Synlett 2023; 34(06): 635-644
DOI: 10.1055/a-1934-1056
cluster
Chemical Synthesis and Catalysis in India

Nickel-Catalyzed Sustainable and Selective Alkylation of Alcohols to α-Alkylated Ketones via Borrowing Hydrogen Approach

Gargi Chakraborty
,
Subhasree Pal
,
,
Nanda D. Paul
The research was supported by the Department of Science and ­Technology (DST), Ministry of Science and Technology, India (Project CRG/2019/001737) and the Council of Scientific and Industrial Research, India (CSIR, 01(3023)/21/EMR-II). G.C. thanks the University Grants Commission (UGC), S.P. thanks the Indian Institute of ­Engineering Science and Technology, Shibpur (IIESTS) for fellowship support.


Abstract

Herein, we report a nickel-catalyzed sustainable, environment­-friendly, and economically affordable borrowing hydrogen approach (BHA) for synthesizing various α-alkylated ketones via dehydro­genative coupling of primary and secondary alcohols. Using a well-­defined, air-stable, inexpensive, and easy-to-prepare four-coordinate macrocyclic Ni(II)-catalyst [Ni(MeTAA)] of a tetra-aza macrocyclic ligand (tetramethyltetraaza[14]annulene (H2MeTAA)), a series of α-alkylated ketones were prepared in good yields. A few control reactions, including deuterium-labelling experiments, were performed to unveil the reaction mechanism.

