Practical construction of taxoid C-ring segments with a consecutive heterodomino transformation as the key reaction step

Article abstract of DOI:10.1002/ejoc.200600751

An efficient preparation of fully functional, optically homogeneous, taxoid C-ring C-10 electrophiles 5, 6 and C-10 nucleophiles 18, 19 that offer distinct linking possibilities with various A-ring precursors is described. The key feature of the synthetic

Full text of DOI:10.1002/ejoc.200600751

FULL PAPER
DOI: 10.1002/ejoc.200600751
Practical Construction of Taxoid C-Ring Segments with a Consecutive
Heterodomino Transformation as the Key Reaction Step
Laure Finet,[a] Mohamed Dakir,[a] Angèle Chiaroni,[a] and Siméon Arseniyadis*[a]
Keywords: Taxoid construction / Domino reactions / Bicyclo[2.2.2]octane / Oxidation
An efficient preparation of fully functional, optically homo-
geneous, taxoid C-ring C-10 electrophiles 5, 6 and C-10 nu-
cleophiles 18, 19 that offer distinct linking possibilities with
various A-ring precursors is described. The key feature of the
aldol 7 in a single synthetic operation. Our retrosynthetic
analysis calls for an introduction of the missing C-2 carbon
in a post-coupling operation where an alkoxymethylenation
would provide the electrophilic partner in the C-1–C-2 bond-
synthetic scheme reported in this paper is the lead tetraace- ing.
tate mediated consecutive domino reaction that enables the
transformation of fused bicyclic diol 1 into bridged bicyclic
(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
Germany, 2007)
Introduction
Three out of six total syntheses of taxol[1] used a conver-
gent A+C approach; in such an approach, two six-mem-
bered ring fragments have to be constructed, coupled and
elaborated to form the taxoid diterpene skeleton. Nicola-
ou,[1a] in his total synthesis of taxol, by proceeding in the
A+C direction, constructed the C-ring precursor starting
from mucic acid, whereas Danishefsky synthesized a fully
functional C-ring starting from (S)-(+)-Wieland–Miescher
ketone.[1c] Finally, Kuawajima[1f] started the synthesis of his
C-ring precursor from 2-bromocyclohexenone, which was Scheme 1.
converted in eight steps into a cyclohexadiene derivative
and used in the segment coupling. Recent papers from these
Even though a retrosynthetic analysis to construct a
laboratories have described a route to taxoid C-ring systems
of type 2 that involved a Pb(OAc)4 mediated domino[2] reac-
tion (oxidative cleavage/cycloaddition/oxymetallation/ring
expansion) of (S)-(+)-Hajos–Parrish ketone derived unsatu-
rated diols of type 1 (Scheme 1). Our previous work, a con-
vergent A+C approach to the taxoid ABC framework with
a Still α-alkoxylithium methodology[3] (top side linking)
and an intramolecular aldol reaction (bottom side linking)
as key bond constructions, had demonstrated the suitability
of the domino chemistry to access ABC-taxoid diterpene
skeleton 3 (longest linear sequence: eight steps).[4] Although
this method was reliable, we investigated an alternative
route, which would produce the desired products more
briefly without recourse to post-coupling operations at the
C-ring level.
pentafunctionalized six-membered ring containing two qua-
ternary centers may seem an easy task, severe length and
selectivity problems could be encountered towards its real-
ization. Our desire to improve the overall efficiency of this
process and expand its applicability to related ring systems
prompted us to examine modifications to this sequence. De-
spite the anticipated difficulty, on the basis of the proposed
mechanism[5] of carrying out a domino reaction with a hin-
dered unsaturated bicyclic diol such as 1b we first investi-
gated the latter as a model system containing the C-5 α-
hydroxy group that is necessary for esterification.[6] To se-
cure the formation of domino product 2b, diol 1b was
treated with lead tetraacetate in a preheated oil bath at
100 °C (instead of the usual 25 °C) and provided the desired
domino product in 21% isolated yield; far too inefficient to
be synthetically useful because of the low mass recovery
and low purity of the crude reaction product. Notwith-
standing the high degree of oxygenation of 2b thus ob-
tained, its synthetic utility was compromised and so we had
[a] Institut de Chimie des Substances Naturelles, CNRS
Avenue de la Terrasse 91198 Gif-sur Yvette, France
Fax: +33-1-69-82-30-29
E-mail: simeon.arseniyadis@icsn.cnrs-gif.fr
342
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Practical Construction of Taxoid C-ring Segments
FULL PAPER
to seek an alternative strategy. The synthetic route chosen with recovered starting material (10%). All were separated
for the construction of the taxoid C-ring is based on the by SiO2 flash chromatography and isolated pure; the dea-
recently developed building block approach to bicy- cetylated product was quantitatively recycled by reacety-
clo[2.2.2]aldol 7a (Scheme 2) which utilizes a more benign lation (Ac2O, pyridine, DMAP). Compound 9 was desi-
version of the Pb(OAc)4 induced heterodomino transforma- lylated with tetrabutylammonium fluoride (TBAF, THF,
tions with the use of only 1 equiv. of lead tetraacetate.[7] 0 °C, 91%) to afford the corresponding alcohol which was
This three-reagent consecutive domino reaction initiated by further oxidized with the Dess–Martin protocol to required
PhI(OAc)2 (oxidative/pericyclic), continued by Pb(OAc)4 ketone
4 in nearly quantitative yield (Dess–Martin
(ring expansion), and completed by a mild base consisting periodinane, CH2Cl2, pyridine, 25 °C, 96%).
of solid K2CO3 (ring system interchange) all in one-pot al-
lowed for a large scale preparation of key intermediate 7a.
This bicyclic aldol framework offered chemoselectivity be-
cause of the threefold different oxygenation pattern, and
stereoselectivity, given that chemical modifications of
bridged polycyclic compounds are highly stereoselective.
Thus, with the aim of minimizing post-coupling elabora-
tion, we focused on 11a as an exact embodiment of a taxoid
right-half moiety (C-ring), which contains all of the ste-
reogenic centers in the desired absolute configuration and
functionality at C-3/C-10 for linking with the A-ring coun-
terpart. Our new goal, therefore, became the generation of
a more functionalized C-ring candidate of type 5 or 6, prior
to C-10–C-11 linkage (taxoid numbering used throughout
the text). Described below is an efficient route starting from
bicyclic diol 1a, which was converted to heavily substituted
cyclohexane derivatives of type 5, 6, 18, or 19 through a
consecutive domino reaction followed by oxidation ring
opening maneuvers (Schemes 3, 4, 5 and 6).
Scheme 2. a) 1.2 equiv. PhI(OAc)2, 24 h, then 1.2 equiv. Pb(OAc)4,
PhMe, 15 h; then K2CO3–MeOH, H2O, 25 °C; b) TBSOTf, collid-
ine, CH2Cl2, 0 °C, 30 min; c) Pb(OAc)4, PhH, 90 °C, 48 h; d)
Bu3SnCH2OMOM, nBuLi, –78 °C; e) TBAF, THF, 0 °C; f) DMP,
pyridine, CH2Cl2, 25 °C, 1 h; g) m-CPBA, NaHCO3, CH2Cl2,
25 °C.
It was expected that Baeyer–Villiger oxidations of
bridged bicyclic aldol 4 could afford lactones with reason-
able control of bridgehead migration over methylene mi-
gration. In light of the intended application of this ap-
Results and Discussion
The taxoid C-ring has to contain a functional moiety proach to the construction of taxoid C-ring precursors 5
that could ultimately be used to introduce the C-5 α-OH and 6, this concern had to be addressed. It thus turned out
and the C-20 carbon that would offer further functionality; to be our initial objective to demonstrate that bicyclo[2.2.2]
this would therefore ensure access to oxirane-, oxetane-, or aldol 4 could be transformed into corresponding lactone
olefin-containing taxoid families. The synthesis started with 11a; reductive or hydrolytic opening of the latter would in
the experimentally simple reactions employed in effecting turn allow access to the desired C-ring candidates. To this
the one-pot transformation of fused bicyclic diol 1a to end, 4 was oxidized with excess m-chloroperbenzoic acid
bridged bicyclic aldol 7a (Scheme 2) and hence to its TBS- in sodium hydrogencarbonate buffered dichloromethane, at
protected derivative 7b in large scale by using the protocol room temperature to lactones 10 and 11a, which result from
published in ref.[7] Two straightforward steps were then re- methylene and bridgehead migration, respectively, in 60%
quired for the incorporation of the oxygen functionalities isolated yield and a 10/11a ratio of 1:4, along with reco-
at C-3 and the C-20 hydroxymethyl substituent. The best vered starting material (35%). The isomers were separated
conversion of 7b into requisite acyloin 8 was achieved by by chromatography and the major product was identified
the anomalous ozonization of the silyl enol ether derivative as lactone 11a. The course of the Baeyer–Villiger oxi-
of 7b (MeOH, –78 °C) as described in the preceding article. dation[9] of 4 was readily determined, as the regiochemistry
This resulted in a 77.4% combined yield of a 21.7:1 mixture of the oxygen insertion was unambiguously confirmed by
of endo-8 and its corresponding exo-8 adduct, separated by long-range heteronuclear couplings observed in the HMBC
chromatography. On the other hand, direct acetoxylation spectra. Ratios of the bridgehead to methylene migrated
of 7b by treatment with Pb(OAc)4 in benzene (90 °C, 2 d) lactones were determined by SiO2 separation and by com-
afforded a modest 35% isolated yield of required α-acetoxy- parison of the integrated areas for the methylene protons
acyloin 8 along with unreacted starting material (40%). that are adjacent to the carbonyl group in bridgehead-mi-
Subsequent addition of the α-alkoxyorganolithium derived grated lactone 11a (at δ = 2.24 and 2.52 ppm) to the oxygen
from Bu3SnCH2OMOM[8] by transmetalation with nBuLi in methylene-migrated lactone 10 (δ = 3.74 and 4.58 ppm)
(nBuLi, Bu3SnCH2OMOM, in dry THF, –78 °C, 30 min) and the bridgehead proton at δ = 3.18 ppm in 10 which is
gave a mixture of two products: 9 and its deacetylated coun- absent in 11a. Interestingly, this oxidation, unlike bicy-
terpart in a 75% combined yield and 1:2.7 ratio, together clo[2.2.2]octanone counterpart 7a,[6] gave a significant
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L. Finet, M. Dakir, A. Chiaroni, S. Arseniyadis
FULL PAPER
amount of isomeric lactone 10. At this stage it was decided
to investigate procedures to improve both the yields and the
11a/10 ratio. On the basis of precedent, it seemed likely that
the nature of the peroxy acid used may influence the results
obtained. Among the various oxidants tried, including
tBuO2H, NaOH, THF,[10] NaBO3, AcOH,[11] MMPP,
DMF,[12] H2O2, AcONa, AcOH,[13] PhSeO2H, H2O2,
CH2Cl2, and H2O,[14] none led to either one of the lactones;
the only new compound was the C-3 deacetylated starting
material when basic conditions were used (tBuO2H–
Scheme 3.
