Radical Zinc-Atom Transfer Based Multicomponent Approaches to 3-Alkylidene-Substituted Tetrahydrofurans

Abstract

A domino 1,4-addition/alkyne carbozincation sequence based on a radical zinc-atom transfer process is disclosed. Two efficient multicomponent approaches to 3-alkylidenetetrahydrofurans from β-(propargyloxy)enoates bearing pendant alkynes (including ynamides) have been established: one involving the direct addition of dialkylzincs, and the second involving the dimethylzinc-mediated addition of alkyl iodides. Both sequences utilize the stereoselective formation of intermediate alkylidenezincs well suited for in situ functionalization with electrophiles.

1 Introduction

2 1,4-Addition/Cyclization of Dialkylzincs on β-(Propargyl­oxy)enoates

2.1 β-(Propargyloxy)enoates with a Pendant Terminal Alkyne

2.2 β-(Propargyloxy)enoates with a Pendant Substituted Alkyne

2.3 β-(Propargyloxy)enoates with a Pendant Ynamide

3 1,4-Addition/Cyclization of Alkylzinc Halides on β-(Propargyloxy)enoates

4 Dialkylzinc-Mediated 1,4-Addition/Cyclization of Alkyl Iodides on β-(Propargyloxy)enoates

5 Conclusion; Current and Future Work

Key words

zinc - radicals - tandem reaction - alkynes - metalation

References

• Reviews:
• 1a Bazin S. Feray L. Bertrand MP. Chimia  2006,  60:  260 
• 1b Akindele T. Yamada K.-i. Tomioka K. Acc. Chem. Res.  2009,  42:  345 
• 2 Historical account, see: Seyferth D. Organometallics  2001,  20:  2940 
• 3a Lewinski J. Marciniac W. Lipkowski J. Justyniak I. J. Am. Chem. Soc.  2003,  125:  12698 
• 3b Lewinski J. Sliwinski W. Dranka M. Justyniak I. Lipkowski J. Angew. Chem. Int. Ed.  2006,  45:  4826 
• 3c Lewinski J. Suwala K. Kubisiak M. Ochal Z. Justyniak I. Lipkowski J. Angew. Chem. Int. Ed.  2008,  47:  7888 
• 3d Lewinski J. Bury W. Dutkiewicz M. Maurin M. Justyniak I. Lipkowski J. Angew. Chem. Int. Ed.  2008,  47:  573 
• 3e Lewinski J. Koscielski M. Suwala K. Justyniak I. Angew. Chem. Int. Ed.  2009,  48:  7017 
• 3f Lewinski J. Suwala K. Kaczorowski T. Galezowski M. Gryko DT. Justyniak I. Lipkowski J. Chem. Commun.  2009,  215 
• 4 Jana S. Berger RJF. Fröhlich R. Pape T. Mitzel NW. Inorg. Chem.  2007,  46:  4293 
• 5 Mileo E. Benfatti F. Cozzi PG. Lucarini M. Chem. Commun.  2009,  469 
• 6 Maury J. Feray L. Bazin S. Clément J.-L. Marque SRA. Siri D. Bertrand MP. Chem. Eur. J.  2011,  17:  1586 
• 7 Davies AG. Roberts BP. Acc. Chem. Res.  1972,  387 ; and references cited therein
• 8 For the first use of Et₂Zn as radical mediator in the presence of oxygen in the context of synthesis, see: Ryu I. Araki F. Minakata S. Komatsu M. Tetrahedron Lett.  1998,  39:  6335 
• 9 Cohen T. Gibney H. Ivanov R. Yeh EA.-H. Marek I. Curran DP. J. Am. Chem. Soc.  2007,  129:  15405 
• 10a Bertrand MP. Feray L. Nouguier R. Perfetti P.
  J. Org. Chem.  1999,  64:  9189 
• 10b Bazin S. Feray L. Siri D. Naubron J.-V. Bertrand MP. Chem. Commun.  2002,  2506 
• 10c Bazin S. Feray L. Vanthuyne N. Bertrand MP. Tetrahedron  2005,  61:  4261 
• 10d Bazin S. Feray L. Vanthuyne N. Siri D. Bertrand MP. Tetrahedron  2007,  63:  77 
• 10e Maury J. Feray L. Perfetti P. Bertrand MP. Org. Lett.  2010,  12:  3590 
• 11 Van der Deen H. Kellog RM. Feringa BL. Org. Lett.  2000,  2:  1593 
• 12a Miyabe H. Asada R. Yoshida K. Takemoto Y. Synlett  2004,  540 
• 12b Miyabe H. Asada R. Takemoto Y. Tetrahedron  2005,  61:  385 
• 13 Yamada K.-i. Umeki M. Maekawa M. Yamamoto Y. Akindele Y. Nakano M. Tomioka K. Tetrahedron  2008,  64:  7258 