Supporting Information



Publication History

Received: 24 May 2022

Accepted after revision: 30 August 2022

Accepted Manuscript online:
30 August 2022

Article published online:
28 November 2022

© 2022. Thieme. All rights reserved

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 
  • References and Notes

    • 1a Jang H-Y, Krische MJ. Acc. Chem. Res. 2004; 37: 653
    • 1b Barreiro EJ, Kümmerle AE, Fraga CA. M. Chem. Rev. 2011; 11: 5215
    • 2a Szekely G, de Sousa MC. A, Gil M, Castelo FerreiraF, Heggie W. Chem. Rev. 2015; 115: 8182
    • 2b Che J, Lam Y. Synlett 2010; 2415
    • 2c Radolko J, Ehlers P, Langer P. Adv. Synth. Catal. 2021; 363: 1
    • 2d Liao J, Zhang S, Wang J, Song S, Zhang D, Kumar R, Jin J, Ren P, You H, Chen F. Green Synth. Catal. 2020;  1: 121
    • 2e Salciccioli M, Stamatakis M, Caratzoulas S, Vlachos DG. Chem. Eng. Sci. 2011; 66: 4319
    • 2f Nakamura I, Yamamoto Y. Chem. Rev. 2004; 104: 2127
    • 2g Trowbridge A, Walton SM, Gaunt MJ. Chem. Rev. 2020; 120: 2613
    • 3a Yeung CS, Dong VM. Chem. Rev. 2011; 111: 1215
    • 3b Ackerman LK. G, Alvarado JI. M, Doyle AG. J. Am. Chem. Soc. 2018; 140: 14059
    • 3c Reddy RS, Lagishetti C, Kiran IN. C, You H, He Y. Org. Lett. 2016; 18: 3818
    • 3d You H, Vegi SR, Lagishetti C, Chen S, Reddy RS, Yang X, Guo Jian, Wang C, He Y. J. Org. Chem. 2018; 83: 4119
    • 3e Lagishetti C, Banne S, You H, Tang M, Guo J, Qi N, He Y. Org. Lett. 2019; 21: 5301
    • 3f Reddy RS, Zheng S, Lagishetti C, You H, He Y. RSC Adv. 2016; 6: 68199
    • 4a Crabtree RH. Chem. Rev. 2017; 117: 9228
    • 4b Maji M, Panja D, Borthakur I, Kundu S. Org. Chem. Front. 2021; 8: 2673
    • 4c Mondal R, Guin AK, Chakraborty G, Paul ND. Org. Biomol. Chem. 2022; 20: 296
    • 4d Luo J, Rauch M, Avram L, Diskin-Posner Y, Shmul G, Ben-David Y, Milstein D. Nat. Catal. 2020; 3: 887
    • 4e Das UK, Ben-David Y, Leitus G, Diskin-Posner Y, Milstein D. ACS Catal. 2019; 9: 479
    • 4f Gunanathan C, Ben-David Y, Milstein D. Science 2007; 317: 790
    • 4g Lu Z, Zheng Q, Yang S, Qian C, Shen Y, Tu T. ACS Catal. 2021; 11: 10796
    • 4h Dai X-J, Li C-J. J. Am. Chem. Soc. 2016; 138: 5433
    • 4i Das UK, Chakraborty S, Diskin-Posner Y, Milstein D. Angew. Chem. Int. Ed. 2018; 57: 13444
    • 4j Vellakkaran M, Singh K, Banerjee D. ACS Catal. 2017; 7: 8152
    • 5a Obora Y. ACS Catal. 2014; 4: 3972
    • 5b Huang F, Liu Z, Yu Z. Angew. Chem. Int. Ed. 2016; 55: 862
    • 5c Corma A, Navas J, Sabater MJ. Chem. Rev. 2018; 118: 1410
    • 5d Polidano K, Allen BD. W, Williams JM. J, Morrill LC. ACS Catal. 2018; 8: 6440
    • 5e Irrgang T, Kempe R. Chem. Rev. 2019; 119: 2524
    • 6a Thiyagarajan S, Gunanathan C. J. Am. Chem. Soc. 2019; 141: 3822
    • 6b Jiménez MV, Fernández-Tornos J, Modrego FJ, Pérez-Torrente JJ, Oro LA. Chem. Eur. J. 2015; 21: 17877
    • 7a Onodera G, Nishibayashi Y, Uemura S. Angew. Chem. Int. Ed. 2006; 45: 3819
    • 7b Chan LK. M, Poole DL, Shen D, Healy MP, Donohoe TJ. Angew. Chem. Int. Ed. 2014; 53: 761
