Concise means for accessing an advanced precursor to 1-deoxypaclitaxel

Article abstract of DOI:10.1021/jo048289g

(Chemical Equation Presented). A program directed toward a total synthesis of 1-deoxypaclitaxel is described. The most direct route consists of six steps from the previously described diketone 12 and proceeds in 18% overall yield. The transformations invo

Full text of DOI:10.1021/jo048289g

Concise Means for Accessing an Advanced Precursor to
1-Deoxypaclitaxel
Xin Guo and Leo A. Paquette*
Evans Chemical Laboratories, The Ohio State University, Columbus, Ohio 43210
paquette.1@osu.edu
Received September 27, 2004
A program directed toward a total synthesis of 1-deoxypaclitaxel is described. The most direct route
consists of six steps from the previously described diketone 12 and proceeds in 18% overall yield.
The transformations involved in reaching the target molecule 22 consist of stereoselective R-ketol
generation, an EtAlCl2-catalyzed transannular hydride shift, regioselective monomesylation, and
a Wagner-Meerwein 1,2-shift. The central issue of this synthesis is the sequential deployment of
these highly controlled steps along the perimeter and across the interior gap of a nine-membered
ring.
The substantial human health benefit offered by
paclitaxel (Taxol, 1) has spawned many studies aimed
at the preparation of analogues for the purpose of
elucidating structure-activity guidelines.1 This explor-
atory thrust has established that reductive removal of
the C-1 hydroxyl group by various protocols is not feasible
because structural rearrangements are invariably trig-
gered during attempted C-O bond cleavage.2-5 1-Deoxy-
paclitaxel (2) is of particular interest because a hydroxyl
group no longer resides on the leading edge known to
contribute to biological activity.6 In this paper, we
describe an expansion of our program aimed at synthe-
sizing 1 from D-camphor7 to include a companion ap-
proach to 2. A comparable economy of steps was envi-
sioned,8,9 so as to allow ultimate access to reasonable
amounts of the target. Ideally, both synthetic plans would
share common intermediates in their early stages. The
key distinction was to be the supplantation of an equi-
librium-controlled R-ketol rearrangement10 by an irre-
versible pinacol-type 1,2-shift.11
At the outset of the present undertaking, the factors
cited above were sufficiently compelling to cause us to
pursue a concise, enantioselective total synthesis of
1-deoxypaclitaxel. Added motivation soon surfaced with
(1) (a) Taxol: Science and Applications; Suffness, M., Ed.; CRC
Press: New York, 1995. (b) Taxane Anticancer Agents: Basic Science
and Current Status; Georg, I. G., Chen, T. T., Ojima, I., Vyas, D. M.,
Eds.; ACS Symposium Series No. 583; American Chemical Society:
Washington, 1995. (c) The Chemistry and Pharmacology of Taxol and
its Derivatives; Farina, V., Ed.; Elsevier: Oxford, 1995.
(2) (a) Samaranayake, G.; Magri, N. F.; Jitrangsri, C.; Kingston, D.
G. I. J. Org. Chem. 1991, 56, 5114. (b) Chordia, M. D.; Kingston, D. G.
I.; Hamel, E.; Lin, C. M.; Long, B. H.; Fairchild, C. A.; Johnston, K.
A.; Rose, W. C. Bioorg. Med. Chem. 1997, 5, 941. (c) Chordia, M. D.;
Kingston, D. G. I. Tetrahedron 1997, 53, 5699.
(7) (a) Paquette, L. A.; Zhao, M.; Montgomery, F.; Zeng, Q.; Wang,
T. Z.; Elmore, S.; Combrink, K.; Wang, H.-L.; Bailey, S.; Su, Z. Pure
Appl. Chem. 1998, 70, 1449. (b) Paquette, L. A.; Hofferberth, J. E. J.
Org. Chem. 2003, 68, 2266.
(8) Paquette, L. A.; Lo, H. Y. J. Org. Chem. 2003, 68, 2282.
(9) Brennan, N.; Guo, X.; Paquette, L. A. J. Org. Chem. 2005, 70,
In press (JO0482965).
(10) Paquette, L. A.; Hofferberth, J. E. Org. React. 2003, 62, 477.
(11) (a) Paquette, L. A.; Elmore, S. W.; Combrink, K. D.; Hickey, E.
R.; Rogers, R. D. Helv. Chim. Acta 1992, 75, 1755. (b) Paquette, L. A.;
Combrink, K. D.; Elmore, S. W.; Zhao, M. Helv. Chim. Acta 1992, 75,
1772. (c) Paquette, L. A.; Zhao, M. J. Am. Chem. Soc. 1998, 120, 5203.
(d) Paquette, L. A.; Wang, H.; Su, Z.; Zhao, M. J. Am. Chem. Soc. 1998,
120, 5213.
(3) Wahl, A.; Gue´ritte-Voegelein, G.; Gue´nard, D.; LeGoff, M.; Potier,
P. Tetrahedron 1992, 48, 6965.
(4) Chen, S. H.; Huang, S.; Wei, J.; Farina, V. J. Org. Chem. 1993,
58, 4520.
(5) Appendino, G.; Varese, M.; Gariboldi, P.; Gabetta, B. Tetrahedron
Lett. 1994, 35, 2217.
(6) (a) Kingston, D. G. I.; Molinero, A. A.; Rimoldi, J. M. Prog. Chem.
Org. Nat. Prod. 1993, 61, 1. (b) Kingston, D. G. I.; Jagtap, P. G.; Yuan,
H.; Samala, L. Prog. Chem. Org. Nat. Prod. 2002, 84, 53.
10.1021/jo048289g CCC: $30.25 © 2005 American Chemical Society
Published on Web 12/10/2004
J. Org. Chem. 2005, 70, 315-320
315

Guo and Paquette
SCHEME 1
SCHEME 2
The initial conversion of 3 to monomesylate 4 pro-
ceeded efficiently. The latter was subsequently heated
with DBU in benzene for 32 h. The desired medium-ring
olefin 5 was isolated chromatographically in 65% yield.
Next to be addressed was the regioselective epoxidation
of the intraannular double bond in 5. On the basis of
precedents,16 it seemed reasonable that reagent attack
would occur from its more open R surface. When MCPBA
was found not to react regioselectively with 5, we turned
to the use of VO(acac)2 and tert-butyl hydroperoxide in
order to take advantage of the capacity of this reagent
combination to oxidize allylic alcohols with high diaste-
reoselectivity.17 The chemistry of 6 so formed was quite
extensively explored. Particularly vexing was the absence
of observable chemical change in the presence of wide
range of Lewis acids (e.g., Et2AlCl, Me3Al, BF3‚OEt2,
TiCl4, CSA, HClO4, etc). An increase in reaction temper-
ature to 0-40 °C only led to loss of the PMB and/or TBS
protecting groups.
