Iridium-Catalyzed Reductive Allylation of Esters

Abstract

The catalytic reductive transformation of carboxylic esters into α-branched ethers is described. The procedure pivots on the chemoselective iridium-catalyzed hydrosilylation of ester and lactone functionality to afford a silyl acetal intermediate. Upon treatment with a Lewis acid, these hemilabile intermediates dissociate to form reactive oxocarbenium ions, which can be intercepted by allyltributyltin nucleophiles, resulting in the formation of valuable α-branched alkyl–alkyl ether derivatives. This reductive allylation procedure was found to be amenable to a range of carboxylic ester starting materials, and good chemoselectivity for ethyl over tert-butyl esters was demonstrated. Furthermore, downstream synthetic manipulation of α-amino acid-derived products led to the efficient formation of pyrrolidine, piperidine, and azepane frameworks.

Step-Economic Synthesis of Biomimetic β-Ketopolyene Thioesters and Demonstration of Their Usefulness in Enzymatic Biosynthesis Studies

“…A further improvement was achieved by adaption of a one-pot–two-step Ir-catalyzed reductive HWE olefination (rHWE) that was recently established by Jeon et al It is based on the reductive silylation of esters to give stable mixed O , O -silyl acetals, like 6 , which can be activated under benign Lewis basic conditions. − These undergo clean, highly stereoselective HWE olefination to trans-configured enoates upon treatment with phosphonates under deprotonative conditions. Jeon et al successfully examined various enoates and ynoates and accessed a methyl trienoate in only three steps from methyl benzoate.…”

α-Tertiary Dialkyl Ether Synthesis via Reductive Photocatalytic α-Functionalization of Alkyl Enol Ethers

“…In spite of the above advances, to date there is no general strategy to construct all-alkyl substituted α-tertiary ethers via the α-oxy radical. As part of our ongoing work into the reductive synthesis of ethers, we reasoned that controlled, photocatalytic single electron transfer to the oxocarbenium ion formed via β-protonation of the enol ether could provide an access point to the α-oxy radical . These nucleophilic radical species would then be reactive toward electrophilic structures such as conjugated alkenes .…”