NaOH). The Sc(OTf)3 or Yb(OTf)3 catalyzed[15] Baeyer– studies and were further corroborated by an X-ray crystal-
Villiger oxidation with m-CPBA in CH2Cl2 was also tried lographic study on 10 and 11a (Figure 1).
but lead only to some tBu-deprotection and poor mass bal-
With lactone 11a available, its conversion to 14 was ex-
ance. The reactions were run under variable conditions. The plored (Scheme 4). TBS protection[18] of the free hydroxy
temperature, number of equivalents of the oxidizing rea- group at C-5 (TBSOTf, collidine, CH2Cl2, 0 °C, 30 min) led
gent, reaction times, and the nature of the oxidant used to 11b (Scheme 2), together with orthoester 11c (95% com-
were all varied. Microbial Baeyer–Villiger oxidation[16] was bined yield, 4.3:1 ratio), which upon fluoride deprotection
also tried with the use of the fungus Cunninghamella echinu- (TBAF, THF, 0 °C), was converted to 11a and recycled. Re-
lata[17] but failed to produce any lactone in a detectable ductive opening of the lactone was first accomplished by
amount. To summarize, while all attempts to increase the treatment with excess LiAlH4, in THF at 0 °C. These condi-
yields of lactones 10/11a were unsuccessful, we were happy tions caused partial cleavage of the TBS ether to afford de-
with an isolated 60% yield because the unreacted starting sired triol 12 (52%) accompanied by tetraol 13 (30%) and
material (35%) was easily recovered by chromatography be- fused bicyclic lactone 5 (11%), which results from partial
cause of its large Rf difference and could therefore be recy- saponification at C-3 and subsequent intramolecular trans-
cled. Also, despite efforts to minimize the formation of un- lactonization. Triol 12 was then converted into target C-
desired lactone 10, the product distribution remained in the ring C-10 electrophile 6 in two straightforward steps. Selec-
range of 4:1. One of the main points about the bridge mi- tive acetonide formation (acetone, p-TsOH, 25 °C, 3 h) fur-
gration during Baeyer–Villiger oxidation of bicyclic aldol 4 nished desired isopropylidene alcohol 14 (84% isolated
was that lactone i (oxabicyclo[3.2.2]nonan), initially formed yield), which in turn was oxidized with the use of the Dess–
as an electronically controlled transition state, is an inter- Martin protocol (DMP, pyridine, CH2Cl2, 25 °C, 30 min)
mediate in the formation of lactone 11a (oxabicyclo[3.3.1]- to afford 6 (86%). Tetraol 13 could also be obtained by
nonan) towards which it evolves by spontaneous translac- direct reduction of C-5-unprotected lactone 11a under the
tonization (Scheme 3).
same conditions. Subsequent selective acetonide formation
The illustrated stereochemistries at the newly installed (acetone, p-TsOH, 0 °C, 2.5 h) furnished 15 in 80% isolated
stereogenic centers, as well as bond connectivities, within yield. The latter can be used in the synthesis due to easy
these products follow from extensive NMR spectroscopic differentiation of the C-5/C-10 positions. The synthesis of a
Figure 1. X-ray structures of 10 and 11a.
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Practical Construction of Taxoid C-ring Segments
FULL PAPER
fully functional taxoid C-ring precursor, C-10 electrophile
6, which offers linking possibilities, is portrayed in
Scheme 4.
Scheme 5. a) K2CO3/MeOH/H2O, 25 °C; b) TMSCHN2, Et2O,
MeOH, 25 °C, 1 h; c) p-TsOH, acetone, 25 °C, 12 h; d) DIBAL,
PhMe, –78° to –40 °C, 2 h.
Scheme 4. a) LiAlH4, THF, 0 °C, 2 h; b) acetone, p-TsOH, 25 °C,
2.5 h; c) Dess–Martin periodinane, CH2Cl2, pyridine, 25 °C, 0.5 h.
As mentioned above, reductive lactone opening was
somehow complicated by loss of the tert-butyldimethylsilyl
group which could reach levels as high as 30% depending
upon reaction time and work up conditions. Other reducing
agents were screened for transformation of 11b into target
molecule 6, though without any significant improvement.
To obviate these complications, we turned our attention to
a hydrolytic lactone opening with K2CO3/MeOH-H2O.
Subjecting 11b to these conditions for 20 h at room tem-
perature gave a 90% combined yield of 16a and 5 in a 4:1
ratio, respectively. Compound 16a, which shows a marked
tendency to lactonize on standing, was esterified
(TMSCHN2, Et2O, MeOH, 25 °C, 1 h) to afford a 90%
yield of 16b, which again showed the same tendency
towards formation of lactone 5. Nearly quantitative forma-
tion of lactone 5 was secured while attempting to form the
corresponding isopropylidene derivative (p-TsOH, acetone,
25 °C, 12 h).
As portrayed in Scheme 5, during the conversion of
bridged bicyclic lactone 11b to desired cyclohexane 16 upon
hydrolytic lactone opening, 11d is formed initially but
rapidly converts to fused bicyclic lactone 5 by an intramo-
lecular transesterification to give a less sterically congested
product. This was proven experimentally by isolating and
identifying 11d during conversion. DIBAL reduction of 5
(DIBAL, PhMe, –78° to –40 °C, 2 h) gave a 93% isolated
yield of lactol 17 along with trace amounts of its epimer
(not isolated pure). Single-crystal X-ray diffraction analysis
of crystalline lactol 17 (Figure 2), enabled unequivocal ste-
reochemical assignment and further confirmed the correct-
ness of previous assignments by NMR techniques through-
out the synthetic scheme.
Figure 2. X-ray structure of 17.
in 1:1 ratio), which were separated by chromatography and
isolated pure. The two α-alkoxyorganostannanes thus ob-
tained will herein be arbitrarily referred to as higher-Rf 18
and lower-Rf 19.
Finally, a two-step umpolung sequence applied to taxoid
C-ring C-10 electrophile 6 then afforded α-alkoxyorgano-
stannanes 18 and 19 to be used as the C-10 nucleophile
precursors in our A+C approach (Scheme 6). Treatment of
6 with lithium tributylstannylate (in dry THF, –78 °C,
20 min) followed by protection of the resulting alcohol with
chloromethyl methyl ether in the presence of Hünig’s base
Scheme 6. a) Bu3SnH, LDA, THF, –78 °C; then MOMCl, iPr2Net,
(iPr2NEt) gave a mixture of two products, 18 and 19 (75% CH2Cl2, 25 °C.
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(300 MHz, CDCl3): δ = 0.08 (s, 3 H), 0.10 (s, 3 H), 0.87 (s, 3 H),
0.90 (s, 9 H), 1.13 (s, 9 H), 1.53 (ddd, J = 1.7, 9.5, 14.7 Hz, 1 H),
1.62 (ddd, J = 2.5, 8.8, 15.0 Hz, 1 H), 1.74 (ddd, 1 H, J = 2.3, 3.9,
15.0 Hz, 1 H), 1.82 (dd, J = 2.3, 14.7 Hz, 1 H), 2.07 (s, 3 H), 2.15
(q, J = 3.5 Hz, 1 H), 3.22 (dd, J = 2.2, 8.8 Hz, 1 H), 3.39 (s, 3 H),
3.60 (d, J = 10.9 Hz, 1 H), 4.00 (ddd, J = 2.3, 3.7, 9.5 Hz, 1 H),
4.09 (dd, J = 2.7, 10.9 Hz, 1 H), 4.54 (d, J = 1.5 Hz, 1 H), 4.69 (s,
2 H), 4.95 (d, J = 2.5 Hz, 1 H) ppm. 13C NMR (75 MHz, CDCl3):
δ = –5.1, –4.9, 17.7, 20.9, 21.3, 25.7, 28.6, 33.0, 36.5, 37.0, 37.3,
55.4, 71.0, 71.1, 73.2, 73.3, 73.5, 97.2, 170.9 ppm. ESIMS (MeOH):
This completes the synthesis of second generation taxoid
C-ring precursors. This process is considerably improved
over the previously published routes. The observation that
Still coupling is a useful reaction for the union of subunits
20 and 21 (first generation taxoid A- and C-rings, respec-
tively) justifies the use of this reaction sequence in conver-
gent strategies. By preparing compounds 5, 6, 18, and 19
an additional functionalization step (the C-5 α-hydroxy
function) was inserted prior to the beginning of the linear
synthesis, while the C-20 hydroxymethyl group at the qua- m/z (%) = 497.2 (100) [M + Na]+. HRESIMS (MeOH): calcd. for
C
24H46O7NaSi 497.2911, found 497.2916. C24H46O7Si (474.30):
ternary C-4 center was already installed.
calcd. C 60.72, H 9.77; found C 60.89, H 10.56.
7-tert-Butoxy-5-(tert-butyldimethylsilanyloxy)-3-methoxymethoxy-
methyl-1-methylbicyclo[2.2.2]octane-2,3-diol: [α]2D0 = +52 (c 1.6,
Conclusions
CHCl ). M.p. 42–43 °C (CH Cl ). IR (film): ν = 3394, 2956, 2930,
˜
3
2
2
From a practical standpoint, unraveling the bicyclo-
[2.2.2]octane moiety in a single step from bicyclic diol 1a,
rapidly introducing the C-3 then C-20 substituents and sub-
jecting it to Baeyer–Villiger conditions offered the opportu-
nity to prepare the second generation C-ring precursors.