The unactivated nature of 6 paralleled that encoun-
tered earlier in our companion quest of paclitaxel. For
reasons not yet completely understood, the presence of
an exocyclic methylene group at C-4 effectively deters
operation of the R-ketol rearrangement in that series.18
The desired bridge migration does operate, however, once
that substituent is converted to an epoxide. Accordingly,
5 was treated with an excess of m-chloroperbenzoic acid
to provide diepoxide 9 (Scheme 2), the structural features
of which were corroborated by NOESY NMR analysis.
Exhaustive screening of different Lewis acids and select
bases (including KHMDS, Al(i-PrO)3, KOt-Bu, and the
like) gave no evidence for conversion to 10. The inoper-
ability of the desired Wagner-Meerwein shifts may arise
from improper orbital overlap since oxirane belting across
C-1/C-2 in both 6 and 9 strictly rigidifies their ground-
state conformation. Enhancing structural flexibility was
therefore alternatively pursued in order to remediate the
present complication.
the issuance of a patent application claiming a synthesis
of 2 but without exemplification.12 The progression of
events has been such that a recent report has identified
2 as a byproduct in the isolation of paclitaxel.13 Evidently,
the absence of the C-1 hydroxyl reduces activity by
approximately one-third in assays involving the HCT116
and A2780 cell lines. The isolation of 2 from natural
sources obviously does not solve the availability problem.
Therefore, the context remains entirely favorable for
proposed routes to 1-deoxypaclitaxel to be evaluated
experimentally. Here we detail the assembly of a tricyclic
intermediate considered to be adequately functionalized
to offer the opportunity for ultimate conversion to 2.
Results and Discussion
Exploration of the Epoxy Alcohol Option. In view
of the ready availability of dihydroxy ketone 3,7b,14 the
decision was made to install an R-epoxide moiety as in 6
for the purpose of effecting an appropriately catalyzed
rearrangement to generate 8 (Scheme 1). Transforma-
tions of this type are well-known.15 We were mindful that
colinear alignment involving the antibonding C-O bond
at C-1 or its p-orbital equivalent (see 7) with the
neighboring bridgehead C-C bonding orbital would prove
to be crucial to our objectives.
Suitability of 1,2-Diol Monomesylates. We were
thus motivated to explore the regioselectivity of the
dihydroxylation of 5 with the OsO4/TMEDA complex as
reported by Donohoe and co-workers to attack at the
(15) For selected examples, see: (a) Maruoka, K.; Hasegawa, M.;
Yamamoto, H. J. Am. Chem. Soc. 1986, 108, 3827. (b) Tu, Y. Q.; Fan,
C. A.; Ren, S. K.; Chan, A. S. C. J. Chem. Soc., Perkin Trans. 1 2000,
3792. (c) Wang, F.; Tu, Y. Q.; Fan, C. A.; Wang, S. H.; Zhang, F. M.
Tetrahedron: Asymmetry 2002, 13, 395. (d) Tanino, K.; Onuki, K.;
Asano, K.; Miyashita, M.; Nakamura, T., Takahashi, Y.; Kuwajima, I.
J. Am. Chem. Soc. 2003, 125, 1498.
(12) Holton, R. A.; Tang, S.; Liang, F.; Somoza, C. PCT Int. Appl.
WO 42,181, 1997.
(16) (a) Johnston, J. N.; Tsui, H.-C.; Paquette, L. A. J. Org Chem.
1998, 63, 129. (b) Zeng, Q.; Bailey, S.; Wang, T. Z.; Paquette, L. A. J.
Org. Chem. 1998, 63, 137.
(13) Benigni, D.; Dillon, J.; Weaver, D.; Haines, K.; Shultis, K.;
Focigle, G.; Lin, H.-Y.; Rourick, R.; Crull, G.; Huang, S.; Baumes, J.;
Long, B.; Fairchild, C. 41st Annual Meeting of the American Chemical
Society of Pharmacognosy, Seattle, WA, July 22-26, 2000. Abstract
P-16.
(17) Rossiter, B. E. In Encyclopedia of Reagents for Organic Syn-
thesis; Paquette, L. A., Ed.-in-Chief; Wiley: Chichester, 1995; Vol. 8,
p 5479.
(14) Hofferberth, J. E.; Lo, H. Y.; Paquette, L. A. Org. Lett. 2001, 3,
1777.
(18) Paquette, L. A.; Lo, H. Y.; Hofferberth, J. E.; Gallucci, J. C. J.
Org. Chem. 2003, 68, 2276.
316 J. Org. Chem., Vol. 70, No. 1, 2005

Accessing an Advanced Precursor to 1-Deoxypaclitaxel
SCHEME 3
SCHEME 5
SCHEME 4
anionically induced variants of this useful transforma-
tion,14 and the use of ethylaluminum dichloride served
our purposes well to deliver 16 in 74% yield. This key
step was matched by the very respectable regioselectivity
that accompanied the monomesylation of this advanced
intermediate. In line with the high level of steric shield-
ing known to reside in the vicinity of the C-10 position,
reaction with methanesulfonyl chloride materialized only
at the C-2 hydroxyl to give 17. Subsequent exposure of
17 to diethylaluminum chloride in CH2Cl2 provided 18
in 61% yield.
The final series of experiments gave attention to the
fact that 1 and 2 carry a benzoate group at C-2. Instal-
lation of this functionality at the level of 14 would serve
to eliminate a later need for the exchange of protecting
groups. Indeed, this plan of action proved to be entirely
workable (Scheme 5). Not only was benzoylation as in
19 easily accomplished, but the transannular hydride
migration leading to 20 also proceeded well. The further
progression from 20 to 21 occurred on a very favorable
note as intended. Attention is called to the high level of
substitution in 21 and the essentially complete overlay
of its stereocenters with those resident in 1-deoxypacli-
taxel (2).
Summary. The feasibility of devising an enantiose-
lective route to 2 by way of a pinacol-like rearrangement
has been demonstrated. The successful pathway consists
of only six steps from 12 and relies on the operability of
a direct transannular hydride shift, regioselective chemi-
cal activation, and 1,2-migration of the gem-dimethyl-
substituted carbon atom. An overall yield of 18% was
realized. Further advancement toward 2 must deal with
the chemical complexities of A-ring functionalization and
introduction of the oxetane ring. We hope to report on
the final stages of this pursuit in due course.
