Radical cyclizations have become a mainstay of synthetic organic chemistry – useful for the construction of C–C bonds in laboratory-scale applications. However, they are seldom used the industrial scale. In large part, this is because of a reliance on Bu3SnH, widely regarded as the best synthetic equivalent to a hydrogen atom.
Transition metal hydrides have emerged as promising alternative hydrogen atom sources. Over the last decade, the Norton group has studied three transition metal systems, with an emphasis on quantifying the M–H bond dissociation energies. Over time, the group has shown that, thermodynamically, first-row transition metal hydrides are good hydrogen atom donors; they often have weak M–H bonds. Modest adjustments to the M–H bond strength result in substantial changes to how a hydride processes a given organic substrate.
The Norton group has also studied the kinetics of hydrogen atom transfer, and shown that transition metal hydrides are kinetically competent at transferring hydrogen atoms, both to olefinic substrates and to organic radicals. Some of the transition metal complexes are made catalytic under modest pressures of H2, so they can be used for effecting atom-economical radical reactions.
I have leveraged the fundamental kinetic and thermodynamic information that has been gathered by the group to develop new radical reactions – ones that cannot be done by Bu3SnH. Herein are described two cases studies: the first is the generation of α-alkoxy radicals by hydrogen atom transfer to enol ethers (Chapter 2). The second is the development of a radical isomerization and cycloisomerization reactions (Chapter 3). Both of these developments have relied upon an understanding of M–H thermochemistry.
Discovering new hydrogen atom donors will lead to discovering new radical reactions. In Chapter 4, I revisit two previously reported transition metal hydrides that are likely to transfer hydrogen atoms: (TMS3tren)CrIV–H and [CpV(CO)3H]–. Although the anionic vanadium hydride was reported as a potent hydrogen atom donor nearly forty years ago, my studies suggest that its M–H bond is actually relatively strong. I have therefore reevaluated the reactivity of [CpV(CO)3H]–, and found that although the 18 electron anionic hydride is not a good hydrogen atom donor, the oxidized 17-electron neutral CpV(CO)3H is an extremely potent one. I have made the reactions with [CpV(CO)3H]– catalytic under H2 (now the reactions are done with an added base). The catalytic reactions that use [CpV(CO)3H]– can enact the exact same transformations that tin does, so I have developed a true catalytic replacement for Bu3SnH.
| Identifer | oai:union.ndltd.org:columbia.edu/oai:academiccommons.columbia.edu:10.7916/D8MG8226 |
| Date | January 2017 |
| Creators | Kuo, Jonathan Lan |
| Source Sets | Columbia University |
| Language | English |
| Detected Language | English |
| Type | Theses |
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