Martin Silicates as Versatile Radical Precursors in Photoredox/ Nickel Dual Catalysis

Abstract

A cross-coupling methodology is described based on the nickel-catalyzed connection of an aryl moiety to an alkyl radical generated by photoinduced single-electron oxidation of a silicate formed from a Martin spirosilane. Complementary to the other anionic radical precursors in photoredox catalysis, Martin silicates permit access to highly reactive alkyl radicals directly engageable in smooth C(sp²)–C(sp³) bond-formation reactions.

Photoredox/nickel dual catalysis has emerged over the last decade as a method for forging C(sp²)–C(sp³) bonds that provides a powerful alternative to the pioneering methodologies employing overstoichiometric amounts of highly reactive organometallic reagents (Schemes 1a and 1b).[1] This method has been rendered productive thanks to the smooth generation of alkyl radicals under low-energy light irradiation by using an appropriate photocatalyst to promote photooxidation.[2] [3] Pioneered by the groups of MacMillan and Doyle,[4] as well as the group of Molander,[5] who employed, respectively, N-methylanilines, alkyl carboxylates, or trifluoroborate salts as radical precursors, the palette of substrates potentially amenable to this methodology has been opportunely extended to sulfinates,[6] dihydropyridines,[7] Katritzky pyridinium salts,[8] [9] and cycloalkanols,[10] as well as radicals arising from direct hydrogen-atom transfer.[11]

Among these alkyl radical precursors, bis-catecholato silicates developed by us[12] [13] and by the Molander group[14] feature the lowest oxidation potentials (E ^ox _1/2 < 1.0 V vs SCE), ensuring the generation of a broad range of radical intermediates compatible with various aryl, vinyl, or acyl halide electrophiles. Moreover, the radical precursors can be readily prepared from commercially available trialkoxy- or trichlorosilanes or, potentially, by the hydrosilylation of alkenes. Another class of silicon-based precursors, namely the Martin silicates, have been reported as radical precursors by Morofuji and Kano and their co-workers.[15] [16] Because their synthesis relies on simple nucleophilic addition of carbanions to the Martin spirosilane 1 (Scheme [2]), Martin silicates significantly expand the scope of useful radicals. Interestingly also, the silicate trick permits a formal single-electron oxidation of highly reactive carbanions (organolithiums or Grignard reagents), which otherwise remains challenging. Because of the higher oxidation potentials of Martin silicates (E ^ox _1/2 > 1.5 V vs SCE),[15] [16] the mesitylacridinium salts developed by the group of Nicewicz,[17] [18] and featuring a strongly oxidizing excited state (E*_ox ≈ 2 V vs SCE), appear to be the most suitable photocatalysts for the oxidation, permitting the smooth generation of radicals that can be readily engaged in Minisci reactions[15] or Giese-type additions.[16] By analogy with the reactivity of the biscatecholato silicates, we wondered whether this photocatalytic generation of radicals from Martin silicates might be connected to a nickel cycle (Schemes 1c and 1d).

Synthesis of the Martin Silicates

We first turned our attention toward the synthesis and the properties of the silicates and their bis-catecholato counterparts. Martin silicates exhibit excellent bench stability and are highly air and moisture stable. Moreover, their synthesis is compatible with a multigram scale and, additionally, suitable for a wide range of organic backbones (Scheme [2]).

Our protocol relies on the addition to the Martin spirosilane of an organometallic alkylating agent, either an organolithium (1c–e) or a Grignard reagent (1a, 1b, and 1f–h) prepared from an alkyl bromide precursor or commercially available. In both cases, the second step is a counterion metathesis, leading to tetraethylammonium silicates 1, which is highly beneficial for their stability and solubility in organic solvents. The resulting solids could be stored at room temperature under air without any degradation and were obtained in good yields of 75–95% (1a, 1b, 1e, 1f–h). Due to the increased steric demand of organic backbones such as sec-butyl or tert-butyl chains, the yields of the corresponding derivatives were reduced to 42% (1c) and 43% (1d).

