Synthesis of the C1-C21 fragment of the serine/threonine phosphatase inhibitor tautomycin

Article abstract of DOI:10.1021/jo952083l

Compound 40 containing the C-1-C-21 region of tautomycin has been synthesized. The two halves (4 and 5) of this spirocyclic section were each constructed using Matteson's chloromethylene insertion reaction. Cr/Ni-mediated coupling of compounds 4 and 5 resulted in a structure containing the C-1-C-21 section of tautomycin. Oxidation of the resultant allylic alcohol to the ketone and removal of the α,β unsaturation yielded compound 39. Treatment with DDQ removed both PMB protecting groups and allowed the spirocyclic ketal to form producing compound 40, ready for further extension to the natural product tautomycin.

Full text of DOI:10.1021/jo952083l

3106
J . Org. Chem. 1996, 61, 3106-3116
Syn th esis of th e C1-C21 F r a gm en t of th e Ser in e/Th r eon in e
P h osp h a ta se In h ibitor Ta u tom ycin
Karl W. Maurer and Robert W. Armstrong*
Department of Chemistry and Biochemistry, University of California, Los Angeles, California 90095
Received November 27, 1995X
Compound 40 containing the C-1-C-21 region of tautomycin has been synthesized. The two halves
(4 and 5) of this spirocyclic section were each constructed using Matteson’s chloromethylene insertion
reaction. Cr/Ni-mediated coupling of compounds 4 and 5 resulted in a structure containing the
C-1-C-21 section of tautomycin. Oxidation of the resultant allylic alcohol to the ketone and removal
of the R,â unsaturation yielded compound 39. Treatment with DDQ removed both PMB protecting
groups and allowed the spirocyclic ketal to form producing compound 40, ready for further extension
to the natural product tautomycin.
In tr od u ction
of calyculin C and nodularin. Using a combination of
molecular modeling and 2D NMR analysis, we have
derived an overlay of the proposed ground state struc-
tures of tautomycin, calyculin, mycrocystin, nodularin,
and okadaic acid in order to understand the common
structural motifs associated with these diverse struc-
tures. The recent elucidation of the X-ray structure of a
cocrystal of PP1 and mycrocystin should further aid in
providing a global analysis of these inhibitors.11 Several
groups have reported on their work associated with the
total synthesis of tautomycin.12 This includes the syn-
thesis of a C-1 to C-26 fragment reported by Shibasaki,
in addition to the total synthesis of the natural product
in 1994 by Oikawa’s group.13 In the context of our
abovementioned work on the SAR studies of PP1 and
PP2A inhibitors, we focused our work on the synthesis
of tautomycin to include a route which would be ame-
nable to isotopic labeling and minor structural modifica-
tions. We have used the chemistry developed by
Matteson14 involving the stereospecific insertion of a
chloromethylene into a boron-carbon bond directed by
Tautomycin (1) is a novel secondary metabolite isolated
from the fermentation broth of Streptomyces spiroverti-
cillatus by Isono et. al. in 1987.1 Karaki and MacKintosh
have shown that tautomycin is a selective inhibitor of
serine/threonine phosphatases PP1 and PP2A, two of the
four main classes of phosphatases in the cytosol of human
cells. The structure of tautomycin shows little similarity
to that of other natural products which competitively
inhibit PP1 and PP2A. These include the calyculins,2
microcystins,3 nodularin,4 motuporin,5 and okadaic acid.6
Of this series, the calyculins, okadaic acid, and tauto-
mycin,7 all possess at least one spiroketal, though struc-
tural similarities resulting from this moiety are difficult
to generalize. The unsaturated anhydride found in
tautomycin is unique in this series of inhibitors and has
been proposed to exist in equilibrium as the diacid in an
aqueous solution.8 The presence of the carboxylate
moiety may be critical for activity9 and is found in all
the inhibitors except calyculin, where a phosphate may
act as the isostere. The anhydride cantharidin, structur-
ally similar to the anhydride side chain of tautomycin,
has also been shown to be an inhibitor of PP1 and PP2A,
albeit at substantially reduced potency.10
(4) Botes, D. P.; Wessels P. L.; Kruger, H.; Runnegar, M. T. C.;
Santikarn, S.; Smith, R. J .; Barna, J . C. J .; Williams, D. H. J . Chem.
Soc., Perkin Trans. 1 1985, 2747-2748.
(5) Schreiber, S. L.; Valentekovich, R. J . J . Am Chem. Soc. 1995,
117, 9069-9070.
(6) Tachibana, K.; Scheuer, P. J .; Tsukitani, Y.; Kikuchi, H.; Engen,
D. V.; Clardy, J .; Gopichand, Y.; Schmitz, F. J . J . Am. Chem. Soc. 1981,
103, 2469-2471.
(7) (a) Ubukata, M.; Cheng, X. C.; Isobe, M.; Isono, K J . Chem. Soc.,
Perkin Trans. 1 1993, 617-24. (b) Hori, M.; Magae, J .; Han, Y. G.;
Heartshorne, D. J .; Karaki, H. FEBS 1991, 25, 145-148. (c) MacK-
intosh, C.; Klumpp, S. FEBS 1991, 277, 137-140.
(8) Ichikawa, Y.; Naganawa, A.; Isobe, M. Synlett 1993, 737-738.
(9) The methyl ester of okadaic acid shows no activity in vitro.
(10) Li, Y. M.; Casida, J . E. Proc. Natl. Acad. Sci. U.S.A. 1992, 89,
11867-11870.
(11) Goldberg, J .; Huang, H.; Kwon, Y.; Greengard, P.; Nairn, A.
C.; Kuriyan, J . Nature 1995, 376, 745-753.
(12) (a) Oikawa, M.; Ueno, T.; Oikawa, H.; Ichihara, A. J . Org. Chem.
1995, 60, 5048-5068. (b) Nakamura, S.; Shibasaki, M. Tetrahedron
Lett. 1994, 35, 4145-448. (c) Oikawa, H.; Oikawa, M.; Ueno, T.;
Ichihara, A. Tetrahedron Lett. 1994, 35, 4809-4812. (d) Naganawa,
A.; Ichikawa, Y.; Isobe, M. Tetrahedron 1994, 50, 8969-8982. (e)
Oikawa, M.; Oikawa, H.; Ichihara Tetrahedron Lett. 1993, 34, 4797-
4800. (f) Ichikawa, Y.; Naganawa, A.; Isobe, M. Synlett 1993, 737-
738. (g) Ichikawa, Y.; Tsuboi, K.; Naganawa, A.; Isobe, M. Synlett 1993,
907-908.
Our interest in this compound stems from our ongoing
work on the synthesis, SAR, and conformational studies
X Abstract published in Advance ACS Abstracts, April 1, 1996.
(1) Cheng, X. C.; Kihara, T.; Kusakbe, H.; Magea, J .; Kobayashi,
Y.; Fang, R. P.; Ni, Z. F.; Shen, Y. C.; Ko, K.; Yamaguchi, I.; Isono, K.
J . Antibiot. 1987, 40, 907-909.
(2) (a) Kato, Y.; Fusetani, N.; Matsunaga, S.; Hashimoto, K. J . Am.
Chem. Soc. 1986, 108, 2780-2781. (b) Kato, Y.; Fusetani, N.; Matsu-
naga, S.; Hashimoto, K. J . Org. Chem. 1988, 53, 3930-3932. (c)
Matsunaga, S.; Fujiki, H.; Sakata, D. Tetrahedron 1991, 47, 2999-
3006.
(13) Oikawa, M.; Ueno, T.; Oikawa, H.; Ichihara, A. J . Org. Chem.
1995, 60, 5048-5068. Oikawa, H.; Oikawa, M.; Ueno, T.; Ichihara, A.
Tetrahedron Lett. 1994, 35, 4809-4812.
(14) (a) Matteson, D. S.; Ray, R.; Rocks, R. R.; Tsai, D. Organome-
tallics 1983, 2, 1536-1543. (b) Matteson, D. S.; Sadhu, K. M.; Peterson,
M. L. J . Am. Chem. Soc. 1986, 108, 810-819. (c) Matteson, D. S.;
Kandil, A. A.; Soundararajan, R. J . Am. Chem. Soc. 1990, 112, 3964-
3969. (d) Matteson, D. S.: Peterson, M. L. J . Org. Chem. 1987, 52,
5116-5121.
(3) Honkanen, R. E.; Zwiller, J .; Moore, R. E.; Daily, S. L.; Khatra,
B. S.; Dukelow, M.; Boynton, A. L. J . Biol. Chem. 1990, 265, 19401-
19404.
S0022-3263(95)02083-4 CCC: $12.00 © 1996 American Chemical Society

Synthesis of the C1-C21 Fragment of Tautomycin
J . Org. Chem., Vol. 61, No. 9, 1996 3107
Sch em e 1
the pinanediol chiral auxiliary to construct stereocenters
at carbons 3, 13, 14, and 15 in the spirocyclic half of
tautomycin.
affords an entry to the synthesis of either of the alkyl
halide isomers by the use of either the (-)- or (+)-
pinanediol auxiliaries. However, continual change of the
ligands on boron in a linear synthesis is severely limited
by the yields for these transformations. An alternative
strategy is to keep the same auxiliary throughout the
synthesis and simply vary the order of nucleophiles to
suit the stereochemical requirements of the desired
diastereomer. Since the (+)-pinanediol chiral auxiliary
is reported to consistently give S- chloromethylene inser-
tion product,15 the construction of the C-10 to C-18
fragment of tautomycin was carried out without changing
the chiral auxiliary during the course of synthesis.
Methaneboric acid was allowed to react with (+)-
pinanediol (6) to give the pinanediolborate ester (7) in
almost quantitative yield (Scheme 1). (Dichloromethyl)-
lithium is generated by deprotonation of CH2Cl2 with
n-butyl lithium at -100 °C in THF solution following the
procedure of Matteson.16 Addition of compound 7 to the
(dichloromethyl)lithium followed by ZnCl2 and warming
to rt over several hours yielded chloride 8 in 61% yield
along with a large amount of recovered starting material.
Compound 8 was treated with homoallylmagnesium
bromide, which is titrated into the reaction until TLC
analysis showed the starting material had been con-
sumed. After stirring overnight, the reaction yielded 80%
of 9. A second insertion with (dichloromethyl)lithium
generated chloride 10 in 92% yield.
The retrosynthesis we have employed is shown in eq
1. We anticipated that an aldol condensation of the C-1/
C-21 methyl ketone with the left half aldehyde could be
controlled to afford the correct stereochemistry at C-22.
Further disconnection of the spirocyclic half was envi-
sioned to occur at the carbonyl carbon via a Ni/Cr
coupling. The stereocenters at C13-C15 could be intro-
duced using Matteson chloromethylene insertion chem-
istry, and the centers at C18 and C19 could readily be
generated using a Brown allylboration. A similar series
of transformations were targeted for fragment 5.
Reaction of chloride 10 with lithium p-methoxybenzyl
oxide generated PMB ether 11 in 76% yield (Scheme 2).
This material is considerably more polar than the chlo-
ride and can be separated by chromatography. To
achieve optimum yield, the reaction must be monitored
carefully and stopped when all chloride has been con-
sumed. Extended reaction time reduced the yield sub-
stantially. A third insertion yielded chloride 12 in 92%
yield. At this point, displacement was attempted with
the Grignard derived from THP-protected 3-bromo-1-
propanol (13). Unfortunately this reaction produced a
mixture containing at least three different acetals in an
inseparable mixture. To avoid this mixture, the THP was
replaced with the tert-butyldimethylsilyl protecting group
(14), and the displacement was performed to produce
compound 15 in a 71% yield. The fourth insertion
proceeded to yield chloride 16, but with somewhat lower
yield of 49% and with the production of 34% of the
elimination product involving boron and the PMB ether.
More rapid warming of the reaction mixture to rt slightly
favored elimination, but slower warming failed to reduce
The asymmetric chloromethylene insertion reaction
provides a method for introduction of vicinal asymmetric
centers by keeping the auxiliary covalently bound to the
growing chain. This method seemed like an ideal choice
for the “insertion” of contiguous stereocenters in the
middle of a larger acyclic fragment (i.e. 4). This method
(15) See reference 14a.
(16) Matteson, D. S.; Majumdar, D. Organometallics 1983, 2, 1529-
1535.

3108 J . Org. Chem., Vol. 61, No. 9, 1996
Maurer and Armstrong
Sch em e 2
Sch em e 3
Sch em e 4
elimination. Compound 16 is readily dechlorinated by
treatment with sodium trimethoxyborohydride to yield
17 which is carried on to the next reaction without
further purification.
We had originally envisioned the simple removal of the
boron functionality by exposure to acid conditions. Un-
fortunately, while organic acids react quickly with tri-
alkylboranes, reaction with monoalkyl species requires
excessively harsh conditions.17 Since these conditions
proved too harsh for these substrates, compound 17 was
carried on as a crude mixture and oxidized with basic
hydrogen peroxide to yield alcohol 18 in 91% yield (from
the starting chloride) (Scheme 3). Alcohol 18 was con-
verted to mesylate 19 in 96% yield by treatment with
mesyl chloride and triethylamine. Finally deoxygenation
by reduction with lithium aluminum hydride yielded
compound 20 in 75% yield.