π-bonds of allylic alcohols as a result of heteroatom
assistance.19 In the event, this reaction pathway was not
observed, and only 11 was produced (Scheme 3). This
eventuality is believed to be the result of steric control
and/or torsional constraints, as protected derivatives of
11 proved to be unreactive to various dihydroxylating
conditions.20
At this juncture, more advanced functionalization of
the previously reported 1218 became our immediate
objective. Cyclization to the p-methoxyphenyl (PMP)
acetal occurred on reaction with DDQ in the presence of
4 Å molecular sieves7c,21 (Scheme 4). With 13 in hand, it
was possible to bring about stereocontrolled R-hydroxy-
lation as in 14 by exposing the potassium enolate to the
Davis sulfonyloxaziridine.22 Following acetylation to
furnish 15, the stage was set to initiate a transannular
hydride shift involving migration of the well aligned
â-hydrogen at C-9 to C-1. We have previously reported
Experimental Section
Mesylate 4. To a solution of 250 mg (0.455 mmol) of 3 in
25 mL of CH2Cl2 at 0 °C were added 0.32 mL (230 mg, 2.28
mmol) of triethylamine, 0.07 mL (104 mg, 0.91 mmol) of
methanesulfonyl chloride, and 56 mg (0.455 mmol) of DMAP.
The reaction mixture was stirred for 20 min at 0 °C, quenched
with 20 mL of saturated NH4Cl solution, and allowed to warm
to room temperature. The aqueous layer was separated and
extracted with CH2Cl2 (20 mL x 3). The organic layers were
combined and dried. Purification of the residue by flash
chromatography on silica gel (elution with 30% EtOAc/hexane)
(19) (a) Donohoe, T. J.; Moore, P. R.; Waring, M. J.; Newcombe, N.
J. Tetrahedron Lett. 1997, 38, 5027. (b) Donohoe, T. J.; Blades, K.;
Moore, P. R.; Waring, M. J.; Winter, J. J. G.; Helliwell, M.; Newcombe,
N. J.; Stemp, G. J. Org. Chem. 2002, 67, 7946.
(20) Guo, X. Unpublished observations from this laboratory.
(21) Stirmer, R.; Ritter, K.; Hoffmann, R. W. Angew. Chem., Int.
Ed. Engl. 1993, 32, 105.
(22) (a) Davis, F. A.; Sheppard, A. C. Tetrahedron 1989, 45, 5703.
(b) Davis, F. A.; Chen, B.-C. Chem. Rev. 1992, 92, 919.
J. Org. Chem, Vol. 70, No. 1, 2005 317

Guo and Paquette
afforded 276 mg (92%) of 4 as a colorless oil: IR (neat, cm-1
)
gel (elution with 50% EtOAc/hexane) to afford 10 mg (95%) of
9 as a white glassy solid: IR (neat, cm-1) 1703, 1614, 1514;
1H NMR (400 MHz, CDCl3) δ 7.31 (d, J ) 8.6 Hz, 2H), 6.89 (d,
J ) 8.6 Hz, 2H), 4.66 (dd, J ) 10.7, 4.2 Hz, 1H), 4.47 (d, J )
3.9 Hz, 1H), 4.31 (d, J ) 10.8 Hz, 1H), 4.20 (d, J ) 10.9 Hz,
1H), 3.82 (s, 3H), 3.13 (d, J ) 4.0 Hz, 1H), 2.84-2.79 (m, 4H),
2.54 (br q, J ) 12.7 Hz, 1H), 2.35 (d, J ) 10.0 Hz, 1H), 2.20-
2.05 (m, 3H), 1.96-1.80 (m, 4H), 1.49 (s, 3H), 1.25 (s, 3H), 1.11
(s, 3H), 0.91 (s, 9H), 0.15 (s, 3H), 0.09 (s, 3H); 13C NMR (100
MHz, CDCl3) δ 212.0, 161.2, 133.4, 130.6 (2C), 115.9 (2C), 88.0,
85.5, 78.3, 73.8, 61.1, 60.5, 60.4, 57.6, 57.5, 56.2, 52.9, 49.8,
38.8, 34.5, 33.4, 32.7, 31.9, 28.8 (3C), 25.8, 21.1, 19.3, 12.9,
0.0 (2C); HRMS m/z calcd for C33H50O7SiNa+ 609.3218, found
1
3542, 1700, 1614; H NMR (250 MHz, CDCl3) δ 7.30 (d, J )
8.7 Hz, 2H), 6.87 (d, J ) 8.7 Hz, 2H), 5.09 (s, 1H), 5.03 (s,
1H), 4.75 (t, J ) 3.0 Hz, 1H), 4.55 (dd, J ) 11.2, 4.6 Hz, 1H),
4.47 (d, J ) 10.9 Hz, 1H), 4.36 (d, J ) 3.1 Hz, 1H), 4.12 (d, J
) 10.9 Hz, 1H), 3.80 (s, 3H), 3.14-3.08 (m, 1H), 3.02 (s, 3H),
2.78-2.56 (m, 2H), 2.52-2.36 (m, 3H), 2.21-1.94 (m, 2H),
1.87-1.54 (m, 4H), 1.13 (s, 3H), 1.11 (s, 3H), 0.91 (s, 3H), 0.83
(s, 9H), 0.064 (s, 3H), 0.056 (s, 3H); 13C NMR (63 MHz, CDCl3)
δ 211.4, 159.3, 143.9, 131.6, 128.8 (2C), 114.0 (2C), 110.9, 88.5,
87.4, 87.2, 76.8, 72.7, 61.3, 57.5, 55.7, 49.1, 38.7, 36.8, 34.6,
34.3, 32.7, 31.9, 28.7, 26.5 (3C), 26.0, 18.8, 17.8, 10.1, -1.9,
-2.8; HRMS m/z calcd for C34H54O8SSiNa+ 673.3201, found
673.3198; [R]23 -13.0 (c 0.47, CHCl3).
609.3211; [R]23 -22.8 (c 0.60, CHCl3).
