Carbonylative coupling of organozinc reagents in the presence and absence of aryl iodides: synthesis of unsymmetrical and symmetrical ketones

Abstract

The utility of the palladium(0) catalysed reaction of the iodoalanine-derived organozinc reagent 6a with functionalised aryl iodides, under a carbon monoxide atmosphere, to give protected 4-aryl-4-oxo α-amino acids 8, is illustrated by a short synthesis of L-kynurenine 4. Treatment of functionalised organozinc reagents with catalytic tetrakis(triphenylphosphine)palladium(0) under an atmosphere of carbon monoxide in the absence of any electrophile leads to the formation of symmetrical functionalised ketones 9 in good yields. This reaction is illustrated by a one-step synthesis of protected (2S,6S)-4-oxo-2,6-diaminopimelic acid 9a from commercially available compounds. It has been established that adventitious molecular oxygen plays a key role in the formation of the symmetrical ketones 9, and that rigorous exclusion of oxygen can result in substantially higher yields of ketones 8 in the cross-coupling with some aromatic iodides.

References

1. R. F. W. Jackson, K. James, M. J. Wythes and A. Wood, J. Org. Chem., 1992, 57, 3397.
2. M. J. Dunn, R. F. W. Jackson, J. Pietruszka and D. Turner, J. Org. Chem., 1995, 60, 2210.
3. S. Bhar and B. C. Ranu, J. Org. Chem., 1995, 60, 745.
4. M. J. Dunn, R. F. W. Jackson, J. Pietruszka, N. Wishart, D. Ellis and M. J. Wythes, Synlett, 1993, 499.
5. For a recent synthesis references to earlier work, see F. G. Salituro and I. A. McDonald, J. Org. Chem., 1988, 53, 6138.
6. N. P. Botting, Chem. Soc. Rev., 1995, 24, 401.
7. J. A. Bajgrowicz, A. El Hallaoui, R. Jacquier, C. Pigiere and P. Viallefont, Tetrahedron, 1985, 41, 1833 The compound is now available from the Aldrich Chemical Company.
8. For a preliminary communication on part of the work discussed in this paper, see: R. F. W. Jackson, D. Turner and M. H. Block, J. Chem. Soc. Chem. Commun., 1995, 2207.
9. For the preparation of unsymmetrical and symmetrical ketones by carbonylation of zinc organometallics, see K. Yasui, K. Fugami, S. Tanaka and Y. Tamaru, J. Org. Chem., 1995, 60, 1365 For the carbonylation of other organometallic reagents, see references cited therein.
10. For an important preliminary report which describes the in situ carbonylative coupling of aryl iodides with alkyl iodides mediated by zinc palladium(0), see Y. Tamaru, H. Ochiai, Y. Yamada and Z.-I. Yoshida, Tetrahedron Lett., 1983, 24, 3869.
11. These conditions are derived from those reported by Salituro and McDonald for an analogous deprotection (ref. 5 above).
12. See R. Pellicciari, M. A. Gallo-Mezo, B. Natalini and A. M. Amer, Tetrahedron Lett., 1992, 33, 3003.
13. R. Pellicciari, B. Natalini, G. Costantino, M. R. Mahmoud, L. Mattoli, B. M. Sadeghpour, F. Moroni, A. Chiarugi and R. Carpenedo, J. Med. Chem., 1994, 37, 647.
14. R. F. W. Jackson, N. Wishart and M. J. Wythes, J. Chem. Soc., Chem. Commun., 1992, 1587.
15. A. Devasagarayaj and P. Knochel, Tetrahedron Lett., 1995, 36, 8411.
16. S. Aoki and E. Nakamura, Tetrahedron, 1991, 47, 3935.
17. For a discussion of the mechanism of self-coupling of arylboronic acids to give biaryls under palladium catalysis which also invokes oxidation by molecular oxygen, see M. Moreno-Mañas, M. Pérez and R. Pleixats, J. Org. Chem., 1996, 61, 2346 and references cited therein. For related observations on the homocoupling of arylstannanes, see V. Farina, B. Krishnan, D. R. Marshall and G. P. Roth, J. Org. Chem., 1993, 58, 5434.
18. J. E. Baldwin, R. M. Adlington, A. U. Jain, J. N. Kolhe and M. W. D. Perry, Tetrahedron, 1986, 42, 4247.
19. S. Tokutake, S. Imanishi and M. Sisido, Mol. Cryst. Liq. Cryst., 1989, 170, 245.