Optimization

Next, we optimized the reaction conditions for the photoredox/nickel dual catalysis by varying various parameters, including the solvent, the catalyst, and the relative proportions of the various reagents (Scheme [3]). A stoichiometric mixture of the acridinium salt PC1 and a bathophenanthroline–nickel complex appeared optimal for the reaction. The extended π-system of the bathophenanthroline seemed to be crucial for the outcome of the reaction, as this ligand exhibited a superior efficiency to that of the bipyridyl ligands that are generally used in most existing dual-catalysis pathways and which were completely inoperative in the present case (Scheme [3], entries 1 and 11). Moreover, contrary to the existing methodologies, the use of polar solvents was detrimental, as reflected by a decreased NMR yield of 8% when MeCN was used as the solvent (entry 4). Whereas no coupling product was observed in the case of the widely used DMF or DMAc solvent (entry 3), the use of nonpolar CH₂Cl₂ proved to be suitable (entry 5). Performing the reaction at a higher concentration using overstoichiometric amounts of the aryl halide had a beneficial impact on the outcome of the reaction (entries 12 and 13). Regarding the photocatalyst, on the basis of previous reports dealing with Martin silicates,[15] [16] two different acridinium salts were probed. Nicewicz’s acridinium PC1, seemed to be more selective and produced fewer byproducts than did Fukuzumi’s photocatalyst[19] (entry 6). Moreover, we confirmed that (4,4′-di-tert-butyl-2,2′-bipyridinyl)bis{3,5-difluoro-2-[5-(trifluoromethyl)-2-pyridinyl]phenyl}iridium(III) hexafluorophosphate [Ir–F] and 4CzIPN were unable to perform the oxidation of the Martin silicates (entries 7 and 8). Furthermore, the halogen substituent (Cl versus Br) on the nickel catalyst appears to be a parameter with a critical impact on the coupling efficiency (entry 5 and 10).

Synthetic Scope

The scope of the cross-coupling was next investigated, and the reaction was shown to be compatible with a wide range of electron-withdrawing substituents and some electron-donating substituents on the aromatic core to be alkylated. Indeed, no byproducts were observed with aromatic cores flanked by boronic ester, ester, trimethylsilyl, ketone, or nitrile groups (5, 7, 8, 11, 15, and 17). Moreover, this permitted the smooth alkylation of several heterocycles, including a pyrrole (4), a benzofuran (9), and a quinoline (12). Ketone synthesis could be carried out from the corresponding acyl chloride to give 19 with no trace of the overreaction leading to a tertiary alcohol with a nucleophilic alkylating agent. The alkynylation reaction involving an alkynyl bromide gave 20 in fair yield, as did vinylation with the corresponding vinyl bromide to give 21, which also demonstrated tolerance of the reaction toward a Boc protecting group. The cross-coupling permitted the installation of primary nonactivated alkyl groups including a butyl group (25), a (trimethylsilyl)methyl group without overoxidation (26),[20] or a 3-oxopropyl unit (27). Moderate to good yields were obtained with secondary alkyl chains, including tetrahydropyranyl (4–18), cyclohexyl (22), and sec-butyl (24) (Scheme [4]). Due to an increased steric hindrance, the cross-coupling product of a tertiary radical 23 was not obtained, and only the dimerization product of the aryl halide was observed.

Mechanistic discussion

Silicate 1a proved to be an efficient quencher of the luminescence of PC1 (k _q = 2.86 × 10¹⁰ L mol^–1 s^–1; see the Supporting Information). Based on the consistent redox potentials (2.10 V vs SCE for [Mes-Acr⁺]*/[Mes-Acr^∙][18] vs 1.50 V for alkyl Martin silicates[15]), an oxidative quenching to provide an alkyl radical that is intercepted by nickel, as shown in Scheme [1c], appears likely.

In summary, we have developed a new photoredox/nickel dual-catalyzed alkylation pathway by providing a new transformation in this field of photocatalysis.[21] Martin silicates exhibit excellent bench stability and undergo efficient photooxidation, as observed for bis-catecholato silicate precursors. Moreover, they permit the introduction of various alkyl groups through dual catalysis, a reaction not accessible from bis-catecholato silicates. The good yields obtained, as well as the broad functional-group tolerance and chemoselectivity, demonstrate that this reaction provides new synthetic opportunities.

