Reaction optimization. Initially, the alkynyl aldehyde 1a and TsCl (2a) were chosen as model substrates for evaluating the reaction conditions. In the presence of 2 mol% of fac-Ir(ppy)3 and 2.0 equiv of K2CO3, the 3-sulfonyl cyclopentenone 3a was isolated in 66% yield after 5 h of irradiation with 15 W of blue LEDs in DMA at 25 °C (Table 1, entry 1). Base screening revealed that Na2CO3 was the most efficient choice, delivering 3a in 76% yield (entries 2-5). Switching the solvent from DMA to MeCN led to 3a in only 5% yield, and interestingly, the 4-sulfonyl dihydropyranol 4a was isolated in 57% yield (entry 6). Encouraged by the result, we examined other bases and solvents for the dihydropyranol production, however, the reaction yields were not improved (entries 7-12). To our delight, running the reaction at 50 oC resulted in full conversion of 1a and produced 4a in 73% yield (entry 13).

Examination of substrate scope. With the optimized reaction conditions in hands, we set about evaluating the scope of this cyclopentenone formation protocol with DMA as the solvent (Fig. 2). In general, the transformation proceeded efficiently to form densely substituted cyclopentenones in moderate to high yields (3a-3w). A broad array of functional groups, such as F, Cl, Br, CN, Ac, OMe, quinoline, pyridine, and thiofuran, are well tolerated under the reaction conditions, which may be utilized for the downtown transformations. Although both the electron-rich and -deficient substituents were accommodated on the benzene ring of 1, relatively lower yields were observed for the latter cases (3g and 3h). In addition to arylalkynyl substrates (G = Ar), the thioalkynyl aldehyde 1o reacted with 2a as well to produce the desired product 3o in 73% yield. Direct construction of spirocyclopentenones was also feasible, as exemplified by the production of 3p. The reaction of 1r, a dicarbonyl substrate, took place uneventfully to afford 3r in 69% yield. Substitution at the propargyl position with two methyl groups led to 3u in a low yield, which may be attributed to the increased hindrance for the radical sulfonylation of C-C triple bonds.
After succeeding in synthesizing tetrasubstituted cyclopentenones, we then examined the feasibility of assembling tri- or disubstituted cyclopentenones. Starting from the α-secondary and α-primary aldehydes 1v and 1w, the 2,3,5-trisubstituted and 2,3-disubstituted cyclopentenones were successfully constructed (3v and 3w). The reaction was also amenable to the access of sulfonylated cyclohexenones, albeit in a moderate yield (3x). In the meantime, sulfonyl chlorides 2 were varied with 1i as the coupling partner. Pleasingly, various arylsulfonyl chlorides proved to be efficient substrates and produced the corresponding sulfonyl cyclopentenones in medium to high yields (3y-3zf). Unfortunately, MeSO2Cl was not engaged in this reaction (3zg). The X-ray crystallographic analysis of 3g49 clearly indicated the structure of 3-sulfonyl cyclopentenones.
The generality of photoredox-catalyzed synthesis of dihydropyranols was then explored with MeCN as the solvent (Fig. 3). Alkynyl aldehydes bearing different substituents such as Me, F, Cl, Br, CN, Ac, and OMe served as competent substrates, delivering a variety of 4-sulfonyl dihydropyranols in moderate to high yields (4a-4i). The electron effects appeared to have an impact on the reaction efficiency. Specifically, the transformation of substrates 1g and 1h, having electron-withdrawing CN and Ac substituents on the benzene ring, produced the desired products 4g and 4h in 70% and 76% yield, respectively, while a moderate yield (42%) was observed in the case of 1i, bearing an electron-donating OMe group (4i). Substituents at the α-position of aldehydes were evaluated. In particular, α-tertiary aldehydes worked well for this reaction (4m-4q), whereas the α-secondary aldehyde failed to provide the corresponding product (4r), presumably due to the reduced stability of secondary alkyl radicals. Additionally, the scope with respect to sulfonyl chlorides was investigated. A wide range of arylsulfonyl chlorides, substituted by groups such as F, CF3, Br, OMe, i-Pr, and CN, underwent the reaction smoothly to generate functionalized dihydropyranols in promising yields (4s-4z). Similarly, 2-furansulfonyl chloride served as an efficient sulfonylation reagent (4za). It's noteworthy that four new chemical bonds are concurrently created under the reaction conditions, thus highlighting the high bond-forming efficiency of this method.
Meanwhile, the one-pot synthesis of polysubstituted dihydropyranones was explored (Fig. 4). As expected, the reaction furnished a set of sulfonylated dihydropyranones in medium to high yields with good functional group tolerance (5a-5e). The structure of 4-sulfonyl dihydropyranones was unambiguously identified by the X-ray crystallographic analysis of 5a49.
