Co-Authors: John Farrokh, Catherine A. Campos, David A. HuntAbstract:Aryl-fused seven membered heterocyclic frameworks appear in a variety of pharmaceutically pertinent compounds. However, only a very few methods for their preparation have been described. This work describes a novel synthesis route to diaryl-fused seven membered heterocyclic ketones through the generation of functionalized aryllithiums by bromine–lithium exchange, followed by intramolecular Cyclization onto an electrophilic nitrile functional group. The resulting N-lithioimine can then be hydrolyzed to the desired ketone, generally in good yields. The order of addition of n-butyllithium is crucial to the process with inverse addition proving to mitigate side product formation and increase yields.
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β-Nitrostyrenes as electrophiles in Parham Cyclization chemistry: reaction with o-lithiobenzonitrile
Tetrahedron Letters, 2009Co-Authors: A. J. Clarke, David A. HuntAbstract:Abstract β-Nitrostyrenes react with o -lithiobenzonitrile, generated from the requisite aryl bromide at −100 °C by bromine–lithium exchange with n -butyllithium in THF, to afford 2-nitro-3-phenyl-3 H -inden-1-ylamines resulting from 1,4-addition to the β-nitrostyrene followed by intramolecular capture of the resultant nitronate anion by the ortho -cyano functional group.
Humberto González-díaz - One of the best experts on this subject based on the ideXlab platform.
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Perturbation-Theory and Machine Learning (PTML) Model for High-Throughput Screening of Parham Reactions: Experimental and Theoretical Studies.
Journal of chemical information and modeling, 2018Co-Authors: Lorena Simon-vidal, Esther Lete, Nuria Sotomayor, Sonia Arrasate, Oihane Garcia-calvo, Uxue Oteo, Humberto González-díazAbstract:Machine learning (ML) algorithms are gaining importance in the processing of chemical information and modeling of chemical reactivity problems. In this work, we have developed a perturbation-theory and machine learning (PTML) model combining perturbation theory (PT) and ML algorithms for predicting the yield of a given reaction. For this purpose, we have selected Parham Cyclization, which is a general and powerful tool for the synthesis of heterocyclic and carbocyclic compounds. This reaction has both structural (substitution pattern on the substrate, internal electrophile, ring size, etc.) and operational variables (organolithium reagent, solvent, temperature, time, etc.), so predicting the effect of changes on substrate design (internal elelctrophile, halide, etc.) or reaction conditions on the yield is an important task that could help to optimize the reaction design. The PTML model developed uses PT operators to account for perturbations under experimental conditions and/or structural variables of all...
Melanie C. Skilbeck - One of the best experts on this subject based on the ideXlab platform.
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Synthesis of 2-hydroxy-3-indolinones and 3-hydroxy-2-indolinones by anionic Cyclization, in situ oxidation and rearrangement
Tetrahedron Letters, 2010Co-Authors: Iain Coldham, Harry Adams, Neil J. Ashweek, Thomas A. Barker, Andrew T. Reeder, Melanie C. SkilbeckAbstract:Abstract Lithiation with butyllithium of 2-(benzylamino)benzamides ( N -benzyl anthranilamides) occurs at the benzylic position to give an α-amino-organolithium that cyclizes to the 3-indolinone (indoxyl) ring (similar to a Parham Cyclization). Autoxidation in air gives 2-hydroxy-3-indolinones. In the absence of a proton source, rearrangement of the aryl group from C-2 to C-3 occurs to give the 3-hydroxy-2-indolinone (oxindole) ring.