Field of Science

Panek's Leucascandrolide A

A colleague presented Panek's leucascandrolide A (LA) synthesis in a group meeting. Several interesting steps were included in the synthesis, and several interesting questions came up.

For example, in one case, when he is doing the [4+2] allylsilane cycloaddition, there is an ester group axial in a TS that gives the 'right' product. When he increases the bulk of the alkyl group on the ester, the proportion of this product actually goes up.

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A larger alkyl group will naturally have a larger A value, so why should it be preferred in an axial disposition? My surmise; as the group size increases, the ester prefers increasingly a conformation in which its carbonyl is directed inward, thus getting rid of the unfavourable interaction. Interesting how steric hindrance can cause a group to orient itself in such a way that makes the reaction more favourable.

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(The conformation to the left is prefered as R becomes larger)

Also, he used Kozmin's spontaneous macrolactonization, an entropically unfavourable event. In another step, he oxidises a secondary alcohol in the presence of a primary one using a tungsten catalyst. How does this happen? My guess; there can be a radical mechanism involved and then the secondary radical will be more stable than the primary radical obviously.

Overall an interesting, if a little long, synthesis.

J. Org. Chem., ASAP Article 10.1021/jo0610412 S0022-3263(06)01041-3
Web Release Date: September 1, 2006


  1. can you provide me some link regarding A value just to refresh my memory? thx

  2. It's the energy difference between the ground states of two conformers, one in which a substituent is axial and the other one in which it's equatorial. Therefore, the A value is for that particular substituent. Take a look at Ernest Eliel's book, or the original reference by Winstein and Holness in JACS (1955), pg. 5562


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