    • 7c Schlepphorst C, Maji B, Glorius F. ACS Catal. 2016; 6: 4184
    • 7d Li Y, Li H, Junge H, Beller M. Chem. Commun. 2014; 50: 14991
    • 7e Miura T, Kose O, Li F, Kai S, Saito S. Chem. Eur. J. 2011; 17: 11146
    • 7f Wang R, Huang L, Du Z, Feng H. J. Organomet. Chem. 2017; 846: 40
    • 8a Alig L, Fritz M, Schneider S. Chem. Rev. 2019; 119: 2681
    • 8b Midya SP, Landge VG, Sahoo MK, Rana J, Balaraman E. Chem. Commun. 2018; 54: 90
    • 8c Mondal R, Chakraborty G, Guin AK, Sarkar S, Paul ND. J. Org. Chem. 2021; 86: 13186
    • 8d Das S, Mondal R, Chakraborty G, Guin AK, Das A, Paul ND. ACS Catal. 2021; 11: 7498
    • 8e Mondal R, Chakraborty G, Guin AK, Pal S, Paul ND. Tetrahedron 2021; 100: 132479
    • 8f Sinha S, Das S, Mondal R, Mandal S, Paul ND. Dalton Trans. 2020; 49: 8448
    • 8g Mondal R, Sinha S, Das S, Chakraborty G, Paul ND. Adv. Synth. Catal. 2020; 362: 594
    • 8h Bains AK, Singh V, Adhikari D. J. Org. Chem. 2020; 85: 14971
    • 8i Mondal R, Guin AK, Chakraborty S, Paul ND. J. Org. Chem. 2022; 87: 2921
    • 8j Das S, Mondal R, Guin AK, Paul ND. Org. Biomol. Chem. 2022; 20: 3105
    • 8k Das S, Sinha S, Samanta D, Mondal R, Chakraborty G, Brandaō P, Paul ND. J. Org. Chem. 2019; 84: 10160
  • 9 Peña-López M, Piehl P, Elangovan S, Neumann H, Beller M. Angew. Chem. Int. Ed. 2016; 55: 14967
  • 10 Chakraborty S, Daw P, Ben DavidY, Milstein D. ACS Catal. 2018; 8: 10300
  • 11 Zhang G, Wu J, Zeng H, Zhang S, Yin Z, Zheng S. Org. Lett. 2017; 19: 1080
  • 12 Babu R, Subaramanian M, Midya SP, Balaraman E. Org. Lett. 2021; 23: 3320
    • 13a Waiba S, Jana SK, Jati A, Jana A, Maji B. Chem. Commun. 2020; 56: 8376
    • 13b Barman MK, Jana A, Maji B. Adv. Synth. Catal. 2018; 360: 3233
    • 14a Zhang M-J, Li H-Xi, Young DJ, Li H-Y, Lang J-P. Org. Biomol. Chem. 2019; 17: 3567
    • 14b Lan X-B, Ye Z, Liu J, Huang M, Shao Y, Cai X, Liu Y, Ke Z. ChemSusChem 2020; 13: 2557
    • 14c Das J, Vellakkaran M, Banerjee D. J. Org. Chem. 2019; 84: 769
    • 14d Bains AK, Biswas A, Adhikari D. Adv. Synth. Catal. 2022; 364: 47
    • 15a Kallmeier F, Kempe R. Angew. Chem. Int. Ed. 2018; 57: 46
    • 15b Liu T, Wang LK. Wu, Yu Z. ACS Catal. 2018; 8: 7201
    • 15c Deibl N, Kempe R. Angew. Chem. Int. Ed. 2017; 56: 1663
    • 15d El-Sepelgy O, Matador E, Brzozowska A, Rueping M. ChemSusChem 2019; 12: 3099
    • 16a Chakraborty G, Sikari R, Mondal R, Mandal S, Paul ND. Asian J. Org. Chem. 2020; 9: 431
    • 16b Parua S, Sikari R, Sinha S, Chakraborty G, Mondal R, Paul ND. J. Org. Chem. 2018; 83: 11154
    • 16c Parua S, Sikari R, Sinha S, Das S, Chakraborty G, Paul ND. Org. Biomol. Chem. 2018; 16: 274
    • 16d Parua S, Das S, Sikari R, Sinha S, Paul ND. J. Org. Chem. 2017;  82:  7165
    • 16e Chakraborty G, Mondal R, Guin AK, Paul ND. Org. Biomol. Chem. 2021; 19: 7217
