Malononitrile as Acylanion Equivalent

Abstract

The oxidation of derivatives of malononitrile with peracid in methanol proceeds with loss of the cyano groups to yield ­methyl esters in high yield. The method was applied to a variety of malononitrile derivatives, some of which were prepared by Pd- or Ir-catalyzed asymmetric allylic substitution.

oxidations - cyanohydrins - allylations - iridium - asymmetric catalyses - Michael additions

References and Notes

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<A NAME="RG23608ST-9">9</A>

GC: Chiraldex γ-Trifluoracetyl (G-TA), 30 m × 0.25 mm × 0.125 µm; injector temperature: 200 ˚C, detector temperature: 250 ˚C; 2a (column temperature: 140 ˚C, isothermal): t _R (-)-(S)-2a = 27 min, t _R (+)-(R)-2a = 28 min; 2b (column temperature: 100 ˚C, isothermal), t _R (+)-(S)-2b = 25 min, t _R (-)-(R)-2b = 26 min.
HPLC: Daicel Chiralcel OD-H, 250 × 4.6 mm, 5 µm, with precolumn 10 × 4 mm, 5 µm; 2c [n-hexane-i-PrOH (99:1), flow = 0.5 mL min^-¹, 20 ˚C, 210 nm], t _R (-)-(S)-2c = 18 min, t _R (+)-(R)-2c = 22 min; 2d (n-hexane-i-PrOH (95:5), 20 ˚C, 220 nm, t _R (-)-(S)-2d = 20 min, t _R (+)-(R)-2d = 28 min.

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<A NAME="RG23608ST-11">11</A>

General Procedure for the Oxidative Degradation Magnesium monoperoxyphthalate hexahydrate (0.75 equiv, 80% technical grade from Sigma Aldrich, used as received) was added in small portions to a suspension of the substrate and M₂CO₃ (1.1 equiv/1.5 equiv) in MeOH (c 0.15 M) at the given temperature. The mixture was stirred for the given time and was then filtered through a short column of SiO₂, which was washed with PE-EtOAc. The solvent was evaporated in vacuo, and the crude product was purified by bulb-to-bulb distillation or recrystallization.

<A NAME="RG23608ST-12A">12a</A>

The ester 4b was treated with PhMgBr to give 1,1-di-phenyl-2-propylbut-3-en-1-ol (4b′). Similarly, 10 was reacted with PhMgBr to produce cyclohex-2-en-1-yl-(diphenyl)methanol (10′), a known compound, see ref. 12b. GC: Chiraldex γ-Trifluoracetyl (G-TA), 30 m × 0.25 mm × 0.125 µm; injector temperature: 200 ˚C, detector temperature: 250 ˚C; 4a (column temperature: 100 ˚C, isothermal), t _R (+)-(S)-4a = 24 min, t _R (-)-(R)-4a = 25 min; 9 (column temperature: 140 ˚C, isothermal), t _R (-)-9 = 12 min, t _R (+)-9 = 13 min.
HPLC: Daicel Chiralcel OD-H, 250 × 4.6 mm, 5 µm, with precolumn 10 × 4 mm, 5 µm; 4b′ [n-hexane-i-PrOH (99:1), flow = 0.5 mL min^-¹, 20 ˚C, 210 nm], t _R (-)-(S)-4b′ = 15 min, t _R (+)-(R)-4b′ = 16 min); 4c [n-hexane-i-PrOH (99.7:0.3), flow = 0.5 mL min^-¹, 20 ˚C, 210 nm], t _R (+)-(S)-4c = 12 min, t _R (-)-(R)-4c = 14 min; Daicel Chiralcel AD-H, 250 × 4.6 mm, 5 µm, with precolumn 10 × 4 mm, 5 µm; 4d [n-hexane-i-PrOH (99.4:0.6), flow = 0.5 mL min^-¹, 20 ˚C, 210 nm), t _R (-)-(R)-4d = 22 min, t _R (+)-(S)-4d = 29 min; 10′ [n-hexane-i-PrOH (98:2), flow = 0.5 mL min^-¹, 20 ˚C, 210 nm), t _R (+)-10′ = 20 min, t _R (-)-10′ = 22 min.

<A NAME="RG23608ST-12B">12b</A> Eisch JJ. Merkley JH. Galle JE. J. Org. Chem.  1979,  44:  587