About

Eric Jacobsen is the Sheldon Emery Professor of Chemistry at Harvard University, having joined the institution as a full professor in 1993. He was named the Sheldon Emery Professor of Organic Chemistry in 2001 and served as Chair of the Department of Chemistry and Chemical Biology from 2010 through 2015. His research group, consisting of 20-25 graduate students and postdoctoral scholars, focuses on discovering useful catalytic reactions and applying advanced mechanistic and computational techniques to analyze these reactions. Several catalysts developed in his labs, including metal-salen complexes for asymmetric epoxidation, conjugate additions, and hydrolytic kinetic resolution of epoxides; chromium-Schiff base complexes for enantioselective pericyclic reactions; and organic hydrogen bond-donor catalysts for activation of electrophiles, have found widespread application in industry and academia. His mechanistic analyses have helped uncover general principles for catalyst design, such as electronic tuning of selectivity, cooperative homo- and hetero-bimetallic catalysis, hydrogen-bond donor asymmetric catalysis, and anion binding catalysis. Prior to Harvard, he served on the faculty of the University of Illinois from 1988 to 1993. He earned his B.S. degree at NYU, his Ph.D. at UC Berkeley, and completed postdoctoral studies at MIT.

Research topics

• Organic chemistry
• Chemistry
• Combinatorial chemistry
• Medicinal chemistry
• Cardiology
• Endocrinology
• Internal medicine
• Stereochemistry
• Medicine

Selected publications

• Ab Initio Molecular Dynamics Simulations for Organic Chemists─It is About Time!

  Journal of the American Chemical Society · 2026-04-15

  articleOpen accessSenior authorCorresponding

  Molecular dynamics simulations model chemical reactions as continuous changes in molecular structure over time instead of static minima and transition states. This perspective argues that time-dependent structural change is a crucial, but often overlooked, mechanistic feature as many reactions simply do not follow a single, equilibrated minimum-energy path. We highlight examples where traditional transition state theory fails, typically cases involving short-lived intermediates, nonequilibrium solvation, momentum-controlled selectivity, post-transition state bifurcations, and "hidden" dynamic intermediates and show how molecular dynamics can reveal the actual sequence of structural change which governs a reaction outcome. We also discuss emerging machine learning-based molecular dynamics which have found applications in photochemistry and solvent modeling. While molecular dynamics will not replace methods based on transition state theory, it offers organic chemists a time-resolved view of molecular structure which can be crucial to understanding a given reaction. However, a central barrier for organic chemists is to understand when and why to apply an advanced computational technique such as molecular dynamics simulations. In this perspective, we aim to introduce the methodology in sufficient detail to enable organic chemists to make this assessment and gain an appreciation for the importance of time in reaction mechanisms.

  PublisherDOI

• Dual-Ligand System for Mild Decarbonylative Suzuki–Miyaura Cross-Coupling of Aroyl Chlorides

  ACS Catalysis · 2026-03-09

  articleOpen accessCorresponding

  Cooperativity between a pair of phosphine ligands enables general Pd-catalyzed decarbonylative Suzuki-Miyaura cross-couplings between (hetero)-aroyl chlorides and (hetero)-arylboronic acids under mild conditions. Experimental and computational studies support a ligand-relay mechanism in which each phosphine preferentially promotes different elementary steps, enhancing the yield and selectivity relative to using either ligand alone. These results validate empirical, mechanism-agnostic screening through pooling-deconvolution as a means for identifying synthetically enabling catalytic methods and mechanisms for multiligand cooperativity.

  PublisherDOI

• Catalyst-Controlled Chemoselective β-Mannosylation of Phenols Via Attractive Noncovalent Interactions

  Journal of the American Chemical Society · 2026-05-11

  articleOpen accessSenior authorCorresponding

  We report the development of chemo- and stereoselective phenolic β-mannosylations catalyzed by precisely tuned bis-thiourea H-bond donors. β-Mannosylation of phenols is demonstrated to occur selectively in the presence of primary and secondary alcohols as well as thiols and thiophenols. Kinetic and computational studies support a mechanism of nucleophile activation promoted by general base-catalysis and enhanced by aromatic interactions between the catalyst and the phenolic substrate. The reactions obey Michaelis-Menten kinetics, and selectivity for glycosylation of phenols over aliphatic alcohols can be ascribed to a combination of stronger binding of the nucleophile to the catalyst and higher reaction rate of the bound complex. In contrast, selectivity of phenols over more acidic thiophenols is achieved exclusively through preferential binding to the catalyst.

