Conformational Bias by a Removable Silyl Group: Construction of Bicyclo[n.3.1]alkenes by Ring Closing Metathesis

Article abstract of DOI:10.1002/chem.201705275

Herein, we report a novel strategy based on a conformationally controlled RCM by a removable silyl group, which allows the facile synthesis of various bicyclo[n.3.1]alkenes, especially a set of highly strained bicyclo[5.3.1]alkenes. Further derivatizations of the silyl group and the resultant double bond of bicyclo[5.3.1]undecene 2 f enabled a concise synthesis of A-B-C ring skeleton of taxol. Density functional theory (DFT) calculations suggest that the introduction of a bulky silyl group at C-5 position of the 1,3-dialkenylcyclohexanol substrates dramatically lowers the energy bias gap between diaxial conformers (to RCM) and diequatorial conformers (to cross metathesis), thereby favoring the expected RCM reaction to give the challenging bridged molecules.

Full text of DOI:10.1002/chem.201705275

A Journal of
Accepted Article
Title: Conformational Bias by a Removable Silyl Group: Construction of
Bicyclo[n.3.1]alkenes via Ring Closing Metathesis
Authors: Minggui Lin, Pei-Jun Cai, Zhixiong Zeng, Na Lin, Yang Shen,
Bin Tang, Fan Li, Chen Chen, Zhi-Xiang Yu, and Yandong
Zhang
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Conformational Bias by a Removable Silyl Group: Construction of
Bicyclo[n.3.1]alkenes via Ring Closing Metathesis
Minggui Lin,+[a] Pei-Jun Cai,+[b] Zhixiong Zeng,[a] Na Lin,[a] Yang Shen,[a] Bin Tang,[a] Fan Li,[a] Chen
Chen,[a] Zhi-Xiang Yu,*[b] and Yandong Zhang*[a]
Dedicated to Professor Robert H. Grubbs on the occasion of his 75th birthday
Abstract: We herein report
a novel strategy based on a
conformationally controlled RCM by a removable silyl group, which
allows the facile synthesis of various bicyclo[n.3.1]alkenes,
especially a set of highly strained bicyclo[5.3.1]alkenes. Further
derivatizations of the silyl group and the resultant double bond of
bicyclo[5.3.1]undecene 2f enabled a concise synthesis of A-B-C ring
skeleton of taxol. Density functional theory (DFT) calculations
suggest that the introduction of a bulky silyl group at C-5 position of
the 1,3-dialkenylcyclohexanol substrates dramatically lowers the
energy bias gap between diaxial conformers (to RCM) and
diequatorial conformers (to cross metathesis), thereby favoring the
expected RCM reaction to give the challenging bridged molecules.
Bridged carbocycles, commonly found in terpene natural
products, are arguably the most topologically complex structures.
As a very important subclass, bicyclo[n.3.1] ring system is the
privileged core skeleton of many biologically active natural
products and drugs, such as aphidicolin,[1] acutifolin A,[2] CP-
263,114,[3] vinigrol,[4] pleuromutilin[5] and taxol[6] (Scheme 1A).
Among them, due to unfavorable entropy and transannular
interactions of eight-membered ring, the construction of
bicyclo[5.3.1] ring systems (also known as 6-8 bridged bicycles)
is one of the most challenging topics in the syntheses of the
related natural products (i.e., taxol and vinigrol). Although a few
strategies have been developed,[7] construction of the
bicyclo[5.3.1] ring system in a sequence of [6]→[8], that is, the
direct formation of a bridged eight-membered ring in a template
of six-membered ring remains a challenging problem.[8]
Scheme 1. Selected Natural Products Containing Bicyclo[n.3.1] Skeleton and
the Construction of Bicyclo[5.3.1] Ring Systems through RCM Reactions.