  • 17 3-(3-Methoxyphenyl)-1-phenylpropan-1-one (4ae) Under an argon atmosphere, a mixture of KOtBu (1.0 mmol) and catalyst 1a (3.0 mol%) was taken in an oven-dried sealed tube fitted with a magnetic stir bar. The reaction vessel was then capped with a rubber septum. A long neck needle connected with a balloon filled with argon was then inserted into the sealed tube. 1.3 mmol of 3-methoxybenzyl alcohol and 1.0 mmol of 1-phenylethanol dissolved in 5.0 mL of degassed xylene were added through a syringe. The sealed tube was then placed in an oil bath preheated at 120 °C for 17 h. Once the reaction was completed, the resulting mixture was concentrated, volatiles were removed under vacuum, and the residue was purified by flash column chromatography (silica gel) using diethyl ether/hexane (1:20) as the eluent to afford 4ae (195 mg, 81%) as white solid (mp 61–63 °C). 1H NMR (400 MHz, CDCl3): δ = 7.97 (d, J = 7.6 Hz, 2 H), 7.56 (t, J = 7.6 Hz, 1 H), 7.46 (t, J = 8.0 Hz, 2 H), 7.25–7.21 (m, 1 H), 6.86–6.75 (m, 3 H), 3.80 (s, 3 H), 3.31 (t, J = 7.6 Hz, 2 H), 3.05 (t, J = 8.0 Hz, 2 H) ppm. 13C{1H} NMR (100 MHz, CDCl3): δ = 199.0, 159.6, 142.8, 136.7, 132.9, 129.3, 128.4, 127.9, 120.6, 114.1, 111.3, 55.0, 40.2, 30.0 ppm. HRMS (ESI, positive ions): m/z calcd for C16H16NaO2 + [M + Na+]: 263.1043; found: 263.1046.
  • 18 3-(4-Isopropylphenyl)-1-phenylpropan-1-one (4ag) Under an argon atmosphere, a mixture of KOtBu (1.0 mmol) and catalyst 1a (3.0 mol%) was taken in an oven-dried sealed tube fitted with a magnetic stir bar. The reaction vessel was then capped with a rubber septum. A long neck needle connected with a balloon filled with argon was then inserted into the sealed tube. 1.3 mmol of 4-isopropylbenzyl alcohol and 1.0 mmol of 1-phenylethanol dissolved in 5.0 mL of degassed xylene were added through a syringe. The sealed tube was then placed in an oil bath preheated at 120 °C for 17 h. Once the reaction was completed, the resulting mixture was concentrated, volatiles were removed under vacuum, and the residue was purified by flash column chromatography (silica gel) using diethyl ether/hexane (1:20) as the eluent to afford 4ag (225 mg, 89%) as yellow oil. 1H NMR (400 MHz, CDCl3): δ = 7.99 (d, J = 7.2 Hz, 2 H), 7.58 (t, J = 7.2 Hz, 1 H), 7.48 (t, J = 7.6 Hz, 2 H), 7.20 (br s, 4 H), 3.33 (t, J = 8.0 Hz, 2 H), 3.07 (t, J = 8.0 Hz, 2 H), 2.95–2.88 (m, 1 H), 1.27 (d, J = 8.0 Hz, 6 H) ppm. 13C{1H} NMR (100 MHz, CDCl3): δ = 199.2, 146.5, 138.4, 136.7, 132.8, 128.4, 128.2, 127.9, 126.4, 40.4, 33.5, 29.5, 23.9 ppm. HRMS (ESI, positive ions): m/z calcd for C18H20NaO+ [M + Na+]: 275.1406; found: 275.1411.
  • 19 3-(2-Bromophenyl)-1-phenylpropan-1-one (4ai) Under an argon atmosphere, a mixture of KOtBu (1.0 mmol) and catalyst 1a (3.0 mol%) was taken in an oven-dried sealed tube fitted with a magnetic stir bar. The reaction vessel was then capped with a rubber septum. A long neck needle connected with a balloon filled with argon was then inserted into the sealed tube. 1.3 mmol of 2-bromobenzyl alcohol and 1.0 mmol of 1-­phenylethanol dissolved in 5.0 mL of degassed xylene were added through a syringe. The sealed tube was then placed in an oil bath preheated at 120 °C for 17 h. Once the reaction was completed, the resulting mixture was concentrated, volatiles were removed under vacuum, and the residue was purified by flash column chromatography (silica gel) using diethyl ether/hexane (1:20) as the eluent to afford 4ai (200 mg, 69%) as white solid (mp 62–64 °C). 