  PublisherDOI

• Chiral Hydrogen-Bond Donor and Gold(I) Cocatalysis Enables Enantioselective Dearomative Spirocyclization of Naphthols

  Journal of the American Chemical Society · 2025-10-28 · 7 citations

  articleOpen accessSenior authorCorresponding

  We report the enantioselective gold(I)-catalyzed dearomative spirocyclization of naphthols enabled by the cooperative effect of chiral dual hydrogen-bond donors (HBDs). The reaction affords carbocyclic and heterocyclic spirocycles bearing a quaternary stereocenter with high enantioselectivity (up to 99% enantiomeric excess). Kinetic analysis supports a mode of catalysis wherein two molecules of a monomeric urea cocatalyst activate the neutral gold(I) sulfonate complex via anion abstraction to induce enantioselectivity and rate acceleration in the cyclization reaction. A systematic investigation of ligand effects identified a correlation between the electronic properties of the gold(I) phosphine ligand and the observed enantioselectivity.

  PublisherOA PDFDOI

• Benzestrol Isomer Stereochemistry Determines the Distinct Estrogenic Activities and Conformations of the Eight Isomers When Bound to Estrogen Receptor α

  ACS Pharmacology & Translational Science · 2025-07-09 · 1 citations

  articleOpen access

  The nonsteroidal estrogen, benzestrol, has potent estrogenic activity, and through a recent stereocontrolled synthesis, we have obtained all eight of its constituent stereoisomers. We find that only one of them, RSS benzestrol, has very high binding affinity for estrogen receptor alpha (ERα); the other seven isomers have 60 to 600-fold lower affinity. We now show that the potencies of the isomers in two cell activity assays, proliferation of ER-positive breast cancer cells and stimulation of estrogenic gene activity, reflect their varying binding affinities for ERα. The crystal structure of the RSS isomer itself is consistent with its presumed absolute configuration and also reveals its conformational flexibility within the solid crystal lattice. We modeled each of the 8 benzestrol stereoisomers bound to ERα. Their calculated binding energies and internal torsional energies grouped with their experimentally measured binding affinities and biological activities, and the conformation for the highest affinity RSS isomer bound to ERα maps closely onto the conformation of the ERα-bound potent nonsteroidal estrogen, trans-diethylstilbestrol. Hence, we now provide a structural context for this congeneric series of benzestrol stereoisomers by proposing energy-based conformations they adopt when bound to ERα that underlie their effectiveness as estrogens.

  PublisherDOI

• An anion-binding approach to enantioselective photoredox catalysis

  Science · 2025-11-20 · 2 citations

  articleSenior authorCorresponding

  Photoredox catalysis has emerged as a transformative strategy in synthetic chemistry, enabling a wide variety of valuable chemical reactions through generation of highly reactive radical ion intermediates. Pairing chiral counteranions with cation radical intermediates provides a potentially generalizable tool for controlling absolute stereochemistry in various reactivity contexts. However, ion-pairing effects on the efficiency of photoinduced processes and the reactivity of radical ion pairs impose severe limits on the chiral anions that can be engaged effectively. In this study, we report that association of neutral chiral small-molecule hydrogen-bond donors with the counteranions of cation radical intermediates can achieve enantioselectivity through ion-pairing and other noncovalent interactions. Applications to four different classes of cycloaddition reactions of electron-rich alkene substrates provide cyclic products with up to four new stereocenters in up to 99% enantiomeric excess.

  PublisherDOI

• Enantioselective Ring Opening of Azetidines via Charge Recognition in Hydrogen-Bond-Donor Catalysis

  Journal of the American Chemical Society · 2025-02-17 · 14 citations

  articleOpen accessSenior authorCorresponding

  We report the highly enantioselective ring-opening of 3-substituted azetidines by alkyl and acyl halides promoted by a chiral squaramide hydrogen-bond donor catalyst. Broad scope is achieved across a variety of substrate combinations possessing disparate steric features. The same catalyst had been identified previously to promote enantioselective opening of oxetanes via both Lewis and Brønsted acid mechanisms. This remarkable generality is interpreted to arise from catalyst recognition of the conserved electrostatic features of the dipolar enantioselectivity-determining transition states in the ring-opening SN2 mechanisms with simultaneous tolerance of variation of the specific functional group and steric features of the reactions. Specific experimental and computational evidence is provided for a network of electrostatic interactions that forms a shared basis for enantioinduction across these transformations. This work provides a framework for designing catalysts that achieve high enantioselectivity across diverse reactions unified by conserved polar mechanisms.