D
D
Unsaturated Hydroxy Ketone 5. A 276 mg (0.425 mmol)
sample of 4 was dissolved in 55 mL of benzene and treated
with 0.095 mL (96.7 mg, 0.638 mmol) of DBU. The reaction
mixture was heated in a 100 °C oil bath for 32 h; 20 mL of
saturated NH4Cl solution was added after return to room
temperature, and stirring was maintained for 10 min. The
separated aqueous layer was extracted with CH2Cl2 (20 mL x
3); the organic layers were combined, dried, and concentated,
and the residue was purified by flash chromatography on silica
gel (elution with 20% EtOAc/hexane) to give 150 mg (65%) of
5 as a colorless oil: IR (neat, cm-1) 3383, 1705, 1614; 1H NMR
(500 MHz, CDCl3) δ 7.34 (d, J ) 8.7 Hz, 2H), 6.90 (d, J ) 8.7
Hz, 2H), 5.54 (d, J ) 12.2 Hz, 1H), 5.43 (dd, J ) 12.1, 11.6
Hz, 1H), 4.98 (s, 1H), 4.76 (s, 1H), 4.64 (dd, J ) 11.3, 4.5 Hz,
1H), 4.47 (d, J ) 3.3 Hz, 1H), 4.41 (d, J ) 11.0 Hz, 1H), 4.16
(d, J ) 11.0 Hz, 1H), 3.84 (s, 3H), 3.66 (d, J ) 11.4 Hz, 1H),
2.91 (d, J ) 12.4 Hz, 1H), 2.67 (br q, J ) 11.0 Hz, 1H), 2.49
(dq, J ) 14.3, 2.4 Hz, 1H), 2.25-2.02 (m, 5H), 1.73 (qd, J )
12.5, 3.5 Hz, 1H), 1.11 (s, 3H), 1.08 (s, 6H), 0.89 (s, 9H), 0.12
(s, 3H), 0.08 (s, 3H); 13C NMR (125 MHz, CDCl3) δ 209.8, 158.8,
143.9, 139.3, 131.4, 128.4 (2C), 125.1, 113.6 (2C), 110.6, 86.4,
84.1, 71.8, 65.8, 59.3, 56.2, 55.3, 51.1, 40.8, 37.1, 33.0, 31.7,
29.1, 26.4 (3C), 26.1, 18.7, 18.5, 9.5, -2.2, -2.6; HRMS m/z
calcd for C33H50O5SiNa+ 577.3320, found 577.3335; [R]23D -21.9
(c 0.68, CHCl3).
Triol 11. To a solution of 10 mg (0.018 mmol) of 5 in 2.0
mL of CH2Cl2 at -78 °C were added 0.0033 mL (2.51 mg,
0.0216 mmol) of TMEDA and 5.5 mg (0.0216 mmol) of OsO4
in 0.1 mL of CH2Cl2. The reaction mixture was stirred for 1 h
at -78 °C, allowed to warm to room temperature, and freed
of solvent. The residue was taken up in 2 mL of THF, treated
with 20 mg of Na2S2O4 dissolved in 2 mL of H2O, and stirred
for 1 h at room temperature. The separated aqueous layer was
extracted with CH2Cl2 (3 mL x 3); the organic layers were
combined and dried, and the residue was purified by flash
chromatography on silica gel (elution with EtOAc/hexane,
gradient from 70% to 80%) to afford 7.0 mg (67%) of 11 as a
1
white amorphous solid: IR (neat, cm-1) 3474, 1698, 1514; H
NMR (400 MHz, CDCl3) δ 7.30 (d, J ) 8.4 Hz, 2H), 6.88 (d, J
) 8.4 Hz, 2H), 5.71 (d, J ) 12.0 Hz, 1H), 5.38 (t, J ) 12.2 Hz,
1H), 4.56 (dd, J ) 11.0, 4.2 Hz, 1H), 4.44 (d, J ) 2.4 Hz, 1H),
4.32 (d, J ) 10.9 Hz, 1H), 4.09 (d, J ) 10.8 Hz, 1H), 3.83-
3.72 (m, 2H), 3.82 (s, 3H), 3.33 (d, J ) 12.5 Hz, 1H), 2.89-
2.82 (m, 2H), 2.65 (br q, J ) 11.7 Hz, 1H), 2.51 (br, 1H), 2.28
(br d, J ) 13.6 Hz, 1H), 2.12-1.98 (m, 3H), 1.77-1.44 (m, 4H),
1.13 (s, 3H), 1.07 (s, 3H), 1.06 (s, 3H), 0.84 (s, 9H), 0.10 (s,
3H), 0.09 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 212.5, 161.0,
146.2, 133.3, 130.6 (2C), 124.5, 115.8 (2C), 88.3, 86.3, 75.7, 74.1,
65.8, 61.1, 58.4, 57.4, 53.6, 45.7, 38.8, 35.0, 34.1, 31.9, 31.5,
28.4 (3C), 28.2, 20.7, 20.5, 14.4, 0.0, -0.9; HRMS m/z calcd
for C33H54O7SiNa+ 611.3375, found 611.3403; [R]23 -30.9 (c
D
Epoxy Ketone 6. A 36.6 mg (0.066 mmol) sample of 5 was
dissolved in 3.7 mL of dry CH2Cl2 and treated with 1.8 mg
(0.0068 mmol) of VO(acac)2 at room temperature, followed by
0.08 mL (0.136 mmol, 1.7 M) of tert-butylhydroperoxide in
CH2Cl2. The mixture was stirred for 24 h; 5 mL of 10%
Na2S2O3 solution was added, and stirring was continued for
15 min. The separated aqueous layer was extracted with
CH2Cl2 (2 mL x 3); the organic layers were combined and dried,
and the crude product was purified by flash chromatography
on silica gel (elution with 15% EtOAc/hexane) to afford 31.7
mg (84%) of 6 as a colorless oil: IR (neat, cm-1) 3388, 1697,
0.33, CHCl3).
