About

Cody Ross Pitts is an Assistant Professor in the Department of Chemistry at UC Davis. His research group, the CRP Laboratory, focuses on organic chemistry with an emphasis on synthetic and physical organic chemistry, method development, reagent design, total synthesis, and mechanistic studies. His work is inspired by unusual retrosynthetic disconnections and 'impossible' reactions, with potential future directions including C-C bond activation, C-O bond formation, and the synthesis and evaluation of unexplored fluorinated functional groups. Dr. Pitts has a distinguished educational background, earning his Ph.D. from Johns Hopkins University in 2017, followed by postdoctoral fellowships at ETH Zurich and the Scripps Research Institute. His research contributions include advancing fluorination techniques, exploring supramolecular chemistry, and developing new reagents and methods in organic synthesis. His publications reflect a strong focus on fluorine chemistry, organophosphorus compounds, and innovative approaches to chemical synthesis.

Research topics

• Chemistry
• Organic chemistry
• Stereochemistry
• Computer Science
• Computational chemistry
• Sociology
• Social Science
• Photochemistry
• Combinatorial chemistry
• Engineering
• Medicine
• Biochemical engineering
• Epistemology
• Materials science
• Philosophy
• Biology
• Nanotechnology
• Mathematics

Selected publications

• Direct <i>N</i> –SF ₅ and <i>N</i> –SF ₄ CF ₃ Bond Formation through Strain-Release Functionalization of 3-Substituted [1.1.0]Azabicyclobutanes

  Journal of the American Chemical Society · 2025-07-23 · 24 citations

  articleSenior authorCorresponding

  In comparison to modern methods for carbon–SF5 bond formation, methods for direct heteroatom–SF5 bond formation are exceptionally scarce, rendering motifs such as “N–SF5” virtually unexplored in the context of organic and medicinal chemistry. Herein, we demonstrate that direct N–SF5 bond formation can be accomplished through strain-release pentafluorosulfanylation of 3-aryl [1.1.0]azabicyclobutanes (ABBs), using an easy-to-access solution of SF5Cl. To our surprise, the resultant N–SF5 azetidines proved to be remarkably chemically stable and amenable to peripheral synthetic modifications (e.g., amination, cross-coupling, oxidation, dehalogenation, SN1, and SNAr reactions). The methodology also extends to direct N–SF4CF3 bond formation using trans-CF3SF4Cl, enabling comparative studies throughout this work. From a mechanistic standpoint, DFT calculations, Hammett analyses, and radical trapping experiments support our proposed radical chain propagation mechanism. From a fundamental standpoint, considering N–SF5 and N–SF4CF3 azetidines are heretofore unknown molecular motifs, this work analyzes their dynamic, spectroscopic, and crystallographic features, as well as computed properties (e.g., BDE and pKb values), to provide foundational knowledge and inform downstream applications. While the carbon-bound SF5 group has been employed as a bioisostere for a CF3 group, we posited the N–SF5 motif could be a potential replacement for a small sulfonamide. Accordingly, we synthesized an N–SF5 derivative of a spleen tyrosine kinase inhibitor reported in the patent literature for comparative ADME studies; results from in vitro profiling indicate that an N–SF5 azetidine could indeed be an alternative for an N–SO2Me azetidine, in cases where enhanced lipophilicity is desirable.

  PublisherDOI

• The Fluorinative Skeletal Rearrangement of Lumisantonin: An Unanticipated Dual Role of Selectfluor

  The Journal of Organic Chemistry · 2025-06-19 · 5 citations

  articleCorresponding

  Synthetic chemists have been intrigued by the rearrangement reactions of α-santonin and santonin-derived natural products for over 150 years. Herein, we report an unprecedented fluorinative skeletal rearrangement of lumisantonin in the presence of Selectfluor. To our surprise, mechanistic studies suggest that the rearrangement proceeds through a thermal two-electron process, rather than a photochemical radical fluorination mechanism as initially conceived. A series of synthetic experiments and transition state studies reveal that the reaction is governed by an unusual, concerted strain-release electrophilic fluorination, followed by rearrangement of the carbon skeleton to generate a key tertiary carbocation intermediate. This intermediate is then readily trapped by either the tetrafluoroborate counteranion (Balz-Schiemann-type fluorination) or acetonitrile (Ritter-type amination), affording novel fluorinated derivatives of isophotosantonic lactone, as confirmed by single crystal X-ray crystallography.

