Molecular Iodine-Catalyzed Imine Activation for Three-Component ­Nucleophilic Addition Reactions

Abstract

β-Amino ketones and α-amino nitriles were synthesized from silyl enol ethers and trimethylsilyl cyanides, via a three-component nucleophilic addition reaction with aromatic aldehydes and amines; the reaction was found to be significantly accelerated by molecular iodine under neutral conditions.

molecular iodine - imine activation - three-component reaction - Mannich-type reaction - Strecker-type reaction

References

1a Córdova A. Acc. Chem. Res.  2004,  37:  102 

1b Gröger H. Chem. Rev.  2003,  103:  2795 

1c Kobayashi S. Ishitani H. Chem. Rev.  1999,  99:  1069 

2a Weinreb SM. Comprehensive Organic Synthesis   Vol. 5:  Trost BM. Fleming I. Pergamon; Oxford: 1991.  p.401 

2b Boger DL. Weinreb SM. Hetero Diels-Alder Methodology in Organic Synthesis   Academic; San Diego: 1987.  Chap. 2.

2c Boger DL. Weinreb SM. Hetero Diels-Alder Methodology in Organic Synthesis   Academic; San Diego: 1987.  Chap. 9.

3a Ojima I. Inaba S.-I. Yoshida K. Tetrahedron Lett.  1977,  18:  3643 

3b Veenstra SJ. Schmid P. Tetrahedron Lett.  1997,  38:  997 

4 Kobayashi S. Sugiura M. Kitagawa H. Lam WW.-L. Chem. Rev.  2002,  102:  2227 

5a Bhosale RS. Bhosale SV. Bhosale SV. Wang T. Zubaidha PK. Tetrahedron Lett.  2004,  45:  7187 

5b Phukan P. J. Org. Chem.  2004,  69:  4005 

5c Yadav JS. Reddy BVS. Rao KV. Raj KS. Rao PP. Prasada AR. Gunasekar D. Tetrahedron Lett.  2004,  45:  6505 

5d Bandgar BP. Bettigeri SV. Joshi NS. Synth. Commun.  2004,  34:  1447 

5e Phukan P. Synth. Commun.  2004,  34:  1065 

5f Karimi B. Golshani B. Synthesis  2002,  784 

5g He Z. Gao G. Hand ES. Kispert LD. Strand A. Liaaen-Jensen S. J. Phys. Chem. A  2002,  106:  2520 

5h Xu X. Zhang Y. Synth. Commun.  2002,  32:  2643 

5i Basu MK. Samajdar S. Becker FF. Banik BK. Synlett  2002,  319 

5j Yadav JS. Reddy BVS. Rao CV. Rao KV. J. Chem. Soc., Perkin Trans. 1  2002,  1401 

5k Ramalinga K. Vijayalakshmi P. Kaimal TNB. Tetrahedron Lett.  2002,  43:  879 

5l Yadav JS. Chand PK. Anjaneyulu S. Tetrahedron Lett.  2002,  43:  3783 

5m Periana RA. Mirinov O. Taube DJ. Gamble S. Chem. Commun.  2002,  20:  2376 

5n Firouzabadi H. Iranpoor N. Sobhani S. Tetrahedron Lett.  2002,  43:  3653 

6 Lee BS. Mahajan S. Janda KD. Tetrahedron Lett.  2005,  46:  807 

7

Typical Procedure for β-Amino Ketone and α-Amino Nitrile Synthesis.
To a MeOH solution (10 mL) was added aldehyde (1.0 mmol), aniline (1.1 mmol) and nucleophile (1.2 mmol, silyl enol ether for β-amino ketone or trimethylsilyl cyanide for α-amino nitrile). Upon completion of the reaction (monitored by TLC), aq Na₂SO₃ (1 mL) and H₂O (100 mL) were added. The organic compounds were extracted with EtOAc (3 × 20 mL) from the aqueous solution and the combined extract was dried over Na₂SO₄. The solvent was evaporated under reduced pressure. The residue was purified by flash chromatography on silica gel to afford pure product, characterized by ¹H NMR, ¹³C NMR and mass spectrometry.