1H NMR (400 MHz, CDCl3): δ = 7.99 (d, J = 7.2 Hz, 2 H), 7.58–7.54 (m, 2 H), 7.46 (t, J = 8.0 Hz, 2 H), 7.33–7.31 (dd, J = 1.6, 7.6 Hz, 1 H), 7.26–7.21 (td, J = 1.2, 7.2 Hz, 1 H), 7.10–7.06 (td, J = 1.6, 8.0 Hz, 1 H), 3.32 (t, J = 6.8 Hz, 2 H), 3.19 (t, J = 7.6 Hz, 2 H) ppm. 13C{1H} NMR (100 MHz, CDCl3): δ = 198.7, 140.4, 136.5, 132.9, 132.7, 130.6, 128.4, 127.9, 127.8, 127.5, 124.2, 38.4, 30.6 ppm. HRMS (ESI, positive ions): m/z calcd for C15H13BrNaO+ [M + Na+]: 311.0042; found: 311.0045.
  • 20 3-(3-Fluorophenyl)-1-phenylpropan-1-one (4aj) Under an argon atmosphere, a mixture of KOtBu (1.0 mmol) and catalyst 1a (3.0 mol%) was taken in an oven-dried sealed tube fitted with a magnetic stir bar. The reaction vessel was then capped with a rubber septum. A long neck needle connected with a balloon filled with argon was then inserted into the sealed tube. 1.3 mmol of 3-fluorobenzyl alcohol and 1.0 mmol of 1-phenyl­ethanol dissolved in 5.0 mL of degassed xylene were added through a syringe. The sealed tube was then placed in an oil bath preheated at 120 °C for 17 h. Once the reaction was completed, the resulting mixture was concentrated, volatiles were removed under vacuum, and the residue was purified by flash column chromatography (silica gel) using diethyl ether/hexane (1:20) as the eluent to afford 4aj (178 mg, 78%) as white solid (mp 47–49 °C). 1H NMR (400 MHz, CDCl3): δ = 7.97–7.95 (m, 2 H), 7.58–7.54 (m, 1 H), 7.48–7.44 (m, 2 H), 7.28–7.22 (m, 1 H), 7.03 (d, J = 7.6 Hz, 1 H), 6.97–6.95 (m, 1 H), 6.91–6.87 (m, 1 H), 3.30 (t, J = 7.2 Hz, 2 H), 3.07 (t, J = 7.6 Hz, 2 H) ppm. 13C{1H} NMR (100 MHz, CDCl3): δ = 198.6, 162.7 (d, J C–F = 244.0 Hz), 143.6 (d, J C–F = 7.0 Hz), 136.5, 133.0, 129.8, 129.7, 128.4, 127.8, 123.9, 123.8, 115.1 (d, J C–F = 21.0 Hz), 112.8 (d, J C–F = 21.0 Hz), 39.8, 29.5 ppm. HRMS (ESI, positive ions): m/z calcd for C15H13FNaO+ [M + Na+]: 251.0843; found: 251.0845.
  • 21 3-(2,4-Dichloropylphenyl)-1-phenylpropan-1-one (4an)Under an argon atmosphere, a mixture of KOtBu (1.0 mmol) and catalyst 1a (3.0 mol%) was taken in an oven-dried sealed tube fitted with a magnetic stir bar. The reaction vessel was then capped with a rubber septum. A long neck needle connected with a balloon filled with argon was then inserted into the sealed tube. 1.3 mmol of 2,4-dichlorobenzyl alcohol and 1.0 mmol of 1-phenylethanol dissolved in 5.0 mL of degassed xylene were added through a syringe. The sealed tube was then placed in an oil bath preheated at 120 °C for 17 h. Once the reaction was completed, the resulting mixture was concentrated, volatiles were removed under vacuum, and the residue was purified by flash column chromatography (silica gel) using diethyl ether/hexane (1:20) as the eluent to afford 4an (190 mg, 68%) as yellow solid (mp 63–65 °C). 