Synlett 2012(5): 649-684  
DOI: 10.1055/s-0031-1290530
ACCOUNT
© Georg Thieme Verlag Stuttgart ˙ New York

Asymmetric Alkyne Addition to Aldehydes Catalyzed by BINOL and Its Derivatives

Mark Turlington, Lin Pu*
Department of Chemistry, University of Virginia, Charlottesville, Virginia 22904-4319, USA
Fax: +1(434)9243710; e-Mail: lp6n@virginia.edu;
Further Information

Publication History

Received 24 July 2011
Publication Date:
24 February 2012 (online)

Abstract

This Account describes our research over the past decade in the asymmetric alkyne addition to aldehydes to generate optically active propargylic alcohols. Our methods employ a dialkylzinc reagent to react with a terminal alkyne to form an alkynylzinc nucleophile, and can be grouped into the BINOL-catalyzed reactions and the functionalized BINOL catalyzed reactions. We first describe the development of the BINOL-ZnEt2-Ti(Oi-Pr)4 catalyst system, and its modification through the use of Lewis base additives to form the alkynylzinc at room temperature. The substrate scope compatible with these methods and the enantioselectivities achieved are discussed. We then describe the functionalized BINOL and H8BINOL catalyst systems, which can be further divided into classes based on the manner in which the BINOL framework has been modified. Generally, these functionalized BINOL and H8BINOL derivatives contain internal Lewis basic sites which can both promote the formation of the nucleophilic alkynylzinc reagents at reduced temperature and modify the catalytic properties of the chiral biaryl unit. In a few cases, these catalysts also show good efficiency even without the use of the Ti(IV) reagent. The catalytic methods in this Account have demonstrated that a wide range of alkyne and aldehyde substrates can be subjected to the asymmetric addition reactions to generate structurally diverse chiral propargylic alcohols with high enantioselectivity. Some of these methods have exhibited high practicality in synthesis.