• 14a Cozzi PG. Angew. Chem. Int. Ed.  2006,  45:  2951 
• 14b Cozzi PG. Adv. Synth. Catal.  2006,  348:  2075 
• 14c Cozzi PG. Mignogna A. Vicennati P. Adv. Synth. Catal.  2008,  350:  975 
• 14d Fernández-Ibañez MA. Maciá B. Minnaard AJ. Feringa BL. Angew. Chem. Int. Ed.  2008,  47:  1317 
• 14e Cozzi PG. Benfatti F. Guiteras Capdevila M. Mignogna A. Chem. Commun.  2008,  3317 
• Furthermore, it has been proposed that transition-metal-promoted zinc/iodine exchange involves a radical mechanism, Cu(I):
• 15a Rozema MJ. AchyuthaRao S. Knochel P. J. Org. Chem.  1992,  57:  1956 
• Pd(0):
• 15b Stadtmüller H. Vaupel A. Tucker CE. Stüdemann T. Knochel P. Chem. Eur. J.  1996,  2:  1204 
• 15c Stadtmüller H. Lentz R. Tucker C. Stüdemann T. Dörner W. Knochel P. J. Am. Chem. Soc.  1993,  115:  7027 
• Ni(0):
• 15d Vaupel A. Knochel P. Tetrahedron Lett.  1994,  35:  8349 
• 15e Vaupel A. Knochel P. J. Org. Chem.  1996,  61:  5743 
• Mn(II)/Cu(I):
• 15f Riguet E. Klement I. Kishan Reddy Ch. Cahiez G. Knochel P. Tetrahedron Lett.  1996,  37:  5865 
• 16a Denes F. Chemla F. Normant J.-F. Angew. Chem. Int. Ed.  2003,  42:  4043 
• 16b Denes F. Pérez-Luna A. Cutri S. Chemla F. Chem. Eur. J.  2006,  12:  6506 
• 16c Denes F. Pérez-Luna A. Chemla F. J. Org. Chem.  2007,  72:  398 
• 16d Giboulot S. Pérez-Luna A. Botuha C. Ferreira F. Chemla F. Tetrahedron Lett.  2008,  49:  3963 
• 17 Feray L. Bertrand MP. Eur. J. Org. Chem.  2008,  3164 
• 18 For a related photoinduced reaction, see: Charette AB. Beauchemin A. Marcoux J.-F. J. Am. Chem. Soc.  1998,  120:  5114 
• For important studies on radical formation by SET from dialkylzinc coordination complexes, see:
• 19a Wissing E. Rijnberg E. van der Schaaf PA. van Gorp K. Boersma J. van Koten G. Organometallics  1994,  13:  2609 
• 19b Wissing E. van der Linden S. Rijnberg E. Boersma J. Smeets WJJ. Spek AL. van Koten G. Organometallics  1994,  13:  2602 ; and references cited therein
• 20 Chen Z. Zhang Y.-X. An Y. Song X.-L. Wang Y.-H. Zhu L.-L. Guo L. Eur. J. Org. Chem.  2009,  5146 
• 22 Vinylcyclopentyl zinc has been prepared by reductive cyclization: Crandall JK. Ayers TA. Organometallics  1992,  11:  473 
• 23 Ni(II)-catalyzed intermolecular carbozincation, see: Stüdemann T. Knochel P. Angew. Chem. Int. Ed.  1997,  36:  93 
• 24 Pérez-Luna A. Botuha C. Ferreira F. Chemla F. Chem. Eur. J.  2008,  14:  8784 
• Selected examples:
• 25a Bertrand MT. Courtois G. Migniniac L. Tetrahedron Lett.  1974,  15:  3147 
• 25b Nakamura M. Fujimoto T. Endo K. Nakamura E. Org. Lett.  2004,  6:  4837 
• 25c Cantagrel F. Pinet S. Gimbert Y. Chavant PY. Eur. J. Org. Chem.  2005,  2694 
• Deprotonation of 1a responsible for the formation of 10 could also be effected by Bu₂Zn, even though deprotonation of terminal alkynes by dialkylzincs in the absence of ligands is not a fast process, see:
• 27a Okhlobystin OY. Zakharkin LI. J. Organomet. Chem.  1965,  3:  257 
• 27b De Koning AJ. Van Rijn PE. Boersma J. Van der Kerk GJM. J. Organomet. Chem.  1979,  174:  129 
• 27c Pinet S. Pandya SU. Chavant PY. Ayling A. Vallée Y. Org. Lett.  2002,  4:  1463 
• 28 Cote A. Charette AB. J. Am. Chem. Soc.  2008,  130:  2771 
• 29 Haaland A. Green JC. McGrady GS. Downs AJ. Gullo E. Lyall MJ. Timberlake J. Tutukin AV. Volden HV. Ostby K.-A. Dalton Trans.  2003,  4356 
• 30 Bamford CH. Newitt DM. J. Chem. Soc., Abstr.  1946,  688 