Conflict of Interest

The authors declare no conflict of interest.

Acknowledgment

The authors thank the Fédération de Chimie Moléculaire for access to analytical platforms and, notably, Gilles Clodic for HRMS. We further thank Studienstiftung des deutschen Volkes e.V. and Erasmus+ for funding the research stay of M.-A.W.

• References and Notes

• 1 Chan AY, Perry IB, Bissonnette NB, Buksh BF, Edwards GA, Frye LI, Garry OL, Lavagnino MN, Li BX, Liang Y, Mao E, Millet A, Oakley JV, Reed NL, Sakai HA, Seath CP, MacMillan DW. C. Chem. Rev. 2022; 122: 1485
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• 2 Crespi S, Fagnoni M. Chem. Rev. 2020; 120: 9790
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• 4 Zuo Z, Ahneman DT, Chu L, Terrett JA, Doyle AG, MacMillan DW. C. Science 2014; 345: 437
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• 5 Tellis JC, Primer DN, Molander GA. Science 2014; 345: 433
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• 6 Knauber T, Chandrasekaran R, Tucker JW, Chen JM, Reese M, Rankic DA, Sach N, Helal C. Org. Lett. 2017; 19: 6566
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• 7 Nakajima K, Nojima S, Nishibayashi Y. Angew. Chem. Int. Ed. 2016; 55: 14106
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• 8 Basch CH, Liao J, Xu J, Piane JJ, Watson MP. J. Am. Chem. Soc. 2017; 139: 5313
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• 9 Klauck FJ. R, James MJ, Glorius F. Angew. Chem. Int. Ed. 2017; 56: 12336
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• 10 Huang L, Ji T, Rueping M. J. Am. Chem. Soc. 2020; 142: 3532
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• 11a Le C, Liang YF, Evans RW, Li XM, MacMillan DW. C. Nature 2017; 547: 79
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• 11b Perry IB, Brewer TF, Sarver PJ, Schultz DM, DiRocco DA, MacMillan DW. C. Nature 2018; 560: 70
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• 11c Shaw MH, Shurtleff VW, Terrett JA, Cuthbertson JD, MacMillan DW. C. Science 2016; 352: 1304
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• 12a Corcé V, Chamoreau L.-M, Derat E, Goddard J.-P, Ollivier C, Fensterbank L. Angew. Chem. Int. Ed. 2015; 54: 11414
  Search in Google Scholar
• 12b Lemière G, Millanvois A, Ollivier C, Fensterbank L. Chem. Rec. 2021; 21: 1119
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• 13 Lévêque C, Chenneberg L, Corcé V, Goddard J.-P, Ollivier C, Fensterbank L. Org. Chem. Front. 2016; 3: 462
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• 14 Jouffroy M, Primer DN, Molander GA. J. Am. Chem. Soc. 2016; 138: 475
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• 15 Ikarashi G, Morofuji T, Kano N. Chem. Commun. 2020; 56: 10006
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• 16 Morofuji T, Matsui Y, Ohno M, Ikarashi G, Kano N. Chem. Eur. J. 2021; 27: 6713
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• 17 Joshi-Pangu A, Lévesque F, Roth HG, Oliver SF, Campeau L.-C, Nicewicz D, DiRocco DA. J. Org. Chem. 2016; 81: 7244
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• 18 White AR, Wang L, Nicewicz DA. Synlett 2019; 30: 827
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• 19 Fukuzumi S, Kotani H, Ohkubo K, Ogo S, Tkachenko NV, Lemmetyinen H. J. Am. Chem. Soc. 2004; 126: 1600
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• 20 Uygur M, Danelzik T, Garcia-Mancheño O. Chem. Commun. 2019; 55: 2980