RCM is one of the most efficient and straightforward
methods for the ring closure and has played crucial roles in the
syntheses of a huge number of polycyclic natural products.[9] In
1998, Grubbs and coworkers[10] reported the construction of a
series of bridged bicycloalkenes via RCM. Unfortunately, in the
cases involving eight-membered ring formation, no desired
bicyclo[5.x.1]alkenes were obtained and only oligomeric
products were observed (Scheme 1B). Additionally, the ring
contracted RCM reactions to form seven-membered rings
through a double bond migration-RCM cascade often occurred
in the reported efforts to make an eight-membered ring via diene
metathesis.[11] To the best of our knowledge, despite the
extensive use of RCM in organic synthesis, there are few
applications to the synthesis of bicyclo[5.3.1]alkenes.[12] To
address these limitations, we envisaged that a bulky yet
removable silyl group[13] might effect a conformational bias[14]
which would enable the synthesis of the challenging
bicyclo[5.3.1]alkenes and other bicyclo[n.3.1]alkenes via
metathesis from 1,3-dialkenylcyclohexanes.
We envisioned that with the introduction of a large silyl group
at C-5 position of the substituted cyclohexane, the
thermodynamically more stable diaxial conformer (B) which is
required for the RCM reaction,[12b] would dominate (or the
energy difference between diequatorial conformer A and diaxial
conformer B could be dramatically reduced) and thus the RCM
reaction would become favored. (Scheme 1C). By contrast,
without this conformational control element, to avoid 1,3-diaxial
interactions, the two terminal enes would occupy the equatorial
positions in a stable chair conformer like A, making the enes far
[a] M. Lin,[+] Z. Zeng, N. Lin, Y. Shen, B. Tang, F. Li, C. Chen. Prof. Dr. Y.
Zhang
Department of Chemistry and Key Laboratory for Chemical Biology of
Fujian Province, iChEM, College of Chemistry and Chemical
Engineering, Xiamen University, Xiamen, Fujian 361005, China
E-mail: ydzhang@xmu.edu.cn
[b] P.-J. Cai,[+] Prof. Dr. Z.-X. Yu
College of Chemistry, Peking University, Beijing 100871, China
E-mail: yuzx@pku.edu.cn
[+] These authors contributed equally to this work.
Supporting information for this article is given via a link at the end of
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away from each other. Consequently, the substrate is prone to
cross metathesis (CM) to give oligomers or polymers. This could
be an explanation for Grubbs’ results shown in Scheme 1B.
Furthermore, the silyl group can be easily removed or converted
to a useful hydroxyl group to provide a desilylated bridged
system. Here we present our successful implementation of such
a conformation control strategy by a bulky silyl group to effect
the RCM reaction for the syntheses of a diverse array of
conformationally controlled RCM strategy to the syntheses of a
series of bicyclo[n.3.1]alkenes (Table 2). By adjusting the
Table 2: Construction of Bicyclo[n.3.1] Ring Systems.[a]
bicyclo[n.3.1]alkenes.
A concise synthesis of A-B-C ring
skeleton of taxol with current method as the key transformation
was also reported.
To reduce these ideas to practice, our studies commenced
with diene 1a (Table 1). A highly stereoselective synthesis of 1a
and other substrates from 5-trimethylsilylcyclohex-2-enone[15]
was developed (for details, see the Supporting Information (SI)).
Initial metathesis reactions were carried out with the four
commonly used Ru-based metathesis catalysts (Table 1, A-D).
Table 1: Optimization of the Reaction Conditions.[a]
Entry
Catalyst
[mol%]
Solvent
t [h]
Additive
Yield [%][b]
(2a:2k)
1
2
3
4
5
6
7
8
A (10)
B (10)
C (10)
D (10)
D (10)
D (10)
D (5)
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
Toluene
CH2Cl2
CH2Cl2
12
12
12
4
4
4
–
–
–
22:16
20:13
17:trace
45:26
61[c]
0:15
60[c]
53:29
–
Ti(OiPr)4
Ti(OiPr)4
Ti(OiPr)4
BQ[d]
4
4
D (5)
[a] Reaction conditions: 1 (1.0 equiv), catalyst D (5 mol%), and Ti(OiPr)4 (1.0
equiv) in refluxing CH2Cl2 (0.005 M) for 2-4 h. [b] Ti(OiPr)4 was not used. [c]
Reaction performed with 10 mol% of catalyst D for 12 h.