The most critical issues of our synthesis were the m-CPBA
mediated Baeyer–Villiger oxidation and subsequent re-
ductive lactone ring opening. Although the yields of these
conversions were far from excellent, practical access to the
required substrates became available. Overall, the approach
represents an interesting application of LTA-mediated dom-
ino methodology, which provides fully functional, optically
pure C-ring precursors minimizing post-coupling elabora-
tion and nicely complements the C-ring syntheses published
to date.
1
2860, 1043, 839 cm–1. H NMR (300 MHz, CDCl3): δ = 0.09 (2s,
6 H), 0.90 (s, 9 H), 0.93 (s, 3 H), 1.11 (s, 9 H), 1.48 (ddd, J = 1.7,
9.7, 14.5 Hz, 1 H), 1.56 (dt, J = 3.3, 14.9 Hz, 1 H), 1.74 (ddd, J =
3.2, 9.3, 14.9 Hz, 1 H), 1.79 (dd, J = 4.4, 14.5 Hz, 1 H), 2.10 (q, J
= 3.2 Hz, 1 H), 3.23 (dd, J = 3.4, 9.3 Hz, 1 H), 3.39 (s, 3 H), 3.41
(d, J = 1.7 Hz, 1 H), 3.46 (s, 1 H), 3.50 (d, J = 10.8 Hz, 1 H), 3.70
(dd, J = 1.7, 10.8 Hz, 1 H), 3.95 (ddd, J = 3.0, 4.4, 9.7 Hz, 1 H),
4.67 (d, J = 6.5 Hz, 1 H) ppm. 13C NMR (75 MHz, CDCl3): δ =
–5.2, –4.8, 17.8, 20.4, 25.7, 28.6, 33.6, 36.0, 37.2, 38.4, 55.3, 68.4,
70.6, 71.7, 72.4, 73.1, 74.2, 96.9 ppm. ESIMS (MeOH): m/z (%) =
455.2 (100) [M + Na]+ . HRESIMS (MeOH): calcd. for
C22H44O6SiNa 455.2805; found 455.2812. C22H44O6Si (432.29):
calcd. C 61.07, H 10.25; found C 61.08, H 10.24.
Preparation of the Baeyer–Villiger Precursor – Bicyclic Ketone 4: To
a magnetically stirred solution of 9 (1.64 g, 3.46 mmol) in dry THF
(35 mL) at –75 °C was added tetrabutylammonium fluoride (1  in
tetrahydrofuran, 10.4 mmol). The reaction mixture was stirred and
warmed from –75 °C to –45 °C for 1 h 30 min (TLC monitoring).
Ethyl acetate was then added, and following extraction the crude
mixture was worked up as usual and purified by silica gel column
chromatography (heptane/EtOAc, 3:1 to EtOAc) to give the diol-
acetate (1.14 g, 91%).
Experimental Section
General experimental details were previously described.[7] The term
“usual work up” refers to washing the organic layer with brine,
drying with anhydrous MgSO4, and evaporating the solvent in
vacuo with a rotary evaporator at aspirator pressure. Experimental
evidence favoring the structures came from a comprehensive range
of 1H- and 13C NMR spectroscopic data (1D and 2D experiments)
and corroborated by spatial proximity (n.O.e) studies. X-ray analy-
sis of 10, 11a, and 17 supports the suggested structures. CCDC-
618901 (10), -618902 (11a), and -618903 (17) contain the supple-
mentary crystallographic data for this paper. These data can be
obtained free of charge from The Cambridge Crystallographic
Data Centre via www.ccdc.cam.ac.uk/data_request/cif.
7-tert-Butoxy-3,5-dihydroxy-3-methoxymethoxymethyl-1-methylbi-
cyclo[2.2.2]oct-2-yl Acetate: [α]2D0 = +75 (c 1.1, CHCl3). M.p. 99–
100 °C (CH Cl ). IR (film): ν = 3396, 2973, 2934, 1732, 1455, 1368,
˜
2
2
1
1247, 1046 cm–1. H NMR (300 MHz, CDCl3): δ = 0.84 (s, 3 H),
1.13 (s, 9 H), 1.57 (td, J = 3.3, 14.9 Hz, 1 H), 1.65 (ddd, J = 1.8,
9.8, 14.7 Hz, 1 H), 1.74 (ddd, J = 3.0, 9.2, 14.9 Hz, 1 H), 1.84 (dd,
J = 3.9, 14.7 Hz, 1 H), 2.11 (s, 4 H), 2.13 (m, 1 H), 3.26 (dd, J =
3.0, 9.2 Hz, 1 H), 3.39 (s, 3 H), 3.66 (d, J = 10.9 Hz, 1 H), 3.87 (td,
J = 3.6, 9.8 Hz, 1 H), 3.94 (br. s, 1 H), 3.96 (d, J = 10.9 Hz, 1 H),
4.63 (d, J = 6.5 Hz, 1 H), 4.67 (d, J = 6.5 Hz, 1 H), 4.74 (d, J =
1.8 Hz, 1 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 20.6, 20.9,
28.7 (3 C), 33.8, 37.3, 37.5, 38.1, 55.6, 70.0, 70.8, 72.2, 73.5, 74.3,
74.5, 97.4, 170.9 ppm. ESIMS (MeOH): m/z (%) = 383.2 (100) [M
+ Na]+. HRESIMS (MeOH): calcd. for C18H32O7Na 383.2046;
found 383.2061. C18H32O7 (360,21): calcd. C 59.98, H 8.95; found
C 60.07, H 8.95.
Elaboration of the C-4 Quaternary Center – Preparation of 9: To a
magnetically stirred solution of Bu3SnCH2OMOM (6.46 g,
17.6 mmol) in anhydrous THF (15 mL) cooled to –78 °C under an
argon atmosphere, nBuLi (1.6  in hexane, 10.8 mL, 17.2 mmol)
was added, and the mixture was stirred at this temperature for
10 min before 8 (2.93 g, 7.37 mmol) was added. After stirring
30 min at –78 °C, the reaction mixture was diluted with ethyl ace-
tate and quenched with a saturated solution of NH4Cl. Following
usual work up, SiO2 column chromatography (heptane/EtOAc, 15:1
to EtOAc) afforded 699 mg (20%) of 9, 1.75 g (55%) of C-3-sapon-
ified diol 9, along with recovered starting material 8 (295 mg, 10%).
7-tert-Butoxy-3-hydroxy-3-methoxymethoxymethyl-1-methyl-5-oxo-
bicyclo[2.2.2]oct-2-yl Acetate (4): A dry flask was charged with
starting diols (1.13 g, 3.14 mmol) in dichloromethane (28 mL), pyr-
idine (2.5 mL, 28.3 mmol), and Dess–Martin periodinane (3.62 g,
7-tert-Butoxy-5-(tert-butyldimethylsilanyloxy)-3-hydroxy-3-meth- 8.54 mmol). The mixture was stirred at room temperature for 1 h,
oxymethoxymethyl-1-methylbicyclo[2.2.2]oct-2-yla Acetate (9): [α]2D0
(TLC monitoring). The reaction was then diluted with dichloro-
= +47 (c 1.0, CHCl ). M.p. 137–139 °C (CH Cl ). IR (film): ν = methane, quenched with a saturated aqueous solution of sodium
˜
3
2
2
3451, 2973, 2953, 2934, 2858, 1731, 1247, 1046 cm–1
.
1H NMR hydrogencarbonate, and worked up as usual to afford, after purifi-
346
www.eurjoc.org
© 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2007, 342–350

Practical Construction of Taxoid C-ring Segments
FULL PAPER
cation on silica gel column chromatography (heptane/EtOAc 2:1 to
(10% aq., 68 µL, 0.17 mmol) in THF (1.4 mL) cooled to 0 °C was
stirred for 30 min, and the mixture was then warmed to room tem-
perature and stirred for ca. 6 h (TLC monitoring). The crude reac-
EtOAc), 1.08 g (96%) of 4.[α]2D0 = +71 (c 1.2, MeOH). M.p. 92–
93 °C (CH Cl ). IR (film): ν = 3446, 2972, 1735, 1373, 1232,
˜
2
2
1055 cm–1. 1H NMR (300 MHz, CDCl3): δ = 0.92 (s, 3 H), 1.12 (s, tion mixture was taken up in ether (20 mL), the excess peracid was
9 H), 1.73 (td, J = 3.0, 15.2 Hz, 1 H), 1.81 (dd, J = 1.7, 19.2 Hz, 1 decomposed by washing with aqueous 5% sodium sulfite, and the
H), 2.02 (ddd, J = 3.0, 9.4, 15.2 Hz, 1 H), 2.06 (s, 3 H), 2.54 (d, J organic phase was worked up as usual to give, after purification by
= 19.1 Hz, 1 H), 2.54 (t, J = 3.1 Hz, 1 H), 3.04 (s, 1 H), 3.33 (s, 3
H), 3.45 (dd, J = 3.0, 9.3 Hz, 1 H), 3.74 (d, J = 11.0 Hz, 1 H), 3.91
(d, J = 11.0 Hz, 1 H), 4.57 (d, J = 6.5 Hz, 1 H), 4.61 (d, J = 6.5 Hz,
1 H), 4.93 (d, J = 1.9 Hz, 1 H) ppm. 13C NMR (75 MHz, CDCl3):
δ = 19.7, 20.7, 28.5 (3 C), 31.6, 41.1, 42.4, 51.4, 55.5, 70.4, 71.0,
72.4, 73.4, 73.8, 97.2, 170.7, 211.5 ppm. ESIMS (MeOH): m/z (%)
= 381.1 (100) [M + Na]+. HRESIMS (MeOH): calcd. for
C18H30O7Na 381.1889; found 381.1854. C18H30O7 (358.20): calcd.
C 60.32, H 8.44; found C 60.27, H 8.52.
silica gel column chromatography (heptane/AcOEt, 2:1 to AcOEt),
only deacetylated starting material (C-3-OH)-4 [41.6 mg (81%)].
