atom delivery occurred on the convex face of the intermediate
tetracyclic benzylic radical. Cyclization of a benzylic radical
with the acetylene to form 6 was expected to occur in a
similar fashion.5 Moreover, an NOE (6.7%) was observed
between the C1-H and the proximate C10-H.
To elucidate the mechanism of the reaction, the hypothesis
of Scheme 3 was tested. Intermediate dioxetane 14,9 as a
Scheme 3
Prior to exploring the introduction of oxygen at C9a,
prudence dictated that a method be developed first for
excising the atoms of the allyl ether moiety of 6 to produce
a styrene. Although the exocyclic double bond of 6 could
be readily isomerized to the endo cyclic position [cat. (Ph3P)3-
RhCl, DABCO, aqueous EtOH, 95 °C, 83%], efforts to
functionalize or cleave oxidatively the endo cyclic double
bond were unsuccessful. However, olefin 6 was converted
to ketone 8 by ozonolysis with the proviso that the basic
nitrogen of 6 was first protected as its N-oxide. Direct
ozonolysis led to decomposition. Not only did dimethyl
sulfide serve its usual role of reducing the ozonide, but it
also effected reduction of the N-oxide.
After several unsuccessful attempts to oxygenate the
carbon adjacent to the carbonyl group in spiro dihydrofura-
none 8, treatment of the furanone under the Gardner protocol6
[KHMDS, (EtO)3P, and O2] also failed to give any R-ketol
but rather surprisingly and rewardingly afforded the desired
styrene 7 in excellent yield! Moreover, the reaction proceeded
in the absence of the phosphite. Olefin 7 had been prepared
previously by Martin sulfurane dehydration (70%)7 where
other more conventional elimination techniques proved
unsuccessful.8
radical or anion, could fragment to the carboxylate anion or
radical 15, which could undergo elimination. The â-formyl-
oxy carboxylic acid of 15 was readily accessible from
â-hydroxy acid 9a. Treatment of the formate ester under
simulated reaction conditions led only to hydroxy acid 9b,
saponification occurring presumably as the result of adventi-
tious hydroxide.
The possibility of a radical decarboxylation of acyloxy
radical 15 to an intermediate benzyl radical prior to elimina-
tion was considered less likely because such radical species
are the product of acyloxy group migration from the benzylic
position to a primary radical.10 Nonetheless, the formyloxy
carboxylic acid was activated as its thiohydroxamate ester
and photolyzed with visible light.11 No styrene was observed,
but stereoisomeric benzyl dimers were identified along with
sulfur-containing products of radical origin.
The generality of the reaction was explored on the less
complex, racemic furanone 12, prepared from (S)-ibuprofen
(9a) as described in Scheme 2. The model retained a
An R-keto-γ-butyrolactone was considered as a likely
intermediate in the elimination procedure. To explore this
possibility, ketolactone 18 was prepared as outlined in
Scheme 4. Upon exposure of this material to K2CO3 in
aqueous THF at room temperature, R-methylstyrene and
oxalic acid were formed. Oxalic acid was identified by 13C
Scheme 2
1
NMR and by H NMR of its dimethyl ester.
McMurry has reported the formation of R-methylene
cyclohexanone from oxalocyclohexanone 20 (Scheme 5)
upon exposure of the latter compound to gaseous formal-
dehyde in aqueous NaHCO3 at 0 °C.12,13 The presumed
1
(4) New compounds were characterized by H and 13C NMR spectros-
copy, combustion analysis, and/or HRMS.
(5) For an example of stereocontrol in spiroalkylation, see: Stork, G.;
Danheiser, R. L., Ganem, B. J. Am. Chem. Soc. 1973, 95, 3414.
(6) (a) Gardner, J. N.; Carlon, F. E.; Gnoj, O. J. Org. Chem. 1968, 33,
3294. (b) Gardner, J. N.; Popper, T. L.; Carlon, F. E.; Gnoj, O.; Herzog, H.
L. J. Org. Chem. 1968, 33, 3695.
(7) Martin, J. C.; Arhart, R. J. J. Am. Chem. Soc. 1971, 93, 4327.
(8) For a related elimination, see: Jones, G. B.; Guzel, M.; Mathews, J.
E. Tetrahedron Lett. 2000, 41, 1123.
(9) For examples of the fragmentation of 1,2-dioxetanes, see: Singlet
Oxygen; Schaap, P. A., Zaklika, K. A., Eds.; Academic Press: New York,
1979; Vol. 40, Chapter 6, p 173.
quaternary carbon and an aromatic ring. The orange enolate
solution of 12 was bleached immediately by O2 to give olefin
11 in the absence of phosphite.
(10) Beckwith, A. L. J.; Crich, D.; Duggan, P. J.; Yao, Q. Chem. ReV.
1997, 97, 3273.
(1) Ziegler, F. E.; Berlin, M. Y. Tetrahedron Lett. 1998, 39, 2455.
(2) Ziegler, F. E.; Belema, M. J. Org. Chem. 1997, 62, 1083.
(3) For total syntheses of mitomycin K, see: (a) Benbow, J. W.; McClure,
K. F.; Danishefsky, S. J. J. Am. Chem. Soc. 1993, 115, 12305. (b) Wang,
Z.; Jimenez, L. S. Tetrahedron Lett. 1996, 37, 6049.
(11) Barton, D. H. R.; Crich, D.; Motherwell, W. B. Tetrahedron 1985,
41, 3901.
(12) Ksander, G. M.; McMurry, J. E.; Johnson, M. J. Org. Chem. 1977,
42, 1180.
(13) See also, Nield, C. H. J. Am. Chem. Soc. 1945, 67, 1145.
3620
Org. Lett., Vol. 2, No. 23, 2000