Synthesis 2019; 51(07): 1561-1564
DOI: 10.1055/s-0037-1610356
psp
© Georg Thieme Verlag Stuttgart · New York

Practical Synthesis of Precursors of Cyclohexyne and 1,2-Cyclohexadiene

Ryo Nakura
,
Kazuki Inoue
,
Department of Chemical Science and Engineering, Kobe University, 1-1 Rokkodai, Nada, Kobe 657-8501, Japan   eMail: okano@harbor.kobe-u.ac.jp
,
Atsunori Mori
› Institutsangaben

This work was financially supported by JSPS KAKENHI Grant Numbers JP16K05774 in Scientific Research (C), JP16H01153 and JP18H04413 in the Middle Molecular Strategy, Creation of Innovation Centers for Advanced Interdisciplinary Research Areas (Innovative Bioproduction Kobe), Kawanishi Memorial ShinMaywa Education Foundation, and the Sasakawa Scientific Research Grant from The Japan Science Society.
Weitere Informationen

Publikationsverlauf

Received: 16. Oktober 2018

Accepted after revision: 14. November 2018

Publikationsdatum:
11. Januar 2019 (online)


Abstract

This study investigated a practical method for regiocontrolled synthesis of precursors of strained cyclohexynes and 1,2-cyclohexadienes, which is a one-pot procedure consisting of a rearrangement of silyl enol ether and subsequent formation of the enol triflates. Triethylsilyl enol ether, derived from cyclohexanone, was treated with a combination of LDA and t-BuOK in n-hexane/THF to encourage the migration of the silyl group to generate an α-silyl enolate. Subsequently, the α-silyl enolate was reacted with Comins’ reagent to yield the corresponding enol triflate. Finally, the α-silylated trisubstituted lithium enolate for the synthesis of 1,2-cyclohexadiene precursor was isomerized in the presence of a stoichiometric amount of water for one hour at room temperature to exclusively provide tetrasubstituted lithium enolate for the synthesis of cyclohexyne precursor in one pot.

