While in China

I have not posted anything for a few days because of my travel to Beijing and, afterwards, to Xuzhou (Jiangsu province). Currently, I am attending the ISOSDD-4 meeting (International Symposium on Organic Synthesis and Drug Discovery). I was invited to attend this conference by an old friend of mine, Professor Guigen Li of Texas Tech, who also has a research outpost in Nanjing (Jiangsu Province). Guigen and I go way back, to our days in the Sharpless lab at Scripps where we were both doing our postdoctoral stints in the late 90’s. Here, by the way, is a link to an important paper by Guigen, Chang, and Sharpless, which constitutes the first disclosure of the asymmetric aminohydroxylation reaction. This was, in fact, Guigen’s discovery, and is one of the many items that come to mind when I look back at those eventful years.

http://onlinelibrary.wiley.com/doi/10.1002/anie.199604511/abstract

Hans Adolfsson of Stockholm University is another person whom I have not seen for many years. He also hails from our days in the Sharpless lab. Hans is attending this meeting as well and I have been very happy to interact with him too. Hans is now full of extra responsibilities as the Vice Chancellor at Stockholm University. Despite his busy schedule, Hans has a vibrant research lab that has done some excellent work in the area of asymmetric hydrogenation using peptide ligands. One of the curious recent findings in the Adolfsson lab is that of amide reduction into enamines. While there is no clear-cut mechanistic rationale for this process, it is one of the most remarkable paths to enamines I know. If you follow my posts, you know that I always emphasize novel approaches to well-established intermediates in organic chemistry. This, in my mind, always offers fertile grounds to discovery.

Image

http://pubs.acs.org/doi/abs/10.1021/ol403302g

2 thoughts on “While in China

  1. the reaction is new and surprising. But the mechanistic rationale seems rather self obvious: The methoxy groups on silane facilitate penta-coordinated silicon anion formation. tBuOK in the form of tBuOSi(OMe)3H(-) K(+) makes the reaction system basic enough for amide enolization, especially with amide that is already pre-coordinated to trimethoxysilane, a weak lewis acid (O-precoordination to silane greatly acidifies alpha-CH2). The amide enolate adds to Si via oxygen, there is a 4-membered ring transition state with hydride adding to oxygen-bearing carbon. (4-membered ring transition state is legitimate on pentacoordinate silicon, just as it is favored on pentacoordinate phosphorus). And that is where the reduction stops, silicon being far less interested in Si-N bonds than Si-O

  2. This sounds plausible indeed, but I would caution against calling any reaction obvious from the standpoint of mechanism. For instance, there is no pure Sn1 or Sn2 reactions. What we have are “in between” cases. One can only disprove a mechanism… But I agree with your explanation, despite the fact that Hans has not done mechanistic work yet.

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