1H NMR (400 MHz, CDCl3): δ = 7.98 (d, J = 6.8 Hz, 2 H), 7.59 (t, J = 7.6 Hz, 1 H), 7.48 (t, J = 7.6 Hz, 2 H), 7.39 (m, 1 H), 7.29–7.27 (m, 1 H), 7.21–7.28 (m, 1 H), 3.32 (t, J = 6.8 Hz, 2 H), 3.17 (t, J = 7.6 Hz, 2 H) ppm. 13C{1H} NMR (100 MHz, CDCl3): δ = 198.5, 137.2, 136.4, 134.4, 133.1, 132.5, 131.5, 129.1, 128.5, 127.8, 127.0, 37.9, 27.5 ppm. HRMS (ESI, positive ions): m/z calcd for C15H12Cl2NaO+ [M + Na+]
  • 22 1-Phenyl-3-(pyren-1-yl)propan-1-one (4aq)Under an argon atmosphere, a mixture of KOtBu (1.0 mmol) and catalyst 1a (3.0 mol%) was taken in an oven-dried sealed tube fitted with a magnetic stir bar. The reaction vessel was then capped with a rubber septum. A long neck needle connected with a balloon filled with argon was then inserted into the sealed tube. 1.3 mmol of 1-pyrenemethanol and 1.0 mmol of 1-phenylethanol dissolved in 5.0 mL of degassed xylene were added through a syringe. The sealed tube was then placed in an oil bath preheated at 120 °C for 17 h. Once the reaction was completed, the resulting mixture was concentrated, volatiles were removed under vacuum, and the residue was purified by flash column chromatography (silica gel) using diethyl ether/hexane (1:20) as the eluent to afford 4aq (204 mg, 61%) as yellow solid (mp 63–65 °C). 1H NMR (400 MHz, CDCl3): δ = 8.30 (d, J = 9.6 Hz, 1 H), 8.19–8.17 (dd, J = 1.6, 7.6 Hz, 2 H), 8.13 (d, J = 8.0 Hz, 1 H), 8.04 (s, 2 H), 8.02–7.94 (m, 4 H), 7.57–7.53 (m, 1 H), 7.46–7.42 (m, 2 H), 3.82 (t, J = 8.0 Hz, 2 H), 3.53 (t, J = 8.0 Hz, 2 H) ppm. 13C{1H} NMR (100 MHz, CDCl3): δ = 199.1, 136.6, 135.3, 133.0, 131.2, 129.9, 128.5, 124.4, 127.9, 127.5, 127.3, 127.1, 126.6, 125.7, 124.9, 124.8, 124.7, 122.1, 40.5, 27.6 ppm. HRMS (ESI, positive ions): m/z calcd for C25H18NaO+ [M + Na+]: 357.1250; found: 357.1254
  • 23 3-Cyclopropyl-1-phenylpropan-1-one (4ar) Under an argon atmosphere, a mixture of KOtBu (1.0 mmol) and catalyst 1a (3.0 mol%) was taken in an oven-dried sealed tube fitted with a magnetic stir bar. The reaction vessel was then capped with a rubber septum. A long neck needle connected with a balloon filled with argon was then inserted into the sealed tube. 1.3 mmol of cyclopropane methanol and 1.0 mmol of 1-phenyl­ethanol dissolved in 5.0 mL of degassed xylene were added through a syringe. The sealed tube was then placed in an oil bath preheated at 120 °C for 17 h. Once the reaction was completed, the resulting mixture was concentrated, volatiles were removed under vacuum, and the residue was purified by flash column chromatography (silica gel) using diethyl ether/hexane (1:20) as the eluent to afford 4ar (72 mg, 41%) as colorless oil. 1H NMR (400 MHz, CDCl3): δ = 7.98 (d, J = 8.0 Hz, 2 H), 7.55 (t, J = 8.0 Hz, 1 H), 7.46 (t, J = 7.6 Hz, 2 H), 3.08 (t, J = 8.0 Hz, 2 H), 1.67–1.61 (m, 2 H), 0.79–0.76 (m, 1 H), 0.5–0.42 (m, 2 H), 0.09–0.06 (m, 2 H) ppm. 13C{1H} NMR (100 MHz, CDCl3): δ = 200.3, 136.9, 132.7, 128.4, 127.9, 138.5, 29.4, 10.5, 4.4 ppm. HRMS (ESI, positive ions): m/z calcd for C12H14ONa+ [M + Na+]: 197.0937; found: 197.0938.
