Unexpected Rearrangement in the Heck Cyclization of Positional Isomers of Chiral 2,3-Disubstituted Perhydro-1,3-benzoxazines

Abstract

The intramolecular Heck cyclization on 2,3-disubstituted perhydro-1,3-benzoxazines, derived from (-)-8-amino menthol, easily proceeds at reflux of acetonitrile or DMF. The behavior of positional isomers was quite different. Reaction of 2-aryl-3-allyl perhydro-1,3-benzoxazines occurred as expected giving exclusively 6-exo cyclization products. On the contrary, regioisomeric 3-(iodobenzyl)-2-vinyl derivatives gave the normal cyclization compounds and rearranged 1,2-dihydroisoquinoline nucleus.

Key words

cyclizations - Heck reaction - palladium - rearrangements

References

• For recent reviews see:
• 1a Cabri W. Candiani I. Acc. Chem. Res.  1995,  28:  2 
• 1b Sodeberg BC. In Comprehensive Organometallic Chemistry II   Vol. 2:  Pergamon; Oxford: 1995.  p.259 
• 1c Gibson SE. Middelton RJ. Contemp. Org. Synth.  1996,  3:  447 
• 1d Negishi E. Copéret C. Ma S. Lion S.-Y. Liu F. Chem. Rev.  1996,  96:  365 
• 1e Shibasaki M. Boden CDJ. Kojima A. Tetrahedron  1997,  22:  7371 
• 1f Crisp GT. Chem. Soc. Rev.  1998,  27:  427 
• 2a Mori M. Ban Y. Tetrahedron Lett.  1979,  20:  1133 
• 2b Grigg R. Sridharan V. Stevenson P. Worakun T. J. Chem Soc., Chem. Commun.  1986,  1697 
• 2c Larock RC. Babu S. Tetrahedron Lett.  1987,  28:  5291 
• 2d Ableman MM. Oh T. Overman LE. J. Org. Chem.  1987,  52:  4130 
• 2e Grigg R. Sridharan V. Stevenson P. Sukirthalingam S. Tetrahedron  1989,  45:  3557 
• 2f Tietze LF. Burkhardt O. Synthesis  1994,  1331 
• 2g Tietze LF. Burkhardt O. Henrich M. Liebigs Ann.  1997,  1407 
• 3a Ashimori A. Matsuura T. Overman LE. Poon DJ. J. Org. Chem.  1993,  58:  6949 
• 3b Ohrai K. Kondo K. Sodeoka M. Shibasaki M. J. Am. Chem. Soc.  1994,  116:  11737 
• 3c Kondo K. Sodeoka M. Shibasaki M. J. Org. Chem.  1995,  60:  4322 
• 3d Tietze LF. Raschke T. Synlett  1995,  597 
• 3e Tietze LF. Thede K. Schimpf R. Sannicoli F. Chem. Commun  2000,  583 
• 3f Gilbertson SR. Fu Z. Org. Lett.  2001,  3:  161 
• 4 Meyers FE. Henniges H. de Meijere A. Tetrahedron Lett.  1992,  33:  8039 
• 5 Grigg R. Dorrity MJR. Malone JF. Mongkolaussavaratana T. Norbert WDJA. Sridharan V. Tetrahedron Lett.  1990,  31:  3075 
• 6a Pedrosa R. Andrés C. Iglesias JM. Obeso MA. Tetrahedron  2001,  57:  4005 
• 6b Pedrosa R. Andrés C. Iglesias JM. J. Org. Chem.  2001,  66:  243 
• 7 Pedrosa R. Andrés C. Iglesias JM. Pérez-Encabo A. J. Am. Chem. Soc.  2001,  123:  1817 
• 8 Kojima A. Kanemoto T. Sodeoka M. Shibasaki M. Synthesis  1998,  581 
• 9 Pedrosa R. Andrés C. Iglesias JM. Obeso MA. Tetrahedron  2001,  57:  4005 
• 10a Jeffery T. Synthesis  1987,  70 
• 10b Jeffery T. J. Chem. Soc., Chem. Commun.  1984,  1287 
• 11 Prepared from PdCl₂ as described in: Stephenson TA. Morehouse SM. Powell AR. Heffer JP. Wilkinson G. J. Chem Soc.  1965,  3632 
• 13 Heck RF. Palladium Reagents in Organic Synthesis   Academic Press; London: 1985. 
• 14a Ableman MM. Overman LE. Tran VD. J. Am. Chem. Soc.  1990,  112:  6959 
• 14b Overman LE. Pure Appl. Chem.  1994,  66:  1423 
• 15 Ripa L. Hallberg A. J. Org. Chem.  1997,  62:  595 
• 16a Hacksell V. Daves GD. Organometallics  1983,  2:  772 
• 16b Nguefack JF. Bolitt V. Sinou D. J. Chem. Soc., Chem. Commun.  1995,  1893 
• 16c Albéniz AC. Espinet AC. Lin Y.-S. Organometallics  1997,  16:  5964 
• 17 Andrés C. Nieto J. Pedrosa R. Villamañán N. J. Org. Chem.  1996,  61:  4130 
• 18a Kraft ME. Wilson AM. Fu Z. Procter MJ. Dasse OA. J. Org. Chem.  1998,  63:  1748 
• 18b Díaz Buezo N. Alonso I. Carretero JC. J. Am. Chem. Soc.  1998,  120:  7129 
• 19 Inue S. Takaya H. Tani K. Otsuka S. Sato T. Noyori R. J. Am. Chem. Soc.  1990,  112:  4897 

12

Heck Cyclization of Compound 5a , Typical Procedure: A stirred suspension of perhydro-1,3-benzoxazine 5a (850 mg, 2 mmol), palladium acetate (17 mg, 0.1 mmol), potassium acetate (754 mg, 8 mmol), tetrabutylammonium bromide (650 mg, 2 mmol) and triphenylphosphine (80 mg, 0.3 mmol) in dry and deoxygenated acetonitrile (20 mL) was refluxed for 8 h. After being cooled to r.t., the solvent was evaporated, and the residue was partially dissolved in boiling hexane and filtered. The filtrate was evaporated giving 9a (535 mg, 1.8 mmol, 90%) as an oily residue. ¹H NMR (δ): 0.85-1.18 (m, 2 H); 0.88 (d, J = 6.5 Hz, 3 H); 1.21-1.32 (m, 1 H); 1.39-1.53 (m, 2 H); 1.41 (s, 3 H); 1.43 (s, 3 H); 1.66-1.72 (m, 2 H); 1.82-1.86 (m, 1 H); 2.01 (s, 3 H); 3.74 (dt, J = 4.0 Hz, 10.4 Hz, 1 H); 6.16 (s, 1 H); 6.48 (s, 1 H); 7.14-7.17 (m, 2 H); 7.28-7.33 (m, 2 H). ¹³C NMR (δ): 16.0; 19.9; 22.2; 25.4; 26.9; 31.3; 34.7; 41.1; 51.5; 57.4; 75.6; 82.4; 104.1; 120.5; 125.0; 126.4; 127.3; 127.9; 128.8; 132.0.