Exploring hypervalent iodine reagents and their potential as exogenous oxidants in redox gold catalysis

Abstract

This thesis explores the use of hypervalent iodine reagents and their potential as external oxidants in redox gold catalysis.
The first chapter presents a brief introduction into the chemistry of gold and iodine. The second chapter gives an outline of gold catalysed homocoupling of arylsilanes and arenes in which both small aromatic molecules (fluorobenzene) and larger aromatics (2-methyl- and 2-methoxynaphthalene) are employed. The homocoupling of 1-trimethylsilyl-naphthalene using [(Ph3P)AuCl] pre-catalyst produced very good yields of binaphthalene when PIDA/AcOH system was employed (85% yield PIDA/AcOH, 100% PIDA/CSA/AcOH) with much smaller yields seen with 1-trimethylsilyl-2-methyl naphthalene (18% yield PIDA/AcOH). Smaller aryl silanes (with various para substituents on the aryl ring) performed worse, all below 18% yield. Gold catalysed homocoupling of arenes showed mixed results, where fluorobenzene produced 37% yield of 4,4’-difluorobiphenyl (10 eq. PIDA/CSA/AcOH/[(Ph3P)AuCl] system). The larger aromatics performed considerably better – 2-methoxynaphthalene producing a 100% yield of 2,2’-dimethoxy-1,1’-binapththalene (PIDA/CSA or TsOH/AcOH system) whereas 2-methylnaphthalene yielded 70% of 2,2’-dimethyl-1,1’-binapththalene with PIDA/CSA/AcOH and 100% with PIDA/TsOH/AcOH system, which presents us with a novel C-H activation of substituted naphthalenes under mild conditions.
The third chapter investigates the substituent influence in R-PIDA and its oxidative ability in gold-catalysed processes. We have determined that in gold(I)-catalysed homocoupling of fluorobenzene the equatorial substituent on the aryl ring of PIDA does have an influence on the yield – the parent PIDA produced 37% yield of 4,4’-difluorobiphenyl whereas the highly electron-withdrawing p-CF3 group improved the yield to 45%. Bulky/electron-donating substituents showed a general decrease in the yield. We have studied a selective oxidation of 4-fluorobenzyl alcohol to 4-fluorobenzaldehyde using gold(III) as a pre-catalyst and found that the equatorial substituent had an effect on the reactivity, however we were unable to quantify it. A kinetic study revealed that the reaction was zero order with respect to PIDA. We were unable to quantify the substituent effect neither via Hammett nor Creary parameters. The best results were seen with F3C-PIDA (63% yield vs 46% PIDA) which is the first example of homogenous-gold-catalysed selective oxidation of benzyl alcohol with very good yields.
The fourth chapter explores the metal-free I(III) catalysed C-H activation of naphthalene. In the case of 2-methylnaphthalene, we saw a complete turnover to 2,2’-dimethyl-1,1’-binapththalene with the use of PIDA/TsOH system, whereas 2-methoxynaphthalene produced a modest yield of 50% 2,2’-dimethoxy-1,1’-binapththalene (PIDA/TsOH), with a large side product of 1-iodo-2-methoxynaphthalene (47% yield) in selective iodination. This reaction was substrate sensitive since a methyl group in position 2 on the naphthalene switched the iodination off completely. Koser-type reagents performed poorly, with 10% yields seen with a parent Koser and up to 20% when a substituent was changed in the para position on the aryl ring. However, Koser-reagents did not require acid-additives, making it the first example of Koser-catalysed homocoupling of naphthalenes.
The fifth chapter focuses on a structural investigation into R-PIDA and R-Koser reagents. With the help of X-ray crystallography, MALDI MS and 1H NMR, we have proven the existence of a complex equilibrium in solution between the mononuclear, dinuclear and polymeric form of R-PIDA, which concedes with the computational calculations rendering the process thermodynamically feasible. We have found evidence that all synthesised R-PIDA contain various amounts of the dimeric and polymeric species. MALDI MS showed that all samples were polymeric in nature, some even showing up to 15-repeat units. We have developed and tested protocols to enable synthesis of: a). exclusively monomeric R-PIDA species (p-EWG substituents on the aryl-ring: I(OAc)3 and arene; p-EDG substituents: peracetic acid, acetic acid and arene – both inert conditions), b). dinuclear R-PIDA (weak base hydrolysis, e.g., with K2CO3,) and c). polynuclear R-PIDA (strong base hydrolysis; e.g., with 3 M NaOH). We have tested the oxidative ability of all the different types of species in the selective oxidation of 4-fluorobenzyl alcohol to 4-fluorobenzaldehyde under mild conditions and found the trend to be: mononuclear<standard<dinuclear<<polynuclear. We have concluded that nuclearity plays a much more important role in oxidative abilities of oxidants of R-PIDA. Furthermore, X-ray data revealed that R-PIDA oxidants with changed electronics/sterics on the equatorial position on the aryl ring exhibited a deviation from the 180° angle predicted by the VSEPR theory, potentially influencing the reactivity. R-Koser produced only one X-ray structure with the I-O-I bond angle of 176° and thus similar to the parent structure.

Date of Award	25 Jan 2022
Original language	English
Awarding Institution	University of Bristol
Supervisor	Chris A Russell (Supervisor) & Thomas Wirth (Supervisor)