Research Summary: Chemical Imaging and Mechanism-Inspired Synthetic Organic Methods Development. Our program addresses challenges in the fundamental understanding and development of reactions for chemical synthesis. We have two main research areas: 1) Chemical Imaging: We develop single-molecule and single-particle microscopy and spectroscopy tools to study chemical reactions in synthetic chemistry and catalysis. Here we combine expertise across an unusually broad range of traditional subdisciplines of chemistry: organic, organometallic, inorganic, polymer, physical, and analytical chemistry, and both homogeneous and heterogeneous catalysis. 2) Mechanism-Inspired Methods Development: We develop and fundamentally study the reactions of metals (and metalloids—i.e., boron) to create new chemical bonds for organic synthesis. Both programs are mechanistically focused and students/postdoctoral scholars receive excellent training in experimental design.
2024
71. Peacock, H.; Blum, S. A. “Buildup and Consumption of Species in Emulsion Droplets during Aqueous Suzuki Coupling Correlate with Yield.” ChemRxiv, 2024, doi:10.26434/chemrxiv-2024-jt42x
70. Zhang, Y.; Blum, S. A. “Surfactant-Dependent Partitioning of Organics in Aqueous–Organic Reaction Systems.” Chemrxiv, 2024. doi:10.26434/chemrxiv-2024-zjhtg
2023
69. Hanada, E.; Lou, H.;+ McShea, P. J.;+ Blum, S. A. “Metal Activation Produces Different Reaction Environments for Intermediates during Oxidative Addition.” Chem. Eur. J. 2023, e202304105. (+ denotes equal second coauthorship)
68. Stang, M.; Mycka, R. J.; Blum, S. A. “Mechanistic Insight from Lewis-Acid-Dependent Selectivity and Reversible Haloboration, as Harnessed for Boron-Based Electrophilic Cyclization Reactions.” J. Org. Chem. 2023, 88, 15159–15167.
67. Hanada, E. M.; McShea, P. J.; Blum, S. A. “Trimethylsilylchloride Aids in Solubilization of Oxidative Addition Intermediates from Zinc Metal.” Angew. Chem., Int. Ed. 2023, e202307787.
66. Kaplan, J. A.; Blum, S. A. “Iodination–Group Transfer Reactions to Generate Trisubstituted Iodoalkenes with Regio- and Stereochemical Control.” J. Org. Chem. 2023, 88, 13236–13247.
65. López, P. A.; Pham, V. H. B.; Blum, S. A. “A General Autofluorescence Method to Characterize Polymerization Progress.” Angew. Chem., Int. Ed. 2023, e202304168.
64. Peacock, H.; Blum, S. A. “Surfactant Micellar and Vesicle Microenvironments and Structures under Synthetic Organic Conditions.” J. Am. Chem. Soc. 2023, 145, 7648–7658.
63. Eivgi, O.; Ravenscroft, A.; Blum, S. A. “Imaging Block-Selective Copolymer Solvation.” J. Am. Chem. Soc. 2023, 145, 2058–2063.
2022
62. Garcia IV, A.; Blum, S. A. “Polymer Molecular Weight Determination via Fluorescence Lifetime Microscopy.” J. Am. Chem. Soc. 2022, 144, 22416–22420.
61. Gao, C.; Blum, S. A. “Silyl Radical Cascade Cyclization of 2-Isocyanothioanisole toward 2-Silylbenzothiazoles through Radical Initiator–Inhibitor Symbiosis.” J. Org. Chem. 2022, 87, 13124–13137.
60. Eivgi, O.; Blum, S. A. “Real-Time Polymer Viscosity–Catalytic Activity Relationships on the Microscale.” J. Am. Chem. Soc. 2022, 144, 13574–13585.
59. Yu, D.; Garcia IV, A.; Blum, S. A.*; Welsher, K. D.* “Growth Kinetics of Single Polymer Particles in Solution via Active-Feedback 3D Tracking,” J. Am. Chem. Soc. 2022, 144, 14698–14705.
