Addition of Trialkylalanes to Imines under Zirconium Catalysis

Abstract

Trialkylalanes, which are inert toward imines, undergo addition to them in the presence of a catalytic amount of dichloro­dicyclopentadienylzirconium(IV) (Cp₂ZrCl₂). The reaction tolerates the presence of several functional groups in the starting imine such as halo, amide, nitrile, and hydroxy groups. A possible reaction pathway is proposed involving metallacyclic intermediates.

Key words

zirconium - catalysis - trialkylalanes - amine synthesis - imines

References

• 1a Gandon V. Bertus P. Szymoniak J. Eur. J. Org. Chem.  2001,  3677 
• 1b Gandon V. Bertus P. Szymoniak J. Synthesis  2002,  1115 
• 2 Takahashi T. Liu Y. Xi C. Huo S. Chem. Commun.  2001,  31 
• 3a Dzhemilev UM. Vostrikova OS. Sultanov RM. Izv. Akad. Nauk SSSR, Ser. Khim.  1983,  218 
• 3b Takahashi T. Seki T. Nitto Y. Saburi M. Rousset CI. Negishi E. J. Am. Chem. Soc.  1991,  113:  6266 
• 3c Lewis DP. Muller PM. Whitby RJ. Jones RVH. Tetrahedron Lett.  1991,  32:  6797 
• Higher Grignard reagents react with alkenes only in the presence of an internal Lewis base, see:
• 4a Hoveyda AH. Morken JP. Houri AF. Xu Z. J. Am. Chem. Soc.  1992,  114:  6692 
• 4b Heron NM. Adams JA. Hoveyda AH. J. Am. Chem. Soc.  1997,  119:  6205 
• 5 Negishi E. Huo S. In Titanium and Zirconium in Organic Synthesis   Marek I. Wiley-VCH; Weinheim: 2002.  Chap. 1.
• 6a Van Horn DE. Negishi E. J. Am. Chem. Soc.  1978,  100:  2252 
• 6b Negishi E. Van Horn DE. Yoshida T. J. Am. Chem. Soc.  1985,  107:  6639 
• 6c Negishi E. Kondakov DY. Choueiry D. Kasai K. Takahashi T. J. Am. Chem. Soc.  1996,  118:  957 
• 7a Kondakov DY. Negishi E. J. Am. Chem. Soc.  1995,  117:  10771 
• 7b Kondakov DY. Negishi E. J. Am. Chem. Soc.  1996,  118:  1577 
• 7c Negishi E.; Chem.-Eur. J.; 1999, 5: 411
• 8a Alberola A. Cermeño FA. Anton A. An. Quim.  1977,  73:  886 
• Lanthanide-catalyzed addition of Et₃Al to aromatic Schiff bases has recently been reported, see:
• 8b Tsvelikhovsky D. Gelman D. Molander GA. Blum J. Org. Lett.  2004,  6:  1995 
• These reactions mainly involve the addition of organolithium and organozinc reagents to imines under Lewis base, acid, or transition-metal catalysis, for reviews, see:
• 9a Denmark SE. Nicaise OJ.-C. In Comprehensive Asymmetric Catalysis   Jacobsen EN. Pfaltz A. Yamamoto H. Springer; Berlin: 1999.  p.923 
• 9b Kobayashi S. Ishitani H. Chem. Rev.  1999,  99:  1069 
• 12 Gridd R. McMeekin P. Sridharan V. Tetrahedron  1995,  51:  13331 
• 13 Ziegler K, and Nagel K. inventors; US  2744127. 
• 14 Samec JSM. Bäckvall J.-E. Chem.-Eur. J.  2002,  8:  2955 
• 15 Chi Y. Zhou Y.-G. Zhang X. J. Org. Chem.  2003,  68:  4120 
• 16 Wu M.-J. Pridgen LN. J. Org. Chem.  1991,  56:  1340 
• 17a Motoyama Y. Mikami H. Kawakami H. Aoki K. Nishiyama H. Organometallics  1999,  18:  3584 
• 17b Nakagawa M. Kaware T. Kakikawa T. Yamada H. Matsui T. Hino T. Tetrahedron  1993,  49:  1739 
• 18 Micovic IV. Ivanovic MD. Piatak DM. Bojic VD. Synthesis  1991,  1043 

10

Ketimines proved to be inert toward Et₃Al in these conditions.

11

In the case of the carboalumination (R ¹ Me) of alkenes, a mechanism switch from cyclic to acyclic was noticed by changing from nonpolar to chlorinated solvents, see ref. 7.