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

Gargi Chakraborty; Subhasree Pal; Subhajit Chakraborty; Nanda D. Paul

doi:10.1055/a-1934-1056

Synlett, Table of Contents

Synlett 2023; 34(06): 635-644
DOI: 10.1055/a-1934-1056

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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

,

Subhajit Chakraborty

,

Nanda D. Paul∗

Abstract

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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.

Key words

nickel catalysis - borrowing hydrogen approach - alcohols - selective alkylation - α-alkylated ketones

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References

References and Notes

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17 3-(3-Methoxyphenyl)-1-phenylpropan-1-one (4ae) Under an argon atmosphere, a mixture of KO^tBu (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 KO^tBu (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 KO^tBu (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 KO^tBu (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 KO^tBu (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 KO^tBu (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 KO^tBu (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 KO^tBu (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 KO^tBu (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.

Supplementary Material

Supporting Information