Library · Materials, chemistry & fabrication
What Lewis Acid Catalysis got wrong, from 32 theses
Summary written by a model from the records below: The records describe diverse challenges encountered when employing Lewis acid catalysts across organic and polymer synthesis. Common complications include complete lack of substrate activation, catalyst deactivation by coordinating basic species, destructive substrate degradation, and compromised stereochemical control. These records come from graduate theses, 2021 to 2026, each labeled with its degree where the repository states it, and each links to its thesis. They were extracted by language models reading the full text, so treat each as a lead to read, not a verdict.
Plus 9 problems the authors left open, listed at the end.
Failure modes, by theses reporting them
Select a mode to jump to its records.
Lewis acid catalysts fail to activate substrates or initiate catalytic turnover
Several Lewis acid catalysts exhibited a complete absence of reactivity or gave trace conversions across various reactions. The screened catalysts failed to abstract halides, ring-open donor-acceptor cyclopropanes, promote cycloadditions, or initiate polymerization.
Tried and failed
Lewis acid mediated fluoride abstraction applied to fluorophosphorane intermediates. Reason: strong Lewis acids failed to abstract fluoride from the organophosphorus fluoride adduct
(De)fluorination of Organic Substrates Mediated by Nontrigonal Phosphorus Triamide · MIT · PhD
Tried and failed
Lewis acid catalysis without Bronsted sites applied to cyclic sugar acetalization with aldehydes. Outcome: no signal. Reason: Lewis acids alone are insufficient to catalyze cyclic sugar acetalization, yielding zero product
Design and Synthesis of Bio-based Amphiphiles from Lignocellulosic Biomass · EPFL · PhD
Tried and failed
heterobimetallic activation with non-silver Lewis acids applied to catalytic ring-opening polymerisation. Outcome: no signal. Reason: harder Lewis acids failed to activate or completely inhibited polymerisation without specific cation-pi interactions
The development of switchable initiators for rac-Lactide ring-opening polymerisation · Imperial · PhD
Tried and failed
Lewis acid catalyzed cationic ring-opening polymerization applied to cyclic acetal monomers. Outcome: no signal. Reason: Screened Lewis acid metal halides exhibited complete lack of polymerization activity.
Developing Dynamic Plastics for Improved Sustainability and Energy Storage Technologies · Cornell · PhD
Tried and failed
Lewis base and dual Lewis acid-base catalysis applied to donor-acceptor aminocyclopropane ring opening. Outcome: no signal. Reason: Catalysts failed to activate the donor-acceptor cyclopropane toward reaction with electron-deficient alkenes
Ring-Opening Reactions of Aminocyclopropanes and Aminocyclobutanes · EPFL · PhD
Tried and failed
Lewis acid activation of alkyl bromide initiators applied to cationic ring-opening polymerization. Outcome: no signal. Reason: Zinc chloride failed to activate the bromide initiator, resulting in zero monomer conversion.
ADVANCED SYNTHETIC ROUTES TO CHEMICALLY RECYCLABLE POLYACETALS · Cornell · PhD
Tried and failed
Lewis or Brønsted acid catalysis applied to ring-closing carbonyl-olefin metathesis. Reason: Catalysts failed to promote the cycloaddition/cycloreversion sequence, resulting in 0% conversion
Tried and failed
boron or Lewis acid catalysis alone applied to carbohydrate redox isomerization and deoxygenation. Outcome: no signal. Reason: catalysts alone without photoredox activation gave trace (<2%) conversion
Radical Tools to Transform Biomass Sugars · MIT · PhD
Tried and failed
Lewis acid or silver activation of benziodoxolones applied to synthesis of alkynyl hypervalent iodine reagents. Reason: acetoxy- and chlorobenziodoxolones failed to activate under Lewis acidic or silver-promoted conditions to yield target reagents
Novel Alkynylation Methods through the Combination of Hypervalent Iodine Reagents and Alkynyl-trifluoroborate Salts · EPFL · PhD
Strong Lewis acidity induces substrate degradation and competing side reactions
Exposure of sensitive starting materials to Lewis acid catalysts frequently triggered substrate decomposition, gelation, or uncontrolled polymerization. Catalysts also promoted unwanted side pathways including non-selective bond cleavage, rearomatization, and anomeric scrambling.
