1674
Anodic Olefin Coupling Reactions: Controlling the Reaction Pathways of Radical Cation Intermediates and Efforts Toward Artemisolide
Though a powerful synthetic tool, anodic olefin coupling reactions do not always proceed well. Radical cations are very reactive intermediates and are thus susceptible to side reactions such as eliminations and polymerization. When the desired intramolecular cyclization is relatively slow, these side reactions outcompete cyclized product formation entirely. Two examples are provided in Scheme 1.1,2 In the first example, simultaneous formation of a 6-membered ring and a quaternary carbon using an allyl silane as a trapping nucleophile led to only elimination products along with other general decomposition. The same problem presents itself in the second example, where the coupling of a furan and enol ether to form a 7-membered ring is too slow to compete with the elimination.
To circumvent this problem, new methodology is being developed that incorporates an additional nucleophile into the electrolysis substrate to allow intramolecular trapping of both ends of the radical cation.3 By tethering an extra alcohol nucleophile to the end of an enol ether to quickly trap the radical cation, cationic decomposition pathways can be avoided, allowing for the desired cyclization occur (Scheme 2).
In the talk to be presented, the development of this methodology will be discussed along with ongoing efforts to apply this methodology towards the synthesis of the 5:7:5-fused core skeleton of the natural product Artemisolide.
References:
1. Tinao-Wooldridge, L.V.; Moeller, K.D.; Hudson, C.M. J. Org. Chem. 1994, 59, 238
2. Redden, A.; Moeller, K.D. Org. Lett. 2011, 13, 1678.
3. Redden, A.; Perkins, R.J.; Moeller, K.D. Angew. Chem. Int. Ed. 2013, 52, 12865.