  PublisherDOI

• Tetrafluoro(aryl)sulfanylated Bicyclopentane Crystals That Self-Destruct upon Cooling

  Journal of the American Chemical Society · 2025-01-06 · 7 citations

  articleOpen accessSenior authorCorresponding

  are relatively rare in the chemical literature. A tetrafluoro(aryl)sulfanylated bicyclopentane synthesized in our laboratory was discovered to exhibit such behavior; i.e., the crystals jumped and forcefully disintegrated upon cooling below ∼193 K. Accordingly, the origin of this low-temperature thermosalient effect was investigated through NMR, SC-XRD, PXRD, microscopy, DSC, Raman, and Brillouin experiments. To our surprise, NMR, SC-XRD, PXRD, and DSC experiments suggest the phenomenon can neither be attributed solely to a chemical transformation nor a phase transition of the entire material. Rather, XRD, Raman, and Brillouin experiments provide evidence that built-up strain released from the crystal upon self-destruction may be associated with crystal microstructure or a phase transition that occurs in another material (i.e., an impurity) in the crystal. This study demonstrates that molecular structural changes in organic material microstructure or impurity phases (which may not necessarily be visible by X-ray diffraction) can have a significant impact on the behavior of the bulk crystalline material. Thus, the role of microstructure may be considered more heavily in future mechanistic studies on mechanically responsive crystals.

  PublisherOA PDFDOI

• Direct N–SF5 and N–SF4CF3 Bond Formation through Strain-Release Functionalization of 3-Substituted [1.1.0]Azabicyclobutanes

  ChemRxiv · 2025-04-28 · 1 citations

  preprintOpen accessSenior author

  In comparison to modern methods for carbon–SF5 bond formation, methods for direct heteroatom–SF5 bond formation are exceptionally scarce, rendering motifs such as “N–SF5” virtually unexplored in the context of organic and medicinal chemistry. Herein, we demonstrate that direct N–SF5 bond formation can be accomplished through strain-release pentafluorosulfanylation of 3-aryl [1.1.0]azabicyclobutanes (ABBs), using an easy-to-access solution of SF5Cl. To our surprise, the resultant N–SF5 azetidines proved to be remarkably chemically stable and amenable to peripheral synthetic modifications (e.g., amination, cross-coupling, oxidation, dehalogenation, SN1, and SNAr reactions). The methodology also extends to direct N–SF4CF3 bond formation using trans-CF3SF4Cl, enabling comparative studies throughout this work. From a mechanistic standpoint, DFT calculations, Hammett analyses, and radical trapping experiments support our proposed radical chain propagation mechanism. From a fundamental standpoint, considering N–SF5 and N–SF4CF3 azetidines are heretofore unknown molecular motifs, this work analyzes their dynamic, spectroscopic, and crystallographic features, as well as computed properties (e.g., BDE and pKb values), to provide foundational knowledge and inform downstream applications. While the carbon-bound SF5 group has been employed as a bioisostere for a CF3 group, we posited the N–SF5 motif could be a potential replacement for a small sulfonamide. Ac-cordingly, we synthesized an N–SF5 derivative of a spleen tyrosine kinase inhibitor reported in the patent literature for comparative ADME studies; results from in vitro profiling indicate that an N–SF5 azetidine could indeed be an alternative for an N–SO2Me azetidine, in instances where enhanced lipophilicity is desirable.

  PublisherOA PDFDOI

• Strain-Release Pentafluorosulfanylation of Carbonyl-Containing Disubstituted Bicyclobutanes: Insight on SF5…C=O Interactions and a Fortuitous Path to SF5-Containing Oxa[2.1.1]bicyclohexanes

  ChemRxiv · 2025-12-02 · 3 citations

  articleSenior author

  The recent merger of pentafluorosulfanylation with strain-release functionalization logic – largely enabled by an increase in reagent accessibility – has begun to reshape the ways we can imagine incorporating the SF5 group into organic molecules. In this study, we first explore how both radical polarity matching and substituent effects, when employed synergistically, can be used to effect regio- and diastereoselective SF5Cl addition across 1,3-disubstituted (viz. 3-aryl-1-carbonyl-substituted) bicyclobutanes (BCBs) to access a class of congested alpha-SF5-carbonyl-containing tetrasubstituted cyclobutanes (CBs). Synthetic, computational, and structural studies not only provide insight on the observed selectivity but reveal a potential to employ the resultant SF5-CBs as model systems for studying unusually close and record-setting intramolecular SF5…C=X (X = C, N, or O) contacts by SC-XRD. DFT calculations characterize these as "weakly attractive" interactions and provide context for how the equatorial fluorine atoms of the SF5 group may behave when forced into proximity of systems. Thereafter, we describe a complementary telescoped protocol to facilitate isolation of SF5-CBs as alcohols, as well as a fortuitous observation that led to the synthesis of the first suite of SF5-substituted oxa[2.1.1]bicyclohexanes (OBHs). The SF5-OBH motif is ostensibly a novel "hybrid bioisostere" for the meta-CF3-Ph motif.