58. Hanada, E. M.; Tagawa, T. K. S.; Kawada, M.; Blum, S. A. “Reactivity Differences of Rieke Zinc Arise Primarily from Salts in the Supernatant, Not in the Solids.” J. Am. Chem. Soc. 2022, 144, 12081–12091. Commentary in Science: “Removing the Witchcraft,” Lowe, D. “In the Pipeline.”
57. Saluga, S. J.; Dibble, D. J.; Blum, S. A. “Superresolved Motions of Single Molecular Catalysts during Polymerization Show Wide Distributions.” J. Am. Chem. Soc. 2022, 144, 10591–10598. Highlighted in C&EN: “Single catalyst molecules tracked in solution.” June 24, 2022.
56. Peacock, H.; Blum, S. A. “Single-Micelle and Single-Zinc-Particle Imaging Provides Insights into the Physical Processes Underpinning Organozinc Reactions in Water.” J. Am. Chem. Soc. 2022, 144, 3285–3296. Spotlighted by the JACS editors: “Micelles in Organometallic Reactions: Ready for Their Close-Up.”
2021
55. Eivgi, O.; Blum, S. A. “Exploring chemistry with single-molecule and -particle fluorescence microscopy.” Trends Chem. 2022, 4, 5–14.
54. Kaplan, J. A.; Issaian, A.; Stang, M.; Gorial, D.; Blum, S. A. ”Repurposing π Electrophilic Cyclization/Dealkylation for Group Transfer.” Angew. Chem. Int. Ed. 2021, 60, 25776–25780.
53. Gao, C.; Blum, S. A. “Main-group Metalated Heterocycles through Lewis acid Cyclization.” Trends Chem. 2021, 3, 645–659.
52. Garcia, A. IV; Saluga S. J.; Dibble, D. J.; López, P.; Saito, N.; Blum, S. A. “Does Molecular Catalyst Selectivity Change with Time? Polymerization Imaged by Single-Molecule Spectroscopy.” Angew. Chem. Int. Ed. 2021, 60, 1550–1555.
2020
51. Gao, C.; Nakao, S.; Blum, S. A. “Borylative Heterocyclization without Air-Free Techniques.” J. Org. Chem. 2020, 85, 10350–10368.
Highlighted as a Featured Article in The Journal of Organic Chemistry.
Highlighted by Synfacts “Air- and Moisture-Tolerant Synthesis of Catechol Boronic Esters”.
50. Jess, K.; Hanada, E. M.; Peacock, H.; Blum, S. A. “Origins of Batch-to-Batch Variation: Organoindium Reagents from Indium Metal.” Organometallics 2020, 39, 2575–2579.
49. Hanada, E. M.; Jess, K.; Blum, S. A. “Mechanism of an Elusive Solvent Effect in Organozinc Reagent Synthesis.” Chem. Eur. J. 2020, 26, 1–6.
2019
48. Easter, Q.; Blum, S. A. “Organic and Organometallic Chemistry at the Single-Molecule, -Particle, and -Molecular-Catalyst-Turnover Level by Fluorescence Microscopy.” Acc. Chem. Res. 2019, 52, 2244-2255.
47. Jess, K.; Kitagawa, K.; Tagawa, T. K. S.; and Blum, S. A. “Microscopy Reveals: Impact of Lithium Salts on Elementary Steps Predicts Organozinc Reagent Synthesis and Structure.” J. Am. Chem. Soc. 2019, 141, 9879-9884.
46. Easter, Q. T.; Garcia IV, A.; Blum, S. A. “Single-Polymer−Particle Growth Kinetics with Molecular Catalyst Speciation and Single-Turnover Imaging.” ACS Catal. 2019, 9, 3375−3383.
45. Tu, K. N., Kim, S., Blum, S. A. “Copper-Catalyzed Aminoboration from Hydrazones To Generate Borylated Pyrazoles.” Org. Lett. 2019, 21, 1283.
2018
44. Bel Abed, H.; Blum, S. A. “Transition Metal-Free Synthesis of Borylated Thiophenes via Formal Thioboration.” Org. Lett. 2018, 20, 6673.
43. Tu, K. N.; Gao, C.; Blum, S. A. “An Oxyboration Route to a Single Regioisomer of Borylated Dihydrofurans and Isochromenes.” J. Org. Chem. 2018, 83, 11204.
