Trouble with elimination

I am at the ACS National meeting in Dallas today, where I took part in the Symposium on Macrocycles. We had a good line-up of speakers, including W. van der Donk, S. Lokey, Allyn Londregan, Keith James, and myself. David Price of Pfizer organized this event, which was a great success (thanks David!). I am writing this post while waiting for David and Scott to go to a steakhouse.

Our event took place in the afternoon, but I woke up bright and early and went to the total synthesis symposium, where lectures were presented by graduate students. I always like to hear these kinds of talks because you get to see what actually happened. Today was no exception and there was a very well selected line-up. The talks were both informative and well presented, despite the fact that only a few people were in attendance this early in the morning (perhaps folks had too many margaritas the night before?). In every synthesis endeavour, there comes a point that defines one’s problem-solving abilities. I am making a subfield-agnostic statement, but such defining points are perhaps best illustrated by way of total synthesis. I was intrigued by Dennis Wright’s synthesis of frondosin A, presented by his student Michael VanHeyst. The paper describing their approach recently appeared in JACS and contains a number of clever mechanistic twists. I will comment on just one of them, as it goes well with the theme of today, which is about problem-solving. A case in point is the attempted cleavage of the oxabicycle shown below. The failed attempt illustrates the capricious nature of the 7-membered ring, which leads to complete lack of selectivity during elimination. After months of trying, a reasonable solution came in the form of a phosphine-mediated rearrangement that “relayed” bonds in a super clever way that culminated in elimination of phosphine oxide. This paper also features a fascinating explanation of stereochemistry inversion that has put to rest some previous controversies.

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http://pubs.acs.org/doi/abs/10.1021/ja413106t

2 thoughts on “Trouble with elimination

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