DBU- and DABCO-Promoted Selective Access to 2,5-Diarylnitrobenzoates and Cyclohexenones via One-Pot Reactions

Abstract

Remarkable organobase-controlled selective synthesis of a wide breadth of valuable 2,5-diaryl-4-nitrobenzoates and 1-hydroxy-4-oxocyclohexencarboxylates bearing a tetrasubstituted stereogenic carbon is reported. This one-pot cyclization reaction operates between a bunch of 3-nitroallylarenes and β,γ-unsaturated α-ketocarbonyls by carefully choosing DBU or DABCO as an organobase under aerobic conditions. Notably, as a nucleophilic base, DABCO favors the Nef reaction over the dehydration–aerial oxidation process, aiming for unexpected cyclohexanone architectures. Moreover, this operationally simple technique holds a few positive qualities: good yields with diastereoselectivities (dr ≤ 91:9), broad substrate scope, no added oxidant, excellent functional group compatibility, 100% carbon-economical, etc. Furthermore, the obtained 4-nitrobenzoate framework has been utilized for the synthesis of a range of valuable compounds such as 2-phenylcarbazole-3-carboxylate, 3-bromoaniline derivative, and 2,5-diphenylbenzoic acid, among others.

Key words

one-pot - organobase-controlled reactions - 3-nitroallylarenes - 2,5-diarylnitrobenzoates - cyclohexenones

• Notes and References

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• 20 Typical Procedure for the Synthesis of Ethyl 5′-Nitro-[1,1′:4′,1′′-terphenyl]-2′-carboxylate (3aa)To a mixture of compounds 1a (32.63 mg, 0.2 mmol) and 2a (51.1 mg, 0.25 mmol) in dry toluene (1.0 mL) was added DBU (0.02 mmol, 10 mol%) at room temperature for 30 min, followed by the addition of DBU (0.28 mmol, 1.4 equiv) further. Afterwards, the reaction mixture was heated at 80 °C under air for 12 h. Then, the reaction mixture was extracted with EtOAc (3 × 10 mL) before being quenched with a few drops of aqueous HCl. The combined organic phases were washed with brine and dried over Na₂SO₄. The solvent was evaporated under reduced pressure to give the crude residue. Then it was purified through column chromatography over silica gel using ethyl acetate/hexane (1:19) as a mixture of solvent to provide a pure colorless solid 3aa (45.8 mg; 66% yield). The product was characterized by its spectroscopic data (¹H and ¹³C NMR, HRMS); mp 118–120 °C. ¹H NMR (500 MHz, CDCl₃): δ = 7.88 (s, 1 H), 7.85 (s, 1 H), 7.48–7.43 (6 H), 7.41–7.34 (m, 4 H), 4.14 (q, J = 7.1 Hz, 2 H), 1.02 (t, J = 7.1 Hz, 3 H) ppm. ¹³C NMR (125 MHz, CDCl₃): δ = 167.1, 150.1, 142.5, 138.8, 136.2, 135.0, 134.9, 133.3, 129.0, 128.8, 128.6, 128.4, 128.3, 128.0, 125.9, 61.8, 13.7 ppm. HRMS (ESI): m/z calcd for C₂₁H₁₇NNaO₄ [M + Na]⁺: 370.1055; found: 370.1057.The above procedure was followed for the access to ethyl 4′′-methoxy-5′-nitro-[1,1′:4′,1′′-terphenyl]-2′-carboxylate (3ac): light yellowish solid; mp 126–128 °C; yield 57% (43.0 mg). ¹H NMR (500 MHz, CDCl₃): δ = 7.86 (s, 1 H), 7.79 (s, 1 H), 7.43 (t, J = 7.1 Hz, 3 H), 7.36 (dd, J = 7.7, 1.8 Hz, 2 H), 7.31 (d, J = 8.6 Hz, 2 H), 6.98 (d, J = 8.7 Hz, 2 H), 4.13 (q, J = 7.1 Hz, 2 H), 3.86 (s, 3 H), 1.01 (t, J = 7.1 Hz, 3 H) ppm. ¹³C NMR (100 MHz, CDCl₃): δ = 167.2, 160.1, 150.2, 142.0, 138.9, 134.7, 134.5, 133.3, 129.3, 128.5, 128.3, 128.3, 128.2, 125.9, 114.4, 61.8, 55.4, 13.7 ppm. HRMS (ESI): m/z calcd for C₂₂H₁₉NNaO₅ [M + Na]⁺: 400.1161; found: 400.1159.
• 21 Representative Procedure for the Synthesis of 4aaTo a stirred solution of 1a (32.63 mg, 0.2 mmol) and 2a (51.1 mg, 0.25 mmol) in dry toluene (1.0 mL) was added DABCO (0.02 mmol, 10 mol%) at room temperature for 30 min under air. Afterwards, DABCO (0.28 mmol, 1.4 equiv) was added to the above solution at 60 °C in an open atmosphere for 15 h. Then, the reaction mixture was quenched with a very diluted HCl, followed by the extraction using EtOAc (3 × 10 mL) and dried over Na₂SO₄. After evaporation of the solvent, the crude residue was purified through column chromatography over silica gel using ethyl acetate/hexane (1:15) as a mixture of solvent to provide a pure colorless solid 4aa (45.1 mg, 67% yield); mp 115–117 °C; dr = 91:9; yield 67%. ¹H NMR (500 MHz, CDCl₃): δ = 7.53 (dd, J = 5.3, 3.3 Hz, 2 H), 7.38–7.35 (m, 5 H), 7.31–7.29 (m, 1 H), 7.22 (d, J = 7.1 Hz, 2 H), 6.40 (s, 1 H), 4.33 (dd, J = 13.5, 4.3 Hz, 1 H), 4.08–4.02 (m, 1 H), 3.95–3.90 (m, 2 H), 2.89 (t, J = 13.4 Hz, 1 H), 2.32 (dd, J = 13.3, 4.4 Hz, 1 H), 0.80 (t, J = 7.1 Hz, 3 H) ppm. ¹³C NMR (125 MHz, CDCl₃): δ = 198.2, 175.1, 154.4, 138.2, 137.5, 129.6, 129.4, 129.0, 128.79, 128.78, 127.4, 126.7, 74.8, 63.0, 48.3, 43.7, 13.5 ppm. HRMS (ESI): m/z calcd for C₂₁H₂₀NaO₄ [M + Na]⁺: 359.1259; found: 359.1266.
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