8-tert-Butoxy-5,6-dihydroxy-6-methoxymethoxymethyl-4-methylbi-
cyclo[2.2.2]octan-2-one: [α]2D0 = +72 (c 0.9, CHCl ). IR (film): ν =
˜
3
3442, 2973, 2933, 1726, 1366, 1075, 1038 cm–1
.
1H NMR
(300 MHz, CDCl3): δ = 1.04 (s, 3 H), 1.15 (s, 9 H), 1.65 (ddd, J =
2.7, 3.8, 15.1 Hz, 1 H), 1.75 (dd, J = 2.1, 19.1 Hz, 1 H), 2.07 (ddd,
J = 3.6, 9.4, 15.1 Hz, 1 H), 2.52 (d, J = 19.1 Hz, 1 H), 2.53 (dd, J
= 2.7, 3.4 Hz, 1 H), 3.1 (d, J = 6.4 Hz, 1 H), 3.41 (s, 3 H), 3.45
(dd, J = 3.8, 9.4 Hz, 1 H), 3.63 (d, J = 11.0 Hz, 1 H), 3.77 (dd, J
= 1.9, 6.0 Hz, 1 H), 3.88 (d, J = 11.0 Hz, 1 H), 3.99 (s, 1 H), 4.66
(d, J = 6.6 Hz, 1 H), 4.69 (d, J = 6.6 Hz, 1 H) ppm. 13C NMR
(75 MHz, CDCl3): δ = 19.5, 28.6 (3 C), 32.0, 42.2 (2 C), 51.4, 55.8,
68.2, 70.7, 72.0, 73.0, 73.7, 97.5, 212.1 ppm. ESIMS (MeOH): m/z
(%) = 339.1 (100) [M + Na]+. HRESIMS (MeOH): calcd. for
C16H28O6Na 339.1784; found 339.1788. C16H28O6 (319.19)
·0.7H2O: calcd. C 58.41, H 9.01; found C 58.43, H 8.75.
Baeyer–Villiger Oxidation of 4: Sodium hydrogencarbonate
(642 mg, 7.64 mmol) and m-chloroperbenzoic acid (3.30 g,
19.10 mmol) were added to 4 (1.14 g, 3.18 mmol) in dichlorometh-
ane (20 mL) at 0 °C. The mixture was stirred at room temperature
for approximately 17 h (TLC monitoring). The crude reaction mix-
ture was diluted with dichloromethane and filtered through a plug
of Celite. The excess peracid was decomposed by washing with
aqueous 5% sodium sulfite. Finally, the organic phase was washed
with saturated NaHCO3 and worked up as usual to afford, after
purification by flash chromatography (CH2Cl2/Me2C=O, 95:5),
398 mg (35%) of starting material, 142 mg (12%) of 10, and 571 mg
(48%) of 11a. For large scale experiments the lactone separation is
better carried out after the TBS-protection step.
TBS-protection of C-5-OH: To a stirred solution of 11a (163 mg,
0.44 mmol) and collidine (0.17 mL, 1.31 mmol) in dry dichloro-
methane (4.0 mL) at 0 °C under an argon atmosphere, was added
TBSOTf (0.20 mL, 0.87 mmol). The mixture was stirred at room
temperature for 30 min (TLC monitoring), diluted with heptane,
washed with diluted NaHCO3 and worked up as usual. After puri-
fication by silica gel column chromatography (heptane/AcOEt, 5:1
to AcOEt), 163 mg (77%) of 11b, and 39 mg (18%) of secondary
product 11c were obtained.
9-tert-Butoxy-7-hydroxy-7-methoxymethoxymethyl-5-methyl-2-oxo-
3-oxabicyclo[3.2.2]non-6-yl Acetate (10): [α]2D0 = +109 (c 0.3,
CHCl ). M.p. 113–114 °C (CH Cl ). IR (film): ν = 3446, 2972,
˜
3
2
2
1735, 1373, 1232, 1055 cm–1. 1H NMR (300 MHz, CDCl3): δ =
0.83 (s, 3 H), 1.18 (s, 9 H), 1.72 (ddd, J = 4.4, 6.0, 15.3 Hz, 1 H),
2.15 (s, 3 H), 2.42 (ddd, J = 3.0, 8.8, 15.3 Hz, 1 H), 3.18 (dd, J =
3.1, 4.3 Hz, 1 H), 3.34 (s, 1 H), 3.39 (s, 3 H), 3.57 (d, J = 10.5 Hz,
1 H), 3.62 (d, J = 10.5 Hz, 1 H), 3.74 (dd, J = 1.5, 12.2 Hz, 1 H),
3.84 (dd, J = 6.0, 8.8 Hz, 1 H), 4.58 (d, J = 12.2 Hz, 1 H), 4.61 (d,
J = 6.5 Hz, 1 H), 4.64 (d, J = 6.5 Hz, 1 H), 5.11 (d, J = 1.5 Hz, 1
H) ppm. 13C NMR (75 MHz, CDCl3): δ = 18.8, 20.9, 28.7 (3 C),
32.3, 42.5, 48.8, 55.8, 68.6, 71.1, 71.9, 72.0, 73.7, 74.1, 97.4, 170.2,
172.9 ppm. ESIMS (MeOH): m/z (%) = 397.1 (100) [M + Na]+.
HRESIMS (MeOH): calcd. for C18H30O8Na 397.1838; found
397.1830. C18H30O8 (374.19): calcd. C 57.74, H 8.08; found C
57.77, H 8.07.
6-tert-Butoxy-8-(tert-butyldimethylsilanyloxy)-1-methoxymethoxy-
methyl-5-methyl-3-oxo-2-oxabicyclo[3.3.1]non-9-yl Acetate (11b):
[α]2D0 = +6 (c 0.8, CHCl ). M.p. 89–90 °C (CH Cl ). IR (film): ν =
˜
3
2
2
2930, 2857, 1741, 1228, 1116, 1038, 837 cm–1. 1H NMR (300 MHz,
CDCl3): δ = 0.06 (s, 3 H), 0.07 (s, 3 H), 0.88 (s, 9 H), 0.94 (s, 3 H),
1.21 (s, 9 H), 1.55 (ddd, J = 2.6, 11.7, 14.3 Hz, 1 H), 1.99 (ddd, J
= 3.0, 5.0, 14.3 Hz, 1 H), 2.12 (s, 3 H), 2.24 (d, J = 19.0 Hz, 1 H),
2.52 (d, J = 19.0 Hz, 1 H), 3.33 (s, 3 H), 3.40 (t, J = 2.7 Hz, 1 H),
3.59 (d, J = 9.1 Hz, 1 H), 3.72 (d, J = 9.1 Hz, 1 H), 4.26 (dd, J =
5.0, 11.7 Hz, 1 H), 4.54 (d, J = 6.6 Hz, 1 H), 4.59 (d, J = 6.6 Hz,
1 H), 5.39 (s, 1 H) ppm. 13C NMR (75 MHz, CDCl3): δ = –4.8,
–4.1, 18.0, 20.7, 22.7, 25.8 (3 C), 28.7 (3 C), 34.6, 38.4, 39.8, 55.9,
64.6, 66.9, 67.7, 73.2, 74.5, 85.6, 97.3, 169.5, 169.8 ppm. ESIMS
(MeOH): m/z (%) = 511.2 (100) [M + Na]+. HRESIMS (MeOH):
calcd. for C24H44O8NaSi 511.2703; found 511.2669. C24H44O8Si
6-tert-Butoxy-8-hydroxy-1-methoxymethoxymethyl-5-methyl-3-oxo-
2-oxabicyclo[3.3.1]non-9-yl Acetate 11a: [α]2D0 = +44 (c 1.6, CHCl3).
M.p. 143–145 °C (CH Cl ). IR (film): ν = 3454, 2973, 1737, 1372,
˜
2
2
1228, 1036 cm–1. H NMR (300 MHz, CDCl3): δ = 0.95 (s, 3 H), (488.28): calcd. C 58.99, H 9.08; found C 59.16, H, 9.03.
1
1.20 (s, 9 H), 1.46 (ddd, J = 2.6, 11.9, 14.5 Hz, 1 H), 2.12 (s, 3 H),
5-tert-Butoxy-1-(tert-butyldimethylsilanyloxy)-8-methoxymethoxy-
2.16 (ddd, J = 2.8, 5.2, 14.5 Hz, 1 H), 2.28 (d, J = 19.0 Hz, 1 H),
methyl-6-methyl-2,9-dioxatricyclo[4.1.1.11,6]dec-7-yl Acetate (11c):
2.54 (d, J = 19.0 Hz, 1 H), 3.35 (s, 3 H), 3.36 (d, J = 8.6 Hz, 1 H),
[α]2D0 = +61 (c 0.5, CHCl ). IR (film): ν = 2929, 2857, 1746, 1367,
˜
3
3.44 (t, J = 2.7 Hz, 1 H), 3.60 (d, J = 9.8 Hz, 1 H), 3.82 (d, J =
1232, 1039, 840 cm–1. H NMR (300 MHz, CDCl3): δ = 0.18 (s, 6
9.8 Hz, 1 H), 4.23 (ddd, J = 5.2, 8.6, 11.5 Hz, 1 H), 4.58 (d, J =
H), 0.84 (s, 3 H), 0.91 (s, 9 H), 1.15 (s, 9 H), 1.54 (ddd, J = 0.9,
6.5 Hz, 1 H), 4.64 (d, J = 6.5 Hz, 1 H), 5.38 (s, 1 H) ppm. 13C
7.5, 14.7 Hz, 1 H), 1.69 (d, J = 13.6 Hz, 1 H), 2.00 (d, J = 13.6 Hz,
NMR (75 MHz, CDCl3): δ = 20.6, 22.5, 28.7 (3 C), 34.0, 38.2,
1 H), 2.14 (s, 3 H), 2.51 (ddd, J = 4.2, 8.1, 14.7 Hz, 1 H), 3.35 (s,
39.8, 55.6, 65.4, 67.0, 67.6, 72.9, 74.7, 85.3, 97.1, 169.4, 169.7 ppm.
3 H), 3.47 (d, J = 10.0 Hz, 1 H), 3.57 (d, J = 10.0 Hz, 1 H), 3.71
ESIMS (MeOH): m/z (%) = 397.1 (100) [M + Na]+. HRESIMS
(t, J = 7.8 Hz, 1 H), 4.19 (dd, J = 0.9, 4.2 Hz, 1 H), 4.58 (d, J =
(MeOH): calcd. for C18H30O8Na 397.1838; found 397.1804.
