Asymmetric Henry Reactions of Aldehydes Using Chiral Biaryl-Based Bis(thiourea) Organocatalysts

Abstract

Biaryl-based bis(thiourea) was found to be an efficient organocatalyst for the asymmetric Henry reaction. High enantioselectivity of up to 93% ee was obtained for the reaction of nitromethane with aryl aldehydes when the combination of N,O-bis(trimethylsilyl)trifluoroacetoamide (BSTFA) with a catalytic amount of potassium acetate was used as the base.

Key words

asymmetric catalysis - bis(thiourea) - Henry reaction - nucleophilic addition - enantioselectivity

• References and Notes

• 1 Present address: Institute for Materials Chemistry and Engineering (IMCE), Kyushu University, Hakozaki, Higashi-ku, Fukuoka 812-8581, Japan.

For reviews on the catalytic asymmetric Henry reaction, see:
• 2a Boura J, Gogoi N, Saikia PP, Barua CN. Tetrahedron: Asymmetry 2006; 17: 3315
• 2b Palomo C, Oiarbide M, Laso A. Eur. J. Org. Chem. 2007; 2561
• 3 Sasai H, Suzuki T, Arai S, Arai T, Shibasaki M. J. Am. Chem. Soc. 1992; 114: 4418

Some selected examples:
• 4a Trost BM, Yeh VS. C. Angew. Chem. Int. Ed. 2002; 41: 861
• 4b Evans DA, Seidel D, Rueping M, Lam HW, Shaw JT, Downey CW. J. Am. Chem. Soc. 2003; 125: 12692
• 4c Palomo C, Oiarbide M, Laso A. Angew. Chem. Int. Ed. 2005; 44: 3881
• 4d Xiong Y, Wang X, Huang X, Wen Y, Feng X. Chem. Eur. J. 2007; 13: 829
• 4e Ma K, You J. Chem. Eur. J. 2007; 13: 1863
• 4f Bandini M, Piccinelli F, Tommasi S, Umani-Ronchi A, Ventrici C. Chem. Commun. 2007; 616
• 4g Arai T, Takashita R, Endo Y, Watanabe M, Yanagisawa A. J. Org. Chem. 2008; 73: 4903
• 4h Blay G, Domingo LR, Hernández-Olmos V, Pedro JR. Chem. Eur. J. 2008; 14: 4725
• 4i Nitabaru T, Kumagai N, Shibasaki M. Tetrahedron Lett. 2008; 49: 272
• 4j Kowalczyk R, Kwiatkowski K, Skarzewski J, Jurczak J. J. Org. Chem. 2009; 74: 753
• 4k Arai T, Suzuki K. Synlett 2009; 3167
• 4l Lee J.-M, Kim J, Shin Y, Yeom C.-E, Lee JE, Hyeon T, Kim BM. Tetrahedron: Asymmetry 2010; 21: 285
• 4m Xin D, Ma Y, He F. Tetrahedron: Asymmetry 2010; 21: 333
• 4n Noole A, Lippur K, Metsala A, Loop M, Kanger T. J. Org. Chem. 2010; 75: 1313
• 4o Panov I, Drabina P, Padělková Z, Šimůnek P, Sedlák M. J. Org. Chem. 2011; 76: 4787
• 4p Didier D, Magnier-Bouvier C, Schulz E. Adv. Synth. Catal. 2011; 353: 1087
• 4q Kodama K, Sugawara K, Hirose T. Chem. Eur. J. 2011; 17: 13584
• 4r Zhou Y, Dong J, Zhang F, Gong Y. J. Org. Chem. 2011; 76: 588
• 4s Cheng H.-G, Lu L.-Q, Wang T, Chen J.-R, Xiao W.-J. Chem. Commun. 2012; 48: 5596
• 4t White DJ, Shaw S. Org. Lett. 2012; 14: 6270
• 4u Angulo B, García IJ, Herrerías IC, Mayoral AJ, Miñana CA. J. Org. Chem. 2012; 77: 5525
• 5 Chinchilla R, Nájera C, Sánchez-Agulló P. Tetrahedron: Asymmetry 1994; 5: 1393
• 6 Ooi T, Doda K, Maruoka K. J. Am. Chem. Soc. 2003; 125: 2054
