Diastereoselective enolate chemistry using atropisomeric amides

Tetrahedron Letters

Volumn 37, Issue 42, 1996, Pages 7607-7610

  Hughes, Adam D ^a   Price, David A ^a   Shishkin, Oleg ^a   Simpkins, Nigel S ^a  

^a UNIVERSITY OF NOTTINGHAM   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

AMIDE;

ARTICLE; DRUG SYNTHESIS; ENANTIOMER; REACTION ANALYSIS; STEREOCHEMISTRY;

EID: 0030583467     PISSN: 00404039     EISSN: None     Source Type: Journal    
DOI: 10.1016/0040-4039(96)01673-5     Document Type: Article

References (17)

1. 1. Houben-Weyl, Methods of Organic Chemistry, Vol E21, Thieme, Stuttgart, 1995.
2. 2. See for example, Evans, D. A.; Ng, H. P.; Clark, J. S.; Rieger, D. L. Tetrahedron 1992, 48, 2127.
3. 3. For a list of examples, see reference 6a. See also (a) Seebach, D.; Wasmuth, D. Angew. Chem. Int. Ed. Engl. 1981, 20, 971. (b) Atkinson R. S.; Barker, E.; Price, C. J.; Russell, D. R. J. Chem. Soc., Chem. Commun. 1994, 1159.
4. For a list of examples, see reference 6a. See also (a) Seebach, D.; Wasmuth, D. Angew. Chem. Int. Ed. Engl. 1981, 20, 971. (b) Atkinson R. S.; Barker, E.; Price, C. J.; Russell, D. R. J. Chem. Soc., Chem. Commun. 1994, 1159.
5. 4. Curran, D. P.; Qi, H.; Geib, S. J.; DeMello, N. C. J. Am. Chem. Soc. 1994, 116, 3131. The work described in this paper was inspired by a lecture delivered by Professor Curran at the 6th Brazilian Meeting on Organic Synthesis, Sao Paulo, 5-9 September 1994.
6. 5. The meta-tert-butyl group was present simply out of synthetic expediency and was not thought to influence the stereochemical outcome of these reactions.
7. 6. Related publications have appeared recently, see (a) Bowles, P.; Clayden, J.; Tomkinson, M. Tetrahedron Lett. 1995, 36, 9219. (b) Thayumanavan, S.; Beak, P.; Curran, D. P. Tetrahedron Lett. 1996, 37, 2899.
8. Related publications have appeared recently, see (a) Bowles, P.; Clayden, J.; Tomkinson, M. Tetrahedron Lett. 1995, 36, 9219. (b) Thayumanavan, S.; Beak, P.; Curran, D. P. Tetrahedron Lett. 1996, 37, 2899.
9. 7. Professor Curran has informed us of his similar findings, from unpublished work conducted by his coworkers H. Qi and A. Balog.
10. 8. The preferred conformations of the anilides themselves are well established to be as shown, see for example Stewart, W. E.; Siddall III, T. H. Chem. Rev. 1970, 70, 517. However, we expect that the loss of amide resonance on formation of the lithium enolate results in greatly increased conformational mobility around the CO-N bond.
11. 1H NMR spectra of crude products.
12. 10. Purification of samples of products 7, by bulb-to-bulb distillation (at ca. 220 °C), resulted in extensive epimerisation, allowing identification of minor atropisomers. Variable temperature NMR studies showed that the isomer ratio of 7 (R = Bn) changed from 25:1 to 2:1 after 65 min at 95 °C.
13. 11. The atropselectivities indicated are with respect to the anilide aryl C-N axis, the aldol products also showed additional minor signals attributed to amide C-N rotamers.
14. 12. Evans, D. A.; Urpi, F.; Somers, T. C.; Clark, J. S.; Bilodeau, M. T. J. Am. Chem. Soc. 1990, 112, 8215.
15. 3).
16. 14. Maintaining a solution of non-racemic (-)-4 at 50 °C for 5h resulted in no change in enantiomeric excess, as monitored by HPLC.
17. 15. Curran, D. P.; Yu, H.; Liu, H. Tetrahedron 1994, 50, 7343.