Substrate‐Controlled Diastereoselective Synthesis of Sugar‐Based Chlorinated Perhydrofuro[2,3‐b]pyrans via Copper(I)‐Catalyzed Radical Cyclization

Abstract

The work describes the first copper(I) chloride/2,2′‐bipyridine‐catalyzed atom transfer radical cyclization (ATRC) of unsaturated carbohydrate‐derived chloroacetals to generate chlorinated perhydrofuro[2,3‐b]pyrans via an effective diastereoselective route. Various glycals (glucal, galactal and lactal) underwent the Ferrier rearrangement with 2,2,2‐trichloroethanols to give acetal precursors stereoselectively, R‐selective with galactal in contrast to S‐selective with glucal. The radical cyclization of the Ferrier products occurred smoothly to afford cis‐fused bicyclic products with the transfer of the chlorine atom at the non‐anomeric carbon in the cyclized radical intermediate predominantly from the equatorial direction. The carbohydrate templates controlled the stereochemistry of both Ferrier rearrangement and ATRC steps. The stereostructures of the products were also supported by single crystal X‐ray diffraction crystallography. The products possess biologically important structural segments such as a glycosidic linkage, a fused bicyclic acetal unit and a chlorosugar unit which are potential sources for biological studies and further synthetic elaborations.magnified image

Radical Cyclization-Initiated Difunctionalization Reactions of Alkenes and Alkynes

“…In 2017, Gupta and coworkers reported a Cu-catalyzed radical cyclization reaction of unsaturated carbohydrate-derived chloroacetals for the synthesis of chlorinated perhydrofuro[2,3- b ]pyrans. The reaction of chloroacetals 105 with CuCl/2,2’-bipyridine in refluxing dichloroehtane (DCE) under N 2 atmosphere for 4 h gave products 106 in good yields ( Scheme 27 ) [ 53 ]. The initial radicals 107 generated from 105 via abstraction of a chlorine atom by [Cu I L]Cl undergo 5- endo -cyclization to give radicals 108 which then react with [Cu II L]Cl 2 to form products 106 .…”

β,β,β‐Trichloroethyl‐NH‐Enamine as Viable System for 5‐Endo‐trig Radical Cyclization via Multifaceted CuI−CuII Redox Catalysis: Single Step Synthesis of Multi‐Functionalized NH‐Pyrroles

“…Our previous experiences with substrate‐ and catalyst‐controlled radical cyclization reactions prompted us to investigate roles of enamine‐structures, radical initiators, additives and reaction conditions in a “disfavored” 5‐ endo ‐mode of radical cyclization in an enamine system. This led to a discovery of an efficient approach to convert a “disfavored mode 5 to a favored mode 9 ” of a 5‐ endo ‐ trig radical cyclization to form pyrrolidine radical 10 which spontaneously converts to N H‐pyrrole 11 having a 4‐halo‐and the carbonyl functionalities at 2‐ and 3‐positions (Scheme ).…”

A Highly Efficient Magnetic Iron(III) Nanocatalyst for Ferrier Rearrangements

“…10 The products of this transformation are versatile chiral intermediates for the synthesis of a variety of important biologically active compounds and natural products. [11][12][13][14][15][16][17][18][19] For instance, the 2,3-unsaturated sugar derivatives of 5-(hydroxymethyl)furfural showed excellent antitumor activities in our previous research, highlighting the significance of exploring more-efficient method for the synthesis of 2,3-unsaturated glycosides. 20 A wide range of reagents have been used to promote this reaction, including Bronsted acids, Lewis acids, oxidants, etc.…”