Photocatalytic Reductive Formation of α-Tertiary Ethers from Ketals

Abstract

A general photocatalytic reductive strategy for the construction of unsymmetrical α-tertiary dialkyl ethers is reported. By merging Lewis acid-mediated ketal activation and visible-light photocatalytic reduction, in situ generated α-alkoxy radicals can engage in addition reactions with a variety of olefinic partners. Good reaction efficiency is demonstrated with a range of ketals of aromatic and aliphatic ketones. Extension to acetal substrates is also described, demonstrating the overall synthetic utility of this methodology for complex ether synthesis.

Dearomative Photocatalytic Construction of Bridged 1,3‐Diazepanes

“…Previously, our group has reported that the use of bespoke Hantzsch ester reductants can modulate reactivity and in turn increase product yield and/or improve diastereoselectivity in reductive functionalization of imines . A survey of Hantzsch ester reductants (Scheme B, entries 2–4) demonstrated that methyl carboxyphenyl derivative ( HE4 ) led to increased conversion to product (90 %) and to a higher diastereomeric ratio (1.9:1, for further optimization details, see Supporting Information).…”

Radikal‐basierte Synthese und Modifikation von Aminosäuren

“…FürR eaktionen vom Giese-Typ mit Dha wurden verschiedene Methoden entwickelt, bei denen RAE, [58] Car-bonsäuren, [59] Imine, [60] Ketale, [61] Tr ifluorborate, [62] Alkylhalogenide [63] oder Thioester [64] als Radikalvorläufer verwendet wurden.…”

Radical‐Based Synthesis and Modification of Amino Acids

“…Several methods have been developed for Giese-type reactions of Dha using RAEs, [58] carboxylic acids, [59] imines, [60] ketals, [61] trifluoroborates, [62] alkyl halides, [63] or thioesters [64] as radical precursors.…”

“…Dixon and co-workers have recently reported acouple of light-mediated methods for the modification of Dha derivatives using imines [60] and ketals [61] as radical precursors.T he first is athree-component procedure where in situ generated imines are reduced by an Ir-based PC to generate a-amino radicals that add to 12,thereby affording UAAs bearing 1,3diamine motifs (Scheme 20 A). [60] Although the products are generated in good to excellent yields,the method displays low to moderate diastereoselectivities.…”

“…Lewis acids can be used to generate oxocarbenium species from ketals.D ixon and co-workers have cleverly exploited this reactivity to develop ap rocedure for the synthesis of atertiary ethers (Scheme 20 B). [61] Thekey step in this process is the reaction of Me 3 SiOTf with ak etal to in situ generate an oxocarbenium species,w hich is subsequently reduced by an Ir-based PC to afford a-alkoxy radicals.T hese add to 12 to afford UAAs.A si nt he previous transformation, low to moderate diastereoselectivities are observed.…”