Indium-Catalyzed Henry-Type Reaction of Aldehydes with Bromonitro­alkanes

 

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Abstract

An economical method to perform the addition of bromonitroalkanes to aldehydes using zinc in the presence of a catalytic amount of indium is established. This procedure affords the corresponding nitroalkanols in good yields and can be easily scaled up to preparative amounts. This indium-catalyzed Henry reaction performs better than the classic base-catalyzed reaction in terms of yields and substrate scope and avoids the use of stoichiometric amounts of the expensive indium powder.

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Sigma Aldrich on-line catalogue.

Physical Data of 2-Nitro-1-phenylethanol (3a) The aqueous workup gave 3a as a yellow oil. ^¹H NMR (300 MHz, CDCl₃): δ = 2.87 (br s, 1 H, OH), 4.53-4.61 (m, 2 H, H-2), 5.29-5.50 (m, 1 H, H-1), 7.41-7.43 (m, 5 H, Ph) ppm.

General Procedure for the Henry-Type Addition of Bromoalkanes 2a-g to Aldehydes 1a-g
The appropriate bromonitroalkane 2a-g (1.5 mmol) was added to a suspension of activated zinc powder (10 mmol) and indium powder (0.12 mmol) in THF (2 mL), and the mixture was sonicated for 20 min. The corresponding aldehyde 1a-g (1 mmol) was then added, and sonication was continued for a further 4 h. The reaction mixture was quenched with sat. aq NaHCO₃ (15 mL) and extracted with Et₂O (3 × 30 mL). The combined organic layers were dried over MgSO₄, filtered, and the solvent was evaporated in vacuo to obtain the corresponding 2-nitroalkanols.

As examples of the obtained nitroalkanols, we present the physical data of compounds 3d,f-h.
1-(4-Methoxyphenyl)-2-methyl-2-nitropropan-1-ol (3d) The aqueous workup afforded 3d as a yellow oil. ^¹H NMR (300 MHz, CDCl₃): δ = 1.41 and 1.55 (2 s, 2 × 3 H, 2 CH₃), 3.79 (s, 3 H, OCH₃), 5.23 (br s, 1 H, OH), 5.28 (s, 1 H, H-1), 6.88 (d, 2 H, H-3,5 of Ar), 7.28 (d, 2 H, H-2,6 of Ar) ppm.
2,5-Dimethyl-2-nitrohexan-3-ol (3f) After the aqueous workup 3f was obtained as a yellow oil. ^¹H NMR (300 MHz, CDCl₃): δ = 0.89-1.01 (m, 2 × 3 H, 2 CH₃), 1.29-1.34 (m, 2 H, CH₂), 1.42 and 1.53 (2 s, 2 × 3 H, 2 CH₃), 1.79-1.83 (m, 1 H), 3.66-3.72 (m, 1 H) ppm.
1-Cyclohexyl-2-nitropropan-1-ol (3g) The aqueous workup gave 3g as a 40:60 mixture of syn/anti isomers. ^¹H NMR (400 MHz, CDCl₃): 1.18-1.25 (m, 6 × 2 H, 6 CH₂, syn + anti), 1.52-1.56 (m, 2 × 3 H, 2 CH₃, syn + anti), 1.66-1.78 (m, 4 × 2 H, 2 × 1 H, 4 CH₂, 2 CH, syn + anti), 3.67 (dd, J = 4.4, 7.3 Hz, 1 H, H-2, syn), 3.94 (dd, J = 3.3, 8.2 Hz, 1 H, H-2, anti), 4.60-4.76 (m, 2 H, H-1, syn + anti) ppm.

Physical Data of 1,2:3,4-Di- O -isopropylidene-6-( R )-(2,2-dimethyl-5-nitro-1,3-dioxan-5-yl)-β- d -galacto-heptopyranose (3h) After aqueous workup and column chromatography (EtOAc-hexane = 1:2) 3h was obtained as a colorless oil (70%). ^¹H NMR (300 MHz, CDCl₃): δ = 1.33, 1.35, 1.36, 1.45, 1.46 and 1.59 (6 s, 6 × 3H, CH₃), 3.16 (d, 1 H, J = 7.1 Hz, OH), 3.92 (dd, 1 H, J = 8.9, 1.9 Hz), 4.03-4.37 (m, 5 H), 4.52-4.71 (m, 3 H), 5.50 (d, 1 H, J = 5.1 Hz, H-1) ppm. ^¹³C NMR (75 MHz, CDCl₃): δ = 19.5, 24.3, 25.6, 25.8 and 27.3 (6 × CH₃), 61.1 and 62.7 (2 × CH₂), 66.6, 70.0, 70.5, 70.6 and 70.8 (5 × CH), 89.9 (CH), 96.1, 98.9, 109.1 and 109.6 (4 × C) ppm.