Scott Miller
Sterling Professor of ChemistryCards
Additional Titles
Professor
Department Chair
Contact Info
About
Titles
Sterling Professor of Chemistry
Professor; Department Chair
Biography
Dr. Miller's laboratory is focused on the creation of new catalysts for complex molecule synthesis and derivatization. Historically, the Miller Lab has endeavored to develop peptide-based catalysts for enantioselective reactions. They have also attempted to bring the principles of asymmetric catalysis into areas of other types of selective synthesis (e.g., regioselectivity, site-selectivity and chemoselectivity), with a particular focus on natural product diversification. They focus on molecular functionality that is ubiquitous in complex natural products, thus allowing these naturally occurring materials to be used as scaffolds for new bioactive entity synthesis. In orthogonal projects, the Miller Lab has developed catalysts for many enantioselective reactions, with a focus on unusual and biochemically relevant aspects of stereochemistry.
The Miller Lab's focus for catalyst development has been on peptide-based catalysts. The catalysts they generate have therefore allowed for a consideration of mechanistic analogies to enzymes. This strategy has also enabled optimization of the catalysts with the development of a range of combinatorial methods for catalyst screening.
Appointments
Chemistry
ProfessorPrimary
Other Departments & Organizations
Research
Overview
Synthesis and Derivation of Complex Molecules; Stereochemistry; Atropisomerism
ORCID
0000-0001-7817-1318
Research at a Glance
Yale Co-Authors
Publications Timeline
Julie Zimmerman
Publications
2024
Catalyst–Substrate Pairings for Carbocyclic and Heterocyclic Systems in Atroposelective Quinazolinone Synthesis
Guo M, Miller S. Catalyst–Substrate Pairings for Carbocyclic and Heterocyclic Systems in Atroposelective Quinazolinone Synthesis. ACS Catalysis 2024, 17226-17232. DOI: 10.1021/acscatal.4c05014.Peer-Reviewed Original ResearchConceptsChiral phosphoric acidPositive nonlinear effectNon-covalent interactionsQuinazolinone synthesisHeterocyclic systemsCatalyst scaffoldHigh enantioselectivityNitrogen heteroatomsEnantiomeric ratioCatalystReaction developmentCatalytic scaffoldMechanistic studiesEnantioselectivityPhosphoric acidSubstrateCarbocyclesCyclocondensationHeterocyclesHeteroatomsScaffoldsReactionSynthesisReactivityYieldCatalytic Enantioselective Sulfoxidation of Functionalized Thioethers Mediated by Aspartic Acid-Containing Peptides
Huth S, Tampellini N, Guerrero M, Miller S. Catalytic Enantioselective Sulfoxidation of Functionalized Thioethers Mediated by Aspartic Acid-Containing Peptides. Organic Letters 2024, 26: 6872-6877. PMID: 39102356, PMCID: PMC11329351, DOI: 10.1021/acs.orglett.4c02452.Peer-Reviewed Original ResearchAltmetricMeSH Keywords and ConceptsConceptsEnantioselective oxidation of sulfidesModel of transition stateLevels of enantioinductionOxidation of sulfidesChiral sulfoxidesPeptide catalystsTransition stateEnantioselective sulfoxidationAspartic acid-containing peptidesSulfoxideThioethersEnantioinductionCatalystMoietySubstrateHydrogenSulfideExperimental evidenceFe/Thiol Cooperative Hydrogen Atom Transfer Olefin Hydrogenation: Mechanistic Insights That Inform Enantioselective Catalysis
Buzsaki S, Mason S, Kattamuri P, Serviano J, Rodriguez D, Wilson C, Hood D, Ellefsen J, Lu Y, Kan J, West J, Miller S, Holland P. Fe/Thiol Cooperative Hydrogen Atom Transfer Olefin Hydrogenation: Mechanistic Insights That Inform Enantioselective Catalysis. Journal Of The American Chemical Society 2024, 146: 17296-17310. PMID: 38875703, PMCID: PMC11209773, DOI: 10.1021/jacs.4c04047.Peer-Reviewed Original ResearchCitationsAltmetricConceptsMetal-catalyzed hydrogen atom transferChiral thiolsAsymmetric hydrogenationSynthesis of complex moleculesMinimally functionalized olefinsSelectivity-determining stepTransition metal catalysisHydrogen atom transferOff-cycle speciesH-atom donorsTransfer of hydrideAsymmetric inductionElectron-richAtom transferMetal catalysisEnantioselective reductionThiol catalystMetal catalystsAlkyl radicalsElectron-neutralIron speciesOlefinsTraditional hydrogenationEnantiomeric ratioRadical catalysisβ‑Amino Acids Reduce Ternary Complex Stability and Alter the Translation Elongation Mechanism
Cruz-Navarrete F, Griffin W, Chan Y, Martin M, Alejo J, Brady R, Natchiar S, Knudson I, Altman R, Schepartz A, Miller S, Blanchard S. β‑Amino Acids Reduce Ternary Complex Stability and Alter the Translation Elongation Mechanism. ACS Central Science 2024, 10: 1262-1275. PMID: 38947208, PMCID: PMC11212133, DOI: 10.1021/acscentsci.4c00314.Peer-Reviewed Original ResearchAltmetricConceptsNon-natural amino acidsComplex stabilityTernary complex stabilityTemplate synthesisDetection limitEnergy transfer measurementsTernary complex formationComplex formationSingle-molecule fluorescence resonance energy transfer measurementsIn vitro detection limitTernary complexFluorescence resonance energy transfer measurementsAmino acidsMechanism of protein synthesisResonance energy transfer measurementsSynthesis of proteinsRate of translocationMRNA decodingElongation substratesStabilityElongation factorIsomersRibosome utilizationAminoacyl-tRNAStereoisomersThank You, Steve Ritter!
