C O M M U N I C A T I O N S
Scheme 3a
a Conditions: (a) Pd2(dba)3, AsPh3, CuCl, DIEA, CH3CN, 70 °C, 4 h, 70%; (b) Super-Hydride, THF, - 78 °C, 1 h, 80% (dr >10 :1); (c) Ti(OiPr)4,
nBu4NOAc, 4 Å MS, CH2Cl2, room temp, 10 h, 60%; (d) Ac2O, pyridine, room temp, 2 h; (e) Et3N-3HF, CH3CN, room temp, 12 h, 67% for two steps; (f)
TPAP, NMO, CH2Cl2, room temp, 20 min; (g) NaClO2, NaH2PO4, 2-methyl-2-butene, tBuOH/H2O, room temp, 12 h, 88% for two steps; (h) TFAA, DCE,
i
4 Å MS, room temp, 1 h, 90%; (i) CBr4, PrOH, 84 °C, 1 h; (j) Pd/C, air, EtOAc, room temp, 30 min, 70% for two steps; (k) TBSNHNHTBS, Sc(OTf)3,
CH2Cl2; (l) PhIF2, 2-chloropyridine, CH2Cl2, 35% for two steps.
K-10 clay20 cleanly afforded the desired epoxyketone 6 (fragment
coordinates and files in CIF format. This material is available free of
A) in 90% yield. The synthesis of fragment B (7) was initiated
from readily available 1,5-naphthoquinone 16 (Scheme 2).21 Protec-
tion of 16 using MOMCl/DIEA afforded naphthalenedione 17,
which was subsequently reduced with Na2S2O4 and further protected
to generate 18. Stannylation of aryl bromide 18 (Pd(PPh3)4, bis-
(tributyltin))22 afforded the desired arylstannane 7 (70%).
References
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With both fragments A and B in hand, we initiated studies on
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pound 19 was found to have two major rotamers (2:1) by 1H-NMR
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26
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Acknowledgment. This paper is dedicated to Prof. James S.
Panek on the occasion of his 50th birthday. Financial support from
the NIH (Grant GM62842), Bristol-Myers-Squibb (Unrestricted Grant
in Synthetic Organic Chemistry), and Merck Research Laboratories
is gratefully acknowledged. We thank Mr. Stephen Scully (Boston
University) for helpful discussions, and Prof. Philip J. Proteau
(Oregon State University) for providing authentic kinamycin D.
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Supporting Information Available: Experimental procedures and
characterization data for all new compounds; X-ray crystal structure
JA066621V
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