Synthesis of atropisomeric diamides with remotely related stereogenic axes by stereoselective additions to imines

Tetrahedron Letters

Volumn 40, Issue 17, 1999, Pages 3331-3334

  Clayden, Jonathan ^a   Westlund, Neil ^a   Wilson, Francis X ^b  

^a UNIVERSITY OF MANCHESTER   (United Kingdom)

^b ROCHE PRODUCTS LTD   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

2 (N METHYLFORMIMINO)BENZAMIDE; DIAMIDE; IMINE; UNCLASSIFIED DRUG;

ARTICLE; CHIRALITY; CONFORMATION; CONFORMATIONAL TRANSITION; DIASTEREOISOMER; MOLECULAR MODEL; REACTION ANALYSIS; STEREOCHEMISTRY; STRUCTURE ANALYSIS; SYNTHESIS; X RAY CRYSTALLOGRAPHY;

EID: 0033597159     PISSN: 00404039     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0040-4039(99)00520-1     Document Type: Article

References (17)

1. 1. Clayden, J. Synlett 1998, 810.
2. 2. Clayden, J.; Pink, J. H.; Yasin, S. A. Tetrahedron Lett. 1998, 39, 105.
3. 3. Clayden, J.; Westlund, N.; Wilson, F. X. (accompanying paper).
4. 4. Ackerman, J. H.; Laidlaw, G. M. Tetrahedron Lett. 1969, 4487.
5. 5. Clayden, J.; Darbyshire, M.; Pink, J. H.; Westlund, N.; Wilson, F. X. Tetrahedron Lett. 1997, 38, 8487.
6. 6. Ahmed, A.; Bragg, R. A.; Clayden, J.; Lai, L. W.; McCarthy, C.; Pink, J. H.; Westlund, N.; Yasin, S. A. Tetrahedron 1998, 54, 13277.
7. 7. Bowles, P.; Clayden, J.; Helliwell, M.; McCarthy, C.; Tomkinson, M.; Westlund, N. J. Chem. Soc., Perkin Trans. 1 1997, 2607.
8. 8. Imine 9 was made in 87% yield by stirring the aldehyde 20 with 40% aqueous methylamine.
9. -1). See ref. 6.
10. 10. The conformers of 11 can interconvert under the conditions of the crystallisation, so the crystal strutcure may not represent the preferred conformation in solution. However, the same conformational preference is evident in the crystal structure of 13a, whose conformers are atropisomers which cannot interconvert under the conditions of the crystallisation.
11. 11. The "conformational interlocking" apparent in benzamides bearing 2-(1-trialkylsilyl)ethyl and 2-(1-trialkylstannyl)ethyl substituents is probably operating here: see ref. 2 and the discussion in ref. 1. The conformational preferences arise because both Me and NHMe are smaller than CH(R)Ar [R = H, Me or NHMe].
12. 12. Both centres are controlled by axis A, whose stereodirecting influence over-rides the expected (ref. 3) ability of axis B to control the direction attack on the imino groups.
13. 13. Why axis A of 18 should not epimerise is unclear, since unlike axis A of 17 it has no adjacent centre to control it while axis B epimerises. The stability of this conformation of axis A may be at least partly due to the presence of a weak hydrogen-bond between NH and C=O of axis A. (The corresponding O-N interatomic distance is 3.28 Å, N-H-O angle 8.2° in the X-ray crystal structure of 11; O-N distance 3.25 Å, N-H-O angle 12.8° in 13a.)
14. 14. Snieckus, V. Chem. Rev. 1990, 90, 879.
15. 15. Court, J. J.; Hlasta, D. J. Tetrahedron Lett. 1996, 37, 1335.
16. 16. Chen, C.-W.; Beak, P. J. Org. Chem. 1986, 51, 3325.
17. 17. Comins, D. L.; Brown, J. D. J. Org. Chem. 1984, 49, 1078.