Synlett 2020; 31(01): 60-64
DOI: 10.1055/s-0039-1690264
letter
© Georg Thieme Verlag Stuttgart · New York

Enantioselective Addition of Alkynyl Esters and Ethers to Aldehydes Catalyzed by a Cyclopropyl Amino Alcohol Based Zinc Catalyst

Yun Zhou
a   Department of Applied Chemistry, China Agricultural University, 2 West Yuanmingyuan Road, Beijing 100193, P. R. of China   Email: zhong@cau.edu.cn
,
Lifeng Wang
a   Department of Applied Chemistry, China Agricultural University, 2 West Yuanmingyuan Road, Beijing 100193, P. R. of China   Email: zhong@cau.edu.cn
,
Shuoning Li
a   Department of Applied Chemistry, China Agricultural University, 2 West Yuanmingyuan Road, Beijing 100193, P. R. of China   Email: zhong@cau.edu.cn
,
Sijie Ma
a   Department of Applied Chemistry, China Agricultural University, 2 West Yuanmingyuan Road, Beijing 100193, P. R. of China   Email: zhong@cau.edu.cn
,
Patrick J. Walsh
b   Roy and Diana Vagelos Laboratories, Department of Chemistry, University of Pennsylvania, 231 South 34th Street, Philadelphia, PA 19104-6323, USA
,
Qinghua Bian
a   Department of Applied Chemistry, China Agricultural University, 2 West Yuanmingyuan Road, Beijing 100193, P. R. of China   Email: zhong@cau.edu.cn
,
Fengqi Li
c   Institute of Plant and Environment Protection, Beijing Academy of Agriculture and Forestry Sciences, No. 9 Shuguang Garden, Central Road, Beijing, 100097, P. R. of China   Email: pandit@163.com
,
Min Wang
a   Department of Applied Chemistry, China Agricultural University, 2 West Yuanmingyuan Road, Beijing 100193, P. R. of China   Email: zhong@cau.edu.cn
,
Jiangchun Zhong
a   Department of Applied Chemistry, China Agricultural University, 2 West Yuanmingyuan Road, Beijing 100193, P. R. of China   Email: zhong@cau.edu.cn
› Author Affiliations
We are grateful to the National Key Technology Research and Development Program of China for financial support (No. 2017YFD0201404).
Further Information

Publication History

Received: 28 August 2019

Accepted after revision: 22 October 2019

Publication Date:
03 December 2019 (online)


Abstract

A novel and highly enantioselective synthesis of hydroxyalkynyl esters and ethers through the asymmetric addition of alkynyl esters or ethers to aldehydes promoted by a cyclopropyl amino alcohol based zinc catalyst has been developed. The method afforded a library of new enantioenriched hydroxyalkynol esters and ethers (up to 93% yield; 95% ee), and it was compatible with a broad range of functional groups. Moreover, it could be used in the synthesis of carbon-chain-elongated enantioenriched hydroxyalkynol esters and (2R,5R)-musclide-A1, a cardiotonic potentiating principle from musk.