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• 21 Cross-Coupling Reaction; General Procedure A flame-dried, sealed, microwave tube, purged by three argon/vacuum cycles, was charged with the appropriate silicate 1a–h (0.2 mmol, 1 equiv), NiBr₂BPhen (5.5 mg, 0.01 mmol, 5 mol%), and photocatalyst PC1 (5.7 mg, 0.01 mmol, 5 mol%) under argon, along with the appropriate aryl bromide or iodide (0.4 mmol, 2 equiv), if solid. (When the aryl bromide was a liquid, it was introduced from a microsyringe after adding the solvent under argon.) Distilled CH₂Cl₂ was then added (0.2 M) under argon, followed by three freeze–pump–thaw cycles to degas the mixture. The mixture was then irradiated with a blue LED for 24 h at r.t. The reaction was then quenched with sat. aq K₂CO₃ (10 mL) and the mixture was extracted with Et₂O (3 × 20 mL) and H₂O (3 × 20 mL). The combined organic layers were concentrated under vacuum, and the crude product was purified by flash chromatography (silica gel). 1-[4-(Tetrahydro-2H-pyran-4-yl)phenyl]-1H-pyrrole (4) Brown solid; yield: 19.2 mg (51%); mp 119.8–124.1 °C. ¹H NMR: (300 MHz, CDCl₃): δ = 7.40–7.34 (m, 2 H), 7.33–7.27 (m, 2 H), 7.09 (t, J = 2.2 Hz, 2 H), 6.37 (t, J = 2.2 Hz, 2 H), 4.19–4.07 (m, 2 H), 3.58 (dt, J = 11.3, 3.1 Hz, 2 H), 2.81 (tt, J = 10.6, 5.5 Hz, 1 H), 1.96–1.75 (m, 4 H). ¹³C NMR: (75 MHz, CDCl₃): δ = 143.5, 139.3, 127.9, 120.9, 119.5, 110.4, 68.5, 41.2, 34.1. HRMS (ESI): m/z [M + H]⁺ calcd for C₁₅H₁₈NO: 228.1383; found: 228.1384. Methyl 6-(Tetrahydro-2H-pyran-4-yl)-2-naphthoate (11) White solid; yield: 37.9 mg (70%); mp 115.1–119.1 °C. ¹H NMR: (400 MHz, CDCl₃): δ = 8.58 (s, 1 H), 8.05 (dd, J = 8.6, 1.7 Hz, 1 H), 7.91 (d, J = 8.5 Hz, 1 H), 7.83 (d, J = 8.6 Hz, 1 H), 7.68 (d, J = 1.7 Hz, 1 H), 7.44 (dd, J = 8.5, 1.8 Hz, 1 H), 4.13 (ddt, J = 11.5, 4.3, 1.6 Hz, 2 H), 3.98 (s, 3 H), 3.59 (td, J = 11.6, 2.5 Hz, 2 H), 2.95 (tt, J = 11.6, 4.2 Hz, 1 H), 2.06–1.78 (m, 4 H). ¹³C NMR: (101 MHz, CDCl₃): δ = 167.3, 146.0, 135.8, 131.3, 130.8, 129.5, 127.8, 126.9, 126.5, 125.4, 124.6, 68.3, 52.2, 41.8, 33.7. HRMS (ESI): m/z [M + H]⁺ calcd for C₁₇H₁₉O: 271.1329; found: 271.1327. tert-Butyl 4-(Tetrahydro-2H-pyran-4-ylmethylene)piperidine-1-carboxylate (21)Brown solid; yield: 27.0 mg (48%); mp 97–100.5 °C. ¹H NMR: (300 MHz, CDCl₃): δ = 5.06 (d, J = 8.5 Hz, 1 H), 3.99–3.87 (m, 2 H), 3.50–3.32 (m, 6 H), 2.55–2.33 (m, 1 H), 2.16 (dt, J = 31.4, 5.7 Hz, 4 H), 1.42 (s, 13 H). ¹³C NMR: (75 MHz, CDCl₃): δ = 154.9, 134.8, 128.8, 79.6, 67.8, 35.9, 33.5, 33.4, 28.8, 28.6. HRMS (ESI): m/z [M + H]⁺ calcd for C₁₆H₂₈NO₃: 282.2064; found: 282.2068. Methyl 6-sec-Butyl-2-naphthoate (24) Yellow oil; yield: 19.7 mg (41%). ¹H NMR: (400 MHz, CDCl₃): δ = 8.57 (d, J = 1.8 Hz, 1 H), 8.03 (dd, J = 8.6, 1.7 Hz, 1 H), 7.85 (dd, J = 27.2, 8.6 Hz, 2 H), 7.64 (d, J = 1.8 Hz, 1 H), 7.41 (dd, J = 8.5, 1.8 Hz, 1 H), 3.98 (s, 3 H), 2.86–2.73 (m, 1 H), 1.78–1.63 (m, 2 H), 1.33 (d, J = 6.9 Hz, 3 H), 0.86 (t, J = 7.4 Hz, 3 H). ¹³C NMR: (101 MHz, CDCl₃): δ = 167.6, 148.1, 136.0, 129.5, 127.9, 126.9, 125.4, 125.3, 52.3, 42.1, 31.1, 21.8, 12.4. HRMS (ESI): m/z [M + H]⁺ calcd for C₁₆H₁₉O₂: 243.1380; found: 243.1376.
• 22 For the introduction of a methyl group and its ¹³C- and ²H-labeled analogues, see: Abdellaoui M, Deis T, Wiethoff M.-A, Bahri C, Lemière G, Ollivier C, Fensterbank L. Adv. Synth. Catal. 2023; 365: 884
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Corresponding Authors