Sch em e 5
Compound 20 was readily converted to aldehyde 21 by
exposure to ozone followed by tributylphosphine reduc-
tion of the resulting ozonide (Scheme 4). Using the
allylboration chemistry developed by Brown,18 aldehyde
21 was converted into alcohol 22 in 71% yield, as a single
diastereomer.19 This alcohol was readily protected with
benzoyl chloride in pyridine to yield the benzoate ester
23. Treatment of compound 23 with TBAF in THF
removed the silyl protecting group, and oxidation of the
resulting alcohol 24 yielded aldehyde 4 containing the
C-21 to C-10 region of tautomycin.
Production of fragment 5 required the enantiomeric
pinanediol chiral auxiliary ((-)-pinanediol). Compounds
25-29 are exact enantiomers of compounds 7-10 and
were generated following the same procedures used for
the synthesis of these compounds with the substitution
of (-)-pinanediol for the (+)-pinanediol chiral auxiliary
(Scheme 5).
Reaction of 29 with methylmagnesium chloride allowed
production of compound 30 in 55% yield (Scheme 6). The
natural product contains a ketone at C-2. Because our
desired final coupling would involve an aldol condensa-
tion of the methyl ketone in fragment 3, we chose to keep
the C-2 carbon at the alcohol oxidation stage. In order
(17) Brown H. C.; Hebert N. C. J . Organomet. Chem. 1983, 255,
135-141.
(18) (a) J adhav, P. K.; Bhat, S. K.; Perumal, P. T.; Brown, H. C. J .
Org. Chem. 1986, 51, 432-439. (b) Brown, H. C.; J adhav, P. K.; Bhat,
S. K. J . Am. Chem. Soc. 1988, 110, 1535-1538.
(19) Only one diastereomer was observed in the 1H (360 MHz) and
13C (90 MHz) NMR spectra.

Synthesis of the C1-C21 Fragment of Tautomycin
J . Org. Chem., Vol. 61, No. 9, 1996 3109
Sch em e 6
Sch em e 8
Sch em e 7
Swern oxidation of compounds 37 yielded 61% of the
ketone 38 along with 31% of an unidentified rearrange-
ment product. Alternatively, Dess-Martin oxidation23
afforded unsaturated ketone 37 in 96% yield. It should
be noted that the usual Na2SO3 quench of the Dess-
Martin oxidation causes reduction of the ketone back to
the alcohol. This quench is therefore not performed, and
the entire reaction mixture is purified by chromatogra-
phy. We had initially intended to reduce the unsaturated
ketone simultaneously with cleavage of the PMB protect-
ing groups via dissolving metal reduction. Unfortu-
nately, compound 38 is not sufficiently robust to survive
these conditions, and no identifiable products were
isolated from these attempted transformations. Reduc-
tion following the dithionite conditions of Gelbard24 also
failed. Reduction of 38 using NaBH4 resulted in mostly
1,2 addition. Removal of the unsaturation was finally
accomplished by the use of (PPh3CuH)6 following the
procedure of Stryker,25 yielding ketone 39. Treatment
of 39 with DDQ removed both PMB protecting groups
and afforded spiroketylization to compound 40.
to avoid bringing through a diastereomeric mixture, we
introduced the alcohol asymmetically. This significantly
simplified NMR interpretation. Oxidative removal of
boron with H2O2/NaOH led to the volatile alcohol 31
which was converted to its TBDPS ether 32 in 71%
overall yield by reaction with tert-butyldiphenylsilyl
chloride and imidazole in DMF. Ozonolysis of 32 followed
by tributylphosphine workup led to the expected alde-
hyde 33 in 92% yield.
Allylboration converted aldehyde 33 to alcohol 34 in
54% yield (Scheme 7). This alcohol was protected as the
p-methoxybenzyl ether 35 using the acid-catalyzed trichlo-
roacetimidate procedure of Yonemitsu.20 The protected
compound is subjected to ozonolysis followed by tribu-
tylphosphine quench of the resulting ozonide to yield
aldehyde 36. This aldehyde underwent elimination if not
subsequently transformed to the vinyl halide in a rapid
fashion.
Following the procedures of Takai,21 the aldehyde was
converted to the vinyl iodide 5. The product vinyl iodide
was a mixture containing less than 10% of the cis isomer.
This mixture of isomers was not separated and was taken
on to be coupled with compound 4 to generate 37 (Scheme
8).
Aldehyde 4 and vinyl iodide 5 were mixed and treated
with NiCl2-doped CrCl2 following the procedures of Kishi
and Nozaki22 resulting in a mixture of allylic alcohols 37.
In order to establish the stereochemistry of the spiroket-
al and to confirm the relative stereochemistry of the other
stereocenters in 40, extensive ROESY26 studies were
carried out. ROESY cross peaks corresponding to the
protons on C-6 and C-14 confirm that the correct spiro-
cycle has formed. The C-14 proton shows both a large
(10.1 Hz), and small (2.2 Hz), coupling corresponding to
the C-15 and C-13 protons, confirming that it is in the
(22) Kishi, Y. Pure Appl. Chem. 1992, 64, 343-350. Takai, K.;
Tagashira, M.; Kuroda, T.; Oshima, K.; Utimoto, K.; Nozaki, H. J . Am.
Chem. Soc. 1986, 108, 6048-6050.
(23) Dess, D. B.; Martin, J . C. J . Am. Chem. Soc. 1991, 113, 7277-
7287.
(24) Louis-Andre, O.; Gelbard, G. Tetrahedron Lett. 1985, 26, 831-
832.
(25) Stryker, J . M.; Brestensky, D. M. Tetrahedron Lett. 1989, 30,
5677-5680. Stryker, J . M.; Brestensky, D. M.; Mahoney, W. S. J . Am.
Chem. Soc. 1988, 110, 291-293. Churchill, M. R.; Bezman, S. A.;
Osborn, J . A.; Wormald, J . Inorg. Chem. 1973, 11, 1818-1825.
(26) Leeflang, B. R.; Bouwstra, J . B. Kerekgyarto, J .; Kamerling, J .
P.; Vliegenthart, J .F. D. Carbohydr. Res. 1990, 208, 117-126.
(20) Nakajima, N.; Horita, K.; Abe, R.; Yonemitsu, O Tetrahedron
Lett. 1988, 29, 4139-4142.
(21) Takai, K., Nitta, K., Utimoto, k. J . Am. Chem. Soc. 1986, 108,
7408-7410.

3110 J . Org. Chem., Vol. 61, No. 9, 1996
Maurer and Armstrong
cooled to -100 °C, butyllithium (10.5 mL 2 M solution in
pentane) was added, and the solution was allowed to stir for
14 min. The solution turned cloudy and slightly yellow.
Compound 7 (4.070 g, 20.98 mmol) in THF (20 mL) was slowly
added and the solution allowed to stir for 10 min at -100 °C.
A solution of ZnCl2 (1.624 g, 11.94 mmol) in THF (12 mL) was
added, and the mixture was allowed to slowly warm to rt and
stirred at rt for 8 h. The mixture was partitioned between
acidic NH4Cl/HCl (100 mL 1.2 M HCl + 200 mL saturated
NH4Cl) and CH2Cl2 (300 mL). The organic extracts were dried
over Na2SO4, evaporated, and purified by column chromatog-
raphy (silica gel, 20% CH2Cl2 in pentane) to yield 3.095 g (61%)
of a partially purified oil. Typically, 15-20% of compound 7
equatorial position. The C-6 proton shows two large
couplings (9.5 Hz), and one small coupling (1.8 Hz). The
coupling of the proton at C-6 to the proton at C-7 is
expected to be large due to the anti relationship in the
spirocycle. The other two couplings are expected to come
from the methylene protons at C-5. The ROESY cross
peaks and the scalar couplings obtained for 40 compare
favorably to fragments isolated by Isobe27 from degrada-
tion of isolated natural tautomycin.
was also recovered. Data for compound 8: [R]25 ) +55.16°
D
(c ) 0.024 g/mL, in benzene); HREIMS m/z 243.1278, 242.1245
calcd for (M+) C12H20ClBO2; IR (NaCl plates neat cm-1) 2970,
2924, 2872, 1448, 1379, 1030, 650; 1H NMR (CDCl3, 360 MHz)
δ 4.33 (d, 1H, J ) 8.9, 1.9 Hz), 3.52 (q, 1H, J ) 7.5 Hz), 2.40-
2.13 (m, 2H) 2.05 (m, 1H) 1.93-1.80 (m, 1H) 1.53 (d, 3H, J )
7.5 Hz), 1.39 (s, 3H) 1.26 (s, 3H) 1.14 (d, 2H, J ) 11.1 Hz),
0.81 (s, 3H); 13C NMR (CDCl3, 90 MHz) δ 87.5, 79.3, 51.9, 40.0,
39.0, 36.0, 29.1, 27.7, 27.0, 24.7, 21.3.
(2R)-2-[(S)-P in a n ed iyld ioxy)b or yl]-5-h exen e (9).
A
Con clu sion
sample of compound 8 (2.845 g, 11.70 mmol) was azeotroped
with toluene, dissolved in THF (50 mL) and cooled to -78 °C.
3-Butenylmagnesium bromide was produced by addition of
1-bromo-3-butene (1.90 mL, 18.30 mmol) to magnesium metal
(0.600 g, 24.69 g atoms) in THF (5 mL). As necessary THF
was used to dilute the mixture, and a cooling bath was used
to control the exothermic reaction. The solution was stirred
until exotherming ceased and was then titrated into the THF
solution of compound 8 until the starting material was
consumed (approximately 1.25 equiv was needed). The reac-
tion was allowed to slowly warm to rt (2 h) and then allowed
to stir for 15 h at rt. The reaction was then partitioned
We have synthesized a fragment containing the C1-
C21 portion of the natural product tautomycin. Use of
Matteson’s chloromethylene insertion reaction has al-
lowed us to place a total of five stereocenters early in
the synthesis of fragment 40, each with a minimum de
of 95%.28 The overall yield of the four-insertion chain in
compound 16 was 11%, and the two-insertion chain in
compound 30 was produced in 22% overall yield. This
chemistry will allow us to selectively label these chains
at any of these stereocenters by the use of 13CH2Cl2 for
future isotope-edited NMR studies of the natural product
bound to PP1 and PP2A.
between HCl (1.2 M, 100 mL), NH4
Cl solution (100 mL
saturated), and CH2Cl2 (200 mL). The aqueous layer was
extracted with CH2Cl2 (100 mL), the organic extracts were
combined, dried over Na2SO4, and evaporated, and the re-
maining oil was purified by column chromatography (silica gel
2% diethyl ether in hexanes) to yield 2.188 g (80%) of a
partially purified oil (95%+ pure). [R]25D ) +30.50° (c ) 0.0239
g/mL in benzene); HREIMS m/z 262.2104, 262.2104 calcd for
(M+) C16H27BO2; IR (NaCl plates neat cm-1) 3076, 2920, 2872,
Exp er im en ta l Section
All reactions were performed under anhydrous conditions
under argon, unless otherwise stated. Insertion reactions
involving -100 °C baths used a ethanol/liquid nitrogen slurry
with a thick syrupy consistency. At this temperature all
reagents were added slowly down the chilled wall of the flask
to insure that the added solution was cooled to -100 °C prior
to entering the reaction mixture. All THF used was distilled
from sodium dispersion and benzophenone, methylene chloride
was distilled from P2O5, toluene and DMF were distilled from
CaH2, methanol was distilled from Mg turnings, and ZnCl2
was dried at 100 °C for 12 h and then fused in vacuum,
crushed, and stored (sealed glass ampules) under argon until
needed. For EI and CI HRMS 2σ ) 4 ppm.
1
1642, 1464, 1387; H NMR (CDCl3, 360 MHz) δ 5.80 (m, 1H,
5.01-4.90 (m, 2H), 4.24 (dd, 1H, J ) 7.7, 0.9 Hz), 2.48-2.28
(m, 1H), 2.25-2.15 (m, 1H), 2.15-2.00 (m, 3H), 1.95-1.80 (m,
3H), 1.67-1.55 (m, 1H), 1.50-1.45 (m, 4H (m 1H, + s 3H)),
1.39 (s, 3H), 1.17-1.05 (m, 1H), 0.98 (d, 3H, J ) 7.0 Hz), 0.83
(s, 3H); 13C NMR (CDCl3, 90 MHz) δ 140.0, 115.0, 86.0, 78.3,
52.0, 40.2, 38.9, 36.5, 33.9, 33.3, 29.4, 27.8, 27.2, 24.7, 16.3.
(1S,2R)-1-Ch lor o-2-m eth yl-1-[(S)-P in a n ed iyld ioxy)bo-
r yl]-5-h exen e (10). A mixture of THF (21 mL) and CH2Cl2
(0.60 mL, 9.176 mmol) was cooled to -100 °C, butyllithium
(3.80 mL, 2 M solution in pentane) was added, and the solution
was allowed to stir for 14 min. The solution turned cloudy
and slightly yellow, and compound 9 (1.999 g, 7.624 mmol,
azeotroped with toluene) in THF (10 mL) was slowly added
and the solution allowed to stir for 5 min at -100 °C at which
point the reaction mixture gelled. After another 5 min at -100
°C a solution of ZnCl2 (0.632 g, 4.644 mmol) in THF (6.2 mL)
was added, and the mixture was allowed to slowly warm to rt
(the gel rapidly liquefied on addition of ZnCl2, fully liquid by
-80 °C) and stirred at rt for 8 h. The mixture was partitioned
between acidic NH4Cl/HCl (100 mL 1.2 M HCl + 100 mL
saturated NH4Cl) and CH2Cl2 (200 mL). The aqueous layer
was extracted with CH2Cl2 (100 mL), and the organic extracts
were combined, dried over Na2SO4, evaporated, and purified
by column chromatography (silica gel, 50% CH2Cl2 in hexanes)
to yield 2.196 g (92%) of a partially purified oil (95+% pure).