[a] Reactions were performed with 0.375 mmol of 1a, 5−10 mol% of catalyst,
and 0 or 1.0 equiv of Ti(OiPr)4 in specified solvent (0.005 M). [b] NMR yield
with anthracene as an internal standard. [c] Isolated yield of 2a. [d] 1.0 equiv of
1,4-benzoquinone (BQ) as additive.
lengths of 1,3-alkenyl chains in substrates, it is expected that not
only different [n.3.1] bicycles but also the same kind of bicycles
bearing a double bond at different positions of the newly forged
bridge can be synthesized, which would allow diverse
postmetathesis transformations. Although formation of the
bicyclo[5.3.1]undecenes in a [6]→[8] sequence is challenging,
four 6-8 bridged bicycles (2a-2d) were successfully synthesized
in moderate to good yields by our strategy. However, an attempt
to construct 2e, which bears an anti-Bredt double bond,[18] failed
and only homo-dimers were identified (see SI). When we used a
more easily removable dimethylphenylsilyl (DMPS) group to
promote the RCM reaction, it was equally efficient (1f→2f, 61%
yield). It is noteworthy that highly strained 6-9 bridged bicycle 2g
could also be prepared by this method, albeit in a low yield.
With these success, four TMS ether substrates (oTMS-1a to
oTMS-1d) were also prepared and subjected to the RCM
conditions (Table 2). We were wondering if oTMS group in the
substrate could have a similar positive impact on RCM reaction
as the Ti(OiPr)4 did. By treatment with standard conditions in the
absence of Ti(OiPr)4, the reaction of oTMS-1a failed to produce
any oTMS-2a and only homo-dimers were obtained in 50% yield
(see SI), presumably for reasons of high steric hindrance.
However, to our delight, the other three TMS ethers (oTMS-1b
to oTMS-1d) were smoothly converted to corresponding
bicyclo[5.3.1]undecenes in 62% to 82% yields. By contrast, in
Interestingly, complete conversion of the starting materials was
observed in almost all cases, whereas the distribution of
products varied. We found that the exposure of diene 1a to 10
mol% of Hoveyda-Grubbs II catalyst (D) in refluxing CH2Cl2
afforded the desired bicyclo[5.3.1]undecene 2a and
bicyclo[4.3.1]decene 2k in a good combined NMR yield (45%
and 26% respectively, Table 1, entry 4). The formation of 2k
could be attributed to the double bond isomerization catalyzed
by ruthenium hydrides prior to RCM.[11] Gratifyingly, in the
[16]
presence of 1.0 equiv of Ti(OiPr)4
under otherwise identical
conditions with entry 4, 2a was obtained in 61% yield and only a
trace amount of 2k was observed (Table 1, entry 5). We
attributed this success to a synergistic conformational effect of
the internal bulky silyl group and the external additive Ti(OiPr)4.
The catalyst loading could be lowered to 5 mol% without an
adverse effect on either the yield or the selectivity (Table 1, entry
7). Moreover, despite the addition of 1,4-benzoquinone (BQ)[17]
which has often been used to suppress the isomerization of the
terminal alkene in RCM, a significant amount of 2k was still
formed (Table 1, entry 8). The structures of 2k and 2a were
confirmed by single crystal X-ray diffraction.
With the optimized conditions in hand, we next applied our
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the aforementioned Grubbs’ studies,[10] a similar silyl ether
substrate devoid of a TMS group at C-5 position of cyclohexane
backbone failed to produce any RCM product but oligomers (the
RCM reaction also failed under our present optimized
conditions) (Scheme 1B). By comparing the above results, we
found that, although the introduction of an oTMS group markedly
promoted the RCM reaction in most cases, it is the C-5 TMS
group that played the pivotal role in this conformationally
controlled RCM reaction.
As shown in the first column of Scheme 2B, the diaxial
conformers are less favored than diequatorial conformers by 5
kcal/mol. When the TMS group was introduced in the substrates,
the energy gap between diaxial conformers and diequatorial
conformers was reduced to only 1-2 kcal/mol (column II,
Scheme 2B). These calculations suggest that, the RCM reaction
should be more favored for substrates in column II than those in
column I. We reasoned that the 1,3-repulsion between two
alkenyl chains can be offset by the strong repulsive interactions
induced by the axial bulky TMS group, thereby lowering the
energy gap between the diaxial and diequatorial conformers of
1a-1d. When the hydroxyl groups were further protected by TMS,
the relative stability of the two conformers is reversed and the
diaxial conformers (column III, Scheme 2B) are now more stable
than the diequatorial conformers by 1-3.5 kcal/mol. This
suggests that the substrates favor RCM further. That can explain
why these substrates usually gave higher yields of RCM
products. Based on a generally accepted role of the additive
Ti(OiPr)4 in RCM reactions as a temporary protecting group[16]
With the successful syntheses of a set of 6-8 bridged
bicycles, this strategy was smoothly extended to the syntheses
of other bridged bicycles, providing bicyclo[3.2.1]octene (2h),
bicyclo[3.3.1]nonenes (2i and 2j) and bicyclo[4.3.1]decenes (2k,
2l and 2m) in good to high yields (Table 2).
