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.

Key words

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

References

• For example:
• 1a Nicolaou KC. Yang Z. Liu JJ. Ueno H. Nantermet PG. Guy RK. Clairborne CF. Renaud J. Couladouros EA. Paulvannan K. Sorensen EJ. J. Am. Chem. Soc.  1995,  117:  634 
• 1b Nazare M. Waldmann H. Angew. Chem. Int. Ed.  2000,  39:  1125 
• 1c Shiina I. Nishimura T. Ohkawa N. Sakoh H. Nishimura K. Saitoh K. Mukaiyama T. Chem. Lett.  1997,  419 
• 2a SmI₂/Mg: Nomura R. Matsuno T. Endo T. J. Am. Chem. Soc.  1996,  118:  11666 
• 2b (EBTHI)TiCl₂/Zn: Gansäuer A. Synlett  1997,  363 
• 2c CpV(CO)₄/Zn/Me₃SiCl: Hirao T. Hasegawa T. Muguruma Y. Ikeda I. J. Org. Chem.  1996,  61:  366 
• 2d CrCl₂/Mn: Svato A. Boland W. Synlett  1998,  548 
• 2e Cp₂Ti(Ph)Cl/Zn: Yamamoto Y. Hattori R. Itoh K. Chem. Commun.  1999,  825 
• 2f Ce(i-PrO)₃/Et₂Zn: Groth U. Jeske M. Angew. Chem. Int. Ed.  2000,  39:  574 
• 2g Ce(t-BuO)₃/Mg, Zn, Mn: Groth U. Jeske M. Synlett  2001,  129 
• 3 Takai K. Morita R. Toratsu C. Angew. Chem. Int. Ed.  2001,  40:  1116 
• For reviews on C-C bond formation involving organochromium reagents see:
• 4a Fürstner A. Chem. Rev.  1999,  99:  991 
• 4b Wessjohann LA. Scheid G. Synthesis  1999,  1 
• 5a Fürstner A. Shi N. J. Am. Chem. Soc.  1996,  118:  2533 
• 5b Fürstner A. Shi N. J. Am. Chem. Soc.  1996,  118:  12349 
• 5c Fürstner A. Pure Appl. Chem.  1998,  70:  1071 
• 5d Fürstner A. Chem.-Eur. J.  1998,  4:  567 
• 5e

  Ref. [2d]

• For mechanistic studies see ref.³ and:
• 6a Buse CT. Heathcock CH. Tetrahedron Lett.  1978,  19:  1685 
• 6b Hiyama T. Kimura K. Nozaki H. Tetrahedron Lett.  1981,  22:  1037 
• 6c Jubert C. Nowotny S. Kornemann D. Antes I. Tucker CE. Knochel P. J. Org. Chem.  1992,  57:  6384 
• 6d Nowotny S. Tucker CE. Jubert C. Knochel P. J. Org. Chem.  1995,  60:  2762 
• 8 Boeckman RK. Hudack RA. J. Org. Chem.  1998,  63:  3524 
• 9 Takai K. Nitta K. Utimoto K. Tetrahedron Lett.  1988,  29:  5266 
• 11 Bandini M. Cozzi PG. Melchiorre P. Umani-Ronchi A. Angew. Chem. Int. Ed.  1999,  38:  3357 
• 12 Martínez LE. Leighton JL. Carsten DH. Jacobsen EN. J. Am. Chem. Soc.  1995,  117:  5897 

7

The substituted acroleins can be easily prepared by Mannich reaction starting with the corresponding aldehyde.

10

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.