A General Procedure for the Synthesis of 1,3-Bis(indolyl) Compounds via Michael­ Addition Catalyzed by InBr₃/TMSCl

Abstract

A new facile entry to the synthesis of 1,3-bis(indol-3-yl)butane-1-ones is presented. The procedure effectively utilizes a InBr₃/TMSCl mixture (10 mol%) as a promoter for the chemoselective Michael addition of variously functionalised indoles to α,β-unsaturated indolyl ketones. The excellent yields and the mildness of the experimental conditions guarantee a widespread applicability of the protocol towards the construction of functionalised keto-bis(indolyl) compounds.

catalysis - enones - indium - indoles - Michael additions

References

1 Zhao S. Liao X. Cook JM. Org. Lett.  2002,  4:  687 ; and references cited therein

2a Faulkner DJ. J. Nat. Prod. Rep.  2001,  18:  1 

2b Miyake FY. Yakushijin K. Horne DA. Org. Lett.  2002,  4:  941 

2c Jiang B. Yang C.-G. Wang J. J. Org. Chem.  2002,  67:  1396 

3 Nenaidenko VG. Baraznenok IL. Balenkova FS. Russ. J. Org. Chem.  1998,  34:  1019 

4a Bandini M. Cozzi PG. Giacomini M. Melchiorre P. Umani-Ronchi A. J. Org. Chem.  2002,  67:  3700 

4b Bandini M. Melchiorre P. Melloni A. Umani-Ronchi A. Synthesis  2002,  1110 

5 Okuachi T. Itonaga M. Minami T. Owa T. Kitoh K. Yoshino H. Org. Lett.  2000,  2:  1485 

The combined use of chlorosilanes and InCl₃ as Lewis acids in organic transformations was first reported by Mukaiyama et al.:

6a Mukaiyama T. Ohno T. Han JS. Kobayashi S. Chem. Lett.  1991,  949 

6b Mukaiyama T. Ohno T. Nishimura T. Han SJ. Kobayashi S. Bull. Chem. Soc. Jpn.  1991,  64:  2524 

For a discussion concerning the accelerating effects of trimethylsilyl halides in catalyzed conjugate additions, see:

7a Corey EJ. Boaz NW. Tetrahedron Lett.  1985,  26:  6015 

7b Corey EJ. Boaz NW. Tetrahedron Lett.  1985,  26:  6019 

7c Pollock P. Dambacher J. Annes R. Brgdahl M. Tetrahedron Lett.  2002,  43:  3639 

8

Benzothiophene and N-methylpyrrole were also reacted with 1a in the presence of InBr₃/TMSCl (10 mol%) affording the corresponding 1,4-adduct in 18% and 72% yields, respectively. With N-methylpyrrole, the product was isolated as a 1:1 mixture of C-2/C-3 nucleophilic addition.

9a Routier S. Saugé L. Ayerbe N. Couder G. Mérour J.-Y. Tetrahedron Lett.  2002,  43:  589 

9b Nettekoven M. Psiorz M. Waldmann H. Tetrahedron Lett.  1995,  36:  1425 

10 A large excess of TMSCl was already found helpful in promoting the Sakurai reaction in combination with catalytic InCl₃: Lee PH. Lee K. Sung S. Chang S. J. Org. Chem.  2001,  66:  8646 

11

No Lewis acid/Lewis base interaction was detectable by ¹H NMR (CD₂Cl₂, r.t.) analysis of a 1a/TMSCl mixture.

12 Bandini M. Cozzi PG. Garelli A. Melchiorre P. Umani-Ronchi A. Eur. J. Org. Chem.  2002,  3243 

13 Onishi Y. Iko T. Yasuda M. Baba A. Tetrahedron  2002,  58:  8227 

14a de Koning CB. Michael JP. Rousseau AL. J. Chem. Soc., Perkin Trans. 1  2000,  1705 

14b Vaillancourt V. Albizati KF. J. Am. Chem. Soc.  1993,  115:  3499 

14c Mahboobi S. Teller S. Pongratz H. Hufsky H. Sellmer A. Botzki A. Uecker A. Beckers T. Baasner S. Schächtele A. Überall F. Kassack MU. Dove S. Böhmer F. J. Med. Chem.  2002,  45:  1200