To gain a preliminary insight into the conformational effects
of C-5 TMS group and oTMS group in RCM reactions and to
support our initial proposal, we used DFT calculations[19] at the
B3LYP/6-31G(d) level[20] to carry out a conformational analysis
on a series of diene substrates (Scheme 2). First, to elucidate
the crucial role of the conformers of substrates in the reaction,
1a was chosen as an example. In general, RCM and CM are two
major competing pathways in the reaction (Scheme 2A). The
RCM pathway requires the diaxial conformer 1a-diax, while the
diequatorial conformer 1a-dieq which is usually more stable, can
only lead to oligomers or polymers through CM pathway. The
repulsive interactions in the two conformers are maintained in
the following steps in both RCM and CM pathways,
consequently the energy gap between the diaxial and
diequatorial conformers would influence the final selectivity
between the two pathways, which means the higher the energy
of diaxial conformer is as compared to diequatorial conformer,
the more inhibited the RCM pathways is.
(for the hydroxyl group in current cases),
a
similar
conformational effect with that of the oTMS group could be
realized. Therefore, the C-5 TMS group together with Ti(OiPr)4
or the oTMS group renders the reactive diaxial conformer as the
preferred conformer, thus experimentally enhanced the RCM
reaction.
In order to demonstrate the value of our strategy for the
synthesis of bridged bicycles, the A-B-C ring skeleton of taxol (6-
8-6 tricycle) was synthesized (Scheme 3). Specifically,
(A) Two competing reaction pathways (exemplified with 1a).[a]
NHC =
N
N
Mes
Mes
Cl
(CH2)
3
NHC
H
(CH2
TMS
)
3
G
CM
Ru
= 1a
Oligomer
G
H
OH TMS
HO
H
1a-dieq
Cl
ring flip
ΔG
H
Cl
H
H H
HO
Ru
Cl
H
RCM
NHC
HO
HO
TMS
1a-diax
TMS
HO
TMS
diaxial
TMS
diaxial
2a
(B) DFT computed energy differences between the diaxial and diequatorial conformers.[b]
Scheme 3. Synthesis of A-B-C Ring Skeleton of Taxol.
ΔG diax-dieq (kcal/mol)
ΔG diax-dieq (kcal/mol)
ΔG diax-dieq (kcal/mol)
HO
TMSO
OTMS
HO
OH
bicyclo[5.3.1] undecene 2f was converted to compound 3 in a
high yield via Fleming-Tamao oxidation[21] followed by TBS
protection. Allylic oxidation and further oxidation furnished enone
4 in 57% overall yield. Ozonolytic cleavage of the terminal olefin
that was derived from enone 4 through conjugate addition
yielded keto-aldehyde 5. Treatment of 5 with NaOH in MeOH
smoothly delivered 6-8-6 tricycles as a pair of diastereomers
(81%, 6a:6b = 1:2). The relative stereochemistry of 6a and 6b
were respectively confirmed by NMR spectroscopic studies and
single crystal X-ray diffraction of a derivative 7. Overall, starting
from bicyclo[5.3.1]undecene 2f, through a series of subsequent
transformations to derivatize the silyl group and the double bond,
a concise construction of the A-B-C ring skeleton of taxol
bearing six stereocenters has been achieved.
TMS
TMS
TMS
TMS
TMS
TMS
oTMS-1a
–1.2
1a
1.2
deTMS-1a
5.1
HO
TMSO
OTMS
HO
OH
TMS
TMS
oTMS-1b
–2.0
1b
2.0
deTMS-1b
5.5
HO
TMSO
OTMS
HO
OH
TMS
TMS
oTMS-1c
–2.6
1c
2.1
deTMS-1c
5.4
HO
TMSO
OTMS
HO
OH
TMS
TMS
oTMS-1d
1d
1.5
deTMS-1d
5.4
–3.5
Scheme 2. Conformational analysis. [a] The depicted reaction initiation sites
of the metathesis reactions are arbitrary). [b] Gibbs free energetic differences
between the thermodynamically lowest diaxial and diequatorial conformers
were calculated at B3LYP/6-31G(d) level of theory.