Tried and failed
Lewis-acid-catalyzed carbohydrate condensation cascade applied to ketoses and alternative beta-dicarbonyl substrates. Outcome: did not generalise. Reason: yielded degradation, gelation, or unreacted starting material with minimal desired product formation
Unprotected Carbohydrate Conversion to Polyhydroxyalkyl Furans and Dihydrofurans: Improvement, Expansion, and Interruption of the Garcia Gonzalez Reaction via Homogeneous and Heter · Georgia Tech · PhD
Tried and failed
Lewis acid promoted Diels-Alder cycloaddition applied to acid-sensitive diene oxazolidines. Outcome: unstable. Reason: Uncatalyzed reaction showed no conversion, whereas Lewis acid catalysts induced substrate degradation
Chemodivergent Asymmetric Synthesis via Catalytically Formed Chiral Auxiliary · EPFL · PhD
Tried and failed
cationic polyene cyclisation for kinetic resolution applied to geometric isomer mixtures. Reason: lewis acid activation produced complex degradation mixtures rather than selective cyclisation
Towards a geometry-selective alkene metathesis method to form new trisubstituted alkenes in functionalised terpenoids · Imperial · PhD
Considered and rejected
Considered and rejected: Rejected triflate-based Lewis acids (TMSOTf, TfOH) for orthoester thioglycosidation because they caused anomeric mixtures and C-2 deacetylation.
Investigation of Synthesis and Application of Thioglycosides · University College Dublin · PhD
Tried and failed
strong Lewis acid catalysts for controlled polymerization applied to cationic ring-opening polymerization of cyclic acetals. Outcome: unstable. Reason: Strong Lewis acids directly activate the monomer rather than the initiator, causing uncontrolled non-living polymerization.
Developing Dynamic Plastics for Improved Sustainability and Energy Storage Technologies · Cornell · PhD
Tried and failed
Lewis acid catalyzed benzannulation applied to indolyl dihydrofurans. Reason: competing rearomatization/elimination pathway selectively yielded furan instead of the annulated product
Dicarbonyl Metal Carbene: A Versatile Synthetic Tool for C-H Functionalization, Formal [3+2] Cycloaddition and Enantioselective Cyclopropanation · Georgia Tech · PhD
Tried and failed
Pd/Fe cocatalytic olefin aminoboration applied to Lewis-acid-sensitive strained bicyclic olefins. Outcome: did not generalise. Reason: Substrates containing Lewis-acid-sensitive functional groups were incompatible with the reaction conditions
Development of palladium catalyzed olefin functionalizations : regiocontrolled synthesis of C–N, C–B, and C–C bonds · UT Austin · PhD
Tried and failed
Intramolecular Friedel-Crafts acylation applied to functionalised phenyl ether intermediates. Reason: Lewis or Brønsted acids induced phenoxy-alkyl bond cleavage instead of cyclisation
Development of structurally novel FMS (CSF-1R) inhibitors for cancer · Imperial · PhD
Coordinating Lewis bases and nucleophiles poison the Lewis acid catalyst
Catalyst turnover was readily suppressed when basic amines, unhindered nitrogen heterocycles, or chelating diols coordinated competitively to the metal center. Similar deactivation occurred when using Lewis basic solvents or when trace moisture quenched the acidic catalyst.
Considered and rejected
Considered and rejected: Rejected methanol/ethanol recrystallization without drying agents for imine substrates due to trace moisture poisoning the Lewis acid/superbase catalyst.