(S)-P in a n ed iol Meth ylbor on a te (7). A mixture of meth-
anboronic acid (1.433 g, 23.94 mmol) and (S)-pinanediol (6)
(3.984 g, 23.39 mmol) in 25 mL diethyl ether was allowed to
stir at rt over Na2SO4 for 40 min. This mixture was parti-
tioned between 10% saturated Na2CO3 solution (50 mL) and
CH2Cl2 (50 mL). The organic extracts were dried over Na2-
SO4, evaporated, and distilled under vacuum (bp 88 °C, 5
mmHg) to yield 4.286 g (94%) of a clear oil. [R]25 ) 51.61° (c
D
) 0.0261 g/mL in benzene) HREIMS m/z 194.1480, 194.1478
calcd for (M+) C11H19BO2; IR (NaCl plates neat cm-1) 2970,
2918, 1475, 1369, 1032; 1H NMR (CDCl3, 360 MHz) δ 4.23 (dd,
1H, J ) 8.7, 1.9 Hz), 2.29 (m, 1H), 2.18 (m, 1H) 2.01 (t, 1H),
1.90-1.87 (m, 1H), 1.84-1.79 (m, 1H), 1.79 (s, 3H), 1.26 (s,
3H), 1.10 (d, 1H, J ) 10.9 Hz), 0.82 (s, 3H), 0.26 (s, 3H); 13C
NMR (CDCl3, 90 MHz) δ 85.3, 77.6, 51.2, 39.4, 38.1, 35.4, 28.6,
27.0, 26.4, 23.7
[R]25 ) +30.0° (c ) 0.0130 g/mL in benzene); HRCIMS m/z
(S)-P in a n ed iol (1S)-(1-Ch lor oeth yl)bor on a te (8).
mixture of THF (46 mL) and CH2Cl2 (1.65 mL, 25.2 mmol) was
A
D
310.1885, 310.1871 calcd for (M+) C17H28BClO2; IR (NaCl
plates neat cm-1) 2972, 2926, 1630, 1475, 1452, 1377, 1030,
909; 1H NMR (CDCl3, 360 MHz) δ 5.79 (m, 1H) 5.04-4.92 (m,
2H) 4.36 (dd, 1H, 9.0, 2.0 Hz), 3.39 (d, 1H, J ) 6.6 Hz), 2.40-
2.30 (m, 1H) 2.28-1.87 (m, 7H) 1.76-1.65 (m, 1H) 1.40-1.32
(27) Ubukata, M.; Cheng, X. C.; Isobe, M.; Isono, K. J . Chem. Soc.,
Perkin Trans. 1 1993, 617-624.
(28) No diastereomers were observed in the 1H NMR spectra.

Synthesis of the C1-C21 Fragment of Tautomycin
J . Org. Chem., Vol. 61, No. 9, 1996 3111
(m, 4H) 1.28 (s, 3H) 1.19 (d, 1H, J ) 11.0 Hz), 1.02 (d, 3H, 6.7
Hz), 0.84 (s, 3H); 13C NMR (CDCl3, 90 MHz) δ 139.3, 115.3,
87.4, 79.2, 51.9, 40.1, 39.0, 37.1, 36.1, 33.9, 31.9, 29.3, 27.8,
27.2, 24.7, 18.1.
partitioned between acidic NH4Cl/HCl (10 mL 1.2 M HCl +
40 mL saturated NH4Cl) and CH2Cl2 (50 mL). The organic
extracts were dried over Na2SO4, evaporated, and purified by
chromatography (50% CH2Cl2 in hexanes to 75% CH2Cl2 in
hexanes) to yield 0.721 g of a thick yellow oil (71%). [R]25
)
(1S ,2R )-1-[(4-Me t h oxyb e n zyl)oxy]-2-m e t h yl-1-[(S )-
p in a n ed iyld ioxy)bor yl]-5-h exen e (11). To a solution of
p-methoxybenzyl alcohol (0.960 mL, 7.6428 mmol) in THF (40
mL) at -78 °C was added butyllithium (3.5 mL, 2 M in
pentane, 7.00 mmol). The solution was allowed to warm to
dissolve frozen p-methoxybenzyl alcohol and then recooled, and
DMSO (0.6 mL) was added, followed by compound 10 (2.096
g, 6.747 mmol) in 10 mL of THF. The reaction was allowed to
warm to rt and monitored by TLC until the starting chloride
had been consumed (about 2 h). The reaction mixture was
partitioned between HCl (100 mL, 1.2 M) and CH2Cl2 (200
mL), and the aqueous layer was extracted with CH2Cl2 (100
mL). The organic extracts were combined, dried over Na2SO4,
evaporated, and purified by column chromatography (silica gel
5% ethyl acetate in hexanes) to yield 2.023 g of pure material
D
+19.32° (c ) 0.0446 g/mL in benzene); HREIMS m/z 598.4234,
598.4225 calcd for (M+) C35H59BO5Si; IR (NaCl plates neat
cm-1) 3077, 2930, 2859, 1615, 1514, 1387, 1248, 1097, 835, 775;
1H NMR (CDCl3, 360 MHz) δ 7.24 (d, 2H, J ) 8.5 Hz), 6.38
(m, 2H) 5.84-5.73 (m, 1H) 5.03-4.90 (m, 2H) 4.60 (d, 1H, J )
11.2 Hz), 4.48 (d, 1H, J ) 11.2 Hz), 4.21 (dd, 1H, J ) 1.8, 8.8
Hz), 3.78 (s, 3H) 3.60 (m, 2H) 3.39 (m, 1H, close to triplet)
2.35-2.20 (m, 1H) 2.20-1.95 (m, 4H) 1.83-1.65 (m, 3H), 1.65-
1.40 (m, 6H) 1.35-1.25 (m, 1H, overlaps next two peaks) 1.29
(s, 3H) 1.25 (s, 3H) 1.18 (d, 1H, J ) 10.5 Hz), 0.95 (d, 3H, J )
6.8 Hz), 0.89 (s, 9H) 0.81 (s, 3H) 0.04 (s, 6H); 13C NMR (CDCl3,
90 MHz, relaxation delay ) 7 s) δ 159.4, 139.6, 132.5, 129.4,
115.0, 114.2, 86.1 (two overlapping signals), 78.2, 73.2, 64.1,
56.0, 51.9, 40.2, 38.9, 36.9, 36.2, 34.1, 33.6, 32.6, 29.5, 27.8,
27.0, 26.7, 25.9, 24.8, 19.1, 15.4, -4.5.
(76%) along with 0.210 g (8%) of impure material. [R]25
)
D
+7.61° (c ) 0.0293 g/mL in benzene); HREIMS m/z 412.2785,
(4S,5R,6R)-1-(ter t-Bu tyld im eth ylsiloxy)-4-{ch lor o-[(S)-
p in a n ed iyld ioxy)b or yl]m et h yl}-5-[(4-m et h oxyb en zyl)-
oxy]-6-m eth yl-9-d ecen e (16). A mixture of THF (2.5 mL)
and CH2Cl2 (0.10 mL, 1.549 mmol) was cooled to -100 °C,
butyllithium (0.61 mL, 1.9 M solution in pentane), was added
and the solution was allowed to stir for 10 min. The solution
turned cloudy. Compound 15 (0.690 g, 1.154 mmol) was
azeotroped with toluene dissolved in THF (5 mL) and then
slowly added to the CHLiCl2 solution generated above. The
solution was allowed to stir for 16 min at -100 °C. A solution
of ZnCl2 (0.595 g) in THF (3 mL) was added, and the mixture
was then allowed to slowly warm to rt and stirred at rt for 10
h. The mixture was partitioned between acidic NH4Cl/HCl (10
mL 1.2 M HCl + 40 mL saturated NH4Cl) and CH2Cl2 (50 mL).
The aqueous layer was extracted with CH2Cl2 (50 mL). The
organic extracts were combined, dried over Na2SO4, evapo-
rated, and purified by column chromatography (silica gel, CH2-
Cl2 50% in hexanes) to yield 0.447 g (49%, excluding 1.8
equivalents of CH2Cl2) of an oil. The B/O elimination product
412.2784 calcd for (M+) C25H37BO4; IR (NaCl plates neat cm-1
)
2926, 1613, 1514, 1377, 1248, 1076, 1030, 823; 1H NMR
(CDCl3, 360 MHz) δ 7.28 (m, 2H) 6.86 (m, 2H) 5.80 (m, 1H)
5.02-4.90 (m, 2H) 4.56 (d, 1H, J ) 11.8 Hz), 4.41 (d, 1H, J )
11.8 Hz), 4.32 (dd, 1H, J ) 8.9, 2.0 Hz), 3.80 (s, 3H) 3.22 (d,
1H, J ) 4.9 Hz), 2.41-2.30 (m, 1H) 2.30-2.21 (m, 1H) 2.15-
2.05 (m, 2H) 2.05-1.75 (m, 4H) 1.71-1.61 (m, 1H) 1.41 (s, 3H)
1.36-1.23 (m, 4H), 1.20 (d, 1H, J ) 10.8 Hz), 0.99 (d, 3H, J )
6.8 Hz), 0.86 (s, 3H); 13C NMR (CDCl3, 90 MHz) δ 158.9, 139.1,
131.3, 129.3, 114.0, 113.5, 86.0, 77.9, 72.2, 55.1, 51.0, 39.5, 38.0,
35.4, 34.9, 33.0, 31.6, 28.7, 27.0, 26.5, 24.0, 16.6.
(1S,2S,3R)-1-Ch lor o-2-[(4-m eth oxyben zyl)oxy]-3-m eth -
yl-1-[(S)-p in a n ed iyld ioxy)bor yl]-9-h ep ta n e (12). A mix-
ture of THF (5 mL) and CH2Cl2 (0.170 mL, 2.600 mmol) was
cooled to -100 °C, and butyllithium (1.10 mL, 1.9 M solution
in pentane) was added, and the solution was allowed to stir
for 15 min. The solution turned cloudy and slightly yellow.
Compound 11 (0.866 g, 2.096 mmol) was azeotroped with
toluene, diluted in THF (5 mL) and was slowly added to the
solution generated above and allowed to stir for 18 min at -100
was also isolated in 34% yield. [R]25 ) +19.92° (c ) 0.0440
D
g/mL in benzene); HREIMS m/z 646.3980, 646.3991 calcd for
(M+) C36H60BClO5Si; IR (NaCl plates neat cm-1) 3076, 2930,
1613, 1515, 1387, 1250, 1099, 1032, 835, 775; 1H NMR (CDCl3,
360 MHz) δ 7.28 (d, 2H, J ) 8.6 Hz), 6.85 (m, 2H) 5.85-5.70
(m, 1H) 5.01-4.91 (m, 2H) 4.63 (d, 1H, J ) 11.2 Hz), 4.50 (d,
1H, J ) 11.2 Hz), 4.30 (dd, 1H, J ) 1.9, 8.8 Hz), 3.84 (d, 1H,
J ) 5.9 Hz), 3.79 (s, 3H) 3.56 (m, 2H) 3.35 (dd, 1H, J ) 1.5,
9.2 Hz), 2.35-2.25 (m, 1H) 2.25-1.98 (m, 5H) 1.90-1.75 (m,
2H), 1.75-1.60 (m, 1H) 1.60-1.20 (m, 13H) 0.92 (d, 3H, J )
6.8 Hz), 0.88 (s, 9H) 0.81 (s, 3H), 0.03 (s, 6H); 13C NMR (CDCl3,
90 MHz) δ 159.1, 138.8, 130.8, 129.5, 114.4, 113.7, 86.6, 82.7,
78.3, 74.6, 63.4, 55.2, 53.4, 51.2, 43.6, 39.3, 38.2, 35.3, 35.2,
34.5, 32.0, 30.0, 28.2, 27.0, 26.2, 25.9, 25.8, 24.0, 18.3, 13.6,
-5.3. Elimination product: HRCIMS (M + H) m/z 283.2457,
283.2457 calcd for (M + H) C17H35OSi; IR (NaCl plates neat
cm-1) 3078, 2928, 2857, 1642, 1472, 1255, 1103, 969. 835, 775;
1H NMR (CDCl3, 360 MHz) δ 5.86-5.74 (m, 1H) 5.38-5.27
(m, 1H) 5.26-5.22 (m, 1H) 5.02-4.91 (m, 2H) 3.61 (t, 2H, J )
6.6 Hz), 2.15-1.95 (m, 5H) 1.58 (pent, 2H, J ) 6.9 Hz), 1.32
(m, 2H) 0.96 (d, 3H, J ) 6.7) 0.90 (s, 9H) 0.05 (s, 6H); 13C NMR
(CDCl3, 90 MHz) δ 139.1, 136.4, 128.3, 114.1, 62.6, 36.3, 32.7,
31.6, 28.8, 26.0, 20.9, 18.4, -5.3.
°C at which point the reaction mixture slowly gelled.
