Copper-catalyzed [1,2]-rearrangements of allylic iodides and aryl α-diazoacetates

Abstract

The [1,2]- and [2,3]-rearrangements of iodonium ylides are synthetically useful reactions for the generation of functionalized α-iodoesters. Allylic iodides are coupled with α-diazoesters in the presence of a copper catalyst and a ligand to generate iodonium ylides, which undergo metal-mediated rearrangements. By fine-tuning the structure of the ligand, we have reversed the regioselectivity of copper-catalyzed reactions of iodonium ylides from [2,3]- to [1,2]-rearrangements with the use of alternate bipyridine ligands. The preference for [1,2]-rearrangements was further improved by using bulky aryl α-diazoester substrates. Several α-iodoesters with a diverse range of functional groups were generated in good yields (up to 88% yield) and high regioselectivities (up to >95:5 regioisomeric ratio). A deuterium-labeled substrate was utilized to gain insight into the mechanism of the reaction.

Mechanistic Studies of Copper(I)-Catalyzed Stereoselective [2,3]-Sigmatropic Rearrangements of Diazoesters with Allylic Iodides/Sulfides

“…Based on experiments ,, and previous reports, , four possible pathways can be proposed for the catalytic [2,3]-sigmatropic rearrangements (Scheme ). After the nucleophilic addition of the allylic iodide/sulfide to the copper­(I)-carbene, Path-A experiences the electrophilic attack of metal-bound iodonium ylide; Path-B undergoes the electrophilic attack of free ylide; Path-C undertakes electrophilic attack after keto–enol tautomerism; and Path-D proceeds via sequential keto–enol tautomerism and electrophilic attack of free ylide.…”

“…It was not until 1998 did Doyle et al develop the first enantioselective iodonium ylide rearrangement but with only moderate yields and low selectivities . Recently, Tambar and co-workers made outstanding contributions in the area of rearrangement reactions of iodonium ylides , and reported a highly stereoselective [2,3]-rearrangement of iodonium ylides by employing a chiral copper catalyst (Scheme , eq (1)) . This reaction represents the first highly enantioselective, diastereoselective, and regioselective [2,3]-rearrangement of substituted iodonium ylides, the products of which can be converted into a series of chiral building blocks including the ones that are inaccessible by classical onium ylide rearrangements.…”

Copper‐Catalyzed Enantio‐, Diastereo‐, and Regioselective [2,3]‐Rearrangements of Iodonium Ylides

“…We recently reported the regioselective [2,3]- and [1,2]-rearrangements of iodonium ylides for the generation of racemic iodoester products. [8] Seminal studies by Doyle and co-workers reported that a single iodonium ylide substrate generated from unsubstituted allylic iodide underwent enantioselective rearrangement (69% ee), but there was no indication of the regioselectivity or diastereoselectivity. [9] To date, there are no catalytic rearrangements of these reactive substrates that can generate one product in high selectivity.…”

Copper‐Catalyzed Enantio‐, Diastereo‐, and Regioselective [2,3]‐Rearrangements of Iodonium Ylides

“…We recently reported the regioselective [2,3]-and [1,2]-rearrangements of iodonium ylides for the generation of racemic iodoester products. [8] Seminal studies by Doyle and co-workers reported that as ingle iodonium ylide substrate generated from unsubstituted allylic iodide underwent enantioselective rearrangement (69 % ee), but there was no indication of either the regio-or diastereoselectivity. [9] To date,there are no catalytic rearrangements of these reactive substrates which can generate one product in high selectivity.H erein we describe the first highly enantioselective,d iastereoselective,a nd regioselective [2,3]-rearrangements of substituted iodonium Scheme 1.…”