6.5 Hz, 1 H), 4.63 (d, J = 6.5 Hz, 1 H), 5.15 (s, 1 H) ppm. 13C
C18H30O8 (374.19): calcd. C 57.74, H 8.08; found C 57.59, H, 8.01.
NMR (75 MHz, CDCl3): δ = –3.4, –3.3, 17.8, 20.7, 20.9, 25.8 (3
1
Baeyer–Villiger Oxidation of 4 with tBuO2H as the oxidant yielded
only deacetylated 4. A mixture of aldol 4 (51.3 mg, 0.14 mmol),
tert-butyl hydroperoxide (70% aq., 55 µL, 0.43 mmol), and NaOH
C), 28.7 (3 C), 35.5, 39.6, 46.8, 55.4, 67.6, 68.3, 73.3, 73.6, 74.6,
80.6, 97.0, 117.1, 170.7 ppm. ESIMS (MeOH): m/z (%) = 511.2
(100) [M + Na]+. HRESIMS (MeOH): calcd. for C24H44O8NaSi
Eur. J. Org. Chem. 2007, 342–350
© 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
347

L. Finet, M. Dakir, A. Chiaroni, S. Arseniyadis
511.2703; found 511.2697. C24H44O8Si (488.28): calcd. C 58.99, H calcd. for C25H50O7NaSi 513.3224; found 513.3208. C25H50O7Si
FULL PAPER
9.08; found C 58.82, H 9.03.
(490.33)·0.2C7H16: calcd. C 62.08, H 10.50; found C 62.24, H 10.28.
{6-tert-Butoxy-3a-methoxymethoxymethyl-7-[2-(1-methoxy-1-meth-
ylethoxy)-ethyl]-2,2,7-trimethyl-hexahydrobenzo[1,3]dioxol-4-
yloxy}tert-butyldimethylsilane: [α]2D0 = +19 (c 1.0, CHCl3).IR (film):
Reductive Opening of Lactone 11b with Lithium Aluminum Hydride
and Selective Acetonide Formation: To a magnetically stirred sus-
pension of LiAlH4 (24 mg, 0.64 mmol) in THF (2 mL) at 0 °C was
added a solution of 11b (156 mg, 0.32 mmol) in THF (2.5 mL). The
mixture was stirred at this temperature for 1 h (TLC monitoring),
diluted with diethyl ether, worked up as usual to give, after purifica-
tion on silica gel column chromatography (heptane/AcOEt, 5:1 to
AcOEt) 15.7 mg (11%) of 5, 75 mg (52%) of 12, along with its
TBS-deprotected counterpart 13 (32 mg, 30%).
ν = 2955, 2933, 2886, 2858, 1464, 1377, 1364, 1256, 1041, 837,
˜
1
775 cm–1. H NMR (300 MHz, CDCl3): δ = 0.06 (s, 3 H), 0.07 (s,
3 H), 0.91 (s, 9 H), 0.92 (s, 3 H), 1.18 (s, 9 H), 1.33 (s, 6 H), 1.35
(s, 3 H), 1.46 (s, 3 H), 1.67 (ddd, J = 4.0, 7.8, 14.0 Hz, 1 H), 1.73–
1.88 (m, 2 H), 1.94 (ddd, J = 5.2, 6.9, 14.0 Hz, 1 H), 3.19 (s, 3 H),
3.36 (s, 3 H), 3.46 (d, J = 10.5 Hz, 1 H), 3.47 (m, 1 H), 3.56 (d, J
= 10.5 Hz, 1 H), 3.57 (m, 1 H), 3.83 (dd, J = 5.3, 7.8 Hz, 1 H),
3.90 (dd, J = 3.9, 6.9 Hz, 1 H), 4.00 (s, 1 H), 4.63 (d, J = 6.5 Hz,
1 H), 4.65 (d, J = 6.5 Hz, 1 H) ppm. 13C NMR (75 MHz, CDCl3):
δ = –4.5, –4.1, 17.3, 18.6, 24.4, 24.6, 26.1, 26.4 (3 C), 27.0, 29.1 (3
C), 36.8, 38.4, 38.6, 48.4, 55.5, 57.0, 68.5, 69.3, 70.3, 73.3, 81.1,
81.7, 96.9, 99.9, 107.2 ppm. ESIMS (MeOH): m/z (%) = 585.3 (100)
[M + Na]+. HRESIMS (MeOH): calcd. for C29H58O8NaSi
585.3799; found 585.3814. C29H58O8Si (562.39)·0.3H2O: calcd. C
63.00, H 10.68; found C 63.15, H 10.38.
4-tert-Butoxy-6-(tert-butyldimethylsilanyloxy)-3-(2-hydroxyethyl)-1-
methoxymethoxymethyl-3-methyl-cyclohexane-1,2-diol (12): [α]2D0
=
+13 (c 1.3, CHCl ). M.p. 50 °C (CH Cl ). IR (film): ν = 3418,
˜
3
2
2
2956, 2929, 2887, 2857, 1471, 1362, 1252, 1045, 836 cm–1. 1H NMR
(300 MHz, CDCl3): δ = 0.11 (s, 6 H), 0.91 (s, 9 H), 1.10 (s, 3 H),
1.20 (s, 9 H), 1.26 (td, J = 3.2, 15.0 Hz, 1 H), 1.60 (br. s, 1 H), 1.75
(ddd, J = 4.0, 4.9, 13.3 Hz, 1 H), 1.91 (ddd, J = 2.0, 11.5, 13.3 Hz,
1 H), 2.45 (td, J = 7.6, 15.0, Hz, 1 H), 2.70 (br. s, 1 H), 3.30 (dd,
J = 2.3, 4.0 Hz, 1 H), 3.35 (d, J = 9.2 Hz, 1 H), 3.39 (s, 3 H), 3.65
(s, 1 H), 3.76 (m, 3 H), 3.77 (d, J = 9.2 Hz, 1 H), 4.20 (d, J = 5.2,
11.4 Hz, 1 H), 4.63 (d, J = 6.2 Hz, 1 H), 4.67 (d, J = 6.2 Hz, 1 H)
ppm. 13C NMR (63 MHz, CDCl3): δ = –4.9, –4.1, 18.0, 21.6, 25.8
(3 C), 28.8 (3 C), 33.4, 39.2, 42.1, 55.5, 58.9, 67.2, 68.1, 70.8, 73.5,
74.1, 77.2, 97.0 ppm. ESIMS (MeOH): m/z (%) = 473.2 (100) [M
+ Na]+. HRESIMS (MeOH): calcd. for C22H46O7NaSi 473.2911;
found 473.2937. C22H46O7Si (450.30)·0.25H2O: calcd. C 57.28, H
10.16; found C 57.55, H 9.79.
Oxidation of 14 with Dess–Martin’s Periodinane: To a solution of
the above isopropylidene alcohol 14 (70 mg, 0.14 mmol) in dry
dichloromethane (2 mL) and pyridine (0.12 mL, 1.4 mmol) was
added periodinane (182 mg, 0.42 mmol). Stirring was continued at
room temperature for 30 min. The reaction was then diluted with
dichloromethane, quenched with a saturated aqueous solution of
sodium hydrogencarbonate, washed with 5% aqueous Na2S2O3 and
then brine, and worked up as usual to give, after silica gel column
chromatography (heptane/EtOAc, 10:1 to 4:1), 60 mg (86%) of 6
as an oil.
5-tert-Butoxy-4-(2-hydroxyethyl)-2-methoxymethoxymethyl-4-meth-
ylcyclohexane-1,2,3-triol (13): [α]2D0 = +20 (c 1.0, MeOH). M.p.
50 °C (CH2Cl2). 1H NMR (300 MHz, CDCl3): δ = 1.03 (s, 3 H),
1.13 (s, 9 H), 1.60 (td, J = 5.6, 14.6 Hz, 1 H), 1.76 (td, J = 4.3,
13.1 Hz, 1 H), 2.01 (ddd, J = 2.0, 12.0, 13.2 Hz, 1 H), 2.28 (ddd, J
= 6.8, 8.2, 14.6 Hz, 1 H), 3.36 (s, 3 H), 3.54 (dd, J = 2.0, 4.3 Hz, 1
H), 3.54 (s, 1 H), 3.54 (d, J = 8.9 Hz, 1 H), 3.58 (d, J = 8.9 Hz, 1
H), 3.63 (m, 1 H), 3.71 (m, 1 H), 4.09 (dd, J = 4.7, 12.0 Hz, 1 H),
4.62 (s, 2 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 22.2, 29.1 (3
C), 33.7, 37.9, 43.5, 55.5, 59.6, 66.6, 69.8, 72.7, 74.4, 74.5, 77.4,
97.9 ppm. ESIMS (MeOH): m/z (%) = 359.2 (100) [M + Na]+.
HRESIMS (MeOH): calcd. for C16H32O7Na 359.2046; found
359.2044.
[5-tert-Butoxy-7-(tert-butyldimethylsilanyloxy)-7a-methoxymeth-
oxymethyl-2,2,4-trimethylhexahydrobenzo[1,3]dioxol-4-yl]acetal-
dehyde (6): [α]2D0 = +38 (c 1.4, CHCl ). IR (film): ν = 2934, 2885,
˜
3
2857, 1720, 1463, 1377, 1257, 1077, 1040, 836 cm–1
.
