The 2020 Chemical Science study by Paulisch, Strieth-Kalthoff, Henkel, Pitzer, Guldi and Glorius established that in the visible-light photoredox reaction of silyl ketene acetals with α,β-unsaturated carbonyls, chemo- and regioselectivity (1,2- versus 1,4-addition) is governed not by the radical addition step itself but by the subsequent chain-propagating electron transfer, with a measured quantum yield of 15.6 indicating an efficient radical chain. The authors themselves flagged three interlocking, still-quantitative gaps in this mechanistic assignment: (1) for α,β-unsaturated ketones, a competing Lewis-acid-mediated (Mukaiyama-type) pathway could not be experimentally excluded and both channels lead to the same 1,4-product; (2) the fraction of product formed through chain propagation versus direct photocatalyst re-oxidation cycles, while asserted to be dominated by the chain on the basis of the high quantum yield, was never quantified; and (3) the selectivity-determining electron-transfer barriers rest on the four-point Marcus–Hush approximation at a single DFT level, whose absolute values carry methodological uncertainty. No study is known that resolves any of these three strands for this reaction system, so the problem of the quantitative mechanistic account of this reaction remains open.

Background

In visible-light photoredox catalysis, a photoexcitable catalyst (here the iridium complex [Ir(dF-CF3-ppy)2(dtbpy)]PF6, PC-1) initiates single-electron transfer (SET) chemistry with visible light under mild conditions. Silyl ketene acetals are silyl enol ethers of esters that classically serve as nucleophilic partners in Lewis-acid-mediated Mukaiyama–Michael and Mukaiyama–aldol additions to carbonyl compounds; in radical chemistry, their oxidation generates α-carbonyl radicals that act as nucleophilic alkyl-radical equivalents in Giese-type conjugate (1,4-) additions to Michael acceptors. α,β-Unsaturated carbonyls possess two electrophilic sites: addition to the carbonyl carbon (C–O double bond) gives a 1,2-addition product, while addition to the β-carbon (C–C double bond) gives the 1,4-(Giese) product. Controlling which site reacts is a long-standing selectivity challenge because both sites are electrophilic and radical additions are fast, low-barrier events. Building on their 2017 discovery that Brønsted-acid-activated aldehydes and ketones act as intermolecular radical acceptors under 'hole catalysis' (a radical chain in which the chain-carrying species is a radical cation or 'hole': after the initial photochemical oxidation event, each product-forming radical cation oxidizes a fresh neutral substrate molecule, so many product molecules form per absorbed photon), Paulisch et al. (Chem. Sci. 2020, 11, 731) reported that photoredox reaction of trimethylsilyl ketene acetals with α,β-unsaturated carbonyls gives exclusively 1,4-addition products for esters and ketones but exclusively 1,2-addition (allylic alcohol) products for aldehydes. Transient-absorption spectroscopy showed diffusion-controlled quenching of the excited photocatalyst by the ketene acetal (kET=(1.25±0.02)×109k_{ET} = (1.25 \pm 0.02) \times 10^9 L mol−1^{-1} s−1^{-1}), and a photochemical quantum yield (ϕ\phi, product molecules per absorbed photon) of 15.6 demonstrated a chain process. DFT at B3LYP-D3/def2-TZVPP/CPCM(MeCN) with electron-transfer barriers estimated by the four-point Marcus–Hush approximation (a semiclassical construction of the ET barrier from four energy points along a reaction coordinate rather than from a full crossing search) indicated that the radical addition is reversible and the subsequent, irreversible ET is selectivity-determining in a Curtin–Hammett-type scenario (product ratio set by the barrier difference from interconverting intermediates). This 'consecutive-step selectivity control' picture is the paper's central mechanistic claim, but the authors explicitly qualified it with three unresolved quantitative issues, which together define the still-open mechanistic problem: for α,β-unsaturated ketones, control experiments adding the Lewis acid TMSOTf in the dark produced significant 1,4-addition product, so a Lewis-acid-mediated pathway (itself known since Sato's 1991 work to involve Lewis-acid-mediated electron transfer in Mukaiyama–Michael reactions of ketene silyl acetals) competes undetermined; the measured ϕ=15.6\phi = 15.6 shows the chain dominates on average but does not quantify the split between chain-propagated turnovers and turnovers closed by re-oxidation of the reduced photocatalyst; and the computed ET barriers (e.g. ΔG‡\Delta G^\ddagger of 3.8 versus 11.8 kcal mol−1^{-1} for the competing ET closures after 1,2- versus 1,4-addition to cinnamaldehyde) rest on a four-point Marcus–Hush treatment the authors themselves describe as not widely established for organic SET.

Problem Statement

For the photoredox reaction of silyl ketene acetals with α,β-unsaturated carbonyls (as reported by Paulisch et al., Chem. Sci. 2020, 11, 731, using [Ir(dF-CF3-ppy)2(dtbpy)]PF6, 455 nm irradiation, MeCN), establish the quantitative mechanistic account that the original study could only assert qualitatively, by resolving its three open issues, conceded as separate caveats: (1) for α,β-unsaturated ketones, determine the relative contributions of the radical hole-catalytic chain pathway and the competing Lewis-acid-mediated pathway — an experimentally non-trivial discrimination because both channels produce the same 1,4-addition product — including whether the partition is substrate-dependent across the ketone scope (aryl and alkyl enones, cyclopentenone, chromone); (2) quantify the fraction of product formed through chain propagation (radical-cation intermediate D oxidizing a fresh ketene acetal molecule) versus through closure by re-oxidation of the reduced photocatalyst, i.e. translate the qualitative inference from the quantum yield of 15.6 into a measured or modelled turnover partition with stated uncertainties; and (3) establish the electron-transfer barrier picture for the selectivity-determining chain-propagation steps at a level of theory beyond, or validated against, the published four-point Marcus–Hush estimates at B3LYP-D3/def2-TZVPP/CPCM(MeCN), determining whether the Curtin–Hammett-type selectivity model (reversible radical addition followed by irreversible, selectivity-determining electron transfer) and its computed barrier differences survive a more rigorous treatment. These three strands jointly constitute one objective — the complete quantitative mechanistic assignment of how the observed chemo- and regioselectivity arises and which catalytic cycle produces the product — where the pathway partition, the turnover partition, and the revised energetics are mutually consistent with all published observables (quantum yield, quenching rate constant, redox potentials, and the 1,2-/1,4-selectivity pattern).

References

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