  • 24 1-(3-Fluorophenyl)-3-phenylpropan-1-one (4fa) Under an argon atmosphere, a mixture of KOtBu (1.0 mmol) and catalyst 1a (3.0 mol%) was taken in an oven-dried sealed tube fitted with a magnetic stir bar. The reaction vessel was then capped with a rubber septum. A long neck needle connected with a balloon filled with argon was then inserted into the sealed tube. 1.3 mmol of benzyl alcohol and 1.0 mmol of 1-(3-fluorophenyl)­ethan-1-ol dissolved in 5.0 mL of degassed xylene were added through a syringe. The sealed tube was then placed in an oil bath preheated at 120 °C for 17 h. Once the reaction was completed, the resulting mixture was concentrated, volatiles were removed under vacuum, and the residue was purified by flash column chromatography (silica gel) using diethyl ether/hexane (1:20) as the eluent to afford 4fa (153 mg, 67%) as white solid (mp 56–58 °C). 1H NMR (400 MHz, CDCl3): δ = 7.76 (d, J = 8.0 Hz, 1 H), 7.67 (d, J = 9.0 Hz, 1 H), 7.49–7.43 (m, 1 H), 7.36–7.23 (m, 6 H), 3.32 (t, J = 8.0 Hz, 2 H), 3.10 (t, J = 8.0 Hz, 2 H) ppm. 13C{1H} NMR (100 MHz, CDCl3): δ = 197.7 (d, J = 2.0 Hz), 162.7 (d, J = 247.0 Hz), 140.8, 138.7 (d, J = 6.0 Hz), 130.7 (d, J = 7.0 Hz), 128.4, 128.2, 126.0, 123.6 (d, J = 3.0 Hz), 119.9 (d, J = 21.0 Hz), 114.6 (d, J = 22.0 Hz), 40.4, 29.8 ppm. HRMS (ESI, positive ions): m/z calcd for C15H13FNaO+ [M + Na+]: 251.0843; found: 251.0837.
  • 25 2-Benzyl-5,6-dimethoxy-2,3-dihydro-1H-inden-1-one (5ba) Under an argon atmosphere, a mixture of KOtBu (1.0 mmol) and catalyst 1a (3.0 mol%) was taken in an oven-dried sealed tube fitted with a magnetic stir bar. The reaction vessel was then capped with a rubber septum. A long neck needle connected with a balloon filled with argon was then inserted into the sealed tube. 1.3 mmol of benzyl alcohol and 1.0 mmol of 5,6-dimethoxy-2,3-dihydro-1H-inden-1-one dissolved in 5.0 mL of degassed xylene was added through a syringe. The sealed tube was then placed in an oil bath preheated at 120 °C for 17 h. Once the reaction was completed, the resulting mixture was concentrated, volatiles were removed under vacuum, and the residue was purified by flash column chromatography (silica gel) using diethyl ether/hexane (1:20) as the eluent to afford 4ba (147 mg, 52%) as yellow solid (mp 65–67 °C).1H NMR (400 MHz, CDCl3): δ = 7.34–7.22 (m, 6 H), 6.83 (s, 1 H), 3.95 (d, J = 8.0 Hz, 6 H), 3.43 (m, 1 H), 3.12–2.95 (m, 2 H), 2.82–2.77 (m, 1 H), 2.69–2.63 (m, 1 H) ppm. 13C{1H} NMR (100 MHz, CDCl3): δ = 206.4, 155.4, 149.3, 148.8, 139.6, 129.0, 128.7, 128.3, 126.1, 107.4, 107.2, 104.2, 56.0, 55.9, 48.9, 37.1, 31.7 ppm. HRMS (ESI, positive ions): m/z calcd for C18H19O3 + [M + H+]: 283.1329; found: 283.1335.