1H NMR
(300 MHz, CDCl3): δ = 0.08 (s, 3 H), 0.09 (s, 3 H), 0.92 (s, 9 H),
1.07 (s, 3 H), 1.19 (s, 9 H), 1.34 (s, 3 H), 1.48 (s, 3 H), 1.71 (ddd,
J = 3.9, 9.1, 14.1 Hz, 1 H), 1.95 (ddd, J = 5.1, 5.7, 14.1 Hz, 1 H),
2.49 (dd, J = 3.7, 15.4 Hz, 1 H), 2.62 (dd, J = 1.5, 15.4 Hz, 1 H),
3.36 (s, 3 H), 3.49 (d, J = 10.4 Hz, 1 H), 3.56 (d, J = 10.4 Hz, 1
H), 3.91 (dd, J = 3.9, 5.7 Hz, 1 H), 4.01 (dd, J = 4.9, 9.1 Hz, 1 H),
4.21 (s, 1 H), 4.63 (d, J = 6.7 Hz, 1 H), 4.66 (d, J = 6.7 Hz, 1 H),
9.88 (dd, J = 1.5, 3.7 Hz, 1 H) ppm. 13C NMR (75 MHz, CDCl3):
δ = –4.6, –4.2, 17.6, 18.6, 26.3, 26.5 (3 C), 27.0, 29.1 (3 C), 36.5,
40.0, 52.1, 55.6, 67.6, 68.9, 70.3, 73.8, 81.0, 82.1, 96.9, 107.8,
203.5 ppm. ESIMS (MeOH): m/z (%) = 511.3 (100) [M + Na]+.
HRESIMS (MeOH): calcd. for C25H48O7NaSi 511.3067; found
511.3065. C25H48O7Si (488.32)·0.35CH2Cl2: calcd. C 58.73, H 9.47;
found C 58.52, H 9.45.
2-[5-tert-Butoxy-7-(tert-butyldimethylsilanyloxy)-7a-methoxymeth-
oxymethyl-2,2,4-trimethyl-hexahydrobenzo[1,3]dioxol-4-yl]ethanol
(14): To a stirred solution of 12 (190 mg, 0.42 mmol) in acetone
(2 mL), dry Na2SO4 (1.0 g) and p-TsOH (20 mg) were added at
0 °C. The mixture was stirred at room temperature for 1 h 15 min
(TLC monitoring) and then filtered through alumina. Purification
by silica gel column chromatography (heptane/AcOEt, 7:1 to 3:1)
afforded 173 mg (84%) of isopropylidene alcohol 14 and 8.3 mg
(7%) of overprotection in the form of mixed acetal. Compound 14:
Selective Acetonide Formation from Tetraol 13: Proceeding as
above, 13 (37 mg, 0.11 mmol) in acetone (1 mL), molecular sieves,
dry Na2SO4 (500 mg), and p-TsOH (catalytic) at 0 °C to room tem-
perature for 3 h afforded, after chromatography (heptane/EtOAc,
3:1 to EtOAc), single acetonide 15 (33 mg, 80%).
[α]2D0 = +25 (c 0.6, CHCl ). IR (film): ν = 3471, 2955, 2930, 2857,
˜
3
1255, 1081, 1041, 835 cm–1. 1H NMR (300 MHz, CDCl3): δ = 0.08
(s, 3 H), 0.09 (s, 3 H), 0.92 (s, 9 H), 0.95 (s, 3 H), 1.19 (s, 9 H),
1.38 (s, 3 H), 1.50 (s, 3 H), 1.71 (ddd, J = 3.9, 8.6, 14.1 Hz, 1 H),
{6-tert-Butoxy-3a-methoxymethoxymethyl-7-[2-(1-methoxy-1-meth-
1.86 (m, 2 H), 1.95 (ddd, J = 5.0, 6.0, 14.1 Hz, 1 H), 2.60 (br. s, 1 ylethoxy)ethyl]-2,2,7-trimethylhexahydrobenzo[1,3]dioxol-4-
H), 3.37 (s, 3 H), 3.48 (d, J = 10.5 Hz, 1 H), 3.58 (d, J = 10.5 Hz,
yloxy}tert-butyldimethylsilane (15): [α]2D0 = +22 (c 0.4, CHCl3). IR
1 H), 3.77 (m, 2 H), 3.89 (dd, J = 3.9, 6.0 Hz, 1 H), 3.90 (dd, J = (film): ν = 3447, 2975, 2939, 2886, 1380, 1043 cm–1 1H NMR
(400 MHz, CDCl3): δ = 0.97 (s, 3 H), 1.21 (s, 9 H), 1.44 (s, 3 H),
J = 6.5, 1 H) ppm. 13C NMR (75 MHz, CDCl3): δ = –4.6, –4.2, 1.53 (s, 3 H), 1.75 (ddd, J = 4.0, 9.1, 14.4 Hz, 1 H), 1.88 (t, J =
.
˜
5.0, 8.6 Hz, 1 H), 4.13 (s, 1 H), 4.64 (d, J = 6.5 Hz, 1 H), 4.67 (d,
17.0, 18.7, 26.2, 26.5 (3 C), 26.9, 29.1 (3 C), 36.6, 39.0, 41.3, 55.5,
59.1, 68.5, 68.7, 70.1, 73.5, 81.3, 82.1, 96.8, 107.4 ppm. ESIMS
(MeOH): m/z (%) = 513.3 (100) [M + Na]+. HRESIMS (MeOH):
6.2 Hz, 2 H), 2.06 (ddd, J = 4.8, 5.7, 14.4 Hz, 1 H), 2.29 (br. s, 1
H), 2.50 (br. s, 1 H), 3.38 (s, 3 H), 3.50 (d, J = 11.0 Hz, 1 H), 3.63
(d, J = 11.0 Hz, 1 H), 3.75 (dd, J = 3.5, 6.2 Hz, 1 H), 3.79 (m, 2
348
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© 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2007, 342–350

Practical Construction of Taxoid C-ring Segments
FULL PAPER
H), 3.92 (dd, J = 4.7, 8.9 Hz, 1 H), 4.23 (s, 1 H), 4.66 (d, J =
6.5 Hz, 1 H), 4.68 (d, J = 6.5 Hz, 1 H) ppm. 13C NMR (100 MHz,
CDCl3): δ = 16.8, 25.5, 26.5, 29.1 (3 C), 34.6, 38.9, 41.1, 55.5, 59.2,
67.8, 68.1, 70.1, 73.8, 81.1, 81.8, 96.8, 107.6 ppm. ESIMS (MeOH):
m/z (%) = 399.2 (100) [M + Na]+. HRESIMS: calcd. for
C19H36O7Na 399.2359; found 399.2354. C19H36O7 (376.25)
·0.25H2O: calcd. C 59.90, H 9.66; found C 59.81, H 9.55.
469.2583. C22H42O7Si (446.27)·0.2C7H16: calcd. C 60.22, H 9.76;
found C 60.23, H 9.41.
Esterification of 16a: To a magnetically stirred solution of 16a
(303 mg, 0.65 mmol) in diethyl ether (6 mL) and methanol (1 mL)
was added TMSCHN2 (1.6 mL, 3.27 mmol) at 0 °C. The mixture
was stirred for 15 min at 0 °C, concentrated under reduced pres-
sure, and purified by silica gel column chromatography (heptane/
AcOEt, 6:1 to 3:1) to afford 279 mg (90%) of expected product 16b
together with γ-lactone 5 (16 mg, 5%).
Cleavage of Lactone 11b by Basic Methanolysis – Preparation of
Key C-Ring Precursors: K2CO3 (378 mg, 2.73 mmol) in MeOH/
H2O (9 mL, 8:1) was added onto 11b (445 mg, 0.91 mmol) at 0 °C
under an argon atmosphere. The solution was stirred overnight at
room temperature. Methanol was removed under reduced pressure.
Water and HCl (1 ) were added to neutralize the mixture, and it
was then extracted with AcOEt. The organic phase was washed
with brine, dried with magnesium sulfate, and concentrated under
reduced pressure. Purification by flash chromatography (heptane/
AcOEt, 6:1 to AcOEt/MeOH, 9:1) afforded 303 mg (72%) of ex-
pected product 16a, 72 mg (18%) of fused-γ-lactone 5, 16 mg (4%)
of recovered starting material 11b and its de-acetylated derivative
11d (15 mg, 4%).
Methyl [6-tert-Butoxy-4-(tert-butyldimethylsilanyloxy)-2,3-dihy-
droxy-3-methoxymethoxymethyl-1-methylcyclohexyl]acetate (16b):
[α]2D0 = +28 (c 1.2, CHCl ). M.p. 61 °C (CH Cl ). IR (film): ν =
˜
3
2
2
3490, 2954, 2930, 2857, 1734, 1464, 1253, 1148, 1061, 1041, 836,
1
777 cm–1. H NMR (400 MHz, CDCl3): δ = 0.11 (s, 6 H), 0.90 (s,
9 H), 1.14 (s, 3 H), 1.19 (s, 9 H), 1.76 (td, J = 4.6, 13.5 Hz, 1 H),
1.89 (ddd, J = 1.9, 11.5, 13.5 Hz, 1 H), 2.45 (s, 1 H), 2.73 (d, J =
14.9 Hz, 1 H), 2.87 (d, J = 14.9 Hz, 1 H), 2.99 (br. s, 1 H), 3.38 (s,
3 H), 3.39 (d, J = 9.4 Hz, 1 H), 3.66 (s, 3 H), 3.70 (d, J = 9.4 Hz,
1 H), 3.70 (s, 1 H), 3.89 (dd, J = 1.9, 3.9 Hz, 1 H), 4.21 (dd, J =
5.1, 11.5 Hz, 1 H), 4.63 (d, J = 6.4 Hz, 1 H), 4.64 (d, J = 6.4 Hz,
1 H) ppm. 13C NMR (100 MHz, CDCl3): δ = –5.0, –4.1, 18.0, 21.8,
25.8 (3 C), 28.7 (3 C), 33.0, 38.1, 41.8, 51.3, 55.5, 67.0, 69.0, 70.9,
72.5, 73.6, 75.8, 97.0, 174.1 ppm. ESIMS (MeOH): m/z (%) = 501.2
(100) [M + Na]+. HRESIMS: calcd. for C23H46O8SiNa 501.2860;
found 501.2856. C23H46O8Si (478.29): calcd. C 57.71, H 9.69; found
C 57.77, H 9.66.
