Aerobic Oxidation Catalysis via Hypervalent Iodine Intermediates
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Hypervalent iodine compounds are ubiquitous oxidants in synthetic chemistry and are often used by both organic and inorganic chemists. Typically, formation of these reagents requires stoichiometric amounts of metal-based oxidants. Methods that leverage O2 as the oxidant to form hypervalent iodine reagents allow for O2 to be utilized as the ultimate oxidant, providing for a pathway to greener oxidation chemistry. In this lab, you will generate (diacetoxyiodo)benzene, a common hypervalent iodine reagent, by intercepting reactive intermediates generated during aldehyde autoxidation (i.e. the reaction between simple aldehydes and O2). In addition, you will use a catalytic amount of an iodobenzene reagent to catalyze a C–N cross-coupling reaction in which O2 is the terminal oxidant. You will also perform the same cross-coupling reaction via a traditional Pd catalyzed method. Comparison of the traditional conditions with the aerobic conditions will provide insight into important design considerations relevant to sustainable synthetic chemistry. Through this lab you will learn how to handle potentially dangerous gases (O2) and reagents with low boiling points.
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Minimum characterization requirements: Yield and 1H NMR of (diacetoxy)iodobenzene and N-methoxy-4-methyl-N-phenylbenzenesulfonamide (as synthesized from both methods)
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New methods: Proper use and handling of O2, reagents with low boiling points, and how to use a pipette for column chromatography.
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References to get you started:
Nat. Chem. 2018, 10, 200. (you might want to refer to the SI for your prelab writeup)
J. Am. Chem. Soc., 1998, 120, 827–828. (see SI for general procedure for Pd cross-coupling)
Org. Lett. 2011, 13, 2564-2567.
J. Am. Chem. Soc. 2017, 139, 9010.
Chem. Rev. 2016, 116, 12564. (read introduction)
Nat. Chem. 2013, 5, 417.
Chem. Rev. 2016, 116, 3328. (Read section 1 & 2. Skim through section 3 & 6)
Anastas, P. T.; Warner, J. C. Green Chemistry: Theory and Practice; Oxford Univ. Press: Oxford, 2000; p 135.
Org. Proc. Res. Dev. 2009, 13, 161-185.
Prelab questions:
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What is the difference between oxygenase and oxidase chemistry?
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Provide a simple molecular orbital picture to describe the electronic structure of O2. Why is O2 not a kinetically competent oxidant for synthesis?
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Why is (diacetoxy)iodobenzene called hypervalent compound? Provide a molecular orbital diagram that rationalizes the T-shaped geometry of (diacetoxy)iodobenzene.
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Describe the features of hypervalent iodine compounds that enable these species to display reaction chemistry commonly observed for transition metal compounds.
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Aldehyde autoxidation generates carboxylic acids via first a radical chain reaction with O2 to generate peracids and subsequent non-radical Baeyer-Villiger reaction that combines a peracid and an aldehyde to generate two equivalents of carboxylic acid. Provide an arrow pushing mechanism for the autoxidation of acetaldehyde to generate acetic acid.
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What is the role of Co(II) in aldehyde autoxidation mechanism? What other metal salts could be use in place of Co(II)?
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Decarbonylation of acyl radicals would generate CO and alkyl radicals and would inhibit the formation of acids from aldehyde autoxidation. Based on the mechanism of aldehyde autoxidation, arrange the given aldehydes in order of decarbonylation rate: i) butyraldehyde, ii) isobutyraldehyde, and iii) pivaldehyde. Provide reasoning for your answer.
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What happens if THF is used as a solvent in the aldehyde autoxidation mediated aerobic oxidation of iodobenzene?
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Draw a generic catalytic cycle for a Pd-catalyzed cross-coupling to generate a C–N bond. Name each organometallic transformation in the cycle. Give the oxidation state and d-electron count of the Pd center at each step.
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Compare the sustainability of C–N bond-forming chemistry catalyzed by Pd or by aryl iodide catalysts.