A
solution of ZnCl2 (0.734 g, 5.394 mmol) in THF (4.5 mL) was
added, and the mixture was allowed to slowly warm to rt (the
gel rapidly liquefied on addition of ZnCl2) and was stirred at
rt for 7 h. The mixture was partitioned between acidic NH4-
Cl/HCl (40 mL saturated + 10 mL 1.2 M) and CH2Cl2 (50 mL),
and the aqueous layer was extracted with CH2Cl2 (50 mL).
The organic extracts were combined, dried over Na2SO4,
evaporated, and purified by column chromatography (silica gel,
CH2Cl2) to yield 0.886 g (92%) of a partially purified oil. [R]25
D
) +9.53° (c ) 0.0511 g/mL in benzene); HREIMS m/z 461.2549,
calcd for (M+) 460.2552 C26H38BClO4; IR (NaCl plates neat
1
cm-1) 3076, 2930, 2872, 1615, 1514, 1248, 1030, 911, 824; H
NMR (CDCl3, 360 MHz) δ 7.32 (d, 2H, J ) 11.2 Hz), 6.87 (m,
2H) 5.83-5.72 (m, 1H) 5.03-4.97 (m, 2H) 4.84 (d, 1H, J )
10.5 Hz), 4.58 (d, 1H, J ) 10.5 Hz), 4.36 (dd, 1H, J ) 9.0, 1.9
Hz), 3.79 (s, 3H) 3.72 (m, 2H) 2.45-2.30 (m, 1H) 2.28-2.20
(m, 1H) 2.20-1.95 (m, 3H) 1.95-1.88 (m, 2H) 1.80-1.65 (m,
1H) 1.65-1.50 (m, 1H) 1.45-1.30 (m, 7H, 2 singlets overlap-
ping a multiplet), 1.20 (d, 1H, J ) 11.0 Hz), 0.93 (d, 3H, J )
6.8 Hz), 0.85 (s, 3H); 13C NMR (CDCl3, 90 MHz) δ 159.9, 139.0,
131.8, 130.1, 115.4, 114.4, 87.5, 84.4, 79.2, 75.7, 56.0, 51.9, 40.1,
39.0, 37.3, 36.0, 34.3, 32.1, 29.1, 27.8, 27.1, 24.8, 14.5.
(4S,5R,6R)-1-(ter t-Bu tyld im eth ylsiloxy)-5-[(4-m eth oxy-
b en zyl)oxy]-6-m et h yl-4-[(S)-p in a n ed iyld ioxy)b or yl]-9-
d ecen e (15). Compound 12 (0.788 g, 1.708 mmol) was
azeotroped with toluene (10 mL) and then diluted with THF
(20 mL) and brought to -78 °C. 3-(tert-Butyldimethylsiloxy)-
propylmagnesium bromide (14) was produced separately from
the reaction of Mg metal (0.336 g, 13.840 g atoms) with
1-bromo-3-(tert-butyldimethylsiloxy)propane (1.32 g, 5.21 mmol)
in THF (10 mL total) at rt. A rt water bath was used to control
the exothermic reaction. The Grignard was slowly added to
the first solution, at -78 °C, and the solution allowed to warm
slowly to rt. The solution was allowed to stir for 5 h and then
(4S,5R,6R)-1-(ter t-Bu tyld im eth ylsiloxy)-5-[(4-m eth oxy-
b en zyl)oxy]-6-m et h yl-4-{[(S)-p in a n ed iyld ioxy)b or yl]m -
eth yl}-9-d ecen e (17). To compound 16 (0.372 g, 0.575 mmol)
in THF (10 mL) was added sodium trimethoxyborohydride
(0.464 g, 5.799 mmol), and the resulting solution stirred for
25 min at rt. The reaction mixture was partitioned between
a saturated solution of NH4Cl (50 mL) and CH2Cl2 (50 mL),
and the aqueous layer was extracted with CH2Cl2 (50 mL).
The organic extracts were combined, dried over Na2SO4, and
evaporated to yield a crude product (ca. 94%) which was used
without further purification. Analysis of the crude provided:
HRCIMS m/z 612.4369, 612.4381 calcd for (M+) C36H61BO5Si;
IR (NaCl plates neat cm-1) 3075, 2930, 1615, 1514, 1377, 1248,
1097, 835, 775; 1H NMR (CDCl3, 360 MHz) δ 7.26 (d, 2H, J )

3112 J . Org. Chem., Vol. 61, No. 9, 1996
Maurer and Armstrong
8.6 Hz), 6.84 (d, 2H, J ) 8.6 Hz), 5.76 (m, 1H) 5.00-4.91 (m,
2H) 4.58 (d, 1H, J ) 11.1 Hz), 4.45 (d, 1H, J ) 11.1 Hz), 4.20
(dd, 1H, J ) 1.8, 8.7 Hz), 3.79 (s, 3H) 3.57 (t, 2H, J ) 6.4 Hz),
3.12 (dd, 1H, J ) 4.0, 6.3 Hz), 2.34-2.24 (m, 1H) 2.24-1.88
(m, 5H) 1.88-1.80 (m, 1H) 1.80-1.62 (m, 2H) 1.62-1.43 (m,
4H) 1.40-1.10 (m, 10H), 1.00-0.83 (m, 16H) 0.03 (s, 6H); 13C
NMR (CDCl3, 90 MHz) δ 159.6, 139.9, 132.4, 129.7, 115.0,
114.3, 86.8, 85.9, 78.2, 75.0, 64.4, 56.0, 52.0, 40.3, 38.9, 38.1,
36.2, 35.9, 34.8, 32.5, 31.3, 30.9, 29.9, 27.8, 27.2, 26.7, 24.8,
19.1, 15.3, -4.5.
2H, J ) 8.6 Hz), 5.81 (m, 1H) 5.04-4.93 (m, 2H) 4.51 (s, 2H)
3.80 (s, 3H) 3.60 (t, 2H, J ) 6.4 Hz), 3.06 (t, 1H, J ) 5.3 Hz),
2.20-1.97 (m, 2H) 1.80-1.67 (m, 2H) 1.67-1.43 (m, 4H) 1.38-
1.16 (m, 2H) 0.97 (d, 3H, J ) 6.7 Hz), 0.96 (d, 3H, J ) 6.7 Hz),
0.91 (s, 9H) 0.06 (s, 6H); 13C NMR (CDCl3, 90 MHz) δ 159.7,
139.8, 132.2, 129.8, 115.1, 114.4, 87.6, 75.4, 64.2, 56.0, 36.3,
35.9, 34.4, 32.3, 31.3, 31.1, 26.7, 19.1, 16.0, 15.6, -4.5.
(4R,5R,6S)-9-(ter t-Bu tyld im eth ylsiloxy)-5-[(4-m eth oxy-
ben zyl)oxy]-4,6-d im eth yln on a n a l (21). A solution of com-
pound 20 (56.0 mg, 0.1288 mmol) in CH2Cl2 (10 mL) was cooled
to -78 °C and exposed to O3 gas until the solution turned pale
blue (approximately 5 min). Residual ozone was removed with
a stream of N2, and tributylphosphine (40 mL, 0.1621 mol, 92%
tech grade) was added. The reaction mixture was allowed to
warm to rt and then stirred at rt for 2.5 h. The mixture was
vacuum evaporated, and the residues were purified by column
chromatography (silica gel 5% ethyl acetate in hexanes) to
(4S,5R,6R)-1-(ter t-Bu t yld im et h ylsiloxy)-4-(h yd r oxy-
m eth yl)-5-[(4-m eth oxyben zyl)oxy]-6-m eth yl-9-decen e (18).
The preceding crude material (compound 17) was dissolved
in THF (15 mL) and treated with H2O2 (0.750 mL, 30% solution
in H2O, 6.617 mmol) and NaOH (0.750 mL, 1.6 M solution,
1.20 mmol) at rt. After stirring for 1 h the reaction mixture
was partitioned between NH4Cl saturated solution (50 mL)
and CH2Cl2 (50 mL), and the aqueous layer extracted with
CH2Cl2 (50 mL). The organic extracts were combined, dried
over Na2SO4, and evaporated, and the resulting mixture
purified by column chromatography (silica gel, 20% ethyl
acetate in hexanes) to yield 0.245 g (87%, for the two steps) of
yield 51.9 mg (93%) of a clear thick oil. [R]25 ) -1.8° (c )
D
32.6 mg/mL in benzene); HREIMS m/z 379.2305, 379.2304
calcd for (M - C4H9)+ C21H35O4Si; IR (NaCl plates neat cm-1
)
2955, 2857, 2716, 1726, 1612, 1514, 1248, 1096, 835; 1H NMR
(CDCl3, 360 MHz) δ 9.76 (t, 1H, J ) 1.7 Hz), 7.26 (m, 2H) 6.86
(m, 2H) 4.55-4.46 (m, 2H, appears as quartet) 3.80 (s, 3H)
3.59 (t, 2H, J ) 6.3 Hz), 3.05 (t, 1H, J ) 5.0 Hz), 2.55-2.32
(m, 2H) 1.84-1.68 (m, 3H) 1.66-1.41 (m, 4H) 1.29-1.17 (m,
1H) 0.98-0.93 (overlapping doublets, 6H) 0.90 (s, 9H) 0.05 (s,
6H); 13C NMR (CDCl3, 90 MHz) δ 203.3, 159.8, 132.0, 129.8,
114.5, 87.3, 75.3, 64.1, 56.0, 42.7, 36.3, 36.0, 31.3, 31.1, 27.2,
26.7, 19.1, 15.9, 15.4, -4.5.
a thick oil. [R]25 ) +11.30° (c ) 0.0415 g/mL in benzene);
D
HRCIMS m/z 451.3227, 451.3244 (MH+), calcd for C26H47O4-
Si; IR (NaCl plates neat cm-1) 3453, 2930, 1613, 1514, 1250,
1095, 835, 775; 1H NMR (CDCl3, 360 MHz) δ 7.25 (d, 2H, J )
8.6 Hz), 6.87 (d, 2H, J ) 9.0 Hz), 5.79 (m, 1H) 5.05-4.94 (m,
2H) 4.47 (d, 1H, J ) 10.5 Hz), 4.49 (d, 1H, J ) 10.5 Hz), 3.79
(s, 3H) 3.63-3.57 (m, 3H) 3.32 (t, 2H, J ) 5.2 Hz), 2.95 (s, 1H,
broad) 2.25-2.12 (m, 1H) 2.12-2.00 (m, 1H) 1.89-1.78 (m,
1H) 1.78-1.68 (m, 1H) 1.68-1.25 (m, 6H) 0.99 (d, 3H, J ) 6.7
Hz), 0.89 (s, 9H) 0.05 (s, 6H); 13C NMR (CDCl3, 90 MHz) δ
160.1, 139.4, 131.2, 130.2, 115.4, 114.6, 88.2, 78.2, 75.7, 64.3,
63.9, 56.0, 42.8, 36.5, 34.2, 32.4, 31.2, 26.7, 19.1, 15.5, -4.5.
(4S,5R,6R)-1-(ter t-Bu t yld im et h ylsiloxy)-4-[(m et h a n e-
su lfon yl)m et h yl]-5-[(4-m et h oxyb en zyl)oxy]-6-m et h yl-9-
d ecen e (19). To a solution of compound 18 (0.216 g, 0.480
mmol, azeotroped with toluene) in CH2Cl2 (10 mL) and TEA
(1 mL) at 0° C was added methanesulfonyl chloride (0.150 mL,
1.938 mmol). The mixture was allowed to stir at 0 °C for 30
min and was then partitioned between acidic NaCl saturated
solution (50 mL of NaCl saturated solution, 10 mL of 1.2 M
HCl) and CH2Cl2 (50 mL) and the aqueous layer extracted with
CH2Cl2 (50 mL). The organic extracts were combined, dried
over Na2SO4, evaporated, and purified by column chromatog-
raphy (silica gel, 20% ethyl acetate in hexanes) to yield 0.240
(4S ,5R ,6R ,9S ,10R )-1-(t er t -B u t y ld im e t h y ls ilo x y )-9-
h yd r oxy-5-[(4-m et h oxyb en zyl)oxy]-4,6,10-t r im et h yl-11-
d od ecen e (22). To a mixture of potassium tert-butoxide (43.5
mg, 0.4223 mmol, freshly sublimed) in THF (1 mL) at -78 °C
was added trans-2-butene (0.5 mL) followed by n-butyllithium
(0.150 mL 1.9 M solution in pentane, 0.2850 mmol, Aldrich).
