1,5-Diketone Synthesis Promoted by Barium Hydride or Barium Alkoxides

Abstract

A tandem cross-coupling reaction of ketones with aldehydes has been achieved using barium hydride or isopropoxide as a promoter, in which barium enolates are generated in situ and then three successive reactions (aldol reaction-β-elimination-Michael addition) follow; this one-pot process is effective for obtaining ­symmetrical 1,5-diketones in good yields.

Key words

aldehydes - barium - coupling reaction - 1,5-diketones - ketones

References and Notes

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7

We examined catalytic activity of NaOi-Pr, KOi-Pr, and Mg(Oi-Pr)₂ in the present reaction, however, these metal isopropoxides were found to be less effective, [M(Oi-Pr)_n, equiv, time, yield]: NaOi-Pr, 0.4 equiv, 4 h, 40%; KOi-Pr, 0.4 equiv, 4 h, 35%; Mg(Oi-Pr)₂, 0.2 equiv, 18 h, <1%.

8

Typical Procedure for Tandem Cross-Coupling Reaction of Ketones with Aldehydes Catalyzed by Barium Isopropoxide: Synthesis of 1,3,5-Triphenylpentane-1,5-dione (Entry 2 in Table 3).
An oven-dried, 30 mL two-necked round-bottomed flask equipped with a Teflon^®-coated magnetic stirring bar was flushed with argon. Then, Ba(Oi-Pr)₂ (26 mg, 0.10 mmol) was put into the apparatus and covered with dry DMF (5 mL) and i-PrOH (1.5 mL, 20 mmol), and the mixture was stirred for 10 min at r.t. To the resulting solution were added acetophenone (0.35 mL, 3.0 mmol) and benzaldehyde (0.10 mL, 1.0 mmol). After being stirred for 7 h at r.t., the mixture was treated with a sat. aq NH₄Cl solution (10 mL) at this temperature and the aqueous layer was extracted with Et₂O (20 mL). The combined organic extracts were dried over anhyd Na₂SO₄ and concentrated in vacuo after filtration. The residual crude product was purified by column chromato­g­-raphy on silica gel to give the 1,5-diketone (0.25 g, 76% yield) as colorless crystals.
Spectral Data of the Product.
TLC: R _f = 0.52 (hexane-EtOAc, 3:1). IR (KBr): 3062, 3025, 2960, 2888, 1686, 1668, 1597, 1580, 1496, 1449, 1422, 1408, 1352, 1268, 1207 cm^-1. ¹H NMR (400 MHz, CDCl₃): δ = 3.36 (dd, 2 H, J = 16.4 Hz, 7.0 H, CH₂), 3.50 (dd, 2 H, J = 16.7 Hz, 7.0 H, CH₂), 4.04-4.11 (m, 1 H, CH), 7.15-7.21 (m, 1 H, arom.), 7.24-7.29 (m, 4 H, arom.), 7.43-7.46 (m, 4 H, arom.), 7.53-7.57 (m, 2 H, arom.), 7.94-7.96 (m, 4 H, arom.). ¹³C NMR (100 MHz, CDCl₃): δ = 36.5, 44.4, 126.2, 127.1, 127.3, 127.7, 128.1, 132.6, 136.4, 143.5, 198.0. The above-mentioned spectral data (IR, ¹H NMR, and ¹³C NMR) of the product indicated good agreement with reported data. [9]