Organic Superbases in Catalytic Antimony-Carbon Bond Formation and Frustrated Lewis Pair Hydrogenation of Imines. · Texas Tech · PhD
Tried and failed
Lewis acid catalysis in Lewis basic solvents applied to nucleophilic alkylation of acetal intermediates. Reason: Strong Lewis basicity of the solvents hindered Lewis acid activation and suppressed reaction progress
THE DEVELOPMENT OF LATE-STAGE FUNCTIONALIZATION STRATEGIES ENABLED BY OXIDATIVE ELECTROCHEMISTRY · Cornell · PhD
Tried and failed
dual hydrogen-bond donor catalysis with Lewis acids applied to multicomponent enantioselective allylation with amines. Reason: strongly basic amine nucleophiles form ammonium salts that inhibit the hydrogen-bond donor catalyst
Tried and failed
Lewis acid catalyzed epoxide ring opening applied to heterocycle-containing nucleophiles. Reason: Unhindered electron-rich nitrogen heterocycles coordinate competitively to the metal catalyst, causing catalyst poisoning and inhibition
Addressing the Extremes of Reactivity in Small-Molecule-Catalyzed Stereoselective Glycosylation · Harvard · PhD
Tried and failed
in-situ catalyst generation with excess ligand applied to epoxide ring-opening polymerization. Reason: Excess uncoordinated amine ligand poisoned the Lewis acidic catalytic centers, preventing monomer conversion
Synthesis, characterization, and applications of mono([mu]-alkoxo)bis(alkylaluminum) catalysts for epoxide polymerization · UT Austin · PhD
Tried and failed
Lewis or Brønsted acid catalyzed direct amination applied to tertiary alcohol substitution with amines. Reason: catalyst deactivation and poisoning by the basic amine nucleophile returned unreacted starting material
Investigation of oxetane reactive intermediates for the synthesis of 3,3-disubstituted oxetanes · Imperial · PhD
Chiral Lewis acid catalysis fails to achieve adequate stereochemical control
Chiral Lewis acids often failed to impart satisfactory enantioselectivity or stereocontrol during asymmetric transformations. Elevated temperatures, steric hindrance, and higher catalyst Lewis acidity eroded selectivity and lowered enantiomeric excess.
Tried and failed
enantioselective 1,2-rearrangement via chiral lithium Lewis acid applied to sterically hindered, unsaturated, or basic boronates. Outcome: did not generalise. Reason: electronic mismatches, steric hindrance, and competitive Lewis base coordination degraded enantioselectivity
Asymmetric Catalysis of Ionic 1,2-Rearrangements · Harvard · PhD
Considered and rejected
Considered and rejected: Abandoned Lewis acid-catalyzed asymmetric ATRA after extensive screening due to poor stereocontrol and Lewis acid inhibition of radical addition.
Synthesis and functionalization of α-Chiral Bicyclo[1.1.1]pentanes · Oxford · PhD
Considered and rejected
Considered and rejected: Abandonment of the chiral Lewis-acid / oxazolidinone approach (156 with Sc(OTf)3 / Ir(dFppy)3) for enantioselective dihydrophenalene synthesis due to failure to establish stereocontrol.
Photoannulierungen zu Dihydrophenalenonen und 1-Tetralonen · University of Marburg · PhD
Considered and rejected
Considered and rejected: Abandoned chiral Brønsted/Lewis acid catalysis for desymmetrization due to high temperature requirements (>80 °C) causing low enantioselectivity (<=10% ee)
Chemical Investigations in Complex Alkaloid Synthesis · UT Southwestern · PhD
Mismatched Lewis acid strength and catalyst loading degrade reaction performance
Deviations from optimal Lewis acidity or catalyst loading led to sharply diminished product yields and inhibited crystallization. Overly strong Lewis acids suppressed conversion or prevented desired complexation, while ultra-low catalyst loadings failed to drive product formation.