The solution was allowed to warm to -40 °C (acetonitrile bath/
dry ice) and allowed to stir at -40 °C for 20 min. The solution
(now dark yellow) was recooled to -78 °C, and (+)-methoxy-
diisopinocamphenylborane in THF was slowly added (0.1782
g, 0.5640 mmol in 0.3 mL of THF) quenching the yellow color,
and the solution was allowed to stir at -78 °C for 30 min. BF3-
OEt2 was then added (85 µL, 0.6884 mmol) followed by a THF
solution of compound 21 (50.0 mg, 0.1145 mmol, in 1 mL of
THF). The resulting reaction mixture was allowed to stir at
-78 °C for 4.5 h, and the reaction was quenched at -78 °C by
the addition of Ca(OAc)2 solution (2.2 M, 0.50 mL, 1.1 mmol),
NaOH solution (5 M, 0.50 mL, 2.5 mmol), and H2O2 (30%
solution, 0.50 mL, 4.4 mmol) and then warmed to rt for 15
min. The resulting mixture was partitioned between NH4Cl
saturated solution and CH2Cl2 (50 mL ea.) and the aqueous
layer extracted with CH2Cl2 (50 mL × 2). Each extraction
caused a severe emulsion which was broken by the addition
of hexanes. The organic extracts were combined, dried over
Na2SO4, and evaporated, and the residue was purified by
column chromatography (7.5% ethyl acetate in hexanes) to
g (94%) of a clear oil. [R]25 ) +21.63° (c ) 47.0 mg/mL in
D
benzene); HRCIMS m/z 527.2871, 527.2863 (M - H)+, calcd
for C27H47O6SSi; IR (NaCl plates neat cm-1) 3073, 2932, 1612,
1514, 1464, 1358, 1250, 1176, 1095, 945, 835; 1H NMR (CDCl3,
360 MHz) δ 7.26 (d, 2H, J ) 8.6 Hz), 6.87 (d, 2H, J ) 8.6 Hz),
5.80 (m, 1H) 5.06-4.95 (m, 2H) 4.56 (d, 1H, J ) 10.6 Hz), 4.47
(d, 1H, J ) 10.6 Hz), 4.38-4.30 (m, 2H) 3.80 (s, 3H) 3.62-
3.57 (m, 2H) 3.33 (dd, 1H, J ) 3.9, 6.6 Hz), 2.93 (s, 3H) 2.25-
2.00 (m, 2H) 2.00-1.87 (m, 1H) 1.87-1.71 (m, 1H) 1.70-1.35
(m, 6H) 0.94 (d, 3H, J ) 6.7 Hz), 0.90 (s, 9H) 0.05 (s, 6H); 13
C
yield 40.0 mg (71%) of a purified oil. [R]25 ) -11.11° (c )
D
NMR (CDCl3, 90 MHz) δ 159.9, 139.4, 131.5, 130.0, 115.5,
114.5, 83.0, 75.3, 70.7, 63.6, 56.0, 41.1, 37.8, 35.8, 34.3, 32.4,
30.7, 26.7, 25.4, 19.1, 14.7, -4.6.
27.5 mg/mL benzene); HRFABMS m/z 493.3712, 493.3713
calcd for (M + H) C29H53O4Si; IR (NaCl plates neat cm-1) 3461,
2932, 2859, 1615, 1514, 1464, 1248, 1095, 835; 1H NMR
(CDCl3, 360 MHz) δ 7.27 (m, 2H) 6.86 (m, 2H) 5.80-5.71 (m,
1H) 5.14-5.08 (m, 2H) 4.51 (s, 2H) 3.79 (s, 3H) 3.59 (t, 2H, J
) 6.4 Hz), 3.38-3.33 (m, 1H) 3.06 (t, 1H, J ) 5.2 Hz), 2.21
(hexet, 2H, J ) 6.9 Hz), 1.78-1.40 (m, 7H + H2O peak) 1.40-
1.12 (m, 4H) 1.04 (d, 3H, J ) 6.8 Hz), 0.97-0.94 (m, 6H,
overlapping doublets) 0.89 (s, 9H) 0.05 (s, 6H); 13C NMR
(CDCl3, 90 MHz) δ 159.7, 140.9, 132.3, 129.8, 117.1, 114.4,
87.6, 75.9, 75.4, 64.2, 56.0, 44.7, 36.7, 36.4, 32.9, 31.3, 31.3,
31.1, 26.7, 19.1, 17.1, 16.0, 15.7, -4.5.
(4S,5R,6R,9S,10R)-9-(Ben zoyloxy)-1-(ter t-bu tyld im eth -
ylsiloxy)-5-[(4-m et h oxyb en zyl)oxy]-4,6,10-t r im et h yl-11-
d od ecen e (23). A solution of compound 22 (30.0 mg, 0.0609
mmol) in pyridine (0.50 mL dry) was treated with catalytic
DMAP and benzoyl chloride (28 µL, 0.240 mmol) in four
portions over a 4.5 h period. The reaction was quenched by
addition of saturated bicarbonate solution (1 mL), and the
mixture was partitioned between saturated sodium bicarbon-
(4S,5R,6R)-1-(ter t-Bu tyld im eth ylsiloxy)-5-[(4-m eth oxy-
ben zyl)oxy]-4,6-d im eth yl-9-d ecen e (20). To a solution of
compound 19 (0.222 g, 0.419 mmol, azeotroped with toluene)
in THF (20 mL) was added LAH (0.171 g, 4.49 mmol), and
the resulting suspension was stirred for 10 min at rt and then
heated at 60 °C for a total of 13 min, until TLC indicated the
consumption of the starting material. The reaction was then
partitioned between acidic NH4Cl solution (50 mL of saturated
NH4Cl solution, 10 mL of 1.2 M HCl) and CH2Cl2 (50 mL).
The aqueous layer was extracted with CH2Cl2 (50 mL), and
the organic extracts were combined, dried over Na2SO4,
evaporated, and purified by column chromatography (silica gel
5% ethyl acetate in hexanes) to yield 0.160 g (88%) of a clear
oil. [R]25D ) -2.6° (c ) 34.9 mg/mL in benzene); HREIMS m/z
434.3205, 434.3216 calcd for (M+) C26H46O3Si; IR (NaCl plates
neat cm-1) 3077, 2930, 2857, 1615, 1514, 1248, 1095, 835, 775;
1H NMR (CDCl3, 360 MHz) δ 7.28 (d, 2H, J ) 8.6 Hz), 6.87 (d,

Synthesis of the C1-C21 Fragment of Tautomycin
J . Org. Chem., Vol. 61, No. 9, 1996 3113
ate solution and CH2Cl2 (50 mL ea.). The aqueous layer was
extracted with CH2Cl2 (50 mL × 2). The organic extracts were
combined, dried over Na2SO4, and evaporated, and the residue
was purified by column chromatography (CHCl3, silica gel) to
yield the desired product contaminated with benzoic anhy-
dride. Addition of 1-amino-2-propanol (2 equiv per 1 equiv of
benzoic anhydride as determined by 1H NMR) and rechro-
matography yielded 31.0 mg (85%) of oil. [R]25D ) -18.2° (c )
0.0290 g/mL in benzene); HRFABMS m/z 595.3799, 595.3817
(25) (5.029 g, 29.52 mmol) in 50 mL of diethyl ether was
allowed to stir at rt over Na2SO4 until TLC indicated comple-
tion of reaction (40 min). The mixture was partitioned
between saturated Na2CO3 solution (50 mL) and CH2Cl2 (100
mL). The organic extracts were dried over Na2SO4, evapo-
rated, and distilled under vacuum (bp 93 °C, 9 mmHg) to yield
5.257 g (92%) of a clear oil. [R]25D ) -51.24° (c ) 0.0391 g/mL
in benzene); HREIMS m/z 194.1474, 194.1478 calcd for (M+)
C11H19BO2; IR (NaCl plates neat cm-1) 2972, 2919, 1476, 1372,
1
calcd for (M - H)+ C36H55O5Si; IR (NaCl plates neat cm-1
)
1032; H NMR (CDCl3, 360 MHz) δ 4.24 (dd, 1H, J ) 8.6, 1.9
3071, 2955, 28.56, 1717, 1612, 1514, 1271, 1248, 1098, 835,
Hz), 2.39-2.25 (m, 1H) 2.25-2.18 (m, 1H) 2.03 (t, 1H, J ) 5.9
Hz), 1.95-1.87 (m, 1H) 1.87-1.78 (m, 1H) 1.37 (s, 3H) 1.28 (s,
3H) 1.11 (d, 1H, J ) 10.9 Hz), 0.83 (s, 3H) 0.28 (s, 3H); 13C
NMR (CDCl3, 90 MHz) δ 85.4, 77.6, 51.2, 39.5, 38.1, 35.4, 28.6,
27.1, 26.4, 24.0.
1
712; H NMR (CDCl3, 360 MHz) δ 8.05-8.02 (m, 2H) 7.57-
7.54 (m, 1H) 7.53-7.40 (m, 2H) 7.23-7.21 (m, 2H) 6.84-6.81
(m, 2H) 5.91-5.82 (m, 1H) 5.12-5.08 (m, 3H) 4.05-4.43 (m,
2H) 3.79 (s, 3H) 3.57 (t, 2H, J ) 6.3 Hz), 3.02 (t, 1H, J ) 5.2
Hz), 2.60-2.48 (m, 1H) 1.78-1.61 (m, 4H) 1.61-1.38 (m, 4H)
1.35-1.15 (m, 2H) 1.08 (d, 3H, J ) 6.9 Hz), 0.93 (d, 6H, J )
6.7 Hz), 0.90 (s, 9H) 0.05 (s, 6H); 13C NMR (CDCl3, 90 MHz) δ
167.1, 159.7, 140.0, 133.6, 132.1, 131.4, 130.3, 129.9, 129.1,
116.5, 114.4, 87.4, 78.7, 75.4, 64.2, 56.0, 42.2, 36.4, 36.4, 31.3,
31.0, 30.1, 26.7, 19.1, 17.1, 16.0, 15.7, -4.5.
(R)-P in a n ed iol (1R)-(1-Ch lor oeth yl)bor on a te (27).
A
mixture of THF (60 mL) and CH2Cl2 (2.00 mL, 31.0 mmol) was
cooled to -100°C, butyllithium (12.6 mL, 1.9 M solution in
pentane, 23.9 mmol) was added, and the solution was allowed
to stir for 15 min. The solution turned cloudy and slightly
yellow. Compound 26 (4.644 g, 23.93 mmol) in THF (9 mL)
was slowly added and the solution allowed to stir for 15 min
at -100 °C. A solution of ZnCl2 (1.965 g, 14.45 mmol) in THF
(8 mL) was added, and the mixture was then allowed to slowly
warm to rt and stirred at rt for 9 h. The mixture was
partitioned between acidic NH4Cl/HCl (50 mL of 1.2 M HCl +
200 mL saturated NH4Cl) and CH2Cl2 (200 mL). The organic
extracts were dried over Na2SO4, evaporated, and purified by
column chromatography (silica gel, 25% CH2Cl2 in hexane) to
yield 3.721 g of a partially purified oil (containing a 60% yield
(4S,5R,6R,9S,10R)-9-(Ben zoyloxy)-1-h ydr oxy-5-[(4-m eth -
oxyben zyl)oxy]-4,6,10-tr im eth yl-11-d od ecen e (24). Com-
pound 23 (60.1 mg, 0.101 mmol) was dissolved in THF was
treated with TBAF (100 µL of 1.0 M solution in THF) at 0 °C
and then warmed to rt. After stirring for 45 min, additional
TBAF (100 µL) was added. After an additional 2 h the reaction
mixture was partitioned between NH4Cl saturated solution
and CH2Cl2 (10 mL ea.) and the aqueous layer extracted with
CH2Cl2 (10 mL) and ethyl acetate (20 mL). The organic
extracts were combined, dried over Na2SO4, and evaporated,
and the resulting crude oil was purified by column chroma-
tography (silica gel, 30% to 50% ethyl acetate in hexanes) to
of the desired material). Data for compound 27: [R]25
)
D
-55.28° (c ) 0.0415 g/mL, in benzene); HREIMS m/z 242.1257,
242.1245 calcd for (M+) C12H20ClBO2; IR (NaCl plates neat
cm-1) 2924, 2872, 1446, 1381, 1287, 1030, 650; 1H NMR
(CDCl3, 360 MHz) δ 4.35 (d, 1H, J ) 8.9, 1.9 Hz), 3.55 (q, 1H,
J ) 7.5 Hz), 2.40-2.30 (m, 1H) 2.30-2.20 (m, 1H) 2.13-2.05
(m, 1H) 1.97-1.85 (m, 2H) 1.55 (d, 3H, J ) 7.5 Hz), 1.41 (s,
3H) 1.28 (s, 3H) 1.15 (d, 2H, J ) 11.1 Hz), 0.82 (s, 3H); 13C
NMR (CDCl3, 90 MHz) δ 87.5, 79.3, 51.9, 40.0, 39.0, 36.0, 29.1,
27.7, 27.0, 24.7, 21.3.
yield 49.4 mg (0.101 mmol, 100%) of a clear oil. [R]25
)
D
-13.89° (c ) 23.8 mg/mL in benzene) HRCIMS 482.3030 m/z,
482.3032 (M+) calcd for C30H42O5; IR (NaCl plates neat cm-1
)
3413, 3067, 2934, 1715, 1613, 1514, 1273, 1111, 712; 1H NMR
(CDCl3, 360 MHz) δ 8.06-8.02 (m, 2H) 7.57-7.53 (m, 1H)
7.45-7.41 (m, 2H) 7.23-7.20 (m, 2H) 6.84-6.81 (m, 2H) 5.86
(m, 1H) 5.13-5.06 (m, 3H) 4.47 (s, 2H) 3.78 (s, 3H) 3.58 (t,
2H, J ) 6.4 Hz), 3.02 (t, 1H, J ) 5.3 Hz), 2.53 (m, 1H) 1.72-
1.39 (m, 9H, 1 from water) 1.29-1.16 (m, 2H) 1.07 (d, 3H, J )
6.9 Hz), 0.93 (d, 6H, J ) 8.5 Hz); 13C NMR (CDCl3, 90 MHz)
δ 166.2, 158.9, 139.3, 132.7, 131.2, 130.5, 129.4, 129.0, 128.2,
115.7, 113.5, 86.3, 77.8, 74.5, 63.1, 55.1, 41.4, 35.5, 35.5, 30.3,
30.1, 30.1, 29.2, 16.3, 15.1, 14.9.