42. Easter, Q. T.; Blum, S. A. “Kinetics of the Same Reaction over Nine Orders of Magnitude in Concentration: When Are Unique Subensemble and Single-Turnover Reactivity Displayed?” Angew. Chem. Int. Ed. 2018, 57, 12027.
41. Easter, Q. T.; Blum, S. A. “Evidence for Dynamic Chemical Kinetics at Individual Molecular Ruthenium Catalysts.” Angew. Chem. Int. Ed. 2018, 57, 1572.
2017
40. Issaian, A.; Tu, K. N.; Blum, S. A. “Boron Heteroatom Addition Reactions via Borylative Heterocyclization: Oxyboration, Aminoboration, and Thioboration.” Acc. Chem. Res. 2017, 50, 2598.
39. Easter, Q. T.; Blum, S. A. “Single Turnover at Molecular Polymerization Catalysts Reveals Spatiotemporally Resolved Reactions.” Angew. Chem. Int. Ed. 2017, 56, 13772.
Highlighted in Angew. Chem. Int. Ed. “Kinetics in the Real World”
Highlighted in UCI News Brief, “Little green flashes unlock secrets of catalytic reactions”
38. Issaian, A.; Faizi, D. J.; Bailey, J. O.; Mayer, P.; Berionni, G.; Singleton, D. A.; Blum, S. A. “Mechanistic Studies of Formal Thioboration Reactions of Alkynes.” J. Org. Chem. 2017, 82, 8165.
37. Kazuhiro, K.; Blum, S. A. "Structure–Reactivity Studies of Intermediates for Mechanistic Information by Subensemble Fluorescence Microscopy.” ACS Catal. 2017, 7, 3786.
36. Feng, C.; Easter, Q. T.; Blum, S. A. "Structure–Reactivity Studies, Characterization, and Transformation of Intermediates by Lithium Chloride in the Direct Insertion of Alkyl and Aryl Iodides to Metallic Zinc Powder." Organometallics 2017, 36, 2389.
Organometallics, Cover, July 2017:
2016
35. Faizi, D. J.; Davis, A. J.; Meany, F. B.; Blum, S. A. "Catalyst-Free Formal Thioboration to Synthesize Borylated Benzothiophenes and Dihydrothiophenes." Angew. Chem. Int. Ed. 2016, 55, 14286.
Highlighted in Synfacts 2017, 13, 71. "Ring-forming Thioboration of C–C π-Bonds."
34. Feng, C.; Cunningham, D. W.; Easter, Q. T.; Blum, S. A. "Role of LiCl in Generating Soluble Organozinc Reagents." J. Am. Chem. Soc. 2016, 138, 11156. Link
Highlighted in Org. Process Res. Dev. 2016, 20, 1691. "Some Items of Interest to Process R&D Chemists and Engineers."
33. Faizi, D. J.; Nava, N. A.; Al-Amin, M.; Blum, S. A. "Oxyboration: Synthesis of Borylated Benzofurans." Org. Synth. 2016, 93, 228.
32. Johnson, J. S.; Chong, E.; Tu, K. N.; Blum, S. A. "Kinetic Study of Carbophilic Lewis Acid Catalyzed Oxyboration and the Noninnocent Role of Sodium Chloride." Organometallics 2016, 35, 655.
31. Faizi, D. J.; Issaian, A.; Davis, A. J.; Blum, S. A. "Catalyst-Free Synthesis of Borylated Lactones from Esters via Electrophilic Oxyboration." J. Am. Chem. Soc. 2016, 138, 2126.
30. Hirner, J. J.; Faizi, D. J.; Blum. S. A. Organoboron Compounds and Methods of Making Organoboron Compounds. U. S. Patent 9,238661, January 19, 2016.
29. Tu, K. N.; Hirner, J. J.; Blum, S. A. "Oxyboration with and without a Catalyst: Borylated Isoxazoles via B–O σ-Bond Addition." Org. Lett. 2016, 18, 480.
Highlighted in Synfacts 2016, 12, 400.
2015
28. Chong, E.; Blum, S. A. "Aminoboration: Addition of B–N σ Bonds Across C–C π Bonds." J. Am. Chem. Soc. 2015, 137, 10144.
