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Ring expansion reactions to form spirocycles and its application to the synthesis of cylindricine B

University of British Columbia

The photochemically initiated semipinacol rearrangement of a substrate bearing an intramolecular alcohol 1.10 was attempted in order to provide spirocyclic ring systems. The syntheses of carbocyclic ring expansion precursors were achieved. Unfortunately, the use of U V light and a photosensitizer to initiate ring expansion reaction was unsuccessful. It was found that a majority of siloxy-epoxide ring expansions of cyclobutane rings to form l-azaspiro[5.4]decanes are unselective. The ring expansion of cyclobutane rings was executed on siloxy-epoxide carbocycles 2.6 and 2.15 and heterocycle 2.34 with the intent of achieving mechanistic elucidation. Three scenarios for the stereochemical outcome of the rearrangements were examined. The rearrangement was deduced to most likely occur via an unselective synchronous mechanism where anti and syn migration of the alkyl (CHfe) group onto the epoxide moiety take place to give 2.4 and 2.5, respectively. Interesting diastereoselectivity was observed by varying the silicon substituent size and the substitution at the 3-position of the heterocycle. Also, chiral Lewis acid initiated ring expansions were attempted as a method of introducing asymmetry. Finally, synthesis of the A ring of cylindricine B via nitrogen addition (Michael reaction) onto an a,8-unsaturated carbonyl 3.7 was attempted. The synthesis of the B and C ring framework was executed following group precedent. The synthesis of the a,6-unsaturated carbonyl side chain was attempted using Kishi-Nozaki and carbonylative Stille coupling reactions on an azaspirocyclic vinyl triflate 3.1. The Michael acceptor side chain was not successfully appended using these coupling reactions. The synthesis of the A ring is key in performing the first asymmetric total synthesis of cylindricine B. Therefore, further investigations on appending the Michael acceptor side chain are necessary in order to achieve this goal.

Thesis/Dissertation

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2009-10-29

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http://hdl.handle.net/2429/14361

Chemistry

University of British Columbia

UBCV

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