(S)-2-[(R)-P in a n ed iyld ioxy)bor yl]-5-h exen e (28). Com-
pound 27 (3.099 g, 12.78 mmol) was azeotroped with toluene,
dissolved in THF (50 mL), and cooled to -78 °C. In a separate
flask 3-buten-1-ylmagnesium bromide was produced by addi-
tion of 1-bromo-3-butene (3.00 mL, 28.89 mmol) to magnesium
metal (1.054 g, 43.35 mmol) in THF (5 mL). As necessary THF
was used to dilute the mixture, and a cooling bath was used
to control the exothermic reaction. The solution was stirred
until the exotherm ceased and was then titrated into the THF
solution of compound 27 until the starting material was
consumed. The reaction mixture was allowed to slowly warm
to rt (2 h) and then allowed to stir for 16 h at rt. The reaction
was then partitioned between HCl (1.2 M, 10 mL), NH4Cl
solution (200 mL saturated), and CH2Cl2 (200 mL). The
organic extracts were dried over Na2SO4, evaporated, and
purified by column chromatography (silica gel 20% CH2Cl2 in
hexanes) to yield 2.697 g (80%) of a partially purified oil (95%+
(4S ,5R ,6R ,9S ,10R )-9-(B e n zo y lo x y )-5-[(4-m e t h o x y -
ben zyl)oxy]-4,6,10-tr im eth yl-11-d od ecen ea l (4). A solu-
tion of oxalyl chloride (2.00 mmol in 11 mL of CH2Cl2) in CH2-
Cl2 was treated with DMSO (0.30 mL, 4.2 mmol in 0.7 mL of
CH2Cl2) at -78 °C and the resulting mixture allowed to stir
for 20 min. A sample of compound 24 (49.4 mg, 0.1017 mmol)
in 2 mL of CH2Cl2 was then added (at -78 °C) and the mixture
allowed to stir for 1 h, followed by addition of triethylamine
(0.86 mL). After stirring for an additional 20 min at -78 °C,
the reaction mixture was allowed to warm to 0 °C and
partitioned between saturated NH4Cl solution and CH2Cl2 (50
mL ea.) and the aqueous layer extracted with CH2Cl2 (50 mL).
The organic extracts were combined, dried over Na2SO4, and
evaporated, and the resulting residue was purified by column
chromatography (silica gel, 10% ethyl acetate in hexanes) to
pure). Data for compound 28: [R]25 ) -30.83° (c ) 0.0432
D
g/mL in benzene); HREIMS m/z 262.2115, 262.2104 calcd for
(M+) C16H27BO2; IR (NaCl plates neat cm-1) 3078, 2921, 2872,
1642, 1464, 1389, 1237, 1030, 908; 1H NMR (CDCl3, 360 MHz)
δ 5.80 (m, 1H) 5.01-4.90 (m, 2H) 4.24 (dd, 1H, J ) 8.7, 2.2
Hz), 2.37-2.28 (m, 1H) 2.25-2.15 (m, 1H) 2.15-2.03 (m, 3H)
1.93-1.85 (m, 1H) 1.85-1.78 (m, 1H) 1.65-1.53 (m, 1H) 1.45-
1.35 (m, 4H (m, 1H, + s, 3H)), 1.36 (s, 3H) 1.09 (d, 1H, J )
10.9 Hz), 0.99 (d, 3H, J ) 7.0 Hz), 0.88 (s, 3H); 13C NMR
(CDCl3, 90 MHz) δ 140.0, 115.0, 86.0, 78.3, 52.0, 40.24, 38.9,
36.4, 33.9, 33.3, 29.4, 27.8, 27.2, 24.7, 16.3.
yield 33.8 mg (69%) of a clear oil. [R]25 ) -16.56° (c ) 43.3
D
mg/mL in benzene); IR (NaCl plates neat cm-1) 3072, 2964,
2721, 1718, 1613, 1514, 1274, 1249, 1112, 714; 1H NMR
(CDCl3, 360 MHz) δ 9.72 (t, 1H, J ) 1.6 Hz), 8.04 (m, 2H) 7.58-
7.53 (m, 1H) 7.45-7.41 (m, 2H) 7.21 (d, 2H, J ) 8.6 Hz), 6.82
(d, 2H, J ) 8.6 Hz), 5.91-5.81 (m, 1H) 5.13-5.06 (m, 3H),
4.49-4.43 (m, 2H) 3.78 (s, 3H) 3.02 (t, 1H, J ) 5.1 Hz), 2.58-
2.48 (m, 1H) 2.48-2.30 (m, 2H) 1.80-1.58 (m, 5H) 1.55-1.35
(m, 2H) 1.29-1.23 (m, 1H) 1.08 (d, 3H, J ) 6.8 Hz), 0.94 (d,
3H, J ) 6.7 Hz), 0.92 (d, 3H, J ) 6.7 Hz); 13C NMR (CDCl3, 90
MHz) δ 202.4, 166.2, 158.9, 139.1, 132.7, 130.9, 130.5, 129.4,
129.0, 128.3, 115.7, 113.6, 86.0, 77.8, 74.4, 55.1, 41.8, 41.4, 35.6,
35.1, 30.2, 29.2, 26.1, 16.3, 14.9, 14.8.
(1R ,2S )-1-Ch lor o-2-m e t h yl-1-[(R )-p in a n e d iyld ioxy)-
bor yl]-5-h exen e (29). A mixture of THF (25 mL) and CH2-
Cl2 (0.85 mL, 13.2 mmol) was cooled to -100°C, butyllithium
(5.40 mL, 1.9 M solution in pentane, 10.26 mmol), was added
and the solution was allowed to stir for 15 min. The solution
turned cloudy and slightly yellow. A solution of compound 28
(2.697 g, 10.29 mmol, azeotroped with toluene) in THF (10 mL)
was slowly added and the solution allowed to stir at -100 °C
(R)-P in a n ed iol Met h ylb or on a t e (26). A mixture of
methaneboronic acid (1.841 g, 30.75 mmol) and (R)-pinanediol

3114 J . Org. Chem., Vol. 61, No. 9, 1996
Maurer and Armstrong
at which point the reaction mixture gelled. After 5 min at
-100 °C a solution of ZnCl2 (0.889 g, 6.539 mmol) in THF (10
mL) was added, and the mixture was then allowed to slowly
warm to rt (the gel rapidly liquefied on addition of ZnCl2, fully
liquid by -80 °C) and stirred at rt for 9 h. The mixture was
partitioned between acidic NH4Cl/HCl (50 mL of 1.2 M HCl +
150 mL of saturated NH4Cl) and CH2Cl2 (200 mL). The
aqueous layer was extracted with CH2Cl2 (100 mL), the organic
extracts were combined, dried over Na2SO4, and evaporated,
and the remaining oil was purified by column chromatography
(silica gel, 20% CH2Cl2 in hexanes) to yield 2.7505 g (86%) of
a partially purified oil (85% pure); HRCIMS m/z 328.2210,
328.2215 calcd for (M + NH4) C17H32BClNO2; IR (NaCl plates
and the residue was purified by chromatography (silica gel,
hexanes to 10% ethyl acetate in hexanes) to yield 0.935 g (66%)
of a clear oil. Retreatment of some recovered starting alcohol
yielded an additional 0.074 g (5%) of the desired compound.
[R]25 ) +9.8° (c ) 30.6 mg/mL in benzene); HRCIMS m/z
D
309.1665, 309.1674 calcd for (M - C4H9)+ C20H25OSi; IR (NaCl
plates neat cm-1) 3073, 2961, 2859, 1641, 1589, 1427, 1111,
1
1039, 910, 702, 613; H NMR (CDCl3, 360 MHz) δ 7.71 (dd,
4H, J ) 1.6, 7.9 Hz), 7.46-7.37 (m, 6H) 5.72 (m, 1H) 4.98-
4.88 (m, 2H) 3.80 (dq, 1H, J ) 2.1, 6.3 Hz), 2.05-1.96 (m, 1H)
1.94-1.82 (m, 1H) 1.67-1.55 (m, 1H) 1.40-1.30 (m, 1H) 1.20-
1.11 (m, 1H) 1.09 (s, 9H) 0.97 (d, 3H, J ) 6.3 Hz), 0.94 (d, 3H,
J ) 6.8 Hz); 13C NMR (CDCl3, 90 MHz) δ 139.1, 135.9, 135.0,
134.5, 129.4, 129.3, 127.5, 127.4, 114.1, 72.5, 39.3, 32.2, 31.5,
27.0, 19.3, 18.1, 13.7.
1
neat cm-1) 3078, 2971, 2924, 1643, 1377, 1287, 1030, 908; H
NMR (CDCl3, 360 MHz) δ 5.79 (m, 1H) 5.04-4.92 (m, 2H) 4.36
(dd, 1H, 9.0, 1.8 Hz), 4.23 (impurity) 3.39 (d, 1H, J ) 6.6 Hz),
2.42-2.30 (m, 1H) 2.30-1.87 (m, 7H) 1.76-1.65 (m, 1H) 1.45-
1.32 (m, 4H) 1.29 (s, 3H) 1.24 (d, 1H, J ) 11.0 Hz), 1.02 (d,
3H, 6.7 Hz), 0.84 (s, 3H); 13C NMR (CDCl3, 90 MHz) δ 139.3,
115.3, 87.5, 79.2, 51.9, 40.1, 39.0, 37.1, 36.4, 36.1, 33.9, 31.9,
29.3, 27.8, 27.2, 24.8, 18.1.
(4 S ,5 R )-5 -(t e r t -B u t y l d i p h e n y l s i l o x y )-4 -m e t h y l -
h exa n a l (33). A solution of compound 32 (0.407 g, 1.104
mmol) in CH2Cl2 (30 mL) was cooled to -78 °C and exposed
to O3 gas until the solution turned blue (ca. 5 min). Residual
ozone was removed with a stream of N2, and tributylphosphine
(0.325 mL, 1.200 mmol, 92% tech grade) was added. The
reaction mixture was allowed to slowly warm to rt and then
stirred at rt for 4 h. The mixture was vacuum evaporated,
and the residues were purified by column chromatography
(silica gel 5% ethyl acetate in hexanes) to yield 0.377 g (92%)
(5S,6R)-5-Meth yl-6-[(R)-p in a n ed iyld ioxy)bor yl]-1-h ep -
ten e (30). A solution of the previous 85% pure material (2.751
g, 7.53 mmol with 1.33 mmol contaminant) in THF (100 mL)
was cooled to -78 °C. A solution of methylmagnesium chloride
(3.00 mL 3.0 M solution in THF, 9.00 mmol, Aldrich) was
added, and the reaction slowly allowed to warm to rt and
stirred at rt for 20 h. The reaction mixture was partitioned
between acidic NH4Cl solution (200 mL of NH4Cl saturated
solution, 10 mL of 1.2 M HCl). The organic layer was extracted
with NH4Cl saturated solution, dried over Na2SO4, and
evaporated, and the residue was purified by column chroma-
tography (20 to 25% CH2Cl2 in hexanes) to yield 1.178 g (54%)
of a partially purified oil (95% purity). Data for compound
of a clear thick oil. [R]25 ) +4.2° (c ) 0.0424 g/mL in
D
benzene); HREIMS m/z 311.1465, 311.1467 calcd for (M -
C4H9)+ C19H23O2Si; IR (NaCl plates neat cm-1) 3071, 2932,
1
2859, 2714, 1728, 1474, 1428, 1381, 1111, 1055, 702, 613; H
NMR (CDCl3, 360 MHz) δ 9.66 (t, 1H, J ) 1.7 Hz), 7.68 (m,
4H), 7.40 (m, 6H), 3.76 (m, 1H), 2.35-2.15 (m 2H), 1.66-1.56
(m, 1H), 1.56-1.49 (m, 1H), 1.43-1.34 (m, 1H), 1.06 (s, 9H),
0.99 (d, 3H, J ) 6.4 Hz), 0.92 (d, 3H, J ) 6.7 Hz); 13C NMR
(CDCl3, 90 MHz) δ 203.4, 136.7, 136.7, 135.5, 134.99, 130.4,
130.2, 128.3, 128.2, 73.1, 42.6, 40.3, 27.8, 25.6, 20.1, 19.2, 14.7.