Synthetic applications. To demonstrate the synthetic utility of this divergent transformation of alkynyl aldehydes, we carried out the derivatization of products (Fig. 5). Reduction of 3a with a combination of NaBH4 and CeCl3 produced the tetrasubstituted cyclopentenol 6a in 77% yield. Michael addition of BnSH to 3a followed by an elimination of sulfinate formed the benzylthiocyclopentenone 6b in 86% yield. Following Orita's protocol50, photocatalytic desulfonylation of 3a and 5a occurred readily to give 6c and 6d in 81% and 84% yield, respectively. Bromination at the allylic position of 5a with NBS and BPO produced 6e in a good yield. Given the significant importance of tetrasubstituted alkenes in organic synthesis, the attempts to establish stereodefined tetrasubstituted alkenes were also performed. Nucleophilic attack of MeMgCl to 5a delivered the tetrasubstituted (E)-alkene 6f in 82% yield. Furthermore, the (E)-enol 6g was selectively assembled in almost quantitative yield upon treatment of 5a with K2CO3 in MeOH at 55 oC for 10 h.
Mechanistic investigations. To gain insights into the reaction mechanism, some control experiments were performed, and the results are summarized in Fig. 6. In the presence of butylated hydroxytoluene (BHT, 2.0 equiv), neither 3a nor 4a could be obtained in a noticeable yield, and instead, the sulfonyl compound 751 was isolated in 11% and 48% yield, respectively. Likewise, adding 2,2,6,6-tetramethylpiperidinooxy (TMEPO, 2.0 equiv) to the standard conditions shut down the reaction (not shown). These results suggested a radical pathway. Additionally, the 18O isotope labeling experiments were conducted. With the addition of 5.0 equiv of H218O, 4a-18O was isolated in 69% yield with 89% 18O incorporation. In addition to the signal of [M+Na]+ ion of 4a-18O, a signal matched with [M+Na-H218O]+ ion was observed by the HRMS analysis, thus indicating that the hydroxy group of 4a is originated from water (see Supporting Information for details).
Based on the above results and previous reports7,15,16, a mechanistic proposal for the divergent cyclization of 1a is summarized in Fig. 7. Initially, the single electron transfer (SET) between the excited photocatalysis Ir(III)* and TsCl affords a Ir(IV) species and sulfonyl radical Ts·33. Radical sulfonylation of the C-C triple bond of 1a and a subsequent addition of vinyl radical I to the intramolecular CHO group produces a cyclopentenyloxy radical II. It may undergo a 1,2-HAT to deliver the neutral ketyl radical III, followed by SET with Ir(IV) and deprotonation to provide 3a (path 1a). Alternatively, the β-C-C cleavage of II52-58 may take place to form a tertiary alkyl radical IV (path 1b), which can be converted into the oxonium ion VI via a 6-endo radical cyclization (path 2a)/SET oxidation sequence. Additionally, a radical oxidation to the cation VII (path 2b) followed by intramolecular nucleophilic attack may also lead to the generation of VI. Finally, the nucleophilic attack of VI by H2O generates 4a as the product.
To shed light on the unique role of solvent in tuning the reaction pathways, we carried out computational studies using DFT calculations, and the results are presented in Fig. 8. As for the reaction performed in DMA, radical sulfonylation of 1a occurring via transition state TS1 requires an activation free energy of 14.3 kcal/mol, which is viable under the reaction conditions. Subsequently, radical addition to the intramolecular CHO group proceeds via a five-membered ring transition state TS2 to give the radical II. This step has a free energy barrier of 9.3 kcal/mol. Starting from II, an unprecedented DMA-assisted 1,2-hydrogen transfer59-61 (via TS3-DMA, with a free energy of 7.6 kcal/mol) is favoured over the 6-endo radical cyclization (via TS5, with a free energy of 9.4 kcal/mol) by 1.8 kcal/mol, thus giving rise to the ketyl radical III. Formation of III is highly exergonic by 30.7 kcal/mol and is therefore an irreversible process. Followed by SET oxidation and deprotonation, 3a can be constructed together with the regeneration of photocatalysis Ir(III), which is strongly exergonic by 63.2 kcal/mol.
With MeCN as the solvent, the MeCN-assisted 1,2-hydrogen transfer of II (via TS3-NCMe) has a higher energy barrier of 15.3 kcal/mol, which is unlikely to compete with the β-C-C cleavage/ 6-endo cyclization sequence. Moreover, the 6-endo radical cyclization of IV requiring a free energy barrier of 4.5 kcal/mol is favoured over the SET oxidation, with a free energy barrier of 9.6 kcal/mol, by 5.1 kcal/mol. Therefore, a stable allyl radical V that lies 25.8 kcal/mol lower in energy than IV is selectively formed. Spin delocalization to the neighboring C-C double bond should be responsible for the increased stability of V, which provides a driving force for the C-C bond cleavage and uncommon addition of alkyl radical to the carbonyl oxygen atom62-64 in the 6-endo radical cyclization step. Subsequently, the radical V is oxidized by Ir(IV) to form an oxonium ion intermediate VI, followed by nucleophilic attack of water to produce 4a, which is strongly exergonic by 39.1 kcal/mol.