27. Hirner, J. J.; Blum, S. A. "NMR Spectroscopy Studies of Electronic Effects and Equilibrium in the Organogold-to-boron Transmetallation Reaction and Studies Towards Its Application to the Alkoxyboration Addition of Boron-Oxygen Sigma-Bonds to Alkynes." Tetrahedron 2015, 71, 4445.
Special invited issue in honor of Yoshi Nakao's Tetrahedron Young Investigator Award.
26. Easter, Q. T.; Trauschke, V.; Blum, S. A. "Catalyst Inefficiencies: Supported Ring-Opening Metathesis Polymerization Catalyst Yields Its Ensemble Rate from a Small Number of Molecular Active Sites." ACS Catal. 2015, 5, 2290.
2014
25. Al-Amin, M.; Johnson, J. S.; Blum, S. A. "Selectivity, Compatibility, Downstream Functionalization, and Silver Effect in the Gold and Palladium Dual-Catalytic Synthesis of Lactones." Organometallics 2014, 33, 5448.
24. Hensle, E. M.; Esfandiari, N. M.; Lim, S. -G.; Blum, S. A. "BODIPY Fluorophore Toolkit for Probing Chemical Reactivity and for Tagging Reactive Functional Groups." Eur. J. Org. Chem. 2014, 3347.
EurJOC, Cover, June 2014
23. Blum, S. A. "Location Change Method for Imaging Chemical Reactivity and Catalysis with Single-Molecule and -Particle Fluorescence Microscopy." Phys. Chem. Chem. Phys. 2014, 16, 16333.
PCCP, Cover, August 2014.
22. Hirner, J. J.; Faizi, D. J.; Blum, S. A. "Alkoxyboration: Ring-Closing Addition of B–O Sigma Bonds Across Alkynes." J. Am. Chem. Soc. 2014, 136, 4740.
Highlighted in Science 2014, 344, 10. "A Big Break for Boron."
Organoboron building blocks for drug discovery from this paper are available from Sigma-Aldrich.
21. Al-Amin, M.; Roth, K. E.; Blum, S. A. "Mechanistic Studies of Gold and Palladium Cooperative Dual-Catalytic Cross-Coupling Systems." ACS Catal. 2014, 4, 622.
2013
20. Cordes, T.; Blum, S. A. "Opportunities and challenges in single-molecule and single-particle fluorescence microscopy for mechanistic studies of chemical reactions." Nat. Chem. 2013, 5, 993.
19. Fast, A.; Esfandiari, N. M.; Blum, S. A. "Small Number of Active Sites and Single-Locus Kinetics Revealed in (salph)Co-Catalyzed Ethylene Oxide Polymerization." ACS Catal. 2013, 3, 2150.
18. Hensle, E. M; Blum, S. A. "Phase Separation Polymerization of Dicyclopentadiene Characterized by In Operando Fluorescence Microscopy." J. Am. Chem. Soc. 2013, 135, 12324.
2012
17. Hirner, J. J.; Roth, K. E.; Shi, Y.; Blum, S. A. "Mechanistic Studies of Azaphilic versus Carbophilic Activation by Gold(I) in the Gold/Palladium Dual-Catalyzed Rearrangement of Alkenyl Vinyl Aziridines." Organometallics 2012, 31, 6843.
16. Gladysz, J. A.; Ball, Z. T.; Bertrand, G.; Blum, S. A.; Dong, V. M.; Dorta, R.; Hahn, F. E.; Humphrey, M. G.; Jones, W. D.; Klosin, J.; Manners, I.; Marks, T. J.; Mayer, J. M.; Rieger, B.; Ritter, J.; Sattelberger, A. P.; Schomaker, J. "Organometallics Roundtable 2011." Organometallics 2012, 31, 1.
15. Cornell, T. P.; Shi, Y.; Blum, S. A. "Synthesis of Alkenylgold(I) Compounds via Sequential Hydrozirconation and Zirconium to Gold Transmetalation." Organometallics 2012, 31, 5990.