1 Introduction

2 BINOL-Based Catalytic Systems

2.1 Catalysis by BINOL-ZnEt2-Ti(Oi-Pr)4

2.2 Catalysis by BINOL-ZnEt2-Ti(Oi-Pr)4-HMPA

2.3 Catalysis by BINOL-ZnEt2-Ti(Oi-Pr)4-NMI

2.4 Catalysis by BINOL-ZnEt2-Ti(Oi-Pr)4-Cy2NH

3 Functionalized BINOL-Based Catalytic Systems

3.1 Catalysis by 3,3′-Dianisyl-BINOLs and -H8BINOLs

3.2 Catalysis by 3,3′-Bis(diphenylmethoxy)methyl Substituted BINOLs

3.3 Catalysis by Acyclic and Macrocyclic Binaphthyl Salens

3.4 Catalysis by 3,3′-Bismorpholinomethyl H8BINOL

3.5 Catalysis by C 1-Symmetric BINOL-Terpyridine

4 Summary

    References

  • 1a Frantz DE. Fässler R. Tomooka CS. Carreira EM. Acc. Chem. Res.  2000,  33:  373 
  • 1b Pu L. Tetrahedron  2003,  59:  9873 
  • 1c Cozzi PG. Hilgraf R. Zimmermann N. Eur. J. Org. Chem.  2004,  4095 
  • 1d Lu G. Li Y.-M. Li X.-S. Chan ASC. Coord. Chem. Rev.  2005,  249:  1736 
  • 1e Trost BM. Weiss AH. Adv. Synth. Catal.  2009,  351:  963 
  • 1f Gao G. Pu L. Sci. China, Ser. B, Chem. Life Sci. Earth Sci.  2010,  53:  21 
  • Selected examples of transformations of propargylic alcohols:
  • 2a Trost BM. Müller TJJ. J. Am. Chem. Soc.  1994,  116:  4985 
  • 2b Trost BM. Müller TJJ. Martinez J. J. Am. Chem. Soc.  1995,  117:  1888 
  • 2c Arcadi A. Cacchi S. Fabrizi G. Marinelli F. Pace P. Eur. J. Org. Chem.  1999,  3305 
  • 2d Marshall JA. Chobanian HR. Yanik MM. Org. Lett.  2001,  3:  3369 
  • 2e Trost BM. Ball ZT. Jöge T. Angew. Chem. Int. Ed.  2003,  42:  3415 
  • 2f Alfonsi M. Arcadi A. Chiarini M. Marinelli F. J. Org. Chem.  2007,  72:  9510 
  • 2g Zhou LH. Yu XQ. Pu L. J. Org. Chem.  2009,  74:  2013 
  • 2h See references 8, 12, 17, and 25. Selected examples of propargylic alcohols in total synthesis: Crimmins MT. Jung DK. Gray JL. J. Am. Chem. Soc.  1993,  115:  3146 
  • 2i Roethle PA. Trauner D. Org. Lett.  2006,  8:  345 
  • 2j Trost BM. Weiss AH. Angew. Chem. Int. Ed.  2007,  46:  7664 
  • 2k Imagawa H. Saijo H. Kurisaki T. Yamamoto MK. Fukuyama Y. Nishizawa M. Org. Lett.  2009,  11:  1253 
  • Selected reviews on BINOL and BINOL derivatives:
  • 3a Rosini C. Franzini L. Raffaelli A. Salvadori P. Synthesis  1992,  503 
  • 3b Pu L. Chem. Rev.  1998,  98:  2405 
  • 3c Chen Y. Yekta S. Yudin AK. Chem. Rev.  2003,  103:  3155 
  • 3d Kočovský P. Vyskočil Š. Smrčina M. Chem. Rev.  2003,  103:  3213 
  • 3e Telfer SG. Kuroda R. Coord. Chem. Rev.  2003,  242:  33 
  • 3f Brunel JM. Chem. Rev.  2005,  105:  857 
  • 3g Shibasaki M. Matsunaga S. Chem. Soc. Rev.  2006,  35:  269 
  • 3h Terada M. Chem. Commun.  2008,  4097 
  • 3i Schenker S. Zamfir A. Freund M. Tsogoeva SB. Eur. J. Org. Chem.  2011,  2209 
  • 4 Pu L. 1,1′-Binaphthyl Based Chiral Materials: Our Journey   Imperial College Press; London / UK: 2009. 
  • A few selected reports by other researchers on the catalytic asymmetric alkyne addition to aldehydes:
  • 5a Frantz DE. Fässler R. Carreira EM. J. Am. Chem. Soc.  2000,  122:  1806 
  • 5b Anand NK. Carreira EM. J. Am. Chem. Soc.  2001,  123:  9687 
  • 5c Li X.-S. Lu G. Kwok WH. Chan ASC. J. Am. Chem. Soc.  2002,  124:  12636 
  • 5d Xu ZQ. Wang R. Xu JK. Da C S. Yan WJ. Chen C. Angew. Chem. Int. Ed.  2003,  42:  5747 
