Global InformationStahl oxidation information
| Stahl oxidation | |
|---|---|
| Named after | Shannon S. Stahl |
| Reaction type | Organic redox reaction |
The Stahl oxidation is a copper-catalyzed aerobic oxidation of primary and secondary alcohols to aldehydes and ketones. Known for its high selectivity and mild reaction conditions, the Stahl oxidation offers several advantages over classical alcohol oxidations.
Key features of the Stahl oxidation are the use of a 2,2'-bipyridyl-ligated copper(I) species in the presence of a nitroxyl radical and N-methyl imidazole in polar aprotic solvent, most commonly acetonitrile or acetone.[1][2][3] Copper(I) sources can vary, though sources with non-coordinating anions like triflate, tetrafluoroborate, and hexafluorophosphate are preferred,[1] with copper(I) bromide[2] and copper(I) iodide[4] salts demonstrating utility in select applications. Frequently, tetrakis(acetonitrile)copper(I) salts are used.[1][5][6][7] For most applications, reactions can be run at room temperature and ambient air contains sufficiently high enough oxygen concentrations to be used as the terminal oxidant. Compared to chromium-, DMSO-, or periodinane-mediated oxidations, this proves safe, environmentally-friendly, practical, and highly economical.[8]
In general, the Stahl oxidation is selective for oxidizing primary alcohols over secondary alcohols (both aliphatic and benzylic), and favors the oxidation of primary benzylic alcohols over primary aliphatic alcohols when TEMPO is used as the nitroxyl radical.[1] This is in contrast to the Oppenauer oxidation, which favors the oxidation of secondary alcohols over primary and several other specialty oxidations.[10][11] Over-oxidation of primary alcohols to carboxylic acids is rare, though lactones can form in certain diol-containing substrates.[1][3][7] The use of less hindered nitroxyl radicals like ABNO[12] or AZADO[13] allow for the oxidation of both primary and secondary alcohols.[14][15]
- ^ a b c d e Hoover, Jessica M.; Stahl, Shannon S. (2011-10-26). "Highly Practical Copper(I)/TEMPO Catalyst System for Chemoselective Aerobic Oxidation of Primary Alcohols". Journal of the American Chemical Society. 133 (42): 16901–16910. doi:10.1021/ja206230h. ISSN 0002-7863. PMC 3197761. PMID 21861488.
- ^ a b Hill, Nicholas J.; Hoover, Jessica M.; Stahl, Shannon S. (2013-01-08). "Aerobic Alcohol Oxidation Using a Copper(I)/TEMPO Catalyst System: A Green, Catalytic Oxidation Reaction for the Undergraduate Organic Chemistry Laboratory". Journal of Chemical Education. 90 (1): 102–105. Bibcode:2013JChEd..90..102H. doi:10.1021/ed300368q. ISSN 0021-9584.
- ^ a b Xie, Xiaomin; Stahl, Shannon S. (2015-03-25). "Efficient and Selective Cu/Nitroxyl-Catalyzed Methods for Aerobic Oxidative Lactonization of Diols". Journal of the American Chemical Society. 137 (11): 3767–3770. doi:10.1021/jacs.5b01036. ISSN 0002-7863. PMID 25751494.
- ^ Ochen, Augustine; Whitten, Robert; Aylott, Helen E.; Ruffell, Katie; Williams, Glynn D.; Slater, Fiona; Roberts, Andrew; Evans, Paul; Steves, Janelle E.; Sanganee, Mahesh J. (2019-01-14). "Development of a Large-Scale Copper(I)/TEMPO-Catalyzed Aerobic Alcohol Oxidation for the Synthesis of LSD1 Inhibitor GSK2879552". Organometallics. 38 (1): 176–184. doi:10.1021/acs.organomet.8b00546. ISSN 0276-7333. S2CID 106029012.
