K. Lee, J.-M. Im / Tetrahedron Letters 42 (2001) 1539–1542
1541
References
91% yield with no observable amount of epoxidized or
Baeyer–Villiger oxidized by-products (entry 2).13 This
result undoubtedly implies that the ylide carbon of 4a
is far more nucleophilic than the other carbons of 4a
toward the electrophilic oxygen of MMPP. The com-
parable high chemoselectivity was reported for the oxi-
dation of sulfide to sulfoxide using MMPP supported
on silica in dichloromethane at rt.14 Other phosphorus
keto ylides (4b,c) with a conjugated double bond, and
phosphorus keto ylide (4d) with an isolated double
bond were also converted cleanly into their corre-
sponding tricarbonyls (5b,c,d) in good yields under the
similar reaction conditions (entries 3–5). The simple
phosphorus keto ylide (4e) with an aromatic sub-
stituent was oxidized to tricarbonyl 5e in 90% yield
without an observable amount of Baeyer–Villiger oxi-
dized by-product (entry 6). The oxidation of bis-phos-
phorus keto ylide 4f is of special interest since a
number of natural and synthetic substances whose
cytotoxicity and antitumor/antibiotic activity is
attributed to interstrand DNA cross-linking ability
have been reported recently.15 Thus, bis-phosphorus
keto ylide 4f was converted into the bis-vicinal tricar-
bonyl 5f, an effective interstrand DNA cross-linking
agent,16 with a little excess of MMPP (79%, entry 7).
In view of the fact that numerous compounds contain-
ing heterocyclic substituents exhibit biologically inter-
esting properties,17 it is of interest to efficiently
synthesize tricarbonyls with heterocyclic moieties.
Thus, thiophene-substituted phosphorus keto ylide 4g
was oxidized selectively to tricarbonyl 5g in 92% with
no detectable amounts of thiophene ring- and/or S-
oxidized by-products (entry 8). Furan-based keto ylide
4h also afforded tricarbonyl 5h in good yield under
similar conditions. Several phosphorus keto ylides with
amino acids (N-Cbz-Phe-, N-Boc-Gly-) and dipeptides
(N-Cbz-Gly-Phe-)18 were also tested under the similar
reaction conditions; however, the results were disap-
pointing (yields <40%) apparently due to the forma-
tion of several by-products.
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12. MMPP used in this experiment was a hexahydrate
(MMPP·6H2O, 80% purity) which was newly purchased
from Aldrich Chem. Co.
13. Typical experimental procedure: MMPP (97.4 mg, 1.05
equiv.) was placed in a 30 mL dry, round-bottomed flask
containing a magnetic stirring bar and fitted with a
rubber septum. H2O (47.3 mL) was added from a syringe
over MMPP drop by drop, and the mixture was stirred
until a thick paste was obtained (for ca. 2–3 minutes).
Dry CH2Cl2 (1.5 mL) was added to the flask from a
syringe, followed by the addition of phosphorus keto
ylide 4a (68.8 mg, 0.15 mmol). The heterogeneous mix-
ture was stirred at rt under Ar. After complete disappear-
ance of 4a (4.5 h), the mixture was filtered. The solid
residue was washed with CH2Cl2 (5 mL×3) and the
washings were combined with the filtrate. Removal of the
solvent under reduced pressure provided a pale-yellow
oil, which was purified on Prep-TLC (SiO2) to afford
tricarbonyl 5a as a hydrate in 91% yield. Rf 0.42 (hex-
anes/EtOAc, 2/1); IR (KBr) 3465 (br), 3419 (br), 2990,
2941, 1728, 1699, 1625, 1447, 1372, 1311, 1277, 1122,
In conclusion, we have shown that unsupported, moist
MMPP is an efficient and practical oxidant for the
selective oxidation of various phosphorus keto ylides
to vicinal tricarbonyls in dichloromethane at ambient
temperature. Considering the advantages of MMPP,
favorable reaction conditions, high selectivity, good to
excellent yields, and operational simplicity, this oxida-
tive protocol should be valuable for preparing vicinal
tricarbonyls from various phosphorus keto ylides
under mild conditions. Further investigation of the
scope, limitations, and application of this oxidation to
the synthesis of complicated molecules is underway
and will be reported in due course.
Acknowledgements
1036, 833, 802, 750 cm−1 1H NMR (400 MHz, CDCl3,
;
ppm) l 1.46 (s, 9H), 1.99 (s, 3H), 2.26 (s, 3H), 5.11 (brs,
2H), 6.17 (s, 1H).
14. Ali, M. H.; Stevens, W. C. Synthesis 1997, 764.
Generous financial support from Woosuk University is
gratefully acknowledged.
.