  • 5e Takita R. Yakura K. Ohshima T. Shibasaki M. J. Am. Chem. Soc.  2005,  127:  13760 
  • 5f Wolf C. Liu S. J. Am. Chem. Soc.  2006,  128:  10996 
  • 5g Trost BM. Weiss AH. von Wangelin AJ. J. Am. Chem. Soc.  2006,  128:  8 
  • 6a Moore D. Pu L. Org. Lett.  2002,  4:  1855 
  • 6b Using BINOL in combination with ZnMe2 and Ti(Oi-Pr)4 for the asymmetric phenylacetylene addition to aromatic aldehydes was reported at about the same time: Lu G. Li XS. Chan ASC. Chem. Commun.  2002,  172 
  • 7a Gao G. Moore D. Xie R.-G. Pu L. Org. Lett.  2002,  4:  4143 
  • 7b Du X. Wang Q. He X. Peng R.-G. Zhang X. Yu X.-Q. Tetrahedron: Asymmetry  2011,  22:  1142 
  • 8 Turlington M. Yue Y. Yu X.-Q. Pu L. J. Org. Chem.  2010,  75:  6941 
  • 9 Okhlobystin OY. Zakharkin LI. J. Organomet. Chem.  1965,  3:  247 
  • 10 Gao G. Xie R.-G. Pu L. Proc. Natl. Acad. Sci. U.S.A.  2004,  101:  5417 
  • 11 Gao G. Wang Q. Yu X.-Q. Xie R.-G. Pu L. Angew. Chem. Int. Ed.  2006,  45:  122 
  • 12 Rajaram AR. Pu L. Org. Lett.  2006,  8:  2019 
  • 13 Yang F. Xi P. Yang L. Lan J. Xie R. You J. J. Org. Chem.  2007,  72:  5457 
  • 14 Turlington M. Catalytic Asymmetric Alkyne Addition to Aldehydes and Applications of Propargylic Alcohols in Synthesis, Ph.D. Thesis   University of Virginia; Charlottesville: 2011. 
  • 16 Du YH. Turlington M. Zhou X. Pu L. Tetrahedron Lett.  2010,  51:  5024 
  • 17 Turlington M. Du Y.-H. Ostrum SG. Santosh V. Wren K. Lin T. Sabat M. Pu L. J. Am. Chem. Soc.  2011,  133:  11780 
  • Previous reports on the asymmetric 1,3-dialkyne addition to aldehydes:
  • 18a Reber S. Knöpfel TF. Carreira EM. Tetrahedron  2003,  59:  6813 
  • 18b Trost BM. Chan VS. Yamamoto D. J. Am. Chem. Soc.  2010,  132:  5186 
  • 19 Huang W.-S. Hu Q.-S. Pu L. J. Org. Chem.  1998,  63:  1364 
  • 20 Huang W.-S. Pu L. Tetrahedron Lett.  2000,  41:  145 
  • 21 Moore D. Huang W.-S. Xu M.-H. Pu L. Tetrahedron Lett.  2002,  43:  8831 
  • 22 Xu M.-H. Pu L. Org. Lett.  2002,  4:  4555 
  • 23 Au-Yeung TT.-L. Chan S.-S. Chan ASC. Adv. Synth. Catal.  2003,  345:  537 
  • 24 Turlington M. DeBerardinis AM. Pu L. Org. Lett.  2009,  11:  2441 
  • 25 Yang Y. Turlington M. Yu X.-Q. Pu L. J. Org. Chem.  2009,  74:  8681 
  • 26 Wang Q. Chen X. Tao L. Wang L. Xiao D. Yu X.-Q. Pu L. J. Org. Chem.  2007,  72:  97 
  • 27 Wang Q. Chen S.-Y. Yu X.-Q. Pu L. Tetrahedron  2007,  63:  4422 
  • 28a Sasaki H. Irie R. Katsuki T. Synlett  1993,  300 
  • 28b DiMauro EF. Kozlowski MC. Org. Lett.  2001,  3:  1641 
  • 28c Annamalai V. DiMauro EF. Carroll PJ. Kozlowski MC. J. Org. Chem.  2003,  68:  1973 
  • 28d DiMauro EF. Kozlowski MC. Organometallics  2002,  21:  1454 
  • 29 Li Z.-B. Pu L. Org. Lett.  2004,  6:  1065 
  • 30 Li Z.-B. Liu T.-D. Pu L. J. Org. Chem.  2007,  72:  4340 
  • 31a Liu L. Pu L. Tetrahedron  2004,  60:  7427 
  • 31b Qin Y.-C. Liu L. Sabat M. Pu L. Tetrahedron  2006,  62:  9335 
  • 32 Chen X. Chen W. Wang L. Yu X.-Q. Huang D.-S. Pu L. Tetrahedron  2010,  66:  1990 
15

When the first step was allowed to proceed for 2 h for the reaction shown in Scheme  [9] b, the propargylic alcohol was formed in only 25% yield and 84% ee.