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.

cyclizations - Heck reaction - palladium - rearrangements

References

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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.

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