Acetalization of 12. To a solution of 650 mg (1.14 mmol)
of 12 in 60 mL of CH2Cl2 at room temperature was added 1.7
g of 4 Å molecular sieves. At the same time, 284 mg (1.25
mmol) of DDQ in 50 mL of CH2Cl2 was treated with 1.7 g of 4
Å molecular sieves. Both suspensions were stirred for 1 h
before the DDQ suspension was cannulated into the suspen-
sion containing 12. The mixture was stirred for 24 h prior to
quenching with 50 mL of saturated NaHCO3 solution and 50
mL of CH2Cl2. The aqueous layer was separated and extracted
with CH2Cl2 (20 mL x 3). The organic layers were combined,
dried, and evaporated to give the crude product. Purification
by flash chromatography on silica gel (elution with 15% EtOAc/
hexane) afforded 490 mg (75%) of 13 as a colorless oil: IR
1
1614; H NMR (400 MHz, CDCl3) δ 7.32 (d, J ) 8.8 Hz, 2H),
6.89 (d, J ) 8.7 Hz, 2H), 5.11 (s, 1H), 5.04 (s, 1H), 4.66 (dd, J
) 11.2, 4.8 Hz, 1H), 4.49 (d, J ) 3.8 Hz, 1H), 4.32 (d, J ) 10.9
Hz, 1H), 4.19 (d, J ) 10.9 Hz, 1H), 3.82 (s, 3H), 3.13 (dd,
J ) 10.7, 4.4 Hz, 1H), 3.01 (d, J ) 1.3 Hz, 1H), 2.86-2.82
(m, 1H), 2.52-2.43 (m, 3H), 2.19-1.72 (m, 6H), 1.28 (s, 3H),
1.18 (s, 3H), 1.11 (s, 3H), 0.90 (s, 3H), 0.13 (s, 3H), 0.07 (s,
3H); 13C NMR (100 MHz, CDCl3) δ 212.9, 161.1, 144.5, 133.5,
130.6 (2C), 115.9 (2C), 113.5, 88.0, 85.8, 76.6, 73.7, 63.9,
60.7, 59.3, 57.5, 56.4, 50.0, 42.4, 35.2, 34.2, 33.2, 32.0, 28.8
(3C), 25.8, 21.1, 19.9, 12.4, 0.0 (2C); HRMS m/z calcd for
C33H50O6SiNa+ 593.3269, found 593.3271; [R]23D -51.0 (c 0.20,
CHCl3).
1
(neat, cm-1) 3535, 1674, 1615; H NMR (400 MHz, CDCl3) δ
7.39 (d, J ) 8.6 Hz, 2H), 6.89 (d, J ) 8.6 Hz, 2H), 5.79 (s, 1H),
4.97 (s, 1H), 4.67 (s, 1H), 4.34-4.30 (m, 2H), 3.81 (s, 3H), 3.67
(d, J ) 9.0 Hz, 1H), 3.11 (s, 1H), 2.94 (dd, J ) 15.4, 2.2 Hz,
1H), 2.86-2.76 (m, 2H), 2.69-2.55 (m, 2H), 2.44 (dt, J ) 13.6,
4.2 Hz, 1H), 2.30-2.23 (m, 1H), 2.14-2.07 (m, 2H), 2.06-1.97
(m, 1H), 1.74-1.64 (m, 2H), 1.17 (s, 3H), 1.16 (s, 3H), 1.04 (s,
3H), 0.95 (s, 9H), 0.16 (s, 3H), 0.11 (s, 3H); 13C NMR (100 MHz,
CDCl3) δ 218.3, 162.2, 148.4, 131.6, 130.3 (2C), 115.6 (2C),
111.2, 102.2, 89.6, 85.0, 83.8, 75.4, 57.2, 50.8, 50.1, 47.0, 46.9,
42.5, 35.8, 34.2, 32.8, 31.3, 28.4 (3C), 27.4, 21.4, 20.9, 14.6,
0.0, -0.6; HRMS m/z calcd for C33H50O6SiNa+ 593.3269, found
Diepoxide 9. To a solution of 10 mg (0.018 mmol) of 5 in
0.5 mL of CH2Cl2 at 0 °C were added 10 mg (0.12 mmol) of
NaHCO3 and 10 mg (0.044 mmol) of MCPBA. The reaction
mixture was allowed to stir for 12 h with the bath warming to
room temperature, at which point 2 mL of 10% Na2S2O3
solution was added and stirring was continued for 15 min. The
aqueous layer was separated and extracted with CH2Cl2 (5 mL
x 3). The organic layers were combined, dried, and evaporated.
The residue was purified by flash chromatography on silica
593.3271; [R]23 6.1 (c 0.93, CHCl3).
D
r-Oxygenation of 13. A 500 mg (0.877 mmol) sample of
13 was dissolved in 45 mL of THF, cooled to -78 °C, treated
with 3.50 mL (1.75 mmol) of 0.5 M KHMDS solution in toluene,
and stirred for 10 min at that temperature. At this point, 458
mg (1.75 mmol) of the Davis reagent dissolved in 20 mL of
318 J. Org. Chem., Vol. 70, No. 1, 2005

Accessing an Advanced Precursor to 1-Deoxypaclitaxel
THF was added and the reaction mixture was allowed to warm
to room temperature over a period of 2 h, treated with 40 mL
of saturated NH4Cl solution, and stirred for 15 min. The
aqueous layer was separated and extracted with CH2Cl2 (20
mL x 3). The combined organic layers were dried and evapo-
rated to leave a residue that was purified by flash chroma-
tography on silica gel (elution with 30% EtOAc/hexane) to
(0.100 mmol) of DMAP and 0.003 mL (0.039 mmol) of meth-
anesulfonyl chloride. The reaction mixture was stirred for 2 h
prior to quenching with 2 mL of saturated NH4Cl solution and
then stirred for 15 min at room temperature. The separated
aqueous layer was extracted with CH2Cl2 (3 mL x 3); the
organic layers were combined, dried, and evaporated, and the
residue was purified by flash column chromatography on silica
gel (elution with 30% EtOAc/hexane). There were isolated 2.9
mg of unreacted 16 and 6.7 mg (57%) of 17 as a white
afford 489 mg (95%) of 14 as a colorless oil: IR (neat, cm-1
)
2948, 2857, 1674, 1615; 1H NMR (400 MHz, CDCl3) δ 7.37 (d,
J ) 8.7 Hz, 2H), 6.90 (d, J ) 8.8 Hz, 2H), 5.76 (s, 1H), 5.26 (s,
1H), 4.84 (s, 1H), 4.54 (d, J ) 11.5 Hz, 1H), 4.28-4.23 (m,
2H), 3.86 (s, 3H), 3.67 (d, J ) 9.0 Hz, 1H), 3.20-3.12 (m, 1H),
2.78-2.70 (m, 2H), 2.62-2.44 (m, 2H), 2.19-1.99 (m, 3H),
1.80-1.60 (m, 2H), 1.20(s, 3H), 1.18 (s, 3H), 1.13 (s, 3H), 0.93
(s, 9H), 0.14 (s, 3H), 0.12 (s, 3H); 13C NMR (100 MHz, CDCl3)
δ 213.9, 162.9, 145.8, 132.0, 130.8 (2C), 116.3 (2C), 113.6,
103.0, 89.7, 84.7, 84.6, 81.1, 75.0, 57.8, 51.7, 50.3, 49.9, 48.3,
36.4, 34.5, 31.9, 31.4, 28.8 (3C), 27.2, 22.2, 21.3, 17.3, 0.0, -0.5;
HRMS m/z calcd for C33H50O7SiNa+ 609.3218, found 609.3222;
1
amorphous solid: IR (neat, cm-1) 3468, 1747, 1684; H NMR
(400 MHz, CDCl3) δ 5.75 (d, J ) 1.1 Hz, 1H), 5.18 (d, J ) 1.4
Hz, 1H), 4.89 (d, J ) 3.0 Hz, 1H), 4.67 (d, J ) 2.5 Hz, 1H),
4.47 (br s, 1H), 4.37 (br s, 1H), 4.22 (dd, J ) 11.2, 4.5 Hz, 1H),
3.19 (dt, J ) 12.9, 3.5 Hz, 1H), 3.08 (s, 3H), 2.95 (br s, 1H),
2.73-2.61 (m, 1H), 2.53 (ddd, J ) 15.6, 10.8, 4.4 Hz, 1H), 2.37
(dt, J ) 13.1, 3.8 Hz, 1H), 2.19-1.92 (m, 3H), 2.10 (s, 3H),
1.89-1.75 (m, 2H), 1.61-1.50 (m, 1H), 1.19 (s, 3H), 1.17 (s,
3H), 1.03 (s, 3H), 0.76 (s, 9H), 0.02 (s, 3H), -0.02 (s, 3H); 13C
NMR (100 MHz, CDCl3) δ 213.7, 168.7, 137.4, 115.7, 87.2, 85.7,
77.3, 74.8, 70.2, 59.9, 55.8, 47.5, 39.7, 37.8, 34.6, 32.5, 31.5,
30.3, 24.3 (3C), 23.9, 19.8, 16.6, 16.2, 9.3, -4.5, -6.5; HRMS
[R]23 0.62 (c 0.81, CHCl3).