• 32 Guijarro A. In The Chemistry of Organozinc Compounds   Rappoport Z. Marek I. Wiley; Chichester: 2007.  p.193-236  
• 33 Jourmet M. Malacria M. J. Org. Chem.  1992,  57:  3085 
• 34 Curran DP. Chen M.-H. Kim DJ. J. Am. Chem. Soc.  1989,  111:  6265 
• Even though α-silyl stabilization of vinyl radicals leads to a tendency towards linearization:
• 35a Lalitha S. Chandrasekhar J. Proc.-Indian Acad. Sci., Chem. Sci.  1994,  106:  259 ; they are better represented as very rapidly Z/E interconverting bent radicals:
• 35b Rubin H. Fischer H. Helv. Chim. Acta  1996,  79:  1670 
• 35c Bucher G. Mahajan AA. Schmittel M. J. Org. Chem.  2009,  74:  5850 
• 36a Chechik-Lankin H. Livshin S. Marek I. Synlett  2005,  2098 
• 36b Prakash Das J. Chechik H. Marek I. Nature Chem.  2009,  1:  128 
• 37a Gourdet B. Lam HW. J. Am. Chem. Soc.  2009,  131:  3802 
• 37b Gourdet B. Rudkin ME. Watts CA. Lam HW. J. Org. Chem.  2009,  74:  7849 
• 38a Yasui H. Yorimitsu H. Oshima K. Chem. Lett.  2007,  36:  32 
• 38b Yasui H. Yorimitsu H. Oshima K. Bull. Chem. Soc. Jpn.  2008,  81:  373 
• 39 Marion F. Courillon C. Malacria M. Org. Lett.  2003,  5:  5095 
• 40a Sato A. Yorimitsu H. Oshima K. Synlett  2009,  28 
• 40b Sato A. Yorimitsu H. Oshima K. Bull. Korean Chem. Soc.  2010,  31:  570 
• 41 Banerjee B. Litvinov DN. Kang J. Bettale JD. Castle SL. Org. Lett.  2010,  12:  2650 
• 43a The Chemistry of Organozinc Compounds   Rappoport Z. Marek I. Wiley; Chichester: 2007. 
• 43b Knochel P. Millot N. Rodrigues AL. Org. React.  2001,  58:  417 
• 44 Blake AJ. Shannon J. Stephens JC. Woodward S. Chem. Eur. J.  2007,  13:  2462 
• 45 Beckwith ALJ. Tetrahedron  1981,  37:  3073 
• 46a Bertrand MP. Feray L. Nouguier R. Perfetti P. Synlett  1999,  1148 
• 46b Bertrand MP. Coantic S. Feray L. Nouguier R. Perfetti P. Tetrahedron  2000,  56:  3951 
• 47a Miyabe H. Ushiro C. Ueda M. Yamakawa K. Naito T. J. Org. Chem.  2000,  65:  176 
• 47b Miyabe H. Konishi C. Naito T. Org. Lett.  2000,  2:  1443 
• 48a Yamada K.-i. Yamamoto Y. Maekawa M. Akindele T. Umeki H. Tomioka K. Org. Lett.  2006,  8:  87 
• 48b Yamada K.-i. Nakano Y. Maekawa M. Akindele T. Tomioka K. Org. Lett.  2008,  10:  3805 
• 49a Vleeschouwer FD. Van Speybroeck V. Waroquier M. Geerlings P. De Proft F. Org. Lett.  2007,  9:  2721 
• 49b Fischer H. Radom L. Angew. Chem. Int. Ed.  2001,  40:  1340 
• 50 Similar stereoselectivities have been reported for other related iodine-atom transfer radical cascades, see for example: Miyabe H. Asada R. Toyoda A. Takemoto Y. Angew. Chem. Int. Ed.  2006,  45:  5863 
• See,
• 51a Chinkov N. Tene D. Marek I. In Metal-Catalyzed Cross Coupling Reactions   2nd ed.:  Diederich D. de Meijere A. Wiley-VCH; New York: 2004.  p.395 
• 51b Denès F. Pérez-Luna A. Chemla F. Chem. Rev.  2010,  110:  2366 

21

Reductive zincation of a vinyl radical has also been suggested to account for the formation of allenoates following zinc-mediated radical addition to propiolates, see ref. 17.

26

See the supporting information in ref. 24.

31

When CH₂Cl₂ was used as solvent, the Z/E ratio of product 5ha might not fully represent the diastereoselectivity of the zinc-atom transfer since in addition to these two diastereomers, a third tetrahydrofuran side product having incorporated a butyl residue was detected (∼20% yield in the crude) but could not be fully identified. In any case the diastereoselectivity of the reaction between 1h and Bu₂Zn in CH₂Cl₂ should at best be mediocre.

42

See the Supporting Information.