• 7a Sohtome Y, Hashimoto Y, Nawasaga K. Adv. Synth. Catal. 2005; 347: 1643
• 7b Sohtome Y, Takemura N, Takada K, Takagi R, Iguchi T, Nagasawa K. Chem. Asian J. 2007; 2: 1150
• 8 Marcelli T, van der Haas RN. S, van Maarseveen JH, Hiemstra H. Angew. Chem. Int. Ed. 2006; 45: 929
• 9 Liu X, Jiang J, Shi M. Tetrahedron: Asymmetry 2007; 18: 2773
• 10 Ube H, Terada M. Bioorg. Med. Chem. Lett. 2009; 19: 3895
• 11 Uraguchi D, Sakaki S, Ooi T. J. Am. Chem. Soc. 2007; 129: 12392
• 12 Tang Z, Iida H, Hu H.-Y, Yashima E. ACS Macro Lett. 2012; 1: 261
• 13 Lang K, Park J, Hong S. Angew. Chem. Int. Ed. 2012; 51: 1620
• 14 Nakayama Y, Gotanda T, Ito K. Tetrahedron Lett. 2011; 52: 6234
• 15a Leutenegger U, Umbricht G, Fahrni C, von Matt P, Pfaltz A. Tetrahedron 1992; 48: 2143
• 15b For a review, see: Trost BM, van Vranken DL. Chem. Rev. 1996; 96: 395
• 16 Use of the combination of BSTFA and KOAc as a base for palladium-catalyzed asymmetric allylic substitution: Ito K, Kashiwagi R, Hayashi S, Uchida T, Katsuki T. Synlett 2001; 284
• 17 Typical Experimental Procedure is Exemplified by Henry Reaction of 4-Nitrobenzaldehyde with Nitromethane Catalyst 1 (8.1 mg, 10.0 μmol) was placed in microtube under nitrogen and to this tube was added BSTFA (5.5 μL, 20.0 μmol) in DMF (100 μL), a catalytic amount of KOAc (0.4–0.5 mg, 4.1–5.1 μmol), and 4-nitrobenzaldehyde (16.1 mg, 0.1 mmol). After the mixture was cooled to –40 °C, MeNO₂ (55 μL, 1.0 mmol) was added at that temperature. After being stirred for 23 h at –40 °C, the mixture was quenched with H₂O and extracted with EtOAc. The organic extract was dried over anhyd MgSO₄ and concentrated. Silica gel chromatography of the residue (hexane–Et₂O = 6:4) gave the desired product (19.3 mg, 91%). The ee of the product was determined to be 91% by HPLC using chiral stationary-phase column as described in the footnote of Table 1.
• 18 Time-course studies suggested that the retro process is not involved in the reaction (3 h: 15% yield, 89% ee, 6 h: 35% yield, 88% ee, 12 h: 47% yield, 88% ee, 24 h: 90% yield, 89% ee). For the retro process in the asymmetric Henry reaction using organocatalyst, see ref. 7b.
• 19 We also examined the reaction of aldehydes and EtNO₂, but the reaction did not proceed.
• 20 Absolute configuration of all nitro alcohols were determined by comparison of elution order of HPLC and specific rotation with the reported value.^4b,g,j,9
• 21a At the moment, we have no evidence that the nitronate anion is generated under the optimized conditions. However, we believe that the nitronate anion from MeNO₂ (pK _a = 10.2) is generated, because the imidate anion generated from BSA or BSTFA and KOAc can deprotonate dimethyl malonate (pK _a = 13).
• 21b For a review on the use of BSA in organic synthesis, see: El Gihani MT, Heaney H. Synthesis 1998; 357