Tried and failed
Lewis acid catalyzed one-pot stepwise framework synthesis applied to covalent organic framework crystallization. Reason: Ultra-low Lewis acid catalyst loading failed to yield crystalline product
DESIGNING NEXT-GENERATION FUNCTIONAL COVALENT ORGANIC FRAMEWORKS FOR WATER TREATMENT · Cornell · PhD
Tried and failed
increasing or decreasing Lewis acid catalyst loading applied to heterocycle condensation reaction. Outcome: worse than baseline. Reason: deviations from optimal catalyst concentration reduced product yield
Synthesis of Nitrogen-Containing and Nitrogen-Substituted Aromatic Compounds for Diverse Applications · Georgia Tech · PhD
Tried and failed
extreme Lewis acid activation applied to deoxygenative fluorination of aliphatic alcohols. Reason: overly strong or weak Lewis acidity fails to promote the catalytic cycle effectively
Expanding Deoxygenative Transformations of Alcohols by Phosphorus Compounds Through Geometric Deformation · MIT · PhD
Lost to a baseline
P2-Et/[9-(4-CF3-C6H4)BBN] reached only 30% conversion at 80 bar H2 for N-benzylideneaniline, outperformed by the less Lewis acidic P2-Et/[9-(4-MeO-C6H4)BBN] (99%).
Organic Superbases in Catalytic Antimony-Carbon Bond Formation and Frustrated Lewis Pair Hydrogenation of Imines. · Texas Tech · PhD
Tried and failed
room-temperature Lewis acid-catalyzed one-pot stepwise synthesis applied to covalent organic framework crystallization. Reason: Reaction conditions and low catalyst loading failed to yield crystalline product
DESIGNING NEXT-GENERATION FUNCTIONAL COVALENT ORGANIC FRAMEWORKS FOR WATER TREATMENT · Cornell · PhD
Considered and rejected
Considered and rejected: Rejected diamagnetic isocyanide TMP adducts for matrix dilution due to excessive Lewis acidity preventing complexation, replacing with TMStrenTiCC4-dmap.
Developing Telecom Band-Compatible Molecular Color Centers for Quantum Networking · MIT · PhD
Strongly electron-withdrawing groups and reagent incompatibilities prevent catalytic conversion
Substrates containing strong electron-withdrawing substituents such as chlorine atoms or trifluoromethyl groups resisted Lewis acid mediated activation. Additionally, acidic promoters proved chemically incompatible with reactive nucleophilic organoboron ate intermediates.
Considered and rejected
Considered and rejected: Rejected acidic promoters (e.g., Lewis/Brønsted acids) typically used with allylic alcohols due to incompatibility with nucleophilic boronate ate complexes.
Iridium-Catalyzed Enantioselective Allylation of Alkenyl Boronates · UT Southwestern
Tried and failed
Lewis acid mediated alkylation of N,O-acetals applied to electron-deficient trifluoromethyl substituted substrates. Reason: strong electron-withdrawing deactivation prevented oxocarbenium/iminium formation
THE DEVELOPMENT OF LATE-STAGE FUNCTIONALIZATION STRATEGIES ENABLED BY OXIDATIVE ELECTROCHEMISTRY · Cornell · PhD
Considered and rejected
Considered and rejected: Rejected 1st generation route using Lewis/Brønsted acid intramolecular Friedel-Crafts cyclization of epoxyketone 14 due to arene deactivation from two chlorine atoms.
Left open by the authors
Problems the authors named and did not get to.
Left open
Deprotect the acetal group of carboxylic acid 4.93 using Lewis acids without causing acid-catalysed decomposition. Blocker: Requires a wet chemistry laboratory, physical reagents, and analytical equipment to perform chemical reactions
Towards a geometry-selective alkene metathesis method to form new trisubstituted alkenes in functionalised terpenoids · Imperial · PhD
Left open
Develop and screen polar-solvent-compatible Lewis acidic chiral catalysts for enantioselective Matteson homologations. Blocker: Requires wet-lab chemical synthesis and experimental reaction screening
Catalytic control over selectivity in the synthesis of glycosides and quaternary centers · Harvard · PhD
Left open
Study aldol addition of aldehyde substrates in polar, non-coordinating solvents like dichloroethane over Lewis acidic zeolites experimentally. Blocker: Requires a wet chemistry laboratory, synthetic zeolites, solvent reagents, and catalytic reactor testing equipment.