  PublisherDOI

• Overcoming a Radical Polarity Mismatch in Strain‐Release Pentafluorosulfanylation of [1.1.0]Bicyclobutanes: An Entryway to Sulfone‐ and Carbonyl‐Containing SF₅‐Cyclobutanes

  Angewandte Chemie International Edition · 2024-01-18 · 52 citations

  articleOpen accessSenior authorCorresponding

  Abstract The first assortment of achiral pentafluorosulfanylated cyclobutanes (SF 5 ‐CBs) are now synthetically accessible through strain‐release functionalization of [1.1.0]bicyclobutanes (BCBs) using SF 5 Cl. Methods for both chloropentafluorosulfanylation and hydropentafluorosulfanylation of sulfone‐based BCBs are detailed herein, as well as proof‐of‐concept that the logic extends to tetrafluoro(aryl)sulfanylation, tetrafluoro(trifluoromethyl)sulfanylation, and three‐component pentafluorosulfanylation reactions. The methods presented enable isolation of both syn and anti isomers of SF 5 ‐CBs, but we also demonstrate that this innate selectivity can be overridden in chloropentafluorosulfanylation; that is, an anti ‐stereoselective variant of SF 5 Cl addition across sulfone‐based BCBs can be achieved by using inexpensive copper salt additives. Considering the SF 5 group and CBs have been employed individually as nonclassical bioisosteres, structural aspects of these unique SF 5 ‐CB “hybrid isosteres” were then contextualized using SC‐XRD. From a mechanistic standpoint, chloropentafluorosulfanylation ostensibly proceeds through a curious polarity mismatch addition of electrophilic SF 5 radicals to the electrophilic sites of the BCBs. Upon examining carbonyl‐containing BCBs, we also observed rare instances whereby radical addition to the 1‐position of a BCB occurs. The nature of the key C(sp 3 )−SF 5 bond formation step – among other mechanistic features of the methods we disclose – was investigated experimentally and with DFT calculations. Lastly, we demonstrate compatibility of SF 5 ‐CBs with various downstream functionalizations.

  PublisherOA PDFDOI

• Controlled oligomerization of [1.1.1]propellane through radical polarity matching: selective synthesis of SF₅- and CF₃SF₄-containing [2]staffanes

  Beilstein Journal of Organic Chemistry · 2024-11-29 · 8 citations

  articleOpen accessSenior author

  Selectivity in radical chain oligomerizations involving [1.1.1]propellane – i.e., to make [ n ]staffanes – has been notoriously challenging to control when n &gt; 1 is desired. Herein, we report selective syntheses of SF 5 - and CF 3 SF 4 -containing [2]staffanes from SF 5 Cl and CF 3 SF 4 Cl, demonstrating cases whereby oligomerization is preferentially truncated after incorporation of two bicyclopentane (BCP) units. Synthetic and computational studies suggest this phenomenon can be attributed to alternating radical polarity matching. In addition, single-crystal X-ray diffraction (SC-XRD) data reveal structurally interesting features of the CF 3 SF 4 -containing [2]staffane in the solid state.

  PublisherOA PDFDOI

• Strain-release trifluoromethoxylation and pentafluorosulfanoxylation of [1.1.0]bicyclobutanes: expanded access to fluorinated cyclobutane hybrid bioisosteres

  Chemical Communications · 2024-12-19 · 17 citations

  articleOpen accessSenior authorCorresponding

  Methods for formal bromo-trifluoromethoxylation and bromo-pentafluorosulfanoxylation of [1.1.0]bicyclobutanes using AgOCF 3 or AgOSF 5 and 1,3-dibromo-5,5-dimethylhydantoin are disclosed.