Supporting Information

 
  • References

    • 1a Hoffmann RW. Dehydrobenzene and Cycloalkynes . Academic Press; New York: 1967
    • 1b Wittig G. Angew. Chem., Int. Ed. Engl. 1962; 1: 415
    • 1c Buchwald SL, Nielsen RB. Chem. Rev. 1988; 88: 1047
    • 1d Johnson RP. Chem. Rev. 1989; 89: 1111
    • 1e Wenk HH, Winkler M, Sander W. Angew. Chem. Int. Ed. 2003; 42: 502
    • 1f Pellissier H, Santelli M. Tetrahedron 2003; 59: 701
    • 1g Suzuki N. Synth. Org. Chem., Jpn 2007; 65: 347
    • 1h Sletten EM, Bertozzi CR. Angew. Chem. Int. Ed. 2009; 48: 6974
    • 1i Gampe CM, Carreira EM. Angew. Chem. Int. Ed. 2012; 51: 3766
    • 1j Yoshida S, Hosoya T. Chem. Lett. 2015; 44: 1450
    • 2a Yoshida H, Tanino K, Ohshita J, Kunai A. Angew. Chem. Int. Ed. 2004; 43: 5052
    • 2b Gampe CM, Boulos S, Carreira EM. Angew. Chem. Int. Ed. 2010; 49: 4092
    • 2c Gampe CM, Carreira EM. Angew. Chem. Int. Ed. 2011; 50: 2962
    • 2d Devlin AS, Du Bois J. Chem. Sci. 2013; 4: 1059
    • 2e Medina JM, McMahon TC, Jiménez-Osés G, Houk KN, Garg NK. J. Am. Chem. Soc. 2014; 136: 14706
    • 2f Tlais SF, Danheiser RL. J. Am. Chem. Soc. 2014; 136: 15489
    • 2g McMahon TC, Medina JM, Yang Y.-F, Simmons BJ, Houk KN, Garg NK. J. Am. Chem. Soc. 2015; 137: 4082
    • 2h Shah TK, Medina JM, Garg NK. J. Am. Chem. Soc. 2016; 138: 4948
    • 2i Picazo E, Anthony SM, Giroud M, Simon A, Miller MA, Houk KN, Garg NK. J. Am. Chem. Soc. 2018; 140: 7605
    • 3a Moore WR, Moser WR. J. Am. Chem. Soc. 1970; 92: 5469
    • 3b Christl M, Schreck M. Angew. Chem., Int. Ed. Engl. 1987; 26: 449
    • 3c Barber JS, Styduhar ED, Pham HV, McMahon TC, Houk KN, Garg NK. J. Am. Chem. Soc. 2016; 138: 2512
    • 3d Lofstrand VA, West FG. Chem. Eur. J. 2016; 22: 10763
    • 3e Barber JS, Yamano MM, Ramirez M, Darzi ER, Knapp RR, Liu F, Houk KN, Garg NK. Nat. Chem. 2018; 10: 953
    • 4a Blomquist AT, Liu LH. J. Am. Chem. Soc. 1953; 75: 2153
    • 4b Wittig G, Krebs A. Chem. Ber. 1961; 94: 3260
    • 4c Wittig G, Pohlke R. Chem. Ber. 1961; 94: 3276
    • 4d Franzen V, Joschek H.-I. Liebigs Ann. Chem. 1967; 703: 90
    • 4e Wittig G, Hutchison JJ. Liebigs Ann. Chem. 1970; 741: 79
    • 4f Agard NJ, Prescher JA, Bertozzi CR. J. Am. Chem. Soc. 2004; 126: 15046
    • 4g Codelli JA, Baskin JM, Agard NJ, Bertozzi CR. J. Am. Chem. Soc. 2008; 130: 11486
    • 4h Sletten EM, Bertozzi CR. Acc. Chem. Res. 2011; 44: 666
    • 5a Orita A, Hasegawa D, Nakano T, Otera J. Chem. Eur. J. 2002; 8: 2000
    • 5b Debets MF, van Berkel SS, Schoffelen S, Rutjes F, van Hest JC. M, van Delft FL. Chem. Commun. 2010; 46: 97
    • 5c Gordon CG, MacKey JL, Jewett JC, Sletten EM, Houk KN, Bertozzi CR. J. Am. Chem. Soc. 2012; 134: 9199
    • 6a Ni R, Mitsuda N, Kashiwagi T, Igawa K, Tomooka K. Angew. Chem. Int. Ed. 2015; 54: 1190
    • 6b Igawa K, Aoyama S, Kawasaki Y, Kashiwagi T, Seto Y, Ni R, Mitsuda N, Tomooka K. Synlett 2017; 28: 2110
    • 7a Moore WR, Moser WR. J. Org. Chem. 1970; 35: 908
    • 7b Harada T, Iwazaki K, Otani T, Oku A. J. Org. Chem. 1998; 63: 9007
    • 7c Fujita M, Sakanishi Y, Kim WH, Okuyama T. Chem. Lett. 2002; 31: 908
    • 7d Al-Omari M, Banert K, Hagedorn M. Angew. Chem. Int. Ed. 2006; 45: 309
    • 7e Yoshida S, Karaki F, Uchida K, Hosoya T. Chem. Commun. 2015; 51: 8745
    • 7f Hioki Y, Okano K, Mori A. Chem. Commun. 2017; 53: 2614
    • 7g Hioki Y, Yukioka T, Okano K, Mori A. Asian J. Org. Chem. 2018; 7: 1298
  • 8 Scardiglia F, Roberts JD. Tetrahedron 1957; 1: 343
  • 9 Wittig G, Fritze P. Angew. Chem., Int. Ed. Engl. 1966; 5: 846
    • 10a Atanes N, Escudero S, Pérez D, Guitián E, Castedo L. Tetrahedron Lett. 1998; 39: 3039
    • 10b Peña D, Iglesias B, Quintana I, Pérez D, Guitián E, Castedo L. Pure Appl. Chem. 2006; 78: 451
    • 10c Quintana I, Peña D, Pérez D, Guitián E. Eur. J. Org. Chem. 2009; 5519

    • Generation of benzyne from 2-trimethylsilylbenzene triflate by fluoride ion:
    • 10d Himeshima Y, Sonoda T, Kobayashi H. Chem. Lett. 1983; 12: 1211
    • 11a Corey EJ, Rücker C. Tetrahedron Lett. 1984; 25: 4345
    • 11b Kuwajima I, Takeda R. Tetrahedron Lett. 1981; 22: 2381
  • 12 Inoue K, Nakura R, Okano K, Mori A. Eur. J. Org. Chem. 2018; 3343
  • 13 The commercially available LDA solution consists of 20–27% (w/w) LDA, in heptane/THF/ethylbenzene.
    • 14a Hoepker AC, Gupta L, Ma Y, Faggin MF, Collum DB. J. Am. Chem. Soc. 2011; 133: 7135
    • 14b Reich HJ. Chem. Rev. 2013; 113: 7130
    • 15a Comins DL, Dehghani A. Tetrahedron Lett. 1992; 33: 6299
    • 15b Comins DL, Dehghani A, Foti CJ, Joseph SP. Org. Synth. 1997; 74: 77
  • 16 Prinsell MR, Everson DA, Weix DJ. Chem. Commun. 2010; 46: 5743