1,5-Hydrogen Atom Transfer/Surzur–Tanner Rearrangement: A Radical Cascade Approach for the Synthesis of 1,6-Dioxaspiro[4.5]decane and 6,8-Dioxabicyclo[3.2.1]octane Scaffolds in Carbohydrate Systems

Abstract

The 1,5-HAT–1,2-(ester)alkyl radical migration (Surzur–Tanner rearrangement) radical/polar sequence triggered by alkoxyl radicals has been studied on a series of C -glycosyl substrates with 3- C -(α,β- d , l -glycopyranosyl)1-propanol and C -(α- d , l -glycopyranosyl)methanol structures prepared from chiral pool d - and l -sugar. The use of acetoxy and diphenoxyphosphatoxy as leaving groups provides an efficient construction of 10-deoxy-1,6-dioxaspiro[4.5]decane and 4-deoxy-6,8-dioxabicyclo[3.2.1]octane frameworks. The alkoxyl radicals were generated by the reaction of the corresponding N -alkoxyphthalimides with group 14 hydrides [ n -Bu 3 SnH(D) and (TMS) 3 SiH], and in comparative terms, the reaction was also initiated by visible light photocatalysis using the Hantzsch ester/ fac -Ir(ppy) 3 procedure. Special attention was devoted to the influence of the relative stereochemistry of the centers involved in the radical sequence on the reaction outcome. The addition of BF 3 •Et 2 O as a catalyst to the radical sequence resulted in a significant increase in the yields of the desired bicyclic ketals.

Synthesis of branched-chain sugars and higher-carbon sugars enabled by site-selective C–H alkylation relying on 1,5-hydrogen atom transfer of ethylenoxy radicals

“…C–H functionalization mediated by 1,5-HAT of alkoxy radicals has witnessed considerable progress in organic synthesis. 20 Employment of this strategy in carbohydrate chemistry is, however, challenging and underexplored 21 due to the presence of dense functional groups and multiple C–H bonds with comparable reactivity in a sugar ring. Inspired by the highly site-selective C(sp 3 )–H allylation and alkenylation reactions induced by 1,5-HAT of ethylenoxy radicals using alkyl (2- N -oxyphthalimido)ethylene ethers as the starting materials, 22 we envisioned that such transformations, if successfully applied to sugars, would provide an attractive and economically viable approach to structurally uncommon branched-chain sugars and higher-carbon sugars from sugar materials that are inexpensive and can be purchased in large quantities.…”

N‐Alkoxyphtalimides as Versatile Alkoxy Radical Precursors in Modern Organic Synthesis

“…The sequence of 1,5‐HAT followed by Surzur‐Tanner rearrangement triggered by alkoxyl radicals was studied by the Suarez group on a series of C‐glycosyl substrates (Scheme 7). [46] The alkoxyl radicals were generated by the reaction of corresponding N ‐alkoxyphthalimides 12 or 15 with n ‐Bu 3 SnH(D), or by visible light photocatalysis employing the Hantzsch ester/ fac ‐Ir(ppy) 3 system. The products of Surzur‐Tanner rearrangement 13 and 16 were accompanied by alkoxy radical reduction products – alcohols 14 and 17 .…”