tag:blogger.com,1999:blog-51846086760422068.post2399383806040099380..comments2024-03-28T08:37:08.964-07:00Comments on Open Flask: (–)-MaximiscinBaranLabhttp://www.blogger.com/profile/01806245988209508968noreply@blogger.comBlogger3125tag:blogger.com,1999:blog-51846086760422068.post-51275611083261043792020-04-30T14:27:04.256-07:002020-04-30T14:27:04.256-07:00Thanks Art! In terms of diacid activation, we did ...Thanks Art! In terms of diacid activation, we did explore some other methods including mixed anhydrides, acid fluorides, as well as various dehydrating conditions directly from the diacid (e.g. T3P), but nothing worked. Thioesters would have been interesting, especially with silver activation. The diacid chloride was actually reasonably stable and could be concentrated on a rotovap with little to no hydrolysis, even on small scale (confirmed by crude NMR). Based on some control studies (see SI) it seemed like we were going through a ketene intermediate using earlier conditions, this was likely the source of our decomposition woes. The diacid chloride was attractive because we could achieve quantitative activation from the diacid within two hours, and then easily step that reactivity up with the silver additive. Based on our observations, we needed a remarkably hot electrophile to engage that reluctant oxime, I think this might be why some of the earlier activation methods failed.<br />Interesting question. It’s difficult to say how the diacid triflate might be existing in solution under the reaction conditions. In the final set of conditions, using acetonitrile as solvent we may be going through an intermediate acyl nitrilium species. We did screen silver sources (see SI) in toluene and found that other soluble silver salts worked to varying degrees (AgSbF6 was about as effective as AgOTf for reference). <br /><br />Kyle<br /><br />Kylenoreply@blogger.comtag:blogger.com,1999:blog-51846086760422068.post-57821842849352613952020-04-25T14:16:40.577-07:002020-04-25T14:16:40.577-07:00Hi Samrat,
Thanks! Good catch. As you might expec...Hi Samrat,<br /><br />Thanks! Good catch. As you might expect, this is a typo, it should be -OTBS as well. Surprisingly, this made it past several sets of eyes, and peer review. It will be addressed in the final formatted version of the manuscript. Sorry for any confusion.<br /><br />KyleKylenoreply@blogger.comtag:blogger.com,1999:blog-51846086760422068.post-48077394745324138012020-04-25T12:55:55.277-07:002020-04-25T12:55:55.277-07:00Hi Kyle, Congratulations! An excellent synthesis a...Hi Kyle, Congratulations! An excellent synthesis and a great insight story as well. I was just curious about the last pyridone ring formation step. In the accepted manuscript, in one of the intermediate of this step, the -OTBS group is replaced by the -NH2 group which after cyclization comes back to -OTBS. I did not understood how that -NH2 group is coming? It would be really helpful if you kindly shed some light.Samrathttps://twitter.com/samcemanoreply@blogger.com