Supporting Information

 
  • References and Notes

    • 1a Robinson A, Aggarwal VK. Angew. Chem. Int. Ed. 2010; 49: 6673
    • 1b Yalla R, Raghavan S. Org. Biomol. Chem. 2019; 17: 4572
    • 2a Radha Krishna P, Narasimha Reddy PV. Tetrahedron Lett. 2006; 47: 7473
    • 2b Kobayashi Y, Yoshida S, Asano M, Takeuchi A, Acharya HP. J. Org. Chem. 2007; 72: 1707
    • 2c Gupta KP, Kumar P. Eur. J. Org. Chem. 2008; 1195 ; corrigendum: Eur. J. Org. Chem. 2008, 1993
    • 3a Yu J, Lai J.-Y, Ye J, Balu N, Reddy LM, Duan W, Fogel ER, Capdevila JH, Falck JR. Tetrahedron Lett. 2002; 43: 3939
    • 3b Pietruszka J, Wilhelm T. Synlett 2003; 1698
  • 4 Barloy-Da Silva C, Pale P. Tetrahedron: Asymmetry 1998; 9: 3951
  • 5 El-Sayed E, Anand NK, Carreira EM. Org. Lett. 2001; 3: 3017
  • 6 Chang X.-W, Zhang D.-W, Chen F, Dong Z.-M, Yang D. Synlett 2009; 3159
  • 7 Georges Y, Allenbach Y, Ariza X, Campagne J.-M, Garcia J. J. Org. Chem. 2004; 69: 7387
    • 8a Adger BM, Carreira EM. WO 2002094741, 2002
    • 8b Sans Diez R, Adger B, Carreira EM. Tetrahedron 2002; 58: 8341
    • 8c Princival IM. R. G, Ferreira JG, Silva TG, Aguiar JS, Princival JL. Bioorg. Med. Chem. Lett. 2016; 26: 2839
    • 8d Princival JL, Ferreira JG. Tetrahedron Lett. 2017; 58: 3525
    • 9a Kadota S, Orito T, Kikuchi T, Uwano T, Kimura I, Kimura M. Tetrahedron Lett. 1991; 32: 1733
    • 9b Amador M, Ariza X, Garcia J, Ortiz J. Tetrahedron Lett. 2002; 43: 2691
    • 9c Ortiz J, Ariza X, Garcia J. Tetrahedron: Asymmetry 2003; 14: 1127
  • 10 Ham P, Deng J, Selvakumar S, Sibi MP. In e-EROS Encyclopedia of Reagents for Organic Synthesis . Wiley; Chichester: 2011. ; DOI: 10.1002/047084289X.rz023.pub2
  • 11 Ferreira JG, Princival CR, Oliveira DM, Nascimento RX, Princival JL. Org. Biomol. Chem. 2015; 13: 6458
    • 12a Zhong J.-C, Hou S.-C, Bian Q.-H, Yin M.-M, Na R.-S, Zheng B, Li Z.-Y, Liu S.-Z, Wang M. Chem. Eur. J. 2009; 15: 3069
    • 12b Zheng B, Li S.-N, Mao J.-Y, Wang B, Bian Q.-H, Liu S.-Z, Zhong J.-C, Guo H.-C, Wang M. Chem. Eur. J. 2012; 18: 9208
  • 13 (4S)-4-Hydroxy-4-phenylbut-2-yn-1-yl Acetate (3a); Typical Procedure Prop-2-ynyl acetate (2a; 294.0 mg, 3.0 mmol, 3 equiv) was added to a stirred solution of ligand L1 (35.1 mg, 0.1 mmol, 0.1 equiv) in anhyd toluene (0.5 mL) at rt under argon, and the mixture was cooled to 0 °C. A 1.2 M solution of Me2Zn in toluene (2.5 mL, 3.0 mmol, 3 equiv) was slowly added over 20 min, and the resulting mixture was warmed to rt (~0.5 h) and then stirred for 1.5 h. The mixture was cooled to 0 °C and PhCHO (1a; 106.1 mg, 1.0 mmol, 1 equiv) was added from a syringe. The mixture was stirred for an additional 48 h at 0 °C until the reaction was complete (TLC; silica gel, hexane–EtOAc, 7:1). The reaction was then quenched with H2O (5 mL) and the mixture was diluted with Et2O (15 mL). The layers were separated, and the aqueous phase was extracted with Et2O (3 × 20 mL). The combined organic layers were washed with brine (15 mL), dried (Na2SO4), filtered, and concentrated under reduced pressure. The residue was purified by chromatography [silica gel, hexane–EtOAc (7:1)] to give a colorless oil; yield: 189.9 mg (93%, 94% ee); [α]D 20 –2.0 (c 2.0, CHCl3) {Lit.5 [α]D 25.8 +1.8 (c 0.51, CHCl3) for 97% ee (R)-enantiomer}. HPLC (Daicel Chiralcel OD-H; 10% i-PrOH in hexane, 1.0 mL/min, λ = 210 nm) t r (major): 13.79 min (S), t r (minor) = 18.29 min (R). 