2011
14. Esfandiari, N. M.; Blum, S. A. "Homogeneous vs Heterogeneous Polymerization Catalysis Revealed by Single-Particle Fluorescence Microscopy." J. Am. Chem. Soc. 2011, 133, 18145.
Highlighted Editor's Choice, Science 2011, 334, 1034. "A Probe of Homogeneity."
13. Esfandiari, N. M.; Wang, Y.; Bass, J. Y.; Blum, S. A. "Deconvoluting Subensemble Chemical Reaction Kinetics of Platinum–Sulfur Ligand Exchange Detected with Single-Molecule Fluorescence Microscopy." Inorg. Chem. 2011, 50, 9201.
12. Roth, K. E.; Blum, S. A. "Direct Observation of Gold/Palladium Transmetalation in an Organogold Heck Reaction." Organometallics 2011, 30, 4811.
11. Hirner, J. J.; Shi, Y.; Blum, S. A. "Organogold Reactivity with Palladium, Nickel, and Rhodium: Transmetalation, Cross-Coupling, and Dual Catalysis." Acc. Chem. Res. 2011, 44, 603.
One of the "Most Read" Accounts articles.
10. Shi, Y.; Blum, S. A. "Gold and Rhodium Transmetalation: Mechanistic Insights and Dual-Metal Reactivity." Organometallics 2011, 30, 1776.
9. Hirner, J. J.; Blum, S. A. "Nickel-Catalyzed Cross-Coupling of Organogold Reagents." Organometallics 2011, 30, 1299.
2010
8. Esfandiari, N. M.; Wang, Y.; Mcintire, T. M.; Blum, S. A. "Real-Time Imaging of Platinum-Sulfur Ligand Exchange Reactions at the Single-Molecule Level via a General Chemical Technique." Organometallics 2010, 30, 2901.
Organometallics Cover, June 2011:
7. Esfandiari, N. M.; Wang, Y.; Bass, J. Y.; Cornell, T. P.; Otte, D. A. L.; Cheng, M. H.; Hemminger, J. C.; Mcintire, T. M.; Mandelshtam, V. A.; Blum, S. A. "Single-Molecule Imaging of Platinum Ligand Exchange Reaction Reveals Reactivity Distribution." J. Am. Chem. Soc. 2010, 132, 15167.
Highlighted in Chem. & Eng. News 2010, 88 (36), 14.
Journal of the American Chemical Society Cover, November 2010:
6. Roth, K. E.; Blum, S. A. "Relative Kinetic Basicities of Organogold Compounds." Organometallics 2010, 29, 1712.
2009
5. Shi, Y.; Roth, K. E.; Ramgren, S. D.; Blum, S. A. "Catalyzed Catalysis Using Carbophilic Lewis Acidic Gold and Lewis Basic Palladium: Synthesis of Substituted Butenolides and Isocoumarins." J. Am. Chem. Soc. 2009, 131, 18022.
4. Lim, S.-G.; Blum, S. A. "A General Fluorescence Resonance Energy Transfer (FRET) Method for Observation and Quantification of Organometallic Complexes under Reaction Conditions." Organometallics 2009, 28, 4643.
3. Shi, Y.; Ramgren, S. D.; Blum, S. A. "Palladium-Catalyzed Carboauration of Alkynes and Palladium/Gold Cross-Coupling." Organometallics 2009, 28, 1275.
Highlighted in ACS-Petroleum Research Fund Feature Story, "A Synergy of Synthetic Chemistry"
2008
2. Canham, S. M.; Bass, J. Y.; Navarro, O.; Lim, S. G.; Das, N.; Blum, S. A. "Toward the Single-Molecule Investigation of Organometallic Reaction Mechanisms: Single-Molecule Imaging of Fluorophore-Tagged Palladium(II) Complexes." Organometallics 2008, 27, 2172.
Highlighted in Chem. & Eng. News 2008, 86, 43.
1. Shi, Y.; Peterson, S. M.; Haberaecker, W. W., III; Blum, S. A. "Alkynes as Stille Reaction Pseudohalides: Synthesis of Tri- and Tetra-Substituted Olefins." J. Am. Chem. Soc. 2008, 130, 2168.
Highlighted in Angew. Chem. Int. Ed. 2008, 47, 5703.
