LETTER
An Improved Promoter System for Aryl Transfer via Orano-Bismuth Reagents
1209
The optimized conditions provided a 65% isolated yield
of 10 on a 4.5 mmol scale, after chromatography (Scheme
15
4
). These conditions also provided increased yields for
the biphenyl transfer reaction (Scheme 5).
Acknowledgment
Useful discussions with Professors Steve Hanessian and Tohru Fu-
kuyama during these studies are gratefully acknowledged.
References and Notes
(
1) Shuker, S. B.; Hajduk, P. J.; Meadows, R. P.; Fesik, S. W.
Science 1996, 274, 1531-1534.
Having identified a set of conditions which minimized
side reactions from the acylate ligands, we briefly investi-
gated use of this system for other copper acylate-mediated
arylation reactions which have been reported in the litera-
ture (Scheme 6). As expected, diols are efficiently
monoarylated. As had been previously reported for copper
acetate-based systems, we did not observe reaction with
alcohols lacking a second coordination site. Copper piv-
alate also can serve as a promoter of aryl transfer to
amines by triaryl Bi(III) compounds. These preliminary
studies suggest that the improved system does not provide
fundamentally new reactivity to the system, but does min-
imize side reactions, giving improved results.
(
2) Hajduk, P. J.; Sheppard, G. S.; Nettesheim, D. G.; Olejniczak,
E. T.; Shuker, S. B.; Meadows, R. P.; Steinman, D. H.;
Carrera, G. M.; Marcotte, P. A.; Severin, J.; Walter, K.; Smith,
H.; Gubbins, E.; Simmer, R.; Holtzman, T. F.; Morgan, D. W.;
Davidsen, S. K.; Summers, J. B.; Fesik, S. W. J. Am. Chem.
Soc. 1997, 119, 5818-5827.
(3) Gresham, T. L.; Jansen, F. W.; Shaver, F. W.; Bankert, R. A.;
Beears, W. L.; Prendergast, M. G. J. Am. Chem. Soc. 1949, 71,
661-663.
(
(
4) Sinclair, P. J.; Wong, F.; Wyvratt, M.; Syaruch, M. J.;
Dumont, F. Bioorg. Med. Chem. Lett. 1995, 5, 1035-1038.
5) For reviews on organobismuth chemistry, see: Freedman, L.
D.; Doak, G. O. Chem. Rev. 1982, 82, 15-57; Barton, D. H. R.;
Finet, J.-P. Pure Appl. Chem. 1987, 59, 937-946.
(
(
(
6) David, S.; Thieffry, A. Tetrahedron Lett. 1981, 22, 5063-
5
066.
7) Barton, D. H. R.; Finet, J.-P. J. Chem. Soc., Chem. Commun.
986, 65-66.
Summary
1
Aryl transfer reactions using in situ generated bismuth(V)
species in combination with a copper(II) promoter were
found useful for access to analogs desired for a medicinal
chemistry program. The efficiency of aryl transfer was in-
creased by removing the competitive acetate nucleophile
8) For a recent review describing this type of inhibitor, see Zask,
A.; Levin, J. I.; Killar, L. M.; Skotnicki, J. S. Curr. Pharm.
Design 1996, 2, 624.
(
9) Experimental procedures for the synthesis of compounds 5
and 7 from 2R-malic acid may be found in Fesik, S. W.;
Summers, J. B.; Davidsen, S. K.; Sheppard, G. S.; Steinman,
D. H.; Carrera, G. M.; Florjancic, A. S.; Holms, J. H.
™
from the system through the use of OXONE as the in situ
oxidant, and copper pivalate as the promoter. Preliminary
studies suggest that the improved system does not provide
fundamentally new reactivity to the system, but does min-
imize side reactions, giving improved results.
“Biphenyl Hydroxamate Inhibitors of Matrix
Metalloproteinases” United States Patent 5,665,777,
September 9, 1997.
Synlett 1999, No. 8, 1207–1210 ISSN 0936-5214 © Thieme Stuttgart · New York