Table 2. Application of the Suarez Oxidation to the C-25,26 Diol Derivatives
substrate
X
Y
R1
R2
C14-C15
PhI(OAc)2:I2 (equiv)
T (°C)
time (h)
productsa
% yield
14
18a
18b
18c
18d
18e
18f
H
OBz
H
H
OBz
OBz
OBz
H
OBz
OBz
H
H
H
H
H
Bz
Bz
H
∆
1.1:0.5
2.5:1.0
2.0:1.0
2.0:2.0
2.0:2.0
2.0:2.0
25
0
0
0
0
5
3
12
8
7
7
19r
94b
TBDPS
Ac
H
H
Bz
14R-H
19â/22â
22r/23r
20r/21r
22â/23â
20â/21â
42/51
78/13
77/14
78/14
75/15
14
∆
14
∆
14
∆
14
H
∆
0
a The R- and â-compounds have the R- and â-C-12 benzoate, respectively. b Using HgO, I2, CCl4, 25 °C, 15 h gives a yield of 19R of 77%.
°C, 1 h, then 40 °C, 2 h) gave 22RH(D) products with a
series of steroids, ruling out internal delivery of hydride, yet
AlCl3 and dithiol at 25 °C gave a C-26 thioacetal.8c
As expected from our previous studies,10 selective asym-
metric dihydroxylation of the olefin moiety proved especially
difficult. Establishment of a workable excess of the requisite
25S diastereomer was only obtained when employing the
(DHQ)2PHAL ligand (Table 1). This effect extended to both
C-12 benzoates but was only seen with the C-14,15 olefins,
while sp3 centers at C-14,15 completely eroded the reagent-
based stereoselection.
variable but minor amounts of the desired primary alcohol
17a (Scheme 4). In stark contrast, silyl benzoate 15b is
Scheme 4
Having developed a satisfactory protocol for installation
of the distal C-25(S),26 diol moiety, we next turned to
reestablishment of the spiroketals. For this transformation
we adopted the hypoiodite method so successfully pioneered
by Suarez. In preparation for reestablishment of the 5/6
spiroketal (1,6-dioxaspiro[4,5]decane) [VITA 143] it was
necessary to protect the tertiary alcohol in order to avoid
oxidative cleavage of the 1,2-diol. While silylation of the
primary alcohol of the C-25(S)-rich diol mixture followed
by acetylation of the tertiary alcohol generates 15a in 21%
overall yield, numerous fluoride and acidic attempts to
deprotect silyl ether 15a to alcohol 17a resulted in extensive
acyl migration, mainly yielding primary acetate 16a with
readily deprotected to tertiary benzoate 17b in 96% yield
without formation of any of the acyl migration product 16b.
Application of the Suarez oxidation11 to the C-25,26 diol
derivatives prepared in Table 1 revealed several important
points (Table 2). The first of these was that diols and mono-
silyl ether were not appropriate substrates as they suffered
significant to extensive cleavage to ketone 19 (18a-b).
Primary monoacetate 17a cyclized with high efficiency to
stereospecifically provide 5/5 spiroketals, revealing the
osmylation ratio of 22R/23R to be 5.9:1 (18c). The mono-
benzoates (18d-f) proved to be the substrates of choice, each
affording a high yield of the desired 5/6 spiroketals 20/21,
which were easily separated by chromatography at this stage.
Global deprotection of 20R, 21R, 20â, 21â, and 22R pro-
vided target spiroketals A, B, C, D, and E (Scheme 1),
respectively.
(9) Ireland, R. E.; Daub, J. P. J. Org. Chem. 1983, 48, 1303-1312.
(10) Sharpless, K. B.; Amberg, W.; Bennani, Y. L. J. Org. Chem. 1992,
57, 2768. Sharpless, K. B.; Crispino, G. A.; Jeong, K. S. J. Org. Chem.
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P. L. J. Am. Chem. Soc. 1999, 121, 2056-2070. Jeong, J. U.; Guo, C.;
Fuchs, P. L. J. Am. Chem. Soc. 1999, 121, 2071-2084.
(11) Concepcion, J. L.; Francisco, C. G.; Hernandez, R.; Salazar, J. A.;
Suarez, E. Tetrahedron Lett. 1984, 25, 1953-1956. de Armas, P.;
Concepcion, J. I.; Francisco, C. G.; Hernanez, R.; Salazar, J. A.; Suarez,
E. J. Chem. Soc., Perkin Trans. 1 1989, 405-411. Martin, A.; Salazar, J.
A.; Suarez, E. Tetrahedron Lett. 1995, 36, 4489-4492. Furuta, K.; Nagata,
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8822-8825.
Using a 3-D presentation of the Kishi comparison format
(Figure 1),12 it appears that the North spiroketal unit of
ritterazine M bears the unusual R axial C-12 alcohol along
with the more typical R C-22 oxygen configuration and C-25
axial alcohol as shown in the corrected structure 1b. A point
(12) Lee, J.; Kobayashi, Y.; Tezuka, K.; Kishi, Y. Org. Lett. 1999, 1,
2181-2184. Kobayashi, Y.; Lee, J.; Tezuka, K.; Kishi, Y. Org. Lett. 1999,
1, 2177-2180.
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