In summary, we have developed
a conformationally
controlled RCM approach by using a removable bulky silyl group
for the synthesis of a diverse array of bicyclo[n.3.1]alkenes,
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[11] a) M. Michalak, J. Wicha, Synlett 2005, 2277; b) G. De Bo, I. E. Markó,
Eur. J. Org. Chem. 2011, 1859; c) G. Liu, D. Romo, Angew. Chem. Int.
Ed. 2011, 50, 7537; Angew. Chem. 2011, 123, 7679.
especially
highly
strained
bicyclo[5.3.1]alkenes.
DFT
calculations suggest that the introduction of a bulky silyl group at
C-5 position of the 1,3-dialkenylcyclohexanol substrates
dramatically promotes the population of diaxial conformers (the
reactive conformer for RCM), as compared to the diequatorial
conformers (the reactive conformer for cross metathesis), thus
[12] a) M. Wenz, D. Grossbach, M. Beitzel, S. Blechert, Synthesis 1999, 607;
b) J. Liu, S. D. Lotesta, E. J. Sorensen, Chem. Commun. 2011, 47,
1500; c) T. Kobayashi, H. Shiroi, H. Abe, H. Ito, Chem. Lett. 2013, 42,
975.
favoring
the
RCM.
Furthermore,
the
subsequent
[13]
For a review, see: I. Fleming, A. Barbero, D. Walter, Chem. Rev. 1997,
97, 2063.
functionalization over the silyl group and newly formed olefin
enables a concise synthesis of the functionalized A-B-C ring
skeleton of taxol. It is worth noting, based on Corey’s protocol[15b]
or Jørgensen’s method[15c] for the preparation of optically pure 5-
trialkylsilylcyclohex-2-enones, enantioselective syntheses of
bicyclo[n.3.1]alkenes through the current strategy could be
expected. Efforts to apply this strategy to the synthesis of
bridged polycyclic natural products are currently underway.
[14] For selected examples, see: a) R. J. Linderman, J. Siedlecki, S. A.
O'neill, H. Sun, J. Am. Chem. Soc. 1997, 119, 6919; b) E. B. Pentzer, T.
Gadzikwa, S. T. Nguyen, Org. Lett. 2008, 10, 5613; c) K. Mori, K.
Ohmori, K. Suzuki, Angew. Chem. Int. Ed. 2009, 48, 5638; Angew.
Chem. 2009, 121, 5748; d) P. Bolduc, A. Jacques, S. K. Collins, J. Am.
Chem. Soc. 2010, 132, 12790; e) M. J. Kim, T.-i. Sohn, D. Kim, R. S.
Paton, J. Am. Chem. Soc. 2012, 134, 20178.
[15] a) M. Asaoka, K. Shima, H. Takei, Tetrahedron Lett. 1987, 28, 5669; b)
G. Sarakinos, E. J. Corey, Org. Lett. 1999, 1, 811; c) P. Bolze, G.
Dickmeiss, K. A. Jørgensen, Org. Lett. 2008, 10, 3753.
[16] A. Fürstner, K. Langemann, J. Am. Chem. Soc. 1997, 119, 9130.
[17] S. H. Hong, D. P. Sanders, C. W. Lee, R. H. Grubbs, J. Am. Chem. Soc.
2005, 127, 17160.
Acknowledgements
We gratefully acknowledge Natural Science Foundation of China
for financial support of this work by grants (nos. 21572187,
21772164, and 21232001−Mechanistic Studies of Several
Important Organic Reactions). We thank the support from
FRFCU (20720160025), NFFTBS (J1310024), NCETFJ, and
PCSIRT. We also thank Prof. Tingbin Wen of Xiamen University
for solving the X-ray structures.
[18] a) J. Y. W. Mak, R. H. Pouwer, C. M. Williams, Angew. Chem. Int. Ed.