6-tert-Butoxy-8-(tert-butyldimethylsilanyloxy)-9-hydroxy-1-meth-
oxymethoxymethyl-5-methyl-cyclohexyl-2-oxabicyclo[3.3.1]nonan-3-
one (11d): [α]2D0 = +19 (c 0.7, CHCl3). M.p. 70–71 °C (CH2Cl2). IR
(film): ν = 3448, 2956, 2929, 2856, 1734, 1718, 1465, 1253, 1115,
˜
1064, 836 cm–1. 1H NMR (300 MHz, CDCl3): δ = 0.05 (s, 3 H),
0.06 (s, 3 H), 0.87 (s, 9 H), 1.08 (s, 3 H), 1.18 (s, 9 H), 1.55 (ddd,
J = 2.5, 11.6, 14.4 Hz, 1 H), 1.88 (ddd, J = 3.0, 4.9, 14.5 Hz, 1 H),
2.12 (d, J = 18.9 Hz, 1 H), 2.64 (d, J = 18.9 Hz, 1 H), 3.37 (t, J =
2.8 Hz, 1 H), 3.40 (s, 3 H), 3.82 (br. s, 1 H), 3.90 (s, 1 H), 3.92 (d,
J = 10.4 Hz, 1 H), 3.99 (d, J = 10.4 Hz, 1 H), 4.03 (dd, J = 4.9,
11.6 Hz, 1 H), 4.66 (s, 2 H) ppm. 13C NMR (75 MHz, CDCl3): δ
= –4.9, –4.2, 17.9, 21.9, 25.7 (3 C), 28.6 (3 C), 34.4, 37.7, 39.8, 55.8,
67.5, 67.9, 69.2, 73.2, 74.1, 85.2, 97.3, 171.1 ppm. ESIMS (MeOH):
m/z (%) = 469.2 (100) [M + Na]+. HRESIMS (MeOH): calcd. for
C22H42O7NaSi 469.2598; found 469.2591. C22H42O7Si (446.27)
·0.5C7H16: calcd. C 61.66, H 10.15; found C 61.73, H 9.83.
DIBAL Reduction of 5: Diisobutylaluminium hydride (30% in tolu-
ene, 0.22 mL, 0.26 mmol) was added slowly to 5 (40 mg,
0.09 mmol) in toluene (1 mL) at –78 °C under an argon atmo-
sphere. The reaction was stirred for 2 h while warming from –78 °C
to –40 °C. The mixture was then quenched by the addition of satu-
rated NH4Cl (a few drops), extracted with ether, and washed with
brine. The organic layer was concentrated under reduced pressure
and SiO2 flash chromatography of the residue (heptane/EtOAc, 5:1
to 3:1) gave 37.2 mg (93%) of lactol 17 as the major isomer; the
minor lactol could not be characterized as it was isolated in an
impure form.
[6-tert-Butoxy-4-(tert-butyldimethylsilanyloxy)-2,3-dihydroxy-3-
1
methoxymethoxymethyl-1-methyl-cyclohexyl]acetic Acid (16a): H
4-tert-Butoxy-6-(tert-butyldimethylsilanyloxy)-7-methyl-7-methoxy-
methoxymethyl-3a-methyloctahydrobenzofuran-2,7-diol (17): IR
NMR (300 MHz, CDCl3): δ = 0.10 (s, 6 H), 0.90 (s, 9 H), 1.18 (s,
9 H), 1.19 (s, 3 H), 1.26 (br. s, 2 H), 1.74 (ddd, J = 3.4, 5.5, 13.5 Hz,
1 H), 1.84 (ddd, J = 1.7, 11.0, 13.5 Hz, 1 H), 2.49 (d, J = 14.7 Hz,
1 H), 3.26 (d, J = 14.7 Hz, 1 H), 3.38 (s, 3 H), 3.48 (d, J = 9.6 Hz,
1 H), 3.67 (dd, J = 1.7, 3.4 Hz, 1 H), 3.71 (d, J = 9.4 Hz, 1 H),
3.78 (s, 1 H), 4.13 (dd, J = 5.5, 11.0 Hz, 1 H), 4.63 (d, J = 6.7 Hz,
1 H), 4.64 (d, J = 6.7 Hz, 1 H) ppm. 13C NMR (75 MHz, CDCl3):
δ = –5.0, –4.1, 17.9, 21.4, 25.7 (3 C), 28.6, (3 C) 32.8, 40.3, 41.3,
55.6, 67.2, 70.8, 72.2, 73.6 (3 C), 73.9, 75.5, 97.1, 176.6 ppm. ES-
IMS (MeOH): m/z (%) = 487.3 (100) [M + Na]+.
(film): ν = 3445, 2956, 2930, 2888, 2858, 1472, 1253, 1044,
˜
1
836 cm–1. H NMR (300 MHz, CDCl3): δ = 0.11 (s, 3 H), 0.12 (s,
3 H), 0.90 (s, 9 H), 1.07 (s, 3 H), 1.18 (s, 9 H), 1.63 (dd, J = 5.1,
12.9 Hz, 1 H), 1.70 (ddd, J = 5.0, 6.1, 13.7 Hz, 1 H), 1.87 (ddd, J
= 2.7, 8.5, 13.7 Hz, 1 H), 1.87 (dd, J = 6.2, 12.9 Hz, 1 H), 3.16 (s,
1 H), 3.29 (d, J = 9.1 Hz, 1 H), 3.36 (s, 3 H), 3.59 (d, J = 9.1 Hz,
1 H), 3.75 (dd, J = 2.7, 6.2 Hz, 1 H), 3.39 (s, 1 H), 4.22 (dd, J =
4.8, 8.4 Hz, 1 H), 4.58 (d, J = 11.5 Hz, 1 H), 4.60 (d, J = 6.2 Hz,
1 H), 4.62 (d, J = 6.2 Hz, 1 H), 5.48 (ddd, J = 5.1, 5.9, 11.5 Hz, 1
H) ppm. 13C NMR (75 MHz, CDCl3): δ = –5.0, –4.2, 18.0, 24.5,
25.8 (3 C), 28.7 (3 C), 34.3, 46.8, 47.7, 55.6, 66.3, 67.4, 69.5, 73.5,
73.6, 82.2, 96.9, 100.1 ppm. ESIMS (MeOH): m/z (%) = 471.2 (100)
[M + Na]+. HRESIMS: calcd. for C22H44O7NaSi 471.2754; found
471.2753. C22H44O7Si (448.29)·0.15C7H16: calcd. C 59.71, H 10.09;
found C 59.76, H 10.09.
4-tert-Butoxy-6-(tert-butyldimethylsilanyloxy)-7-hydroxy-7-meth-
oxymethoxymethyl-3a-methylhexahydrobenzofuran-2-one (5): [α]2D0
=
+20 (c 0.4, CHCl ). IR (film): ν = 3489, 2954, 2929, 2856, 1784,
˜
3
1039, 1020, 837 cm–1. H NMR (400 MHz, CDCl3): δ = 0.10 (s, 3
1
H), 0.12 (s, 3 H), 0.90 (s, 9 H), 1.15 (s, 3 H), 1.18 (s, 9 H), 1.75
(ddd, J = 5.2, 7.5, 14.1 Hz, 1 H), 1.81 (ddd, J = 3.1, 6.4, 14.1 Hz,
1 H), 2.09 (d, J = 16.6 Hz, 1 H), 2.79 (d, J = 16.6 Hz, 1 H), 2.81
(s, 1 H), 3.28 (d, J = 9.4 Hz, 1 H), 3.36 (s, 3 H), 3.54 (d, J = 9.4 Hz,
1 H), 3.90 (dd, J = 3.1, 7.5 Hz, 1 H), 4.18 (dd, J = 5.2, 6.4 Hz, 1
H), 4.20 (s, 1 H), 4.60 (d, J = 6.3 Hz, 1 H), 4.62 (d, J = 6.3 Hz, 1
H) ppm. 13C NMR (100 MHz, CDCl3): δ = –5.0, –4.2, 17.9, 23.3,
25.8 (3 C), 28.6 (3 C), 34.7, 42.0, 43.3, 55.7, 65.6, 67.2, 69.0, 73.5,
73.9, 83.5, 96.8, 177.2 ppm. ESIMS (MeOH): m/z (%) = 469.2 (100)
[M + Na]+. HRESIMS: calcd. for C22H42O7NaSi 469.2598; found
Preparation of α-Alkoxyorganostannanes – C-10 Nucleophile Pre-
cursors: To a magnetically stirred solution of diisopropylamine
(0.19 mL, 1.19 mmol) in dry THF (0.7 mL) under an argon atmo-
sphere at 0 °C, nBuLi (1.6  hexane solution, 0.81 mL, 1.35 mmol)
was added dropwise. The solution was stirred for 10 min, nBu3SnH
(0.36 mL, 1.35 mmol) was added, and stirring was continued for
15 min at 0 °C. The reaction mixture was chilled to –78 °C before
a solution of 6 (53 mg, 0.11 mmol) in dry THF (1.8 mL) was added
Eur. J. Org. Chem. 2007, 342–350
© 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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349

L. Finet, M. Dakir, A. Chiaroni, S. Arseniyadis
FULL PAPER
Soc. 1995, 117, 653–659 and preceding papers; b) R. A. Hol-
ton, H.-B. Kim, C. Somoza, F. Liang, R. J. Biediger, P. D.
Boatman, M. Shindo, C. C. Smith, S. Kim, H. Nadizadeh, Y.
Suzuki, C. Tao, P. Vu, S. Tang, P. Zhang, K. K. Murthi, L. N.
Gentile, J. H. Liu, J. Am. Chem. Soc. 1994, 116, 1599–1600
and preceding papers; c) S. J. Danishefsky, J. J. Masters, W. B.
Young, J. T. Link, L. B. Snyder, T. V. Magee, D. K. Jung,
R. C. A. Isaacs, W. G. Bornmann, C. A. Alaimo, C. A. Co-
brun, M. J. Di Grandi, J. Am. Chem. Soc. 1996, 118, 2843–
2859 and preceding papers; d) P. A. Wender, N. F. Badham,
S. P. Conway, P. E. Floreansic, T. E. Glass, J. B. Houze, N. E.
Krauss, D. Lee, D. J. Marquess, P. L. McGrane, W. Meng,
M. G. Natchus, A. J. Shuker, J. C. Sutton, R. E. Taylor, J. Am.
Chem. Soc. 1997, 119, 2757–2758 and preceding papers; e) T.
