ZHAO-DISSERTATION-2020.pdf (6.28 MB)

Copper-Catalyzed Carbonylation of Alkyl Iodides

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thesis
posted on 01.12.2020, 00:00 by Siling Zhao
Metal-catalyzed radical carbonylation complements two-electron chemistry by expanding the reactant scope to sp3-carbon substrates. We have developed a reductive carbonylation method by which unactivated alkyl iodides can be hydroxymethylated to provide one-carbo-extended alcohol products under Cu-catalyzed conditions. The method is tolerant of alkyl β-hydrogen atoms, is robust towards a wide variety of functional groups, and was applied to primary, secondary, and tertiary alkyl iodide substrates. Mechanistic experiments indicate that the transformation proceeds by atom-transfer carbonylation (ATC) of the alkyl iodide followed in tandem by two CuH-mediated reductions in rapid succession. This radical mechanism renders the Cu-catalyzed system complementary to precious-metal-catalyzed reductive carbonylation reactions. We also reported the development of a Cu-catalyzed reductive aminocarbonylation of alkyl iodides using nitroarenes as the nitrogen source. The reaction proceeds with a single copper catalyst playing dual roles of synergistically mediating both carbonylation of alkyl iodides and reduction of nitroarenes, providing acyl iodides and anilines as possible reactive intermediates that then do amide coupling spontaneously. A diverse range of secondary N-aryl alkylamides are accessible from a variety of primary, secondary, and tertiary alkyl iodides using this method. The last method enables efficient synthesis of aliphatic potassium acyltrifluoroborates (KATs) in high yields by treating in-situ formed tetracoordinated acylboron intermediates with aqueous KHF2. A variety of functional groups are tolerated under the mild reaction conditions, and primary, secondary and tertiary alkyl halides are all applicable. In addition, this method also provides facile access to N-methyliminodiacetyl (MIDA) acylboronates as well as 𝛼-methylated potassium acyltrifluoroborates in a one-pot manner. Mechanistic studies indicate a radical atom transfer carbonylation (ATC) mechanism to form acyl halide intermediates that are subsequently borylated by (NHC)CuBPin.

History

Advisor

Mankad, Neal P

Chair

Mankad, Neal P

Department

Chemistry

Degree Grantor

University of Illinois at Chicago

Degree Level

Doctoral

Degree name

PhD, Doctor of Philosophy

Committee Member

Wink, Donald J Mohr, Justin T Nagib, David A Lee, Daesung

Submitted date

December 2020

Thesis type

application/pdf

Language

en

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