2014, 53, 13664; Angew. Chem. 2014, 126, 13882; b) E. H. Krenske, C.
M. Williams, Angew. Chem. Int. Ed. 2015, 54, 10608; Angew. Chem.
2015, 127, 10754.
[19] M. J. Frisch, et al, Gaussian 09, Revision D.01; Gaussian, Inc.,
Wallingford CT, 2013. See Supporting Information for full citation.
[20] a) A. D. Becke, J. Chem. Phys. 1993, 98, 5648; b) C. Lee, W. Yang, R.
G. Parr, Phys. Rev. B: Condens. Matter Mater. Phys. 1988, 37, 785.
[21] J. Wu, Y. Pu, J. S. Panek, J. Am. Chem. Soc. 2012, 134, 18440.
Conflict of interest
The authors declare no conflict of interest.
Keywords: conformational control • ring closing metathesis •
silyl group • bridged ring system • taxol
[1] K. M. Brundret, W. Dalziel, B. Hesp, J. A. J. Jarvis, S. Neidle, J. Chem.
Soc., Chem. Commun. 1972, 1027.
[2] J. Takashima, A. Ohsaki, J. Nat. Prod. 2001, 64, 1493.
[3] T. T. Dabrah, T. Kaneko, W. Massefski, E. B. Whipple, J. Am. Chem. Soc.
1997, 119, 1594.
[4] I. Uchida, T. Ando, N. Fukami, K. Yoshida, M. Hashimoto, T. Tada, S.
Koda, Y. Morimoto, J. Org. Chem. 1987, 52, 5292.
[5] F. Kavanagh, A. Hervey, W. J. Robbins, Proc. Natl. Acad. Sci. U. S. A.
1951, 37, 570.
[6] M. C. Wani, H. L. Taylor, M. E. Wall, P. Coggon, A. T. McPhail, J. Am.
Chem. Soc. 1971, 93, 2325.
[7] For selected examples, see: a) B. R. Bear, S. M. Sparks, K. J. Shea,
Angew. Chem. Int. Ed. 2001, 40, 820; Angew. Chem. 2001, 113, 864; b)
S. F. Martin, J. B. White, R. Wagner, J. Org. Chem. 1982, 47, 3190; c) B.
M. Trost, H. Hiemstra, J. Am. Chem. Soc. 1982, 104, 886; d) J. D. Winkler,
J. P. Hey, P. G. Williard, J. Am. Chem. Soc. 1986, 108, 6425; e) F.
Barabe, G. Betournay, G. Bellavance, L. Barriault, Org. Lett. 2009, 11,
4236; f) A. Mendoza, Y. Ishihara, P. S. Baran, Nat. Chem. 2012, 4, 21; g)
S. Zhu, Q. Zhang, K. Chen, H. Jiang, Angew. Chem. Int. Ed. 2015, 54,
9414; Angew. Chem. 2015, 127, 9546.
[8] G. Tessier, L. Barriault, Org. Prep. Proced. Int. 2007, 39, 311.
[9] For selected reviews, see: a) K. C. Nicolaou, P. G. Bulger, D. Sarlah,
Angew. Chem. Int. Ed. 2005, 44, 4490; Angew. Chem. 2005, 117, 4564;
b) A. H. Hoveyda, S. J. Malcolmson, S. J. Meek, A. R. Zhugralin, Angew.
Chem. Int. Ed. 2010, 49, 34; Angew. Chem. 2010, 122, 38.
[10] A. Morehead Jr, R. Grubbs, Chem. Commun. 1998, 275.
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Minggui Lin,+ Pei-Jun Cai,+ Zhixiong
Zeng, Na Lin, Yang Shen, Bin Tang, Fan
Li, Chen Chen, Zhi-Xiang Yu,* and
Yandong Zhang*
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Conformational Bias by a Removable
Silyl Group: Construction of
Bicyclo[n.3.1]alkenes via Ring
Closing Metathesis
Conformation decides: we report a novel strategy based on a conformationally
controlled RCM by a removable silyl group, which allows the facile synthesis of
various
bicyclo[n.3.1]alkenes,
especially
a
set
of
highly
strained
bicyclo[5.3.1]alkenes. Further derivatizations of the silyl group and the resultant
double bond enabled a concise synthesis of A-B-C ring skeleton of taxol.
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