Direct Access to Monoprotected Homoallylic 1,2-Diols via Dual Chromium/Photoredox Catalysis

Abstract

Herein, we present a dual catalytic strategy to efficiently obtain mono-protected homoallylic 1,2-diols by coupling abundant aldehydes with simple (silyl) enol ethers, thus providing direct access to this important motif without the (super)stoichiometric use of prefunctionalized metal-allyl species. The modularity of our approach is shown by the introduction of several silyl-and alkyl-based protecting groups, enabling a diverse protecting group strategy. To highlight functional group tolerance and chemoselectivity, we demonstrate the functionalization of a variety of aliphatic, aromatic and heteroaromatic aldehydes, even in presence of ketones and esters. The applicability was further supported by a large scale experiment and a robustness screening. Mechanistic studies support a radical mechanism, starting from the single electron oxidation of the silyl enol ether, facilitated by the β-silicon effect.

Recent Progress in Chromium-Mediated Carbonyl Addition Reactions

“…This dual catalysis was applied to the synthesis of monoprotected homoallylic 1,2-diols by using aldehydes 1 and enol ethers 41 as starting materials (Scheme 12). 49 Although Glorius and Kanai's achievements have enabled catalytic and direct formation of allylchromium(III) species from alkenes via C-H bond activation, substrate scope of alkenes was limited to relatively electron-rich alkenes such as allyl (hetero)arenes, -alkyl styrenes and enol ethers for Glorius' reaction 48,49 and cyclic or tri-and tetrasubstituted hydrocarbon alkenes for Kanai's reaction. 50 Because those reactions began with one-electron abstraction from alkenes by excited photoredox catalysts, the scope of alkenes depended on their oxidation potentials.…”

“…This dual catalysis was applied to the synthesis of monoprotected homoallylic 1,2-diols by using aldehydes 1 and enol ethers 41 as starting materials (Scheme 12 ). 49 Allyl radical 42 was generated via photocatalyzed one-electron oxidation of 41 ( E 1/2 {triisopropyl[(2-methylprop-1-en-1-yl)oxy]silane} = 1.64 V vs SCE in MeCN) by the oxidizing excited-state iridium(III) photoredox catalyst [ E 1/2 (*Ir(III)/Ir(II)) = 1.68 V vs SCE in MeCN]. After trapping the allyl radical by chromium(II), ( Z )-γ-silyloxyallylchromium(III) species 43 , which was stabilized by coordination of the internal oxygen atom, reacted with an aldehyde 1 , affording anti -diol derivative 44 .…”

Radical Carbonyl Propargylation by Dual Catalysis

“…In recent years, dual catalytic manifolds have emerged as attractive tools to promote energetically unfavorable reaction steps and achieve synthetically valuable transformations under increasingly mild conditions [20] . Since 2018, our group, [21a–c] Kanai, Mitsunuma and co‐workers [21d,e] have independently achieved allylation of aldehydes using dual photoredox and chromium catalysis [21f] . Compared to dual nickel/photoredox [20e–j] or copper/photoredox [20k–n] catalysis, dual chromium/photoredox catalytic mode is much less explored in synthetic chemistry, but provides a range of opportunities to achieve challenging radical‐to‐polar crossover‐based transformations.…”

On the application of 3d metals for C–H activation toward bioactive compounds: The key step for the synthesis of silver bullets

“…A good example is a redox-neutral reaction for the allylation of aldehydes promoted by a dual catalytic system comprising CrCl 3 and an iridium-based photocatalyst that was recently developed by Schwarz and co-workers [119]. Similar conditions were further employed to synthesize monoprotected 1,2-homoallylic diols from aldehydes and silyl and alkyl enol ethers as the allylic counterpart [120].…”