D
Acetylation of 14. To a solution of 23.6 mg (0.040 mmol)
of 14 in 2.5 mL of CH2Cl2 at room temperature were added
0.05 mL (0.619 mmol) of pyridine, 0.012 mL (0.127 mmol) of
acetic anhydride, and 5 mg (0.041 mmol) of DMAP. The
reaction mixture was allowed to stir for 12 h, quenched with
3 mL of saturated NaHCO3 solution, and extracted with
CH2Cl2 (5 mL x 3). The combined organic layers were dried
and evaporated to leave a residue that was purified by flash
chromatography on silica gel (elution with 25% EtOAc/hexane).
There was isolated 24.3 mg (96%) of 15 as a colorless oil: IR
(neat, cm-1) 3478, 1753, 1690, 1615; 1H NMR (400 MHz,
CDCl3) δ 7.37 (d, J ) 8.7 Hz, 2H), 6.90 (d, J ) 8.7 Hz, 2H),
5.75 (s, 1H), 5.67 (d, J ) 12.1 Hz, 1H), 5.03 (s, 1H), 4.49 (s,
1H), 4.26-4.23 (m, 2H), 3.82 (s, 3H), 3.80 (d, J ) 9.2 Hz, 1H),
3.05 (ddd, J ) 14.8, 10.2, 3.5 Hz, 1H), 2.82 (d, J ) 12.2 Hz,
1H), 2.77 (br d, J ) 11.6 Hz, 1H), 2.62-2.52 (m, 1H),
2.48-2.42 (m, 1H), 2.22-2.15 (m, 1H), 2.11-1.96 (m, 2H), 2.06
(s, 3H), 1.81-1.72 (m, 1H), 1.70-1.62 (m, 1H), 1.20 (s, 3H),
1.16 (s, 6H), 0.92 (s, 9H), 0.12 (s, 3H), 0.11 (s, 3H); 13C
NMR (100 MHz, CDCl3) δ 210.5, 172.1, 163.3, 144.5, 132.3,
131.1 (2C), 116.7 (2C), 112.9, 103.6, 89.9, 85.3, 85.2, 81.3, 74.8,
58.2, 52.2, 50.3, 49.0, 48.2, 35.8, 34.6, 32.1, 31.5, 29.1 (3C),
27.6, 23.8, 22.5, 21.5, 18.2, 0.0, -0.3; HRMS m/z calcd for
C35H52O8SiNa+ 651.3324, found 651.3336; [R]23D -9.6 (c 0.95,
CHCl3).
m/z calcd for C28H48O9SSiNa+ 611.2681, found 611.2691; [R]23
-26.2 (c 0.51, CHCl3).
D
Conversion of 17 to 18. A 3.5 mg (0.006 mmol) sample of
17 was dissolved in 0.5 mL of dry CH2Cl2, cooled to -78 °C,
and treated with 0.06 mL (0.06 mmol) of 1.0 M Et2AlCl solution
in hexane. The reaction mixture was stirred for 5 min at -78
°C and allowed to warm to room temperature over a period of
45 min prior to the addition of 2 mL of 1.0 M tartaric acid
solution. After 15 min, the separated aqueous layer was
extracted with CH2Cl2 (3 mL x 3); the organic layers were
combined, dried, and evaporated, and the crude product was
purified by flash chromatography on silica gel (elution with
20% EtOAc/hexane) to afford 1.8 mg (61%) of 18 as a colorless
oil: IR (neat, cm-1) 3490, 1732, 1704; 1H NMR (500 MHz,
CDCl3) δ 5.27 (dd, J ) 11.0, 5.5 Hz, 1H), 5.08 (s, 1H), 4.68 (br,
1H), 4.39 (s, 1H), 3.87 (d, J ) 11.0 Hz, 1H), 3.80 (t, J ) 2.6
Hz, 1H), 3.16 (br, 1H), 2.73-2.60 (m, 3H), 2.44 (td, J ) 11.8,
7.1 Hz, 1H), 2.29-2.27 (m, 2H), 2.19-2.13 (m, 1H), 2.03 (s,
3H), 1.95-1.89 (m, 1H), 1.86-1.81 (m, 1H), 1.71-1.68 (m, 1H),
1.40 (s, 3H), 1.09 (s, 3H), 1.00 (s, 3H), 0.95 (s, 9H), 0.09 (s,
3H), 0.06 (s, 3H); 13C NMR (125 MHz, CDCl3) δ 221.5, 210.4,
170.9, 145.2, 111.8, 80.6, 75.6, 70.7, 63.2, 59.0, 53.3, 42.9, 38.1,
36.0, 34.1, 33.2, 32.6, 28.4, 26.6 (3C), 21.7, 18.8, 17.9, 14.5,
-3.0, -3.9; HRMS m/z calcd for C27H44O6SiNa+ 515.2799,
found 515.2808; [R]23 -89.7 (c 0.12, CHCl3).