Dehnen S, Chirik P, Kozlowski M, Miller S, Rossen K. Thank You, Steve Ritter! The Journal Of Organic Chemistry 2024, 89: 7353-7354. PMID: 38801183, DOI: 10.1021/acs.joc.4c01178.Peer-Reviewed Original ResearchAltmetricThank You, Steve Ritter!
Dehnen S, Chirik P, Kozlowski M, Miller S, Rossen K. Thank You, Steve Ritter! Organic Letters 2024, 26: 4581-4582. PMID: 38801189, DOI: 10.1021/acs.orglett.4c01749.Peer-Reviewed Original ResearchThank You, Steve Ritter!
Dehnen S, Chirik P, Kozlowski M, Miller S, Rossen K. Thank You, Steve Ritter! Inorganic Chemistry 2024, 63: 10453-10454. PMID: 38801179, DOI: 10.1021/acs.inorgchem.4c01965.Peer-Reviewed Original ResearchAltmetricScaffold‐Oriented Asymmetric Catalysis: Conformational Modulation of Transition State Multivalency during a Catalyst‐Controlled Assembly of a Pharmaceutically Relevant Atropisomer
Tampellini N, Mercado B, Miller S. Scaffold‐Oriented Asymmetric Catalysis: Conformational Modulation of Transition State Multivalency during a Catalyst‐Controlled Assembly of a Pharmaceutically Relevant Atropisomer. Chemistry - A European Journal 2024, 30: e202401109. PMID: 38507249, PMCID: PMC11132932, DOI: 10.1002/chem.202401109.Peer-Reviewed Original ResearchCitationsAltmetricConceptsHydrogen bond donorAtroposelective synthesisAsymmetric catalysisGuanidine catalystCatalyst controlChiral axisBond donorNoncovalent interactionsConformational modulationCatalystFolded stateN-capAtroposelectivityAtropisomersSuperbasesPhenylCatalysisQuinazolinedionesMultivalencyBTK inhibitorsMechanistic frameworkStructureEnantioselective Sulfonimidamide Acylation via a Cinchona Alkaloid-Catalyzed Desymmetrization: Scope, Data Science, and Mechanistic Investigation
Haas B, Lim N, Jermaks J, Gaster E, Guo M, Malig T, Werth J, Zhang H, Toste F, Gosselin F, Miller S, Sigman M. Enantioselective Sulfonimidamide Acylation via a Cinchona Alkaloid-Catalyzed Desymmetrization: Scope, Data Science, and Mechanistic Investigation. Journal Of The American Chemical Society 2024, 146: 8536-8546. PMID: 38480482, PMCID: PMC10990064, DOI: 10.1021/jacs.4c00374.Peer-Reviewed Original ResearchCitationsAltmetricMeSH Keywords and ConceptsConceptsDensity functional theoryStructure-activity relationshipBis-acylationExcellent yieldsAsymmetric acylationTetrahedral intermediateSynthetic chemistryFunctional theoryMechanistic investigationsReaction kineticsMechanistic studiesSulfonimidamidesDesymmetrizationEnantioselectivityStructural studiesCatalystAcylPharmacophoreCinchonaIntermediateReactionChemistryKineticsYield
2023
Introduction: Remote and Late Stage Functionalization
Miller S, Ritter T. Introduction: Remote and Late Stage Functionalization. Chemical Reviews 2023, 123: 13867-13868. PMID: 38148744, DOI: 10.1021/acs.chemrev.3c00800.Peer-Reviewed Original ResearchCitations
Academic Achievements & Community Involvement
activity Synthesis and Study of Organocatalysts Tethered to Dendronized Polymer Support
ResearchDetails01/01/2009 - 01/01/2013Israel; United StatesAbstract/SynopsisWe are trying to develop a new class of catalysts for synthetic chemistry that are based on simple organic molecules that are immobilized on dendritic polymer supports. These studies have fundamental value in that they may unveil new effects that are specific to a polymeric scaffold. Catalysts may also offer improved efficiency and recyclability which has advantages for reducing environmental impacts. URL: http://onlinelibrary.wiley.com/doi/10.1002/chem.201102474/abstract
News
News
- June 14, 2018
New university report recommends science priorities for the decade ahead
- April 16, 2012
Scott J. Miller
- November 27, 2011
Grant awarded for study of artificial enzymes