Publication History

Received: 31 January 2023

Accepted after revision: 21 March 2023

Accepted Manuscript online:
21 March 2023

Article published online:
21 April 2023

© 2023. Thieme. All rights reserved

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• References and Notes

• 1 Chan AY, Perry IB, Bissonnette NB, Buksh BF, Edwards GA, Frye LI, Garry OL, Lavagnino MN, Li BX, Liang Y, Mao E, Millet A, Oakley JV, Reed NL, Sakai HA, Seath CP, MacMillan DW. C. Chem. Rev. 2022; 122: 1485
  CrossrefPubMedSearch in Google Scholar
• 2 Crespi S, Fagnoni M. Chem. Rev. 2020; 120: 9790
  CrossrefPubMedSearch in Google Scholar
• 3 Corcé V, Ollivier C, Fensterbank L. Chem. Soc. Rev. 2022; 51: 1470
  CrossrefPubMedSearch in Google Scholar
• 4 Zuo Z, Ahneman DT, Chu L, Terrett JA, Doyle AG, MacMillan DW. C. Science 2014; 345: 437
  CrossrefPubMedSearch in Google Scholar
• 5 Tellis JC, Primer DN, Molander GA. Science 2014; 345: 433
  CrossrefPubMedSearch in Google Scholar
• 6 Knauber T, Chandrasekaran R, Tucker JW, Chen JM, Reese M, Rankic DA, Sach N, Helal C. Org. Lett. 2017; 19: 6566
  CrossrefPubMedSearch in Google Scholar
• 7 Nakajima K, Nojima S, Nishibayashi Y. Angew. Chem. Int. Ed. 2016; 55: 14106
  CrossrefPubMedSearch in Google Scholar
• 8 Basch CH, Liao J, Xu J, Piane JJ, Watson MP. J. Am. Chem. Soc. 2017; 139: 5313
  CrossrefPubMedSearch in Google Scholar
• 9 Klauck FJ. R, James MJ, Glorius F. Angew. Chem. Int. Ed. 2017; 56: 12336
  CrossrefPubMedSearch in Google Scholar
• 10 Huang L, Ji T, Rueping M. J. Am. Chem. Soc. 2020; 142: 3532
  CrossrefPubMedSearch in Google Scholar
• 11a Le C, Liang YF, Evans RW, Li XM, MacMillan DW. C. Nature 2017; 547: 79
  CrossrefPubMedSearch in Google Scholar
• 11b Perry IB, Brewer TF, Sarver PJ, Schultz DM, DiRocco DA, MacMillan DW. C. Nature 2018; 560: 70
  CrossrefPubMedSearch in Google Scholar
• 11c Shaw MH, Shurtleff VW, Terrett JA, Cuthbertson JD, MacMillan DW. C. Science 2016; 352: 1304
  CrossrefPubMedSearch in Google Scholar
• 12a Corcé V, Chamoreau L.-M, Derat E, Goddard J.-P, Ollivier C, Fensterbank L. Angew. Chem. Int. Ed. 2015; 54: 11414
  Search in Google Scholar
• 12b Lemière G, Millanvois A, Ollivier C, Fensterbank L. Chem. Rec. 2021; 21: 1119
