Chromium(II)-Catalyzed Diastereoselective Pinacol Type Cross Coupling between α,β-Unsaturated Carbonyl Compounds and Aliphatic Aldehydes

Abstract

Using only 10 mol% of CrCl₂ as catalyst, acroleins and α,β-unsaturated ketones were coupled with aliphatic aldehydes to obtain substituted 1,2-diols using manganese powder as reducing agent and TMS-Cl as scavenger. Diastereoselectivities depend on the substituents especially on R¹ of the unsaturated carbonyl compound. Formation of the syn-diols is preferred with sterically demanding R¹, the anti-diols are obtained with smaller substituents.

chromium - catalysis - cross-coupling - pinacols - C-C coupling

References

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Typical Procedure: Reactions were carried out under an argon atmosphere using Schlenk techniques. The chromium catalysts and the manganese powder were stored in a glove box under nitrogen atmosphere. In a Schlenk tube 8 mL of DMF and 0.51 mL of TMS-Cl (4 mmol) were added to 220 mg (4 mmol) of Mn powder and 25 mg (0.2 mmol) of CrCl₂. The resulting suspension was stirred at room temperature for 15 min, 2 mmol of the less reactive coupling component [the vinylketones for reactions as shown in Table [1] except for 2-methylene-1-tetralone (Table [1] , entry 4); the aliphatic aldehydes in the cases of coupling reactions with acroleins (Table [2] ) or 2-methylidene-1-tetralone (Table [1] , entry 4)] was added in one portion. 2 mL of a 0.5 M solution of the second coupling component (1 mmol) was added slowly over a period of 40 hours by use of a syringe pump. 20 mL of ether and 20 mL of water were added. After separation of the organic layer, the aqueous layer was extracted with diethyl ether (3 × 20 mL), the combined organic layers were dried over MgSO₄ and concentrated in vacuo. To the residue 10 mL of THF and 1.4 g (4 mmol, 2 equiv) of TBAF were added and stirred for 45 min at room temperature. After adding 10 mL of water and 20 mL of ether the aqueous layer was extracted with ether (4 × 20 mL), the combined organic layers were dried over MgSO₄ and concentrated in vacuo. The residue was purified by flash chromatography on 25 g of silica gel (petroleum ether-ethyl acetate, 9:1). The relative configuration was determined by either NOE spectroscopy of the corresponding acetonides or by Corey-Winter-reaction followed by NMR examination of the resulting olefins.
Table 1, entry 1: ¹H NMR (CDCl₃, 400 MHz) δ 7.14 (m, 5 H), 5.11 (s, 1 H), 5.04 (s, 1 H), 3.34 (m, 1 H), 2.87 (m, 1 H), 2.55 (m, 1 H), 2.28 (m, 2 H), 1.84-1.11 (m, 12 H); ¹³C NMR (CDCl₃, 100 MHz) δ 155.3, 142.2, 128.4, 128.3, 125.7, 113.8, 80.1, 75.7, 34.8, 34.5, 32.5, 31.5, 30.9, 23.0; Anal. calcd for C₁₇H₂₄O₂: C, 78.42; H, 9.29; O, 12.29. Found: C, 78.22; H, 9.15.
Table 2, entry 1: ¹H NMR (CDCl₃, 400 MHz) δ 5.32 (s, 1 H), 5.12 (s, 1 H), 4.48 (s, 1 H), 3.20 (s, 1 H), 2.55 (br s, 1 H), 2.06 (bs, 1 H), 1.12 (s, 9 H), 1.00 (s, 9 H); ¹³C NMR (CDCl₃, 100 MHz) δ 160.8, 109.0, 79.2, 67.0, 35.8, 35.7, 29.4, 26.6. Anal. calcd for C₁₂H₂₄O₂: C, 71.95; H, 12.08; O, 15.97. Found: C, 72.03; H, 11.98.
Table 2, entry 2, syn -diol: ¹H NMR (CDCl₃, 400 MHz) δ 5.14 (s, 1 H), 5.11 (s, 1 H), 3.98 (d, J = 6.6 Hz, 1 H), 3.56 (m, 1 H), 2.66 (bs, 2 H), 1.55 (m, 1 H), 1.37 (m, 1 H), 1.10 (s, 9 H), 1.00 (t, J = 7.4 Hz, 3 H); ¹³C NMR (CDCl₃, 100 MHz) δ 158.6, 109.6, 75.4, 72.3, 35.7, 29.0, 26.0, 10.6. Anal. calcd for C₁₀H₂₀O₂ (mixture of syn and anti, not separable by column chromatography): C, 69.72; H, 11.70; O, 18.58. Found: C, 69.60, H, 11.76. anti -diol: ¹H NMR (CDCl₃, 400 MHz) δ 5.27 (s, 1 H), 5.21 (s, 1 H), 4.14 (d, J = 6.2 Hz, 1 H), 3.61 (m, 1 H), 2.66 (br s, 2 H), 1.81 (m, 1 H), 1.22 (m, 1 H), 1.11 (s, 9 H), 1.02 (t, J = 7.4 Hz, 3 H); ¹³C NMR (CDCl₃, 100 MHz) δ 159.1, 109.7, 75.1, 72.6, 35.7, 29.1, 24.3, 10.3.

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