# What type of reaction is this? (Modified organic nucleoside synthesis)

What type of reaction is shown in step F of this patent image?

I tried looking it up in SciFinder, but I didn't get any results, and I have not seen this before.

Thank you!

Edit 1: I'm also wondering if there is a specific name for this reaction, so that I can look it up. Edit 2 Yes I'm sorry I forgot the reagents. The patent number is WO2014078463A1 (Bennett et al.) and I included a screenshot below of the relevant description.

• Complement your query with Elsevier's «Reaxys» database. Because its roots -- Beilstein (organic, overlap into organometallic) and Gmelin (inorganic chemistry) -- followed a different approach to index literature references for reactions differ from the more bibliographic approach taken by Scifinder. If your school has the money, Science of Synthesis (once Houben-Weyl, by Thieme), too. None of the databases covers all and everything; the point is to complement their results, regardless of the obvious overlap of them indexing the literature. And cite the source of the drawing shown. Apr 21, 2021 at 21:06
• What are the reagents and conditions? This is essential information which needs to be added into the question. If it is a patent the corresponding procedure may take a bit more time to find, but this is no excuse. Can you please also cite the patent from which this is taken as Buttonwood already suggested? Apr 21, 2021 at 21:20
• Thank you Buttonwood and orthocresol. I edited my post to include the patent number and reaction description. Apr 21, 2021 at 23:00
• This is an osmium dihydroxylation en.wikipedia.org/wiki/Dihydroxylation The interesting part is the cyclisation through the carbamate NH Apr 22, 2021 at 6:39
• @Waylander: Now with the knowledge about excesi K osmate, there is no net oxidation or reduction. Is the "fancy" N-O bond somehow oxidizing the osmate ester? Or is the Na sulfite reducing the N-O bond? Interesting! Apr 22, 2021 at 19:43

My thoughts are along the lines of @Andrew and @Waylander. Step F doesn't tell us much, @orthocresol! I prefer a cyclization, 1 $$\rightarrow$$ 2a, followed by hydrolysis of ester 2a to alcohol 2b. Alternatively, N-O bond homolysis with light would probably involve a cage mechanism.

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EDIT: I miss read the image and saw a carbonyl group where there was an alkene. This explanation has been changed.

This is my guess on what is occurring (an electrophilic addition to an alkene):

1. The nitrogen-oxygen bond on the amide is severed, forming a carboxylic acid an an electron deficient amide. The electron pair of this carboxylic acid is stabilized by resonance. What is left is a nitrenium ion ($$\ce{NR2^{+}}$$), which is described on Wikipedia as

Nitrenium species have been exploited as intermediates in organic reactions. They are typically generated via heterolysis of N–X (X = N, O, Hal) bonds. For instance, they are formed upon treatment of chloramine derivatives with silver salts or by activation of aryl hydroxylamine derivatives or aryl azides with Brønsted or Lewis acids. The Bamberger rearrangement is an early example of a reaction that is now thought to proceed via an aryl nitrenium intermediate. They can also act as electrophiles in electrophilic aromatic substitution.

The mechanism for an electrophilic aromatic substitution is similar to that of an electrophilic addition to an alkene.

1. The nitrenium ion then performs an electrophilic attack on the alkene (second carbon of the oxolane), with beta carbon undergoing a nucleophilic attack by either water in neutral solution or a hydroxyl group in basic solution, forming the primary alcohol. These two processes are likely concerted (otherwise, there would be the formation of a primary carbonation).

Below is a scheme for the predicted mechanism.

• A concerted reaction seems more likely than stepwise Apr 21, 2021 at 20:29
• It looks a bit like a variation on a Zard radical cyclisation reaction warwick.ac.uk/fac/sci/chemistry/research/clark/clarkgroup/… Apr 21, 2021 at 20:44
• All good points--I have updated the answer. Apr 21, 2021 at 21:13
• How can you suggest a mechanism if you don't know what chemicals are used to effect this transformation? It's not even obvious whether if it's an ionic or radical process. Apr 21, 2021 at 21:22