  CrossrefPubMedSearch in Google Scholar
• 13 Lévêque C, Chenneberg L, Corcé V, Goddard J.-P, Ollivier C, Fensterbank L. Org. Chem. Front. 2016; 3: 462
  CrossrefPubMedSearch in Google Scholar
• 14 Jouffroy M, Primer DN, Molander GA. J. Am. Chem. Soc. 2016; 138: 475
  Search in Google Scholar
• 15 Ikarashi G, Morofuji T, Kano N. Chem. Commun. 2020; 56: 10006
  CrossrefPubMedSearch in Google Scholar
• 16 Morofuji T, Matsui Y, Ohno M, Ikarashi G, Kano N. Chem. Eur. J. 2021; 27: 6713
  CrossrefPubMedSearch in Google Scholar
• 17 Joshi-Pangu A, Lévesque F, Roth HG, Oliver SF, Campeau L.-C, Nicewicz D, DiRocco DA. J. Org. Chem. 2016; 81: 7244
  CrossrefPubMedSearch in Google Scholar
• 18 White AR, Wang L, Nicewicz DA. Synlett 2019; 30: 827
  Thieme ConnectPubMedSearch in Google Scholar
• 19 Fukuzumi S, Kotani H, Ohkubo K, Ogo S, Tkachenko NV, Lemmetyinen H. J. Am. Chem. Soc. 2004; 126: 1600
  CrossrefPubMedSearch in Google Scholar
• 20 Uygur M, Danelzik T, Garcia-Mancheño O. Chem. Commun. 2019; 55: 2980
  CrossrefPubMedSearch in Google Scholar
• 21 Cross-Coupling Reaction; General Procedure A flame-dried, sealed, microwave tube, purged by three argon/vacuum cycles, was charged with the appropriate silicate 1a–h (0.2 mmol, 1 equiv), NiBr₂BPhen (5.5 mg, 0.01 mmol, 5 mol%), and photocatalyst PC1 (5.7 mg, 0.01 mmol, 5 mol%) under argon, along with the appropriate aryl bromide or iodide (0.4 mmol, 2 equiv), if solid. (When the aryl bromide was a liquid, it was introduced from a microsyringe after adding the solvent under argon.) Distilled CH₂Cl₂ was then added (0.2 M) under argon, followed by three freeze–pump–thaw cycles to degas the mixture. The mixture was then irradiated with a blue LED for 24 h at r.t. The reaction was then quenched with sat. aq K₂CO₃ (10 mL) and the mixture was extracted with Et₂O (3 × 20 mL) and H₂O (3 × 20 mL). The combined organic layers were concentrated under vacuum, and the crude product was purified by flash chromatography (silica gel). 