Synthesis of atropisomeric 2-(1-aminoalkyl)-1-naphthamides by stereoselective addition of organolithiums to a 2-imino-1-naphthamide

Tetrahedron Letters

Volumn 40, Issue 17, 1999, Pages 3329-3330

  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 IMINO 1 NAPHTHAMIDE; NAPHTHALENE DERIVATIVE; ORGANOLITHIUM COMPOUND; UNCLASSIFIED DRUG;

ARTICLE; CRYSTAL STRUCTURE; MOLECULAR MODEL; REACTION ANALYSIS; STEREOCHEMISTRY; SYNTHESIS; THERMODYNAMICS;

EID: 0033597321     PISSN: 00404039     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0040-4039(99)00519-5     Document Type: Article

References (9)

1. 1. Ahmed, A.; Bragg, R. A.; Clayden, J.; Lai, L. W.; McCarthy, C.; Pink, J. H.; Westlund, N.; Yasin, S. A. Tetrahedron 1998, 54, 13277.
2. 2. Clayden, J. Synlett 1998, 810.
3. 3. Clayden, J.; Pink, J. H. Tetrahedron Lett. 1997, 38, 2561.
4. 4. Clayden, J.; Darbyshire, M.; Pink, J. H.; Westlund, N.; Wilson, F. X. Tetrahedron Lett. 1997, 38, 8487.
5. 5. Clayden, J.; Pink, J. H.; Yasin, S. A. Tetrahedron Lett. 1998, 39, 105.
6. 6. Clayden, J.; Westlund, N.; Wilson, F. X. Tetrahedron Lett. 1996, 37, 5577.
7. 7. Clayden, J.; Pink, J. H. Tetrahedron Lett. 1997, 38, 2565.
8. 8. For a discussion of control of amide conformation by an adjacent stereogenic centre, and the importance of the size of the groups carried by the centre, see ref. 5
9. 9. The low yield is due to cyclisation of the N-lithio amine product onto the amide (to give a lactam 5) which outpaces N-alkylation by BnBr. LDA is eliminated, which re-deprotonates 5 α to nitrogen, and the anion formed is alkylated to give 6 in 64% (R = Me) or 54% (R = Bu) yield. The reaction giving 3 (Scheme 1) also produces traces of 5 (4% after 1 h; 15% after 3 h). (formula presented)