Mukaiyama, I. Shiina, H. Iwadare, M. Saitoh, T. Nishimura,
N. Ohkawa, H. Sakoh, K. Nishimura, Y. Tani, M. Hasegawa,
K. Yamada, K. Saitoh, Chem. Eur. J. 1999, 5, 121–161 and
preceding papers; f) H. Kusama, R. Hara, S. Kawahara, T.
Nishimori, H. Kashima, N. Nakamura, K. Morihara, I. Kuwa-
jima, J. Am. Chem. Soc. 2000, 122, 3811–3820 and preceding
papers. Review articles: A. N. Boa, P. R. Jenkins, N. J. Law-
rence, Contemp. Org. Synth. 1994, 1, 47–75; K. C. Nicolaou,
W. M. Dai, R. K. Guy, Angew. Chem. Int. Ed. Engl. 1994, 33,
15–44; O. N. Zefirova, E. V. Nurieva, A. N. Ryzhov, N. V. Zyk,
N. S. Zefirov, Russ. J. Org. Chem. 2005, 41, 315–351.
[2] According to Tietze’s classification, a sequence of reactions
with different mechanisms are called “heterodomino” reactions
while in a consecutive reaction, another reagent is added after
the first transformation without isolation of the first formed
product: L. F. Tietze, U. Beifuss, Angew. Chem. Int. Ed. Engl.
1993, 32, 131–163; L. F. Tietze, Chem. Rev. 1996, 96, 115–136;
L. F. Tietze, A. Modi, Med. Res. Rev. 2000, 20, 304–322.
[3] W. C. Still, J. Am. Chem. Soc. 1978, 100, 1481–1486.
[4] J. I. Martín Hernando, M. Rico Ferreira, J. I. Candela Lena,
N. Birlirakis, S. Arseniyadis, Tetrahedron: Asymmetry 2000, 11,
951–973.
dropwise. The mixture was stirred at –78 °C for 30 min and then
quenched with saturated NH4Cl, diluted with Et2O, and extracted.
The combined organic layers were washed with brine, dried with
magnesium sulfate, and concentrated under reduced pressure.
iPr2NEt (0.29 mL, 1.66 mmol) was added, followed by MOMCl
(0.08 mL, 1.11 mmol) 10 min later, at 0 °C on the crude residue
thus obtained in dichloromethane (1 mL). The solution was stirred
overnight at room temperature, quenched with H2O (at 0 °C), and
extracted with CH2Cl2. The organic phase was washed with water
and saturated NaHCO3 and worked up as usual to afford, after
purification by flash chromatography (heptane/AcOEt, 1:0 to 5:1),
a 75% combined yield of the desired α-alkoxyorgano stannanes,
faster eluting isomer 18 (34 mg) and slower eluting isomer 19
(32 mg), in a 1:1 ratio.
{6-tert-Butoxy-3a-methoxymethoxymethyl-7-[2-methoxymethoxy-2-
(tributylstannanyl)ethyl]-2,2,7-trimethylhexahydrobenzo[1,3]dioxol-
4-yloxy}tert-butyldimethylsilane (18/19): Faster Eluting Isomer 18:
[α]2D0 = –13 (c 1.0, CHCl ). IR (film): ν = 2956, 2928, 2856, 1463,
˜
3
1377, 1252, 1146, 1042, 836 cm–1. H NMR (400 MHz, CDCl3): δ
1
= 0.08 (s, 6 H), 0.86–0.94 (m, 9 H), 0.93 (s, 9 H), 0.95 (s, 3 H), 1.18
(s, 9 H), 1.25–1.40 (m, 6 H), 1.35 (s, 3 H), 1.48 (s, 3 H), 1.48–1.56
(m, 6 H), 1.60–1.69 (m, 6 H), 1.72 (ddd, J = 4.5, 5.8, 14.0 Hz, 1
H), 1.75 (dd, J = 3.1, 14.6 Hz, 1 H), 2.03 (ddd, J = 6.4, 8.5, 14.0 Hz,
1 H), 2.31 (dd, J = 12.0, 14.6 Hz, 1 H), 3.34 (s, 3 H), 3.37 (s, 3 H),
3.52 (d, J = 10.2 Hz, 1 H), 3.59 (d, J = 10.2 Hz, 1 H), 3.73 (t, J =
5.8 Hz, 1 H), 4.05 (dd, J = 4.5, 8.9 Hz, 1 H), 4.31 (dd, J = 3.1,
11.3 Hz, 1 H), 4.39 (s, 1 H), 4.49 (d, J = 6.7 Hz, 1 H), 4.58 (d, J =
6.7 Hz, 1 H), 4.62 (d, J = 6.5 Hz, 1 H), 4.64 (d, J = 6.5 Hz, 1 H)
ppm. 13C NMR (100 MHz, CDCl3): δ = –4.3, –4.1, 9.7, 13.6 (3 C),
16.3, 17.5 (2 C), 18.5, 26.2, 26.4 (3 C), 26.9 (2 C), 27.0, 27.6, 27.9
(2 C), 29.2 (3 C), 29.3, 37.2, 40.8 (2 C), 55.4, 55.9, 67.6, 69.6, 69.7,
70.4, 73.3, 81.2, 82.5, 96.0, 96.9, 106.9 ppm. ESIMS (MeOH): m/z
(%) = 847.4 (100) [M + Na]+. HRESIMS: calcd. for C39H80O8NaS-
[5] C. Unaleroglu, V. Aviyente, S. Arseniyadis, J. Org. Chem. 2002,
67, 2447–2452.
iSn 847.4542; found 847.4497. C39H80O8SiSn (824.46)·0.9C7H16
:
[6] Usually, taxoids of the C-4(20)-olefin containing group are es-
terified at C-5: G. Appendino, Nat. Prod. Rep. 1995, 12, 349–
360.
calcd. C 59.45, H 10.40; found C 59.44, H 10.09. Slower Eluting
Isomer 19: [α]2D0 = +16 (c 0.3, CHCl ).IR (film): ν = 2956, 2927,
˜
3
2856, 1463, 1377, 1257, 1147, 1041, 834 cm–1. 1H NMR (400 MHz,
CDCl3): δ = 0.08 (s, 3 H), 0.09 (s, 3 H), 0.86–0.95 (m, 15 H), 0.93
(s, 9 H), 1.08 (s, 3 H), 1.21 (s, 9 H), 1.25–1.36 (m, 6 H), 1.37 (s, 3 H),
1.46 (s, 3 H), 1.47–1.56 (m, 6 H), 1.71 (ddd, J = 3.7, 8.7, 14.1 Hz, 1
H), 1.88 (d, J = 14.3 Hz, 1 H), 1.91 (ddd, J = 5.0, 5.9, 14.1 Hz, 1
H), 2.26 (dd, J = 11.3, 14.3 Hz, 1 H), 3.37 (s, 3 H), 3.38 (s, 3 H),
3.49 (d, J = 10.5 Hz, 1 H), 3.60 (d, J = 10.5 Hz, 1 H), 3.81 (dd, J
= 5.0, 8.8 Hz, 1 H), 3.91 (dd, J = 3.7, 5.9 Hz, 1 H), 4.20 (s, 1 H),
4.44 (d, J = 11.0 Hz, 1 H), 4.54 (d, J = 6.5 Hz, 1 H), 4.56 (d, J =
6.5 Hz, 1 H), 4.66 (s, 2 H) ppm. 13C NMR (100 MHz, CDCl3): δ
= –4.5, –4.1, 9.5 (3 C), 13.7 (3 C), 17.4, 18.7, 26.2, 26.6 (3 C), 27.0,
27.6 (3 C), 29.2 (3 C), 29.4, 29.7 (2 C), 36.7, 40.7, 43.6, 55.4, 56.2,
69.0, 69.4, 70.5, 71.3, 73.3, 81.1, 81.2, 96.9, 97.0, 107.1 ppm. ES-
IMS (MeOH): m/z (%) = 847.4 (100) [M + Na]+. HRESIMS: calcd.
for C39H80O8NaSiSn 847.4542; found 847.4564. C39H80O8SiSn
(824.46)·1.1C7H16: calcd. C 59.97, H 10.52; found C 60.16, H 10.04.
[7] L. Finet, J. I. Candela, T. Kaoudi, N. Birlirakis, S. Arseniyadis,
Chem. Eur. J. 2003, 9, 3813–3820.
[8] R. L. Danheiser, K. R. Romines, H. Koyama, S. F. Gee, C. R.
Johnson, J. R. Medich, Org. Synth. 1992, 71, 133–139.
[9] The factors which determine the regioselectivity in Baeyer–Vil-
liger oxidations, electronic, steric, and stereoelectronic, have
been reviewed: G. R. Krow, Org. React. 1993, 43, 251–798.
[10] P. A. Grieco, T. Oguri, C. L. J. Wang, E. Williams, J. Org.
Chem. 1977, 42, 4113.
[11] A. McKillop, J. A. Tarbin, Tetrahedron 1987, 43, 1753.
[12] P. Brougham, M. S. Cooper, D. A. Cummerson, H. Heaney, N.
Thompson, Synthesis 1987, 1015.
[13] Z. Grudzinski, S. M. Roberts, C. Howard, R. F. Newton, J.
Chem. Soc., Perkin Trans. 1 1978, 1182.
[14] P. A. Grieco, Y. Yokoyama, S. Gilman, Y. Ohfune, J. Chem.
Soc., Chem. Commun. 1977, 870.
[15] H. Kotsuki, K. Arimura, T. Araki, T. Shinohara, Synlett 1999,
462–464.
[16] M. D. Mihovilovic, B. Muller, P. Stanetty, Eur. J. Org. Chem.
2002, 3711–3730.
[17] J. Lebreton, V. Alphand, R. Furstoss, Tetrahedron 1997, 53,
145–160.
[18] Our initial plans to introduce at this stage the TMS group at
C-5 were abandoned because this function proved too labile to
survive the conditions of the ensuing reactions.
Acknowledgments
The authors wish to thank Professor Jean-Yves Lallemand for his
kind interest and constant encouragements.
[1] a) K. C. Nicolaou, H. Ueno, J.-J. Liu, P. G. Nantermet, Z.
Received: August 25, 2006
Published Online: November 3, 2006
Yang, J. Renaud, K. Paulvannan, R. Chadha, J. Am. Chem.
350
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Eur. J. Org. Chem. 2007, 342–350