  PublisherOA PDFDOI

• Overcoming a Radical Polarity Mismatch in Strain‐Release Pentafluorosulfanylation of [1.1.0]Bicyclobutanes: An Entryway to Sulfone‐ and Carbonyl‐Containing SF₅‐Cyclobutanes

  Angewandte Chemie · 2024-01-18 · 2 citations

  articleSenior authorCorresponding

  Abstract The first assortment of achiral pentafluorosulfanylated cyclobutanes (SF 5 ‐CBs) are now synthetically accessible through strain‐release functionalization of [1.1.0]bicyclobutanes (BCBs) using SF 5 Cl. Methods for both chloropentafluorosulfanylation and hydropentafluorosulfanylation of sulfone‐based BCBs are detailed herein, as well as proof‐of‐concept that the logic extends to tetrafluoro(aryl)sulfanylation, tetrafluoro(trifluoromethyl)sulfanylation, and three‐component pentafluorosulfanylation reactions. The methods presented enable isolation of both syn and anti isomers of SF 5 ‐CBs, but we also demonstrate that this innate selectivity can be overridden in chloropentafluorosulfanylation; that is, an anti ‐stereoselective variant of SF 5 Cl addition across sulfone‐based BCBs can be achieved by using inexpensive copper salt additives. Considering the SF 5 group and CBs have been employed individually as nonclassical bioisosteres, structural aspects of these unique SF 5 ‐CB “hybrid isosteres” were then contextualized using SC‐XRD. From a mechanistic standpoint, chloropentafluorosulfanylation ostensibly proceeds through a curious polarity mismatch addition of electrophilic SF 5 radicals to the electrophilic sites of the BCBs. Upon examining carbonyl‐containing BCBs, we also observed rare instances whereby radical addition to the 1‐position of a BCB occurs. The nature of the key C(sp 3 )−SF 5 bond formation step – among other mechanistic features of the methods we disclose – was investigated experimentally and with DFT calculations. Lastly, we demonstrate compatibility of SF 5 ‐CBs with various downstream functionalizations.

  PublisherDOI

• Tetrafluoro(aryl)sulfanylated Bicyclopentane Crystals that Self-Destruct upon Cooling: An Organic "Cryosalient" Material

  ChemRxiv · 2024-07-01

  preprintOpen accessSenior author

  Whereas single crystals of organic compounds that respond to heat ("thermosalient") or light ("photosalient") have been reported and studied in detail, crystalline organic compounds that elicit an extreme mechanical response at cryogenic temperatures ("cryosalient") are relatively rare in the chemical literature. During an attempt to measure an X-ray crystal structure of a tetrafluoro(aryl)sulfanylated bicyclopentane synthesized in our laboratory, we discovered that the crystals jump and forcefully disintegrate upon cooling below ~193 K. Accordingly, we investigated the origin of this cryogenic mechanical response (CMR) through NMR, SC-XRD, DSC, Raman, Brillouin, and microscopy experiments. To our surprise, NMR, SC-XRD, and DSC experiments suggest the phenomenon can neither be attributed to a chemical transformation nor a crystalline-crystalline or crystalline-amorphous phase transition. Rather, microscopy, Raman, and Brillouin experiments provide evidence that the built-up strain released from the crystal upon self-destruction may be associated with a phase transition that occurs in amorphous microstructure within the crystal. This study demonstrates that molecular structural changes within organic material microstructure – which may not necessarily be visible by SC-XRD – can have a significant impact on the thermodynamic behavior of the bulk crystal-line material. Thus, the role of microstructure may be considered more heavily in future mechanistic studies on mechanically responsive crystals.

  PublisherOA PDFDOI

Recent grants

• Synthetic Methods to Make Emerging Fluorinated Groups More Accessible

  NIH · $1.1M · 2023–2028

Frequent coauthors

• Thomas Lectka

  Johns Hopkins University

  64 shared

• Antonio Togni

  42 shared

• Dustin Bornemann

  41 shared

• Nils Trapp

  ETH Zurich

  32 shared

• Desta Doro Bume

  Frederick National Laboratory for Cancer Research

  23 shared

• Yannick Kraemer

  22 shared

• Nico Santschi

  University of Münster

  22 shared

• Clément Ghiazza

  21 shared

Labs

• CRP LaboratoryPI

Education

• Ph.D. in Organic Chemistry, Chemistry

  Johns Hopkins University

  2017

• B.S. in Chemistry with minors in Physics and Musical Theatre, Chemistry

  Monmouth University

  2010

Awards & honors

• Francesca Miller Undergraduate Research Award
• R.B. Miller Research, Service, and Mentorship Award
• R. Bryan Miller Summer Graduate Fellowship