- ^ Forster, Michael; Chaikuad, Apirat; Dimitrov, Teodor; Döring, Eva; Holstein, Julia; Berger, Benedict-Tilman; Gehringer, Matthias; Ghoreschi, Kamran; Müller, Susanne; Knapp, Stefan; Laufer, Stefan A. (2018-05-31). "Development, Optimization, and Structure–Activity Relationships of Covalent-Reversible JAK3 Inhibitors Based on a Tricyclic Imidazo[5,4-d]pyrrolo[2,3-b]pyridine Scaffold". Journal of Medicinal Chemistry. 61 (12): 5350–5366. doi:10.1021/acs.jmedchem.8b00571. ISSN 0022-2623. PMID 29852068. S2CID 46919031.
- ^ Lowell, Andrew N.; DeMars, Matthew D.; Slocum, Samuel T.; Yu, Fengan; Anand, Krithika; Chemler, Joseph A.; Korakavi, Nisha; Priessnitz, Jennifer K.; Park, Sung Ryeol; Koch, Aaron A.; Schultz, Pamela J. (2017-06-14). "Chemoenzymatic Total Synthesis and Structural Diversification of Tylactone-Based Macrolide Antibiotics through Late-Stage Polyketide Assembly, Tailoring, and C—H Functionalization". Journal of the American Chemical Society. 139 (23): 7913–7920. doi:10.1021/jacs.7b02875. ISSN 0002-7863. PMC 5532807. PMID 28525276.
- ^ a b Alfonzo, Edwin; Beeler, Aaron B. (2019). "A sterically encumbered photoredox catalyst enables the unified synthesis of the classical lignan family of natural products". Chemical Science. 10 (33): 7746–7754. doi:10.1039/C9SC02682G. ISSN 2041-6520. PMC 6761868. PMID 31588322.
- ^ US EPA, OCSPP (2014-09-30). "Presidential Green Chemistry Challenge: 2014 Academic Award". US EPA. Retrieved 2020-02-02.
- ^ Hoover, Jessica M.; Stahl, Shannon S. (2011-10-26). "Highly Practical Copper(I)/TEMPO Catalyst System for Chemoselective Aerobic Oxidation of Primary Alcohols". Journal of the American Chemical Society. 133 (42): 16901–16910. doi:10.1021/ja206230h. ISSN 0002-7863. PMC 3197761. PMID 21861488.
- ^ Mello, Rossella; Martínez-Ferrer, Jaime; Asensio, Gregorio; González-Núñez, María Elena (November 2007). "Oppenauer Oxidation of Secondary Alcohols with 1,1,1-Trifluoroacetone as Hydride Acceptor". The Journal of Organic Chemistry. 72 (24): 9376–9378. doi:10.1021/jo7016422. ISSN 0022-3263. PMID 17975928.
- ^ Tojo, Gabriel. (2006). Oxidation of alcohols to aldehydes and ketones : a guide to current common practice. Fernández, Marcos (Marcos I.). New York, NY: Springer. ISBN 978-0-387-23607-0. OCLC 190867041.
- ^ "9-Azabicyclo[3.3.1]nonane N-Oxyl, ABNO". The Organic Chemistry Portal.
- ^ "2-Azaadamantane N-Oxyl, AZADO". The Organic Chemistry Portal.
- ^ Steves, Janelle E.; Stahl, Shannon S. (2013-10-23). "Copper(I)/ABNO-Catalyzed Aerobic Alcohol Oxidation: Alleviating Steric and Electronic Constraints of Cu/TEMPO Catalyst Systems". Journal of the American Chemical Society. 135 (42): 15742–15745. doi:10.1021/ja409241h. ISSN 0002-7863. PMC 6346749. PMID 24128057.
- ^ Ryland, Bradford L.; Stahl, Shannon S. (2014-08-18). "Practical Aerobic Oxidations of Alcohols and Amines with Homogeneous Copper/TEMPO and Related Catalyst Systems". Angewandte Chemie International Edition. 53 (34): 8824–8838. doi:10.1002/anie.201403110. PMC 4165639. PMID 25044821.