1-[4-(Tetrahydro-2H-pyran-4-yl)phenyl]-1H-pyrrole (4) Brown solid; yield: 19.2 mg (51%); mp 119.8–124.1 °C. ¹H NMR: (300 MHz, CDCl₃): δ = 7.40–7.34 (m, 2 H), 7.33–7.27 (m, 2 H), 7.09 (t, J = 2.2 Hz, 2 H), 6.37 (t, J = 2.2 Hz, 2 H), 4.19–4.07 (m, 2 H), 3.58 (dt, J = 11.3, 3.1 Hz, 2 H), 2.81 (tt, J = 10.6, 5.5 Hz, 1 H), 1.96–1.75 (m, 4 H). ¹³C NMR: (75 MHz, CDCl₃): δ = 143.5, 139.3, 127.9, 120.9, 119.5, 110.4, 68.5, 41.2, 34.1. HRMS (ESI): m/z [M + H]⁺ calcd for C₁₅H₁₈NO: 228.1383; found: 228.1384. Methyl 6-(Tetrahydro-2H-pyran-4-yl)-2-naphthoate (11) White solid; yield: 37.9 mg (70%); mp 115.1–119.1 °C. ¹H NMR: (400 MHz, CDCl₃): δ = 8.58 (s, 1 H), 8.05 (dd, J = 8.6, 1.7 Hz, 1 H), 7.91 (d, J = 8.5 Hz, 1 H), 7.83 (d, J = 8.6 Hz, 1 H), 7.68 (d, J = 1.7 Hz, 1 H), 7.44 (dd, J = 8.5, 1.8 Hz, 1 H), 4.13 (ddt, J = 11.5, 4.3, 1.6 Hz, 2 H), 3.98 (s, 3 H), 3.59 (td, J = 11.6, 2.5 Hz, 2 H), 2.95 (tt, J = 11.6, 4.2 Hz, 1 H), 2.06–1.78 (m, 4 H). ¹³C NMR: (101 MHz, CDCl₃): δ = 167.3, 146.0, 135.8, 131.3, 130.8, 129.5, 127.8, 126.9, 126.5, 125.4, 124.6, 68.3, 52.2, 41.8, 33.7. HRMS (ESI): m/z [M + H]⁺ calcd for C₁₇H₁₉O: 271.1329; found: 271.1327. tert-Butyl 4-(Tetrahydro-2H-pyran-4-ylmethylene)piperidine-1-carboxylate (21)Brown solid; yield: 27.0 mg (48%); mp 97–100.5 °C. ¹H NMR: (300 MHz, CDCl₃): δ = 5.06 (d, J = 8.5 Hz, 1 H), 3.99–3.87 (m, 2 H), 3.50–3.32 (m, 6 H), 2.55–2.33 (m, 1 H), 2.16 (dt, J = 31.4, 5.7 Hz, 4 H), 1.42 (s, 13 H). ¹³C NMR: (75 MHz, CDCl₃): δ = 154.9, 134.8, 128.8, 79.6, 67.8, 35.9, 33.5, 33.4, 28.8, 28.6. HRMS (ESI): m/z [M + H]⁺ calcd for C₁₆H₂₈NO₃: 282.2064; found: 282.2068. Methyl 6-sec-Butyl-2-naphthoate (24) Yellow oil; yield: 19.7 mg (41%). ¹H NMR: (400 MHz, CDCl₃): δ = 8.57 (d, J = 1.8 Hz, 1 H), 8.03 (dd, J = 8.6, 1.7 Hz, 1 H), 7.85 (dd, J = 27.2, 8.6 Hz, 2 H), 7.64 (d, J = 1.8 Hz, 1 H), 7.41 (dd, J = 8.5, 1.8 Hz, 1 H), 3.98 (s, 3 H), 2.86–2.73 (m, 1 H), 1.78–1.63 (m, 2 H), 1.33 (d, J = 6.9 Hz, 3 H), 0.86 (t, J = 7.4 Hz, 3 H). ¹³C NMR: (101 MHz, CDCl₃): δ = 167.6, 148.1, 136.0, 129.5, 127.9, 126.9, 125.4, 125.3, 52.3, 42.1, 31.1, 21.8, 12.4. HRMS (ESI): m/z [M + H]⁺ calcd for C₁₆H₁₉O₂: 243.1380; found: 243.1376.
• 22 For the introduction of a methyl group and its ¹³C- and ²H-labeled analogues, see: Abdellaoui M, Deis T, Wiethoff M.-A, Bahri C, Lemière G, Ollivier C, Fensterbank L. Adv. Synth. Catal. 2023; 365: 884
  CrossrefPubMedSearch in Google Scholar

• Supplementary Material