Selective hydrogenolysis of novel benzyl carbamate protecting groups

Organic Letters

Volumn 2, Issue 8, 2000, Pages 1049-1051

  Papageorgiou, Edward A ^a   Gaunt, Matthew J ^a   Yu, Jin Quan ^a   Spencer, Jonathan B ^a  

^a UNIVERSITY OF CAMBRIDGE   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

EID: 0001066380     PISSN: 15237060     EISSN: None     Source Type: Journal    
DOI: 10.1021/ol005589l     Document Type: Article

References (17)

1. Greene, T. W.; Wutts, P. G. M. Protection for the Amino Group. In Protective Groups in Organic Synthesis, 3rd ed.;, John Wiley & Sons Inc: New York, 1999. Kunz, H.; Waldmann, H. In Protecting Groups. Comprehensive Organic Synthesis: Selectivity, Strategy and Efficiency in Modern Organic Chemistry; Trost, B. M., Fleming, I., Eds.; Pergamon Press: Elmsford, NY, 1991; Vol. 6, pp 631-642. Kocienski, P. J. In Protecting Groups; Georg Thieme: Stuttgart, 1994 and references therein.
2. Greene, T. W.; Wutts, P. G. M. Protection for the Amino Group. In Protective Groups in Organic Synthesis, 3rd ed.;, John Wiley & Sons Inc: New York, 1999. Kunz, H.; Waldmann, H. In Protecting Groups. Comprehensive Organic Synthesis: Selectivity, Strategy and Efficiency in Modern Organic Chemistry; Trost, B. M., Fleming, I., Eds.; Pergamon Press: Elmsford, NY, 1991; Vol. 6, pp 631-642. Kocienski, P. J. In Protecting Groups; Georg Thieme: Stuttgart, 1994 and references therein.
3. Greene, T. W.; Wutts, P. G. M. Protection for the Amino Group. In Protective Groups in Organic Synthesis, 3rd ed.;, John Wiley & Sons Inc: New York, 1999. Kunz, H.; Waldmann, H. In Protecting Groups. Comprehensive Organic Synthesis: Selectivity, Strategy and Efficiency in Modern Organic Chemistry; Trost, B. M., Fleming, I., Eds.; Pergamon Press: Elmsford, NY, 1991; Vol. 6, pp 631-642. Kocienski, P. J. In Protecting Groups; Georg Thieme: Stuttgart, 1994 and references therein.
4. Gaunt, M. J.; Yu, J.; Spencer, J. B. J. Org. Chem. 1998, 63, 4172-4173.
5. Gaunt, M. J.; Boschetti, C. E.; Yu, J.; Spencer, J. B. Tetrahedron. Lett. 1999, 40, 1803-1806.
6. Bergmann, M.; Zervas, L. Ber. Dtsch. Chem. Ges. 1932, 65, 1192-1201.
7. For discussions, see: Berse, C.; Boucher, R.; Piché, L. J. Org. Chem. 1957, 22, 805-808. Carpino, L. A.; Tunga, A. J. Org. Chem. 1986, 51, 1930-1932.
8. For discussions, see: Berse, C.; Boucher, R.; Piché, L. J. Org. Chem. 1957, 22, 805-808. Carpino, L. A.; Tunga, A. J. Org. Chem. 1986, 51, 1930-1932.
9. 2O/hexane as the eluent. Both chloroformates could be stored for long periods (12 months) without decomposition in a refrigerator.
10. tBoc groups. They were also found to be resistant to hydrolysis by aqueous base (NaOH or LiOH), conditions used for the saponification of methyl esters.
11. For the purposes of subsequent discussion the mono-deprotected amines carry the designations 6a-h.
12. 1H NMR.
13. 2 (20%) without detectable reduction of the nitrile, but not with Pd-C (10%).
14. For selective hydrogenolysis of CNAP over hydrogenation of the aromatic nitro group, the reaction had to be performed in dry EtOAc.
15. 1H NMR of the crudes showed a single product in each case. The lower than expected isolated yields resulted from the purification procedure that had to be employed with these compounds. Their very polar nature excluded flash column chromatography.
16. The generality of this approach is being investigated.
17. Attempts to selectively reduce the aromatic nitro group in N-Cbz 3-nitrophenylamine with Pd-C (10%) afforded a mixture of all possible products (23% of desired product). Similar results have been reported with Pd-C/diamine complexes, with which hydrogenolysis of benzyl-type groups is generally inhibited in the presence of other reducible functionality (Sajiki, H.; Hattori, K.; Hirota, K. J. Org. Chem. 1998, 63, 7990-7992).