Isomerization of 15 to 16. A solution containing 11.2 mg
(0.018 mmol) of 15 dissolved in 2.0 mL of dry CH2Cl2 was
cooled to -78 °C, treated with 0.09 mL (0.09 mmol) of 1.0 M
EtAlCl2 solution in hexane, and stirred for 5 min at -78 °C.
The dry ice bath was removed, and the reaction vessel was
allowed to warm to room temperature over a period of 15 min
and treated with 2 mL of MeOH followed by 6 mL of 1.0 M
KNa tartrate solution. The mixture was stirred for 15 min;
the separated aqueous layer was extracted with CH2Cl2 (3 mL
x 3), and the organic layers were combined and dried to give
the crude product, purification of which by flash chromatog-
raphy on silica gel (elution with 25% EtOAc/hexane) afforded
6.8 mg (74%) of 16 as a colorless oil: IR (neat, cm-1) 3472,
1742, 1673; 1H NMR (400 MHz, CDCl3) δ 5.27 (d, J ) 11.8
Hz, 1H), 5.09 (s, 1H), 4.44 (s, 1H), 4.43 (br s, 1H), 4.27 (br s,
1H), 4.26 (dd, J ) 11.2, 4.6 Hz, 1H), 3.61 (br s, 1H), 3.23 (d, J
) 11.8 Hz, 1H), 2.74-2.60 (m, 2H), 2.50-2.39 (m, 2H),
2.17-2.06 (m, 2H), 2.10 (s, 3H), 1.99-1.93 (m, 1H), 1.76-1.68
(m, 1H), 1.63-1.52 (m, 1H), 1.21 (s, 3H), 1.03 (s, 3H), 0.92 (s,
3H), 0.80 (s, 9H), 0.06 (s, 3H), 0.05 (s, 3H); 13C NMR (100 MHz,
CDCl3) δ 215.3, 174.8, 142.8, 111.9, 81.6, 79.7, 77.6, 77.3, 71.7,
60.4, 54.7, 50.0, 46.4, 35.4, 33.1, 31.4, 27.8, 26.0 (3C), 23.8,
21.3, 18.3, 17.7, 11.9, -2.5, -4.8; HRMS m/z calcd for
C27H46O7SiNa+ 533.2905, found 533.2935; [R]23D -94.2 (c 0.85,
CHCl3).
D
Benzoylation of 14. To a solution of 115 mg (0.196 mmol)
of 14 in 3.0 mL of dry pyridine at room temperature were
added 0.20 mL (242 mg, 1.72 mmol) of benzoyl chloride and
24 mg (0.196 mmol) of DMAP. The reaction mixture was
allowed to stir for 19 h, quenched in turn with 10 mL of
saturated NaHCO3 solution, 10 mL of H2O, and 20 mL of
CH2Cl2, and stirred for 15 min prior to extraction of the
aqueous layer with CH2Cl2 (25 mL x 3). The combined organic
layers were dried and evaporated to leave the crude product,
purification of which by flash chromatography on silica gel
(elution with 15% EtOAc/hexane) afforded 120 mg (89%) of
19 as a colorless oil: IR (neat, cm-1) 3556, 1728, 1689, 1615;
1H NMR (400 MHz, CDCl3) δ 7.97 (d, J ) 8.0 Hz, 2H),
7.57-7.53 (m, 1H), 7.44-7.36 (m, 4H), 6.90 (d, J ) 8.0 Hz,
2H), 5.93 (d, J ) 12.0 Hz, 1H), 5.77 (s, 1H), 4.98 (s, 1H), 4.59
(s, 1H), 4.30-4.27 (m, 2H), 3.88 (d, J ) 9.2 Hz, 1H), 3.80 (s,
3H), 3.21-3.14 (m, 1H), 2.99 (d, J ) 12.0 Hz, 1H), 2.84 (s,
1H), 2.79 (d, J ) 11.6 Hz, 1H), 2.67-2.56 (m, 1H), 2.48-2.41
(m, 1H), 2.25-1.98 (m, 3H), 1.82-1.64 (m, 2H), 1.22 (s, 6H),
1.14 (s, 3H), 0.92 (s, 9H), 0.13 (s, 3H), 0.11 (s, 3H); 13C NMR
(100 MHz, CDCl3) δ 210.5, 168.0, 163.3, 144.0, 136.2, 132.7
(2C), 132.4, 132.3, 131.4 (2C), 131.1 (2C), 116.7 × 2, 113.4,
103.7, 90.0, 85.4, 85.3, 81.8, 74.8, 58.2, 52.3, 50.5, 49.1, 48.4,
35.8, 34.6, 32.2, 31.9, 29.1 (3C), 27.8, 22.5, 21.5, 18.3, 0.0, -0.3;
HRMS m/z calcd for C40H54O8SiNa+ 713.3480, found 713.3474;
Mesylate 17. To a solution of 10.0 mg (0.020 mmol) of 16
in 1.0 mL of CH2Cl2 at room temperature were added 12.2 mg
[R]23 +58.4 (c 1.1, CHCl3).