(3R,4R,7S,8R)-8-(ter t-Bu tyld ip h en ylsiloxy)-4-h yd r oxy-
3,7-d im eth yl-1-n on en e (34). A mixture of potassium tert-
butoxide (0.336 g, 3.258 mmol) in dry THF (3 mL) was cooled
to -78 °C, trans-2-butene was added via cannula (2 mL 29
mmol), n-butyllitium was added (1.50 mL of a 1.9 M solution
in pentane, 2.85 mmol), and the mixture was brought to -42
°C for 20 min, generating a dark yellow solution. The mixture
was recooled to -78 °C, and (+)-methoxydiisopinocamphey-
lborane in THF (1.636 g, 5.176 mmol, in 3 mL of THF) was
slowly added, causing the yellow color to fade. The solution
was allowed to stir for 40 min, and BF3OEt2 was then added
(0.70 mL, 5.669 mmol) followed by a THF solution of the
aldehyde 33 (0.347 g, 0.9424 mmol, in 2 mL of THF). The
reaction mixture was allowed to stir at -78°C for 6 h and was
then quenched with excess NaOH/H2O2 and allowed to warm
to rt for 1.5 h. The mixture was partitioned between CH2Cl2
and saturated NH4Cl solution (100 mL ea.) and the aqueous
layer extracted with CH2Cl2 (100 mL). The organic extracts
were combined, dried over Na2SO4, and evaporated, and the
resulting residue was purified by chromatography (silica gel,
5% ethyl acetate in hexanes) to yield 0.271 g (54%) of a clear
30: [R]25 ) -46.65° (c ) 0.0382 g/mL in benzene); HRCIMS
D
m/z 290.2424, 290.2417 calcd for (M+) C18H31BO2; IR (NaCl
plates neat cm-1) 3076, 2923, 1642, 1458, 1385, 1281, 1032,
909; 1H NMR (CDCl3, 360 MHz) δ 5.80 (m, 1H) 5.01-4.89 (m,
2H) 4.25 (dd, 1H, J ) 2.1, 8.8 Hz), 2.38-2.28 (m, 1H) 2.25-
2.17 (m, 1H, 2.17-1.93 (m, 3H) 1.93-1.87 (m, 1H) 1.87-1.79
(m, 1H) 1.70-1.55 (m, 1H) 1.50-1.39 (m, 1H) 1.36 (s, 3H)
1.31-1.20 (m, 1H + s, 3H at 1.28) 1.17-0.95 (m, 2H) 0.92 (d,
3H, J ) 7.3 Hz), 0.88 (d, 3H, J ) 6.8 Hz), 0.84 (s, 3H); 13C
NMR (CDCl3, 90 MHz) δ 140.2, 114.7, 85.39, 78.2, 52.0, 40.3,
38.9, 36.5, 35.9, 35.1, 32.6, 29.5, 27.8, 27.3, 24.8, 18.6, 12.0.
(5S,6R)-6-(Hyd r oxy)-5-m eth yl-1-h ep ten e (31). A solu-
tion of compound 30 (1.178 g, 4.060 mmol) in THF (10 mL) at
rt was treated with NaOH (1.6 M aqueous solution, 2.5 mL,
4.00 mmol) and H2O2 (30% aqueous solution, 0.60 mL, 5.3
mmol) (exothermic reaction) and the resulting suspension
allowed to stir at rt for 90 min. The reaction mixture was
partitioned between acidic NH4Cl solution (50 mL of saturated
NH4Cl solution + 5 mL of HCl 1.2 M) and CH2Cl2 (50 mL),
and the aqueous phase was extracted with CH2Cl2 (50 mL).
The organic extracts were combined and dried over Na2SO4,
solvents were removed by careful distillation (1 atm, vigreux
column), and the crude mixture was purified by chromatog-
raphy (silica gel, CH2Cl2 followed by 20% ethyl acetate in
hexanes.). The fractions containing the desired alcohol were
concentrated and used directly in the next step (substantial
amounts of CH2Cl2 and THF remained). The identity of the
oil. [R]25 ) +4.8° (c ) 0.0350 g/mL in benzene); HREIMS
D
m/z 367.2099, 367.2093 calcd for (M - C4H9)+ C23H31O2Si; IR
(NaCl plates neat cm-1) 3424, 3071, 2961, 2859, 1462, 1428,
1379, 1111, 739, 702; 1H NMR (CDCl3, 360 MHz) δ 7.71-7.68
(m, 4H), 7.42-7.35 (m, 6H), 5.70 (m, 1H), 5.12-5.05 (m, 2H),
3.82-3.75 (m, 1H), 3.23 (q, 1H, J ) 5.8 Hz), 2.14 (hexet, 1H,
J ) 7.1 Hz), 1.60-1.45 (m, 2H), 1.35-1.12 (m, 4H), 1.07 (s,
9H), 0.99 (d, 3H, J ) 6.8 Hz), 0.97 (d, 3H, J ) 5.2 Hz), 0.91 (d,
3H, J ) 6.8 Hz); 13C NMR (CDCl3, 90 MHz) δ 141.1, 136.7,
135.7, 135.3, 130.2, 130.1, 128.2, 128.1, 117.0, 75.4, 73.4, 44.8,
40.6, 32.7, 29.6, 27.8, 20.1, 18.7, 17.0, 14.4.
1
alcohol was confirmed by H and 13C NMR. 1H NMR (CDCl3,
360 MHz) δ 5.79 (m, 1H) 5.03-4.91 (m, 2H) 3.65 (pentet, 1H,
J ) 6.2 Hz), 2.32-2.10 (m, 1H) 2.05-1.92 (m, 1H) 1.70-1.60
(s, 1H, broad) 1.60-1.45 (m, 2H) 1.19-1.14 (m, 1H) 1.11 (d,
3H, J ) 6.3 Hz), 0.86 (d, 3H, J ) 6.8 Hz); 13C NMR (CDCl3, 90
MHz) δ 139.7, 115.1, 72.4, 40.2, 32.4, 32.2, 20.1, 15.1.
(5S,6R)-6-(ter t-Bu t yld ip h en ylsiloxy)-5-m et h yl-1-h ep -
ten e (32). The preceding partially evaporated mixture and
catalytic DMAP (ca. 5 mg) were dissolved in a mixture of DMF
(distilled, dry, 5 mL), 2,6-lutidine (2 mL, 17 mmol), and tert-
butyldiphenylsilyl chloride (3.0 mL, 12 mmol). The mixture
was brought to 85 °C for 12 h. After cooling, the reaction
mixture was partitioned between NH4Cl saturated solution (50
mL) and CH2Cl2 (50 mL). The organic extracts were washed
with HCl (1.2 M, 50 mL), dried over Na2SO4, and evaporated,
(3R,4R,7S,8R)-8-(ter t-Bu tyld ip h en ylsiloxy)-4-[(4-m eth -
oxyben zyl)oxy]-3,7-d im eth yl-1-n on en e (35). A solution of
alcohol 34 (0.392 g, 0.923 mmol) and p-methoxybenzyl 2,2,2-
trichloroacetimidate (0.285 g, 1.01 mmol) in diethyl ether (18
mL) was treated with trifluoromethylsulfonic acid (0.25 µL,
2.8 × 10-4 mmol in 0.25 mL of ether). The reaction was stirred
for 20 min, with the addition of more p-methoxybenzyl 2,2,2-
trichloroacetimidate (0.122 g, 0.432 mmol, in 2 portions at 10
min and 15 min) during this time. The reaction mixture

Synthesis of the C1-C21 Fragment of Tautomycin
J . Org. Chem., Vol. 61, No. 9, 1996 3115
29
was partitioned between CH2Cl2 and H2O (50 mL ea.). The
organic extracts were dried over Na2SO4/MgSO4 and evapo-
rated, and the remaining oil was purified by column chroma-
tography (silica gel, 5% ethyl acetate/hexanes) to yield a clear
colorless oil (0.352 g, 70%) with 0.050 g of recovered starting
was diluted with THF (1.2 mL) and DMF (0.3 mL), and CrCl2
doped with 0.1% NiCl2 was added (60 mg, 0.49 mmol). The
reaction mixture was allowed to stir for 60 h and then opened
to air and partitioned between CH2Cl2 and saturated NH4Cl
solution (50 mL ea.). The aqueous layer was extracted with
CH2Cl2 (2 × 50 mL) and ethyl acetate (3 × 50 mL). The
combined organic extracts were dried over Na2SO4 and evapo-
rated to a green paste, and this was paste purified by column
chromatography (silica gel, 10% to 15% ethyl acetate in
hexanes) to yield 55.1 mg (65%) of the coupled allylic alcohol
as a clear oil containing trace ethyl acetate. This mixture of
diastereomers is not separable, and is taken on as a mixture
to the next step. HRFABMS 1023.6147 m/z, ((M - H)+)30
material (13%) [R]25 ) +1.06 ° (c ) 51.4 mg/ mL in benzene);
D
HREIMS 487.2653 m/z, 487.2668 (M - C4H9)+ calcd for
C31H39O3Si; IR (NaCl plates neat cm-1) 3071, 2963, 2858, 1613,
1514, 1248, 1111, 822, 702; 1H NMR (CDCl3, 360 MHz) δ 7.75-
7.72 (m, 4H), 7.48-7.37 (m, 6H), 7.27-7.25 (m, 2H), 6.91-
6.87 (m, 2H), 5.86-5.76 (m, 1H), 5.10-5.01 (m, 2H), 4.45 (d,
1H, J ) 11.0 Hz), 4.37 (d, 1H, J ) 11.0 Hz), 3.86-3.78 (m,
4H), 3.17 (m, 1H), 2.55-2.42 (m, 1H), 1.60-1.50 (m, 1H), 1.50-
1.40 (m, 1H), 1.29-1.21 (m, 3H), 1.11 (s, 9H), 1.03 (d, 3H, J )
1023.6170 calcd for C65H87O8Si; IR (NaCl plates neat cm-1
)
8.0 Hz), 0.99 (d, 3H, J ) 6.3 Hz), 0.95 (d, 3H, J ) 6.7 Hz); 13
C
3475, 3074, 2932, 1717, 1614, 1514, 1271, 1248, 1109, 821, 702;
1H NMR (CDCl3, 360 MHz) δ 8.1-8.03 (m, 2H), 7.70-7.67 (m,
4H), 7.57-7.52 (m, 1H), 7.45-7.33 (m, 8H), 7.24-7.19 (m, 4H),
6.85-6.80 (m, 4H), 5.92-5.82 (m, 1H), 5.62-5.53 (m, 1H),
5.47-5.39 (m, 1H), 5.12-5.07 (m, 3H), 4.50-4.43 (m, 2H),
4.38-4.30 (m, 2H), 4.02-3.92 (m, 1H), 3.80-3.73 (m, 7H), 3.14-
3.09 (m, 1H, 3.04-3.00 (m, 1H), 2.59-2.49 (m, 1H), 2.45-2.37
(m,1H), 1.73-1.65 (m, 4H), 1.55-1.35 (m, 7H), 1.35-1.10 (m,
4H), 1.08 (d, 3H, J ) 7.0 Hz), 1.06 (s, 9H), 1.00-0.89 (m, 15H);
13C NMR (CDCl3, 90 MHz) δ 171.1, 166.2, 166.2, 159.0, 158.8,
139.1, 135.8, 134.8, 134.4, 134.2, 133.7, 133.1, 133.0, 132.7,
131.2, 130.9, 130.5, 129.5, 129.4, 129.3, 129.1, 129.1, 129.0,
128.3, 127.4, 127.3, 115.7, 113.6, 113.5, 86.3, 86.3, 82.7, 82.7,
77.8, 74.5, 73.4, 73.0, 72.6, 71.5, 71.4, 60.3, 55.1, 41.4, 41.4,
39.9, 39.3, 39.1, 35.7, 35.6, 35.5, 34.9, 34.8, 30.2, 30.1, 30.0,
29.7, 29.3, 28.6, 28.6, 26.9, 20.9, 19.2, 18.1, 18.0, 16.3, 16.3,
15.8, 15.6, 15.2, 15.2, 15.1, 14.9, 14.8, 14.1, 13.8.
NMR (CDCl3, 90 MHz) δ 159.0, 141.0, 135.8, 134.9, 134.5,
131.1, 129.9, 129.3, 129.2, 127.4, 127.3, 114.3, 113.6, 82.7, 72.6,
71.4, 55.2, 40.4, 39.99, 28.9, 28.4, 27.0, 19.3, 18.0, 14.9, 13.8.
(3R,4R,7S,8R)-8-(ter t-Bu tyld ip h en ylsiloxy)-4-[(4-m eth -
oxyben zyl)oxy]-3,7-d im eth yl-1-octa n a l (36). A solution of
compound 35 (0.676 g, 1.241 mmol) in CH2Cl2 was subjected
to O3 gas at -78 °C until a light blue color was discernible.
The resulting ozonide was quenched by the addition (at -78
°C) of tributylphosphine (0.318 mL, approximately 1 equiv
adjusted for purity) followed by slow warming to rt. After 1.5
h the reaction mixture was evaporated and purified by column
chromatography (silica gel 5% ethyl acetate in hexanes) to
yield 0.516 g (76%) of aldehyde as a clear oil. This material
is unstable to â elimination and is used in the next step
without delay. [R]25 ) +0.9° (c ) 2.5 mg/mL in benzene);
D
HREIMS 545.3087 m/z, 545.3087 (M - H)+ calcd for C34H45O4-
Si; IR (NaCl plates neat cm-1) 3068, 2933, 2857, 1726, 1613,
1514, 1248, 1109, 1037, 822; 1H NMR (CDCl3, 360 MHz) δ 9.70
(d, 1H, J ) 2.2 Hz), 7.72-7.69 (m, 4H), 7.46-7.36 (m, 6H),
7.22-7.18 (m, 2H), 6.86-6.85 (m, 2H), 4.40 (d, 1H, J ) 11.1
Hz), 4.34 (d, 1H, J ) 11.0 Hz), 3.82-3.76 (m, 4H), 3.58 (m,-
1H), 2.61 (dp, 1H, J ) 2.1, 6.8 Hz), 5.55-1.46 (m, 2H), 1.38-
1.26 (m, 2H), 1.15-1.11 (m, 1H), 1.09 (s, 9H), 1.05 (d, 3H, J )
(3R,4S,7R,8R,9S,15R,16R,19S,20R)-4-(Ben zoyloxy)-20-
(ter t-b u t yld im et h ylsiloxy)-8,16-b is[(4-m et h oxyb en zyl)-
oxy]-3,7,9,15,19-p en t a m et h yl-1,13-h en icosa d ien -12-on e
(38). Allylic alcohol 37 (48.3 mg, 0.0471 mmol) was dissolved
in CH2Cl2 (not distilled) and treated with a solution of Dess-
Martin periodinane (0.3878 g, 0.9146 mmol) dissolved in CH2-
Cl2 (10 mL, not distilled) and pyridine (0.80 mL, not distilled).