Promotion of Heterogeneous Acid and Base Catalysts for Biomass Upgrading · MIT · PhD
Left open
Develop a frustrated Lewis pair catalyzed [3+2] annulation of donor-acceptor aminocyclopropanes with electron-deficient alkenes. Blocker: Requires a wet lab, organic synthesis equipment, and chemical reagents.
Ring-Opening Reactions of Aminocyclopropanes and Aminocyclobutanes · EPFL · PhD
Left open
Investigate the kinetic behavior of epoxide polymerizations using non-1:1 stoichiometric ratios of amine and aluminum substituents in Lewis pairs. Blocker: Requires a wet chemistry laboratory and analytical instrumentation to conduct polymerization kinetics experiments.
Synthesis, characterization, and applications of mono([mu]-alkoxo)bis(alkylaluminum) catalysts for epoxide polymerization · UT Austin · PhD
Left open
Quantify N-Al Lewis pair interaction strengths in MOB catalysts and measure their effects on epoxide polymerization rate, molecular weight, and polymer composition. Blocker: Requires wet lab chemical synthesis and polymerization experiments with organoaluminum catalysts.
Synthesis, characterization, and applications of mono([mu]-alkoxo)bis(alkylaluminum) catalysts for epoxide polymerization · UT Austin · PhD
Left open
Develop reaction conditions or catalysts like oxophilic Lewis acids to achieve clean Edman-type single-step cyclization of carbamate terminal amines. Blocker: Requires wet lab chemical synthesis and reaction optimization.
Proving 2-aminobiphenyl nitric oxide probes in cells and designing sequence-defined oligomers for sequencing · UT Austin · PhD
Left open
Investigate the substrate scope and reaction mechanism of the Lewis acid-catalyzed Cope rearrangement. Blocker: Requires a wet organic chemistry laboratory and synthetic chemical reagents
Application of new methodologies using principles of green chemistry in organic synthesis · Texas Tech · PhD
Left open
Investigate allosteric control in tethered frustrated Lewis pairs under varied small molecules and external stimuli such as temperature and pressure. Blocker: Requires a synthetic chemistry wet lab to prepare complexes and measure reactivity under varying physical conditions
Who has worked on this
Authors of the public theses cited on this page, most-cited first.
- Nara Zorigt · Cornell · PhD · 2025
DESIGNING NEXT-GENERATION FUNCTIONAL COVALENT ORGANIC FRAMEWORKS FOR WATER TREATMENT - Jacob James Culvyhouse · Texas Tech · PhD · 2025
Organic Superbases in Catalytic Antimony-Carbon Bond Formation and Frustrated Lewis Pair Hydrogenation of Imines. - Justin Ho · Cornell · PhD · 2024
THE DEVELOPMENT OF LATE-STAGE FUNCTIONALIZATION STRATEGIES ENABLED BY OXIDATIVE ELECTROCHEMISTRY - Zhensheng Shi · Imperial · PhD · 2022
Towards a geometry-selective alkene metathesis method to form new trisubstituted alkenes in functionalised terpenoids - Mingming Wang · EPFL · PhD · 2022
Ring-Opening Reactions of Aminocyclopropanes and Aminocyclobutanes - Rachel Snyder · Cornell · PhD · 2021
Developing Dynamic Plastics for Improved Sustainability and Energy Storage Technologies - Agata A Bikovtseva · Harvard · PhD · 2026
Catalytic control over selectivity in the synthesis of glycosides and quaternary centers - Jake Matthew Aquilina · UT Southwestern · PhD · 2026
Chemical Investigations in Complex Alkaloid Synthesis - Peyton David Beyer · Harvard · PhD · 2025
Addressing the Extremes of Reactivity in Small-Molecule-Catalyzed Stereoselective Glycosylation - Soohyun Lim · MIT · PhD · 2025
(De)fluorination of Organic Substrates Mediated by Nontrigonal Phosphorus Triamide - Rianna Bliss Greer · MIT · PhD · 2025
Developing Telecom Band-Compatible Molecular Color Centers for Quantum Networking - Zoe Beato · University College Dublin · PhD · 2025
Investigation of Synthesis and Application of Thioglycosides
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