D
J. Org. Chem, Vol. 70, No. 1, 2005 319

Guo and Paquette
Isomerization of 19. To a solution of 244 mg (0.354 mmol)
of 19 (azeotropically dried with benzene and evacuated for 2
h) in 38.0 mL of dry CH2Cl2 at -78 °C was added 1.42 mL
(1.42 mmol) of 1.0 M EtAlCl2 solution in hexane. The reaction
mixture was allowed to stir for 5 min at -78 °C, warmed to
room temperature over a period of 15 min, quenched by adding
20 mL of MeOH and 40 mL of 1.0 M KNa tartrate solution,
and stirred for 20 min. The separated aqueous layer was
extracted twice with 20 mL of CH2Cl2. The organic layers were
combined, dried, and evaporated to leave the crude product,
which was purified by flash chromatography on silica gel
(elution with 15% EtOAc/hexane) to afford 150 mg (74%) of
20 as a white foam: IR (neat, cm-1) 3474, 1719, 1602; 1H NMR
(400 MHz, CDCl3) δ 7.93-7.91 (m, 2H), 7.52-7.50 (m, 1H),
7.39-7.35 (m, 2H), 5.47 (d, J ) 11.8 Hz, 1H), 4.98 (s, 1H),
4.56 (d, J ) 5.6 Hz, 1H), 4.46 (s, 1H), 4.41 (t, J ) 4.2 Hz, 1H),
4.27-4.21 (m, 2H), 3.66 (d, J ) 5.6 Hz, 1H), 3.51 (s, 1H), 3.35
(d, J ) 11.8 Hz, 1H), 2.72-2.65 (m, 2H), 2.44-2.34 (m, 2H),
2.14-2.05 (m, 2H), 1.93-1.89 (m, 1H), 1.76-1.74 (m, 1H),
1.60-1.54 (m, 1H), 1.20 (s, 3H), 0.95 (s, 3H), 0.87 (s, 3H), 0.75
(s, 9H), 0.00 (s, 6H); 13C NMR (100 MHz, CDCl3) δ 215.4, 169.8,
142.3, 134.1, 130.5 (2C), 129.4, 128.9 × 2, 112.6, 81.7, 79.7,
78.3, 71.6, 60.5, 54.7, 50.0, 46.5, 35.5, 33.1, 31.7, 27.8, 26.2,
26.0 (3C), 24.0, 18.3, 17.8, 11.9, -2.5, -4.7; HRMS m/z calcd
1H), 3.10 (s, 1H), 3.02 (s, 3H), 2.71-2.60 (m, 1H), 2.58-2.53
(m, 1H), 2.45-2.42 (m, 1H), 2.25-2.19 (m, 1H), 2.09-2.03 (m,
2H), 1.92-1.77 (m, 2H), 1.62-1.56 (m, 1H), 1.28 (s, 3H), 1.20
(s, 3H), 1.01 (s, 3H), 0.74 (s, 9H), 0.01 (s, 3H), -0.01 (s,
3H); 13C NMR (100 MHz, CDCl3) δ 215.3, 166.3, 138.9, 133.7,
130.4 (2C), 129.9, 128.9 (2C), 117.4, 89.0, 87.4, 78.9, 76.4,
72.6, 61.4, 57.5, 49.2, 42.0, 39.4, 35.9, 34.2, 32.9, 31.6, 25.8
(3C), 25.6, 18.1, 17.9, 11.0, -3.0, -4.9; HRMS m/z calcd for
C33H50O9SSiNa+ 673.2837, found 673.2830; [R]23D -0.9 (c 1.0,
CHCl3).
Conversion of 21 to 22. To a solution of 740 mg (1.14
mmol) of 21 (azeotropically dried with benzene and evacuated
for 2 h) in 114 mL of dry CH2Cl2 at -78 °C was added 11.4
mL (11.4 mmol) of 1.0 M Et2AlCl solution in hexane. The
reaction mixture was allowed to stir for 5 min at -78 °C,
warmed to room temperature over a period of 1.5 h, quenched
with 120 mL of 1.0 M tartaric acid aqueous solution, and
stirred for 20 min. The separated aqueous layer was extracted
twice with 60 mL of CH2Cl2. The organic layers were combined,
dried, and concentrated to leave the crude product. Purification
by flash chromatography on silica gel (elution with 15% EtOAc/
hexane) afforded 334 mg (52%) of 22 as a white foam: IR (neat,
1
cm-1) 3490, 1710, 1646, 1602; H NMR (400 MHz, CDCl3) δ
8.02-7.99 (m, 2H), 7.54-7.42 (m, 1H), 7.40-7.38 (m, 2H), 5.45
(dd, J ) 10.0, 4.2 Hz, 1H), 4.92 (s, 1H), 4.56 (t, J ) 7.9 Hz,
1H), 4.40 (s, 1H), 4.04 (d, J ) 10.0 Hz, 1H), 3.78 (br s, 1H),
3.20 (d, J ) 8.1 Hz, 1H), 2.72-2.60 (m, 3H), 2.36-2.26 (m,
3H), 2.19-2.13 (m, 1H), 1.93-1.87 (m, 1H), 1.76-1.72 (m, 2H),
1.45 (s, 3H), 1.11 (s, 3H), 1.04 (s, 3H), 0.90 (s, 9H), 0.04 (s,
3H), 0.00 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 222.0, 210.4,
166.3, 143.9, 133.3, 130.8, 130.3 (2C), 128.7 (2C), 113.4, 80.2,
76.2, 70.8, 63.4, 58.6, 53.7, 41.9, 38.1, 36.1, 34.5, 32.5, 31.4,
28.3, 26.5 (3C), 26.1, 18.7, 18.1, -3.1, -4.0; HRMS m/z calcd
for C32H48O7SiNa+ 595.3062, found 595.3074; [R]23 -29.1 (c
D
1.18, CHCl3).
Mesylate 21. To a solution of 1.2 g (2.1 mmol) of 20 in 100
mL of dry CH2Cl2 at 0 °C were added 563 mg (4.6 mmol) of
DMAP, 0.32 mL (4.2 mmol) of methanesulfonyl chloride, and
0.99 mL of triethylamine in order. The mixture was allowed
to stir for 20 min at 0 °C and then quenched with 100 mL of
saturated NaHCO3 solution at 0 °C. The mixture was allowed
to warm to room temperature over a period of 15 min. The
separated aqueous layer was extracted twice with 50 mL of
CH2Cl2. The organic layers were combined, dried, and evapo-
rated. Purification of the residue by flash chromatography on
silica gel (elution with 35% EtOAc/hexane) afforded 270 mg
of unreacted 20 and 740 mg (54%) of 21 as a white foam: IR
(neat, cm-1) 3470, 1723, 1686, 1602; 1H NMR (400 MHz,
CDCl3) δ 8.05-8.03 (m, 2H), 7.57-7.54 (m, 1H), 7.45-7.42 (m,
2H), 5.97 (br s, 1H), 5.33 (br s, 1H), 5.17 (d, J ) 3.0 Hz, 1H),
4.83 (d, J ) 2.8 Hz, 1H), 4.52 (d, J ) 2.9 Hz, 1H), 4.41 (t, J )
3.6 Hz, 1H), 4.25 (dd, J ) 10.7, 4.8 Hz, 1H), 3.24-3.20 (m,
for C32H46O6SiNa+ 577.2956, found 577.2919; [R]23 -92.7 (c
D
1.0, CHCl3).
1
Supporting Information Available: High-field H and
13C NMR spectra for all compounds described herein. This
material is available free of charge via the Internet at
http://pubs.acs.org.
JO048289G
320 J. Org. Chem., Vol. 70, No. 1, 2005