1H NMR (300 MHz, CDCl3): δ = 7.54–7.50 (m, 2 H), 7.42–7.31 (m, 3 H), 5.51 (d, J = 6.0 Hz, 1 H), 4.76 (d, J = 1.8 Hz, 2 H), 2.39 (d, J = 6.1 Hz, 1 H), 2.10 (s, 3 H). 13C NMR (75 MHz, CDCl3): δ = 170.3, 140.1, 128.5, 128.4, 126.5, 86.4, 80.4, 64.3, 52.2, 20.6. HRMS (APCI-TOF): m/z [M + H]+ calcd for C12H13O3: 205.0865; found: 205.0874. (4S)-4-Hydroxy-4-phenylbut-2-yn-1-yl Cyclohexanecarboxylate (4f) Colorless oil; yield: 236.9 mg (87%; 93% ee); [α]D 20 +10.0 (c 1.3, CHCl3). HPLC (Daicel Chiralpak AD-H; 10% i-PrOH–hexane, 1.0 mL/min, λ = 210 nm): t r (major): 10.06 min (S); t r (minor): 11.14 min (R). 1H NMR (300 MHz, CDCl3): δ = 7.52 (dd, J = 7.9, 1.5 Hz, 2 H), 7.41–7.32 (m, 3 H), 5.50 (d, J = 6.1 Hz, 1 H), 4.75 (d, J = 1.8 Hz, 2 H), 2.44 (d, J = 6.2 Hz, 1 H), 2.39–2.29 (m, 1 H), 1.93–1.89 (m, 2 H), 1.77–1.63 (m, 3 H), 1.51–1.39 (m, 2 H), 1.35–1.15 (m, 3 H). 13C NMR (75 MHz, CDCl3): δ = 175.3, 140.1, 128.6, 128.5, 126.6, 86.2, 81.0, 64.5, 52.0, 42.9, 28.9, 25.7, 25.3. HRMS (APCI-TOF): m/z [M + H]+ calcd for C17H21O3: 273.1491; found: 273.1495. (4S,5E)-7-Ethoxy-4-hydroxy-5-methyl-7-oxohept-5-en-2-yn-1-yl Benzoate (6h) Colorless oil; yield: 154.0 mg (51%, 95% ee); [α]D 21 –8.0 (c 2.5, CHCl3). HPLC (Daicel Chiralcel OD-H; 5% i-PrOH–hexane, 1.0 mL/min, λ = 220 nm): t r (major): 11.34 min (S); t r (minor): 11.93 min (R). 1H NMR (300 MHz, CDCl3): δ = 8.02 (dd, J = 5.2, 3.3 Hz, 2 H), 7.59–7.53 (m, 1 H), 7.42 (dd, J = 10.5, 4.7 Hz, 2 H), 6.09–6.08 (m, 1 H), 4.93 (d, J = 1.7 Hz, 2 H), 4.86 (s, 1 H), 4.15 (q, J = 7.1 Hz, 2 H), 3.26 (br s, 1 H), 2.21 (d, J = 1.2 Hz, 3 H), 1.25 (t, J = 7.1 Hz, 3 H). 13C NMR (75 MHz, CDCl3): δ = 166.6, 165.9, 154.5, 133.3, 129.8, 129.2, 128.4, 116.4, 84.7, 80.4, 66.5, 60.0, 52.6, 15.0, 14.1. HRMS (APCI-TOF): m/z [M – OH]+ calcd for C17H17O4: 285.1127; found: 285.1125.
    • 14a Kitamura M, Okada S, Suga S, Noyori R. J. Am. Chem. Soc. 1989; 111: 4028
    • 14b Yamakawa M, Noyori R. J. Am. Chem. Soc. 1995; 117: 6327
    • 14c Trost BM, Weiss AH, von Wangelin AJ. J. Am. Chem. Soc. 2006; 128: 8
    • 14d Trost BM, Chan VS, Yamamoto D. J. Am. Chem. Soc. 2010; 132: 5186
  • 15 Kimura I, Takamura Y, Uwano T, Hata Y, Kimura M, Kikuchi T. Phytother. Res. 1995; 9: 16
    • 16a Gao Y, Klunder JM, Hanson RM, Masamune H, Ko SY, Sharpless KB. J. Am. Chem. Soc. 1987; 109: 5765
    • 16b Fujita T, Tanaka M, Norimine Y, Suemune H, Sakai K. J. Org. Chem. 1997; 62: 3824
  • 17 Tezuka Y, Kudoh M, Hatanaka Y, Kadota S, Kikuchi T. J. Tradit. Med. 1998; 15: 168
  • 18 Zhylitskaya HA, Chashchina NM, Litvinovskaya RP, Zavadskaya MI, Zhabinskii VN, Khripach VA. Steroids 2017; 117: 2
  • 19 Tezuka Y, Kudoh M, Hatanaka Y, Kadota S, Kikuchi T. Nat. Prod. Lett. 1997; 9: 297