It was a valuable experience for me to participate in the intellectual and scientific development of a young laboratory, and a privilege to have an advisor so willing to listen to (or at least tolerate) my opinions ). Brian's willingness to explore areas outside of his primary area of expertise played a major role in the outcome of my graduate career, and I am grateful to have had this freedom. Professor Bob Grubbs has continually had insightful comments on my work, and he and his group contribute enormously to the special atmosphere of the Caltech chemistry department, whether through Nobel prizes or pub crawls.
I also would not be where I am today without my experience at UW-Madison in the labs of Professor Chuck Casey. Simply put, he worked hard and his efforts have benefited many members of the group, including myself. Dan Caspi, Dave Ebner, and Ryan McFadden's contributions to OKR synthetic applications were an essential phase of the project.
It was an intense time in the lab, and the amount of work we got done in the early years is now almost unimaginable. Neil's chemistry skills, work ethic, thoughtfulness and dedication have been inspirational throughout my time at Caltech and were a major influence in the early years. Of the younger generations, there are a number of people I would like to acknowledge: Dan Caspi for late nights at Amigos, other party times and his attention to detail – Caspi, your love of Vegas may only be overshadowed by your obsession with everything. things computer; Mike Krout, JT Mohr and Caspi for entertaining lunch conversations over tacos; JT Mohr, Jenny Roizen, Mike Krout, Jenn Stockdill, Dave Ebner, Dan Caspi, and John Enquist for important proofreading and general assistance with thesis assembly.
Jen Love and James Tsai provided helpful discussions and experimental advice in the early days. There are many other people to thank: Smith Nielsen of the Goddard Laboratory for his willingness to perform calculations on a complicated system and his continuing interest in sparteine-related chemistry; Connie Lu and Dr. Cora MacBeth of the Peters Laboratory for experimental advice and electrochemistry assistance; the infamous Joel Austin of the DMAC lab; Rebecca Connor, Meghana Bhatt and Yen Nguyen for friendship;.
Leonard, without whose pioneering work in the synthesis of lupine alkaloids this thesis would not be the same. I would like to thank the wonderful support staff in the Chemistry Department who manage to make things run smoothly despite demands from all sides. The NMR facility has seen many ups and downs during my time at Caltech, and most of the ups and downs are due to the amazing efforts of Scott Ross.
Scott, I really enjoyed working with you to improve the facility and I wish you all the best in the future. The mechanism of the oxidative heteroatom/olefin cyclizations was investigated via stereospecifically deuterium-labeled substrates. The origin of stereoselectivity in the oxidative kinetic resolution of secondary alcohols using the Cl symmetric ligand (–)-sparteine was investigated through structural and reactivity studies of a series of ((–)-sparteine) palladium(II) complexes.
Experiments with the C2-symmetric diastereomers of (–)-sparteine highlight the special properties of (–)-sparteine that make it a uniquely effective ligand in the kinetic resolution.
LIST OF ABBREVIATIONS
DMF N,N-dimethylformamide
- INTRODUCTION AND BACKGROUND
- PALLADIUM(II) AS A CATALYST FOR ENANTIOSELECTIVE OXIDASE-TYPE REACTIONS.REACTIONS
- NOTES AND REFERENCES
In oxidative processes, O2 can be the source of an oxygen atom that is transferred to a substrate (Figure 1.1.1, left). The metalloenzymes that catalyze this process often do so via a metal-oxo species in the metalloenzyme and are classified as oxygenases. Members of this class include the cytochrome P-450 enzymes, which are essential for the initial phase of animal metabolism.
On the other hand, a substrate can act as a proton and electron donor, with O2 as an acceptor, without transferring an oxygen atom to the substrate (Figure 1.1.1, right). Metalloenzymes of this type are classified as oxidases, of which cytochrome oxidase is the last example. This effort has made oxidation one of the most effective ways for chemists to induce asymmetry in organic transformations for the production of enantioenriched materials.1 Most enantioselective oxidations involve the transfer of a heteroatom, usually oxygen, to a substrate on a manner analogous to that of oxygenase metalloenzymes.
Some of the most important examples of reactions of this type are Sharpless-Katsuki asymmetric epoxidation (3 4) and sharp asymmetric dihydroxylations (4 5), or reactions of the mono and dioxygenase type (Figure. Although racemic reactions of this type, of such as alcohol oxidations, alkane dehydrogenations, and aromatic oxidations, are widespread, there are few asymmetric examples.5 Since its inception, the Stoltz laboratory at the California Institute of Technology has been interested in the development of asymmetric oxidase-type reactions, in other words, enantioselective catalytic dehydrogenations.
For example, enantioselective oxidation of an alcohol would affect the kinetic resolution of the secondary alcohol (7) by selectively converting one enantiomer to the ketone (8). Asymmetric aromatic oxidation may also be possible for the synthesis of interesting products or reactive intermediates. Fortunately, a series of achiral dehydrogenation reactions have been known for decades for the same transition metal: palladium(II).
In the well-known Wacker process, ethylene (15) is oxidized to acetaldehyde (16) by palladium(II) chloride in the presence of O2 and a copper cocatalyst (Figure 1.2.2).6 In 1977, Blackburn and Schwartz reported palladium. Catalyzed oxidation of alcohol (II) in the presence of sodium acetate and O2.7 Because the oxidized metal is required for the oxidation of the substrate in these cases, a stoichiometric oxidant is necessary. Both of the above reactions use O2 as the final oxidant in a manner analogous to oxidase enzymes, although the Wacker process requires a copper cocatalyst. Several other reoxidants have been used, such as peroxides, benzoquinone and DMSO/O2, which have enabled the execution of the rest of the reactions shown in Figure 1.2.2, among others. 8,9 Thus palladium(II) appears to be an optimal candidate for the development of a set of asymmetric oxidase-type reactions.
Indeed, over the past six years, our group has realized the potential of palladium(II) to perform several enantioselective oxidase-type reactions. During this work, several interesting questions regarding the mechanism and selectivity of these processes arose.