  PublisherOA PDFDOI

• (Salen)Metal-Catalyzed β-Glucuronidation of Alcohols, Phenols, and Anilines

  Journal of the American Chemical Society · 2025-09-30 · 3 citations

  articleSenior author

  β-Glucuronidation is an important metabolic pathway for a variety of chemicals, including drugs and endogenous substances. We report here that simple (salen)cobalt and (salen)chromium complexes catalyze the β-glucuronidation of alcohols, phenols, and anilines via stereospecific opening of 1,2-anhydroglucuronate electrophiles. The optimized protocol is mild and pH-neutral, enabling the β-glucuronidation of complex pharmaceuticals and natural products bearing acid-sensitive and Lewis-basic functionalities. Kinetic studies reveal a first-order kinetic dependence on catalyst concentration, which stands in contrast to the (salen)metal-catalyzed opening of simple epoxides where second-order rate dependence on the catalyst has been observed consistently.

  PublisherDOI

• Molecular Dynamics Simulations for Organic Chemists – It’s About Time!

  ChemRxiv · 2025-12-22

  articleOpen accessSenior author

  Molecular dynamics simulations model chemical reactions as continuous changes in molecular structure over time in-stead of static minima and transition states. This perspective argues that time-dependent structural change is a crucial, but often overlooked, mechanistic feature as many reactions simply do not follow a single, equilibrated minimum-energy path. We highlight examples where traditional transition state theory fails, typically cases involving short-lived interme-diates, non-equilibrium solvation, momentum-controlled selectivity, post-transition state bifurcations, and “hidden” dy-namic intermediates and show how molecular dynamics can reveal the actual sequence of structural change which gov-erns a reaction outcome. We also discuss emerging machine learning-based molecular dynamics which have found appli-cations in photochemistry and solvent modelling. While molecular dynamics will not replace methods based on transi-tion state theory, it offers organic chemists a time-resolved view of molecular structure which can be crucial to under-standing a given reaction. However, a central barrier for organic chemists is to understand when and why to apply an ad-vanced computational technique such as molecular dynamics simulations. In this perspective, we aim to introduce the methodology in sufficient detail to enable organic chemists to make this assessment and gain an appreciation for the im-portance of time in reaction mechanisms.

  PublisherDOI

• Accelerating the discovery of multicatalytic cooperativity

  Nature · 2025-11-03 · 3 citations

  articleOpen accessSenior author
  PublisherOA PDFDOI

Recent grants

• Broadly Applicable, Small Molecule Catalysts for Stereoselective and Site-Selective Glycosylation Reactions

  NIH · $1.4M · 2019–2023

• Small-Molecule Catalysts for the Stereoselective Synthesis of Oligosaccharides

  NIH · $1.2M · 2015–2018

• NIH Grant P50GM069721

  NIH · $32.1M · 2014

• NIH Grant R37GM043214

  NIH · $6.6M · 2011

• NIH Grant R01GM059316

  NIH · $2.8M · 2008

Frequent coauthors

• Tehshik P. Yoon

  University of Wisconsin–Madison

  52 shared

• Christopher D. Vanderwal

  University of California, Irvine

  49 shared

• C. Rose Kennedy

  University of Rochester

  42 shared

• Noah Z. Burns

  Stanford University

  42 shared

• Steven M. Banik

  38 shared

• David D. Ford

  34 shared

• Dan Lehnherr

  Merck & Co., Inc., Rahway, NJ, USA (United States)

  32 shared

• Scott E. Schaus

  Boston University

  26 shared

Labs

• Jacobsen GroupPI

Education

• Ph.D., Chemistry

  Harvard University

  2005

• B.S., Chemistry

  University of California, Berkeley

  2000

Awards & honors

• Sheldon Emory Professor of Organic Chemistry (2001)