Chiral Diaryliodonium Phosphate Enables Light Driven Diastereoselective α-C(sp³)–H Acetalization

Abstract

C(sp)-H bond functionalization has emerged as a robust tool enabling rapid construction of molecular complexity from simple building blocks, and the development of asymmetric versions of this reaction creates a powerful methodology to access enantiopure sp-rich materials. Herein, we report the stereoselective functionalization of C(sp)-H bonds of cyclic ethers employing a photochemically active diaryliodonium salt in combination with an anionic phase-transfer catalyst. The synthetic strategy outlined herein allows for regio- and stereochemical control in the α-C-H acetalization of furans and pyrans using alcohol nucleophiles, thus providing the ability to control the configuration at the stereogenic exocyclic acetal carbon.

Reengineering Chemical Glycosylation: Direct, Metal‐Free Anomeric O‐Arylation of Unactivated Carbohydrates

“…Aryl‐λ 3 ‐iodane salts have emerged as powerful and versatile arylating reagents . Pertinent examples include Olofsson's elegant functionalisation of diaryliodonium salts to decorate the periphery of sugars, and Toste's diastereoselective acetalisation with chiral diaryliodonium phosphates . Knowing that these reagents undergo facile O−H functionalisation of various alcohols, we sought to explore the competence of aryl iodonium salts for the functionalisation of the hemi‐acetal of unactivated, reducing sugars.…”

“…[17] Pertinent examples include Olofsson's elegant functionalisation of diaryliodonium salts to decorate the periphery of sugars, [18a] and To ste's diastereoselective acetalisation with chiral diaryliodonium phosphates. [19] Knowing that these reagents undergo facile OÀHf unctionalisation of various alcohols, we soughtt oe xplore the competence of aryl iodoniums alts fort he functionalisation of the hemi-acetal of unactivated,r educing sugars. As as tarting point fort his study,c ommerciallya vailable diphenyliodonium hexafluorophosphate 2a was investigated as am odel electrophile fort he arylation of 2,3,4,6-tetra-O-benzylated-d-glucopyranose 1a (Table 1).…”

Decatungstate‐Mediated C(sp3)–H Heteroarylation via Radical‐Polar Crossover in Batch and Flow

“…Next, we set out to trap the oxocarbenium ionic intermediate by adding an excess of CH 3 OH or t-BuOH (18 equiv) (Scheme 3 c). [18] In both cases, the corresponding orthoesters 43 and 44 could be detected via HRMS and 1 H NMR spectroscopy. Despite significant efforts, this C(sp 3 )-H heteroarylation method could not be extended to unactivated aliphatic C(sp 3 )ÀH bonds (see the Supporting Information, Section 5 for limitations of the scope).…”

Photochemical C–H acetalization of O-heterocycles utilizing phenylglyoxylic acid as the photoinitiator

“…Except from the use of metals, the synthesis of 2-alkoxy-tetrahydrofuran has also been reported with n-tetrabutylammonium peroxy-disulfate; however, excess of the reagents were used, limiting the green character of the method [16]. Two photocatalyzed iodine-based methods were recently developed by Toste [17] and Hashmi [18] (Scheme 1, B and C). Toste and coworkers described the use of a chiral diaryliodonium phopshate to generate controlled diastereoselective cis-or trans-fused acetals (Scheme 1, B) [17].…”