This work can be separated into two parts; the first will encompass chapters one and two, which discuss the use of the Catellani reaction to access different heterocycles. The second part will encompass the remaining chapters and deals with stereoselective reactions of arynes.
Chapter one outlines the development of a general and high yielding synthesis of the phenanthridine nucleus via a palladium-catalyzed domino reaction of aryl iodides with N-H or N-trimethylsilyl imines. This strategy was applied in a succinct synthesis of benzo[c]phenanthridine alkaloids nitidine and NK109.
Chapter two details the development of a Catellani-type reaction of aryl iodides with 2H-azirines. Conditions were found to selectively provide access to either the indole nucleus or unusual dihydroimidazoles. The yields of the products ranged from moderate to good, however, the success of the reaction is highly dependent on the structure of the 2H-azirine. A mechanism was proposed involving oxidative addition of the azirine to generate an azaalyl intermediate.
In Chapter three the foray into the area of aryne chemistry begins. A stereoselective nickel- catalyzed [2+2+2] cycloaddition of 1,6-enynes with aryne intermediates was developed. Attempts were made at the development of an asymmetric variant of the reaction, however, only low enantiomeric excess was observed. Good diastereoselectivity could be obtained when an allylic substituent was present. The yields of the products ranged from moderate to excellent. However, the yields vary greatly and in a number of cases the reactions were unsuccessful.
Finally, in chapter four the development of a general and high yielding annulation strategy for the synthesis of various carbo- and heterocycles, based on an intramolecular aryne ene reaction is described. It was found that the geometry of the olefin is crucial to the success of the reaction and it that regioselective hydrogen migration occurs. Furthermore, the electronic nature of the aryne was found to be important to the success of the reaction. Deuterium labeling studies and DFT calculations provided insight into the reaction mechanism. The data suggested a concerted asynchronous transition state, resembling a nucleophilic attack on the aryne. This strategy was successfully applied to the formal synthesis of the ethanophenanthridine alkaloid (±)-crinine. In a similar vein, preliminary results demonstrating an intramolecular, formal [2+2] cycloaddition of an aryne with an S, O-ketene acetal to give interesting tricyclic benzocyclobutene products are disclosed.
| Identifer | oai:union.ndltd.org:TORONTO/oai:tspace.library.utoronto.ca:1807/33945 |
| Date | 10 December 2012 |
| Creators | Candito, David |
| Contributors | Lautens, Mark |
| Source Sets | University of Toronto |
| Language | en_ca |
| Detected Language | English |
| Type | Thesis |
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