Tributyltin Hydride as a Selective Reducing Agent for Aryl Enones

Abstract

Aryl enones undergo selective 1,4-reduction to the corresponding saturated ketones with two equivalents of tributyltin hydride in the presence of a wide range of other potentially reducible functional groups, including alkyl enone. Additionally during this investigation reductive cyclization of bisenones to give five- and six-membered carbocycles via an α,β-coupling process was observed.

Key words

chemoselectivity - selective 1,4-reduction - cyclization - stannane - enone

References and Notes

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12

All commercially procured chemicals were used as received. Dichloromethane, triethylamine, diethyl ether, benzene (C₆D₆) were distilled from calcium hydride. THF was distilled from lithium aluminum hydride. Reagent grade solvents were used for solvent extraction and organic extracts were dried over anhyd Na₂SO₄. Silica gel 60 (230-400 mesh ASTM) was used for flash chromatography with anhyd hexane-EtOAc. ^¹H NMR spectra were recorded on 500 MHz Varian, 500 MHz Bruker or 300 MHz Varian spectrometers. The proton chemical shifts (δ) are reported as parts per million relative to 7.26 ppm for CDCl₃, 7.14 ppm for C₆D₆, 5.32 for CD₂Cl₂.
Typical Procedure for the Selective Reduction of Aryl Enones: To a stirred solution of the aryl vinyl ketone (1.0 mmol) in benzene (3.3 mL, 0.3 M) in a resealable tube at r.t. under argon was added tributyltin hydride (0.58 g, 2.0 mmol). The reaction mixture was subsequently heated to 80 ˚C for 3 h. Upon completion the reaction mixture was concentrated en vacuo and purified by flash column chromatography to give the reduced product as a clear oil.

13

NMR data: 1b,^¹4 3b,^² 4b,^¹5 5b,^¹6 6b,^¹7 7b,^¹8 8b,^¹9 9b,^²0 11b,^²¹ 15b,^²² 17b and 18b,^²³ 17c.^²4 Compound 2b: ^¹H NMR (300 MHz, CD₂Cl₂): δ = 7.95 (m, 2 H), 7.55 (m, 1 H), 7.47 (m, 2 H), 6.78 (dt, J = 15.95, 6.9 Hz, 1 H), 6.09 (dd, J = 16.0, 1.4 Hz, 1 H), 2.96 (t, J = 7.2 Hz, 2 H), 2.20 (s, 3 H), 2.09 (tdd, J = 7.0, 7.0, 1.5 Hz, 2 H), 1.71 (tt, J = 7.15, 7.15 Hz, 2 H), 1.29-1.53 (m, 10 H). ^¹³C NMR (75 MHz, CD₂Cl₂): δ = 200.5, 198.6, 148.8, 137.7, 133.2, 131.7, 129.0, 128.4, 38.9, 32.9, 29.9, 29.7, 29.6, 28.6, 27.0, 24.7. Compound 10b: ^¹H NMR (300 MHz, CD₂Cl₂): δ = 9.48 (d, J = 8.0 Hz, 1 H), 7.95 (m, 2 H), 7.55 (m, 1 H), 7.47 (m, 2 H), 6.85 (dt, J = 15.7, 6.6 Hz, 1 H), 6.09 (dd, J = 15.2, 7.7 Hz, 1 H), 2.96 (t, J = 7.2 Hz, 2 H), 2.32 (dt, J = 7.4, 7.2 Hz, 2 H), 1.71 (tt, J = 7.2, 6.9 Hz, 2 H), 1.50 (tt, J = 6.9, 6.9 Hz, 2 H) 1.35 (m, 8 H). ^¹³C NMR (75 MHz, CD₂Cl₂): δ = 200.2, 194.1, 159.17, 137.4, 133.1, 132.9, 128.7, 1281, 38.7, 32.8, 29.6, 29.5, 29.4, 29.3, 28.0, 24.4. Compound 12b: ^¹H NMR (300 MHz, CD₂Cl₂): δ = 7.93 (m, 2 H), 7.55 (m, 1 H), 7.46 (m, 2 H), 6.94 (dt, J = 15.7, 6.9 Hz, 1 H), 5.80 (dd, J = 15.4, 1.4 Hz, 1 H), 3.67 (s, 3 H), 2.94 (t, J = 7.4 Hz, 2 H), 2.19 (tdd, J = 7.9, 6.9, 1.1 Hz, 2 H), 1.71 (tt, J = 7.2, 6.8 Hz, 2 H), 1.24-1.52 (m, 10 H). ^¹³C NMR (75 MHz, CD₂Cl₂): δ = 200.3, 167.1, 149.8, 137.9, 132.9, 128.7, 128.1, 120.9, 51.4, 38.7, 32.3, 29.6, 29.5, 29.4, 29.2, 28.2, 24.4.