CC BY-ND-NC 4.0 · Synthesis 2019; 51(05): 1253-1262
DOI: 10.1055/s-0037-1611657
paper
Copyright with the author

Lewis Acid Promoted Trapping of Chiral Aza-enolates

Francesco Lanza
,
Juana M. Pérez
,
Ravindra P. Jumde
,
Stratingh Institute for Chemistry, Rijksuniversiteit Groningen, Nijenborgh 4, 9747 AG, Groningen, The Netherlands   Email: s.harutyunyan@rug.nl
› Author Affiliations
Financial support from NWO (Vidi and ECHO to S.R.H.) and the Ministry of Education, Culture and Science (Gravity programme 024.001.035 to S.R.H.) is acknowledged. J.M.P. thanks the European Commission for an Intra-European Marie Curie fellowship (grant 746011–ChirPyr).
Further Information

Publication History

Received: 07 December 2018

Accepted after revision: 17 December 2018

Publication Date:
29 January 2019 (eFirst)

Published as part of the 50 Years SYNTHESIS – Golden Anniversary Issue

Abstract

We present a study on sequential conjugate addition of ­Grignard reagents to alkenyl-heteroarenes followed by trapping of the resulting enolates, yielding moderate to good diastereoselectivities. Contrary to conventional wisdom, one-pot conjugate addition/trapping using two reactive Michael acceptors in combination with Grignard reagents can proceed via conjugate addition to the least reactive Michael acceptor. This unusual chemoselectivity is triggered by the presence of a Lewis acid, reverting the usual reactivity order of Michael acceptors.

Supporting Information

 
  • References

    • 1a Cauble DF, Gipson JD, Krische MJ. J. Am. Chem. Soc. 2003; 125: 1110
    • 1b Agapiou K, Cauble DF, Krische MJ. J. Am. Chem. Soc. 2004; 126: 4528
    • 1c Bocknack BM, Wang LC, Krische MJ. Proc. Natl. Acad. Sci. U.S.A. 2004; 101: 5421
    • 2a Germain N, Schlaefli D, Chellat M, Rosset S, Alexakis A. Org. Lett. 2014; 16: 2006
    • 2b Posner GH, Webb KS, Asirvatham E, Jew SS, Degl’Innocenti A. J. Am. Chem. Soc. 1988; 110: 4754
    • 3a Calvo BC, Madduri AV. R, Harutyunyan SR, Minnaard AJ. Adv. Synth. Catal. 2014; 356: 2061
    • 3b den Hartog T, Rudolph A, Maciá B, Minnaard AJ, Feringa BJ. J. Am. Chem. Soc. 2010; 132: 14349
    • 3c Bleschke C, Tissot M, Müller D, Alexakis A. Org. Lett. 2013; 15: 2152
    • 3d Germain N, Guenée L, Mauduit M, Alexakis A. Org. Lett. 2014; 16: 118
    • 3e Howell GP, Fletcher SP, Geurts K, ter Horst B, Feringa BL. J. Am. Chem. Soc. 2006; 128: 14977
    • 3f Brown MK, Degrado SJ, Hoveyda AH. Angew. Chem. Int. Ed. 2005; 44: 5306
    • 3g Pineschi M, Del Moro F, Gini F, Minnaard AJ, Feringa BL. Chem. Commun. 2004; 1244
    • 4a Taylor RJ. K. Synthesis 1985; 364
    • 4b Guo H.-C, Ma J.-A. Angew. Chem. Int. Ed. 2006; 45: 354
    • 4c Galeštoková Z, Šebesta R. Eur. J. Org. Chem. 2012; 6688
    • 4d Germain N, Alexakis A. Chem. Eur. J. 2015; 21: 8597
    • 4e Feringa BL, Pineschi M, Arnold LA, Imbos R, De Vries AH. M. Angew. Chem. Int. Ed. 1997; 36: 2620
    • 4f Alexakis A, Trevitt GP, Bernardinelli G. J. Am. Chem. Soc. 2001; 123: 4358
  • 5 Degrado SJ, Mizutani H, Hoveyda AH. J. Am. Chem. Soc. 2001; 123: 755
  • 6 Jumde RP, Lanza F, Veenstra MJ, Harutyunyan SR. Science 2016; 352: 433
    • 7a Reetz MT, Gosberg A, Moulin D. Tetrahedron Lett. 2002; 43: 1189
    • 7b Schuppan J, Minaard AJ, Feringa BL. Chem. Commun. 2004; 792
    • 7c Lopez F, Harutyunyan SR, Meetsma A, Minaard AJ, Feringa BL. Angew. Chem. Int. Ed. 2005; 44: 2752
    • 7d Wang S.-Y, Loh T.-P. Chem. Commun. 2010; 46: 8694
    • 8a Miura T, Nakamuro Y, Miyakawa S, Murakami M. Angew. Chem. Int. Ed. 2016; 55: 8732
    • 8b Selander N, Worrell BT, Chuprakov S, Velaparthi S, Fokin VV. J. Am. Chem. Soc. 2012; 134: 14670
    • 8c Bernardi A, Gennari C, Goodman JM, Leue V, Paterson I. Tetrahedron 1995; 51: 4853
    • 8d Florio S, Capriati V, Luisi R, Abbotto A. Tetrahedron Lett. 1999; 40: 7421
    • 8e Meyers AI, Yamamoto Y. J. Am. Chem. Soc. 1981; 103: 4277
    • 9a Hatakeyama T, Ito S, Nakamura M, Nakamura E. J. Am. Chem. Soc. 2005; 127: 14192
    • 9b Stork G, Dowd SR. J. Am. Chem. Soc. 1963; 85: 2178
    • 9c Gates M, Zabriskie JL. J. Org. Chem. 1974; 39: 222
    • 9d Wittig G, Reiff H. Angew. Chem., Int. Ed. Engl. 1968; 7: 7
    • 9e Pearce GT, Gore WE, Silverstein RM. J. Org. Chem. 1976; 41: 2797
    • 9f Kochi T, Tang TP, Ellman JA. J. Am. Chem. Soc. 2003; 125: 11276
    • 9g Peltier HM, Ellman JA. J. Org. Chem. 2005; 70: 7342
    • 9h Hayashi K, Kogiso H, Sano S, Nagao Y. Synlett 1996; 1203
  • 10 Madduri AV. R, Harutyunyan SR, Minnaard AJ. Angew. Chem. Int. Ed. 2012; 51: 3164
    • 11a Hamrick PJ. Jr, Hauser CR. J. Am. Chem Soc. 1959; 81: 493
    • 11b Stork G, Rosen P, Goldman N, Coombs RV, Tsuji J. J. Am. Chem. Soc. 1965; 87: 275
  • 12 Zhang Z, Wang Z. J. Org. Chem. 2006; 71: 7485
  • 13 Roy ID, Burns AR, Pattison G, Michel B, Parker AJ, Lam HW. Chem. Commun. 2014; 50: 2865
  • 14 Wang YD, Kimball G, Prashada AS, Wanga Y. Tetrahedron Lett. 2005; 46: 8777
  • 15 Evindar G, Batey RA. J. Org. Chem. 2006; 71: 1802