After allowing the reaction mixture to stir for 1 h at rt it was
diluted with hexanes (15 mL) and the entire reaction mixture
(approximately 31 mL volume) was purified by column chro-
matography (silica gel, 10% ethyl acetate in hexanes, ap-
proximately 30 mL of dry vol silica gel) to yield 39.9 mg (83%)
of pure ketone and 6.4 (13%, 0.00625 mmol) mg of ketone
containing some aromatic contaminant for an overall yield of
7.1 Hz), 0.99 (d, 3H, J ) 6.2 Hz), 0.93 (d, 3H, J ) 6.7 Hz); 13
C
NMR (CDCl3, 90 MHz) δ 204.5, 159.1, 135.8, 134.7, 134.4,
130.2, 129.4, 129.3, 129.3, 127.4, 127.3, 113.7, 79.0, 72.5, 71.2,
55.2, 49.2, 40.0, 28.7, 27.6, 27.0, 19.2, 18.1, 13.8, 9.9.
(3R,4R,7S,8R)-8-(ter t-Bu t yld ip h en ylsiloxy)-1-iod o-4-
[(4-m eth oxyben zyl)oxy]-3,7-d im eth yl-1-n on en e (5). Al-
dehyde 36 (86 mg, 0.1372 mmol) from the previous reaction
(freshly prepared) was azeotroped with toluene and then
dissolved in THF (1 mL), and iodoform (139 mg, 0.3515 mmol)
was added. This solution was added to a suspension of CrCl2
(135. mg, 1.099 mmol) in THF (2 mL) at 0 °C. The reaction
mixture rapidly turned brown and was allowed to stir at 0 °C
for 3 h. The reaction mixture was then partitioned between
diethyl ether and water (50 mL ea.), the aqueous layer
extracted with diethyl ether (50 mL × 2) and ethyl acetate
(50 mL), the organic extracts were dried over MgSO4/Na2SO4
and evaporated, and the residue was taken up in CH2Cl2,
redried with Na2SO4, evaporated, and purified by column
chromatography (silica gel, 25% CH2Cl2 in hexanes) to yield
46.3 mg (96%). [R]25 ) -0.1 ° (c ) 39.9 mg/ mL in benzene);
D
HRFABMS 1021.6017 m/z, 1021.6014 (M - H)+ calcd for
C65H85O8Si; IR (NaCl plates neat cm-1) 3073, 3033, 2963, 1717,
1612, 1514, 1271, 1248, 1111, 824, 708; 1H NMR (CDCl3, 360
MHz) δ 8.06-8.03 (m, 2H), 7.70-7.66 (m, 4H), 7.57-7.52 (m,
1H), 7.46-7.33 (m, 8H), 7.23-7.18 (m, 4H), 6.86-6.57 (m, 5H),
6.05 (dd, 1H, J ) 0.9, 16.1 Hz), 5.92-5.82 (m, 1H), 5.13-5.07
(m, 3H), 4.50-4.43 (m, 2H), 4.35 (s, 2H), 3.80-3.70 (m, 4H),
3.22-3.18 (m, 1H), 3.04 (t, 1H, J ) 5.1 Hz), 2.60-2.40 (m, 4H),
1.80-1.60 (m, 5H), 1.55-1.36 (m, 4H), 1.34-1.10 (m, 4H),
1.09-1.01 (m, 15H), 0.96-0.88 (m, 12H); 13C NMR (CDCl3, 90
MHz) δ 200.4, 166.2, 159.0, 158.9, 149.1, 139.1, 135.8, 134.8,
134.4, 132.7, 131.1, 130.5, 130.5, 129.9, 129.5, 129.4, 129.3,
129.2, 129.0, 128.2, 127.4, 127.3, 115.7, 113.6, 113.5, 86.4, 82.0,
77.8, 74.5, 72.5, 71.6, 55.1, 53.3, 41.4, 39.9, 37.9, 35.6, 35.4,
30.2, 29.3, 28.9, 28.3, 26.9, 19.2, 18.1, 16.3, 15.0, 15.0, 14.8,
13.8.
44 mg (48%) of a clear oil. [R]25 ) +9.78° (c ) 71.7 mg/ mL
D
in benzene); HREIMS 669.2264 m/z, 669.2261 (M - H)+ calcd
for C35H46IO3Si; IR (NaCl plates neat cm-1) 3070, 2961, 2856,
1612, 1514, 1248, 1109, 1037, 953, 908, 821, 737, 702; 1H NMR
(CDCl3, 360 MHz) δ 7.76-7.72 (m, 4H), 7.48-7.38 (m, 6H),
7.31-7.23 (m, 2H), 6.91-6.88 (m, 2H), 6.55-6.49 (m, 1H),
6.05-6.00 (m, 1H), 4.41 (s, 2H), 3.82 (m, 4H), 3.15-3.10 (m,
1H), 2.45-2.35 (m, 1H), 1.60-1.34 (m, 2H), 1.35-1.11 (m, 3H),
1.11 (s, 9H), 1.06-0.99 (m, 6H), 0.95 (d, 3H, J ) 6.7 Hz); 13C
NMR (CDCl3, 90 MHz) δ 159.1, 148.7, 135.8, 134.9, 134.4,
133.6, 129.5, 129.4, 129.3, 127.4, 127.3, 113.7, 81.8, 75.0, 72.5,
71.8, 55.2, 43.8, 39.9, 28.9, 28.6, 27.0, 19.3, 18.0, 15.2, 13.8.
(3R,4S,7R,8R,9S,15R,16R,19S,20R)-4-(Ben zoyloxy)-20-
(ter t-b u t yld im et h ylsiloxy)-8,16-b is[(4-m et h oxyb en zyl)-
oxy]-3,7,9,15,19-p en t a m et h yl-1-h en icosen -12-on e (39).
Enone 38 (39.3 mg, 0.0383 mmol) was dissolved in degassed
benzene-d6 (1.5 mL) and water (30 µL). A solution of (CuH-
(29) CrCl2 was obtained from RocRic as “anhydrous”. This material
was green and was heated at 160 °C for 6 days under high vacuum
before the gray color, indicating truly anhydrous CrCl2, was obtained.
(30) While it is unusual to observe (M - H)+ in FAB mass
spectroscopy we found that vinyl iodide 5 exhibited this ion in both
FAB and EI spectra. Additionally in the EI spectra (M - C4H9)+ was
also found confirming that we have the correct structure. We believe
that the anomaly that is causing (M - H)+ to occur in the FAB spectra
of 5 is also occurring in this case.
(3R,4S,7R,8S,9S,15R,16R,19S,20R)-4-(Ben zoyloxy)-20-
(ter t-bu tyld im eth ylsiloxy)-12-h yd r oxy-8,16-bis[(4-m eth -
oxyb en zyl)oxy]-3,7,9,15,19-p en t a m et h yl-1,13-h en icosa -
d ien e (37). A mixture of aldehyde 4 (41.0 mg, 0.0843 mmol)
and vinyl iodide (5) (134.1 mg, 0.200 mmol) was azeotroped
with toluene to assure dryness. In a glove box this mixture

3116 J . Org. Chem., Vol. 61, No. 9, 1996
Maurer and Armstrong
PPh3)6 in deuterated benzene (0.1068 g, in 3.0 mL of benzene,
degassed) was then titrated into the enone solution over 1 h
(initial 1.40 mL portion followed by two 0.30 mL portions for
an over all 2.00 mL of solution, 0.0328 mmol) until NMR
showed complete removal of the enone 1H peak at 6.05 ppm
in the 1H NMR spectra. The reaction was opened to air and
vacuum evaporated to a paste which was purified by column
chromatography (silica gel, 20% ethyl acetate in hexanes and
then again in 5-10% ethyl acetate in hexanes) to yield 39.2
mg (99.7%) of a clear oil containing only trace starting
saturated sodium bicarbonate solution (10 mL) and the aque-
ous layer extracted with CH2Cl2 (4 × 10 mL). The organic
extracts were combined, dried over Na2SO4, and evaporated,
and the resulting oil was purified by column chromatography
(silica gel, 5% ethyl acetate in hexanes and then in 2.5% ethyl
acetate in hexanes) to yield 19.3 mg (67%) of spirocyclic
compound 40. [R]25 ) -20.4° (c ) 19.3 mg/mL in benzene);
D
HRFABMS 765.4894 m/z, 765.4914 (M - H)+ calcd for
C49H69O5Si, also possible MH+ overlapping isotope peak from
(M - H)+ 767.5068, 767.5071 calcd for C49H71O5Si; HREIMS
found 709.4285 m/z, 709.4288 calcd for (M - C4H9)+ C45H61O5-
Si; IR (NaCl plates neat cm-1) 3071, 2932, 1719, 1271, 1111,
material. [R]25 ) -2.0° (c ) 39.2 mg/ mL in benzene);
D
HRFABMS 1024.6238 m/z, (M+) 1024.6248 calcd for C65H88O8-
Si; IR (NaCl plates neat cm-1) 3073, 2961, 1717, 1613, 1514,
1248, 1111, 822, 708; 1H NMR (CDCl3, 500 MHz) δ 8.10-8.08
(m, 2H), 7.74-7.72 (m, 4H), 7.61-7.58 (m, 1H), 7.49-7.39 (m,
8H), 7.31-7.24 (m, 4H), 6.89-6.83 (m, 4H), 5.95-5.88 (m, 1H),
5.16-5.12 (m, 3H), 4.51 (s, 2H), 4.39 (d, 1H, J ) 11.0 Hz),
4.33 (d, 1H, J ) 11.0 Hz), 3.83-3.81 (m, 7H), 3.13-3.11 (m,
1H), 3.06 (t, 1H, J ) 5.1 Hz), 2.61-2.55 (m, 1H), 2.50-2.32
(m, 4H), 1.80-1.65 (m, 7H), 1.59-1.50 (m, 2H), 1.45-1.20 (m,
7H), 1.13 (d, 3H, J ) 6.9 Hz), 1.11 (s, 9H), 1.10-0.93 (m, 12H),
0.87 (d, 3H, J ) 6.7 Hz); 13C NMR (CDCl3, 125 MHz) δ 211.1,
166.2, 159.0, 159.0, 139.2, 135.9, 135.0, 134.5, 132.8, 131.2,
131.1, 130.6, 129.5, 129.4, 129.3, 129.3, 129.1, 128.3, 127.5,
127.4, 115.8, 113.7, 113.6, 86.4, 82.9, 77.9, 74.5, 72.7, 71.2, 55.2,
55.2, 41.5, 40.9, 40.6, 40.1, 35.7, 35.4, 34.9, 30.3, 29.4, 28.6,
28.1, 27.6, 27.0, 26.8, 19.3, 18.1, 16.4, 15.0, 14.9, 14.6, 13.8.
Sp ir ocyclic Com p ou n d 40. A solution of compound 39
(37.7 mg, 0.0368 mmol) in CH2Cl2 (8 mL) and water (0.40 mL)
was treated with DDQ (31.5 mg, 0.139 mmol) in CH2Cl2 (1
mL), and the resulting mixture was allowed to stir at rt for
40 min. The reaction mixture was partitioned between
1
706; H NMR (CDCl3, 360 MHz) δ 8.04-8.02 (m, 2H), 7.69-
7.65 (m, 4H), 7.55-7.53 (m, 1H), 7.44-7.34 (m, 8H), 5.88-
5.81 (m, 1H), 5.08-5.02 (m, 3H), 3.82-3.78 (m, 1H), 3.22 (dd,
1H, J ) 2.2, 10.1) 3.06 (ddd, 1H, J ) 9.5, 9.5, 1.8) 2.56-1.95
(m, 1H), 1.76-1.65 (m, 2H), 1.60-1.48 (m, 7H), 1.48-1.10 (m,
11H), 1.07-1.03 (m, 12H), 0.97-0.90 (m, 9H), 0.85-0.79 (m,
4H), 0.75 (d, 3H, J ) 6.5); 13C NMR (CDCl3, 90 MHz) δ 166.3,
139.1, 135.1, 134.5, 132.8, 130.6, 129.5, 129.4, 129.3, 128.3,
127.4, 127.3, 115.8, 95.5, 77.9, 74.6, 74.6, 72.5, 41.31, 40.2, 36.1,
34.8, 34.8, 31.0, 30.2, 28.7, 28.5, 28.2, 27.5, 27.4, 27.0, 26.6,
19.3, 18.3, 18.0, 16.6, 16.5, 14.4, 10.8.
Su p p or tin g In for m a tion Ava ila ble: 90-MHz 13C NMR
spectra of new compounds (34 pages). This material is
contained in libraries on microfiche, immediately follows this
article in the microfilm version of this journal, and can be
ordered from the ACS; see any current masthead page for
ordering information.
J O952083L