Double Functionalization of Alcohols

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  • Published: 10 March 2020
  • Copyright: Wiley-VCH Verlag GmbH & Co. KGaA
  • Source / Publisher: Journal of the American Chemical Society/ACS Publications
  • Associated Societies: American Chemical Society (ACS), USA
thumbnail image: Double Functionalization of Alcohols

Organic compounds with multiple different functional groups can be useful, e.g., in pharmaceutical chemistry or as intermediates for further reactions. β-Amino alcohols, for example, combine –OH and –NR2 groups and are usually prepared from alkenes.

David A. Nagib, The Ohio State University, Columbus, USA, and colleagues have developed a method for the synthesis of β,γ-functionalized alcohols (pictured) via double C–H functionalization. They converted a range of aliphatic alcohols to a variety of β,γ-substituted alcohols, which bear heteroatoms on three adjacent carbons. The reaction proceeds via a radical-polar-crossover cascade.

First, an alcohol is converted to an N-iodo-imidate by coupling it with a nitrile and reacting it with AcOI, which is prepared in situ from sodium iodide and PhI(OAc)2. The N-iodo-imidate can then react further, initiated by visible light that splits the N–I bond. The resulting N-based radical initiates a 1,5-hydrogen atom transfer (HAT), followed by the formation of a β-iodinated intermediate. This intermediate is converted to an allyl intermediate. Finally, this intermediate undergoes a cyclization to give a γ-iodo oxazoline, which can be hydrolyzed to give the desired substituted alcohol.

The reaction can be performed as a one-pot process. The γ-iodo substituent in the products can be replaced by a variety of nucleophiles, further broadening the range of possible products.



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