Ring strain-promoted allylic transposition of cyclic silyl ethers

Article abstract of DOI:10.1021/ol2013473

Relief of the ring strain of medium-sized rings promotes a regioselective allylic transposition of a C-O bond when catalyzed by rhenium oxide. Through the allylic transposition, eight-membered cyclic silyl ethers undergo ring contraction to the corresponding six-membered siloxacycles.

Full text of DOI:10.1021/ol2013473

ORGANIC
LETTERS
2011
Vol. 13, No. 13
3530–3533
Ring Strain-Promoted Allylic
Transposition of Cyclic Silyl Ethers
Ivan Volchkov,† Sangho Park,‡ and Daesung Lee*,†
Department of Chemistry, University of Illinois at Chicago, 845 West Taylor Street,
Chicago, Illinois 60607, United States, and Samsung Electronics Co., LTD., San 14-1
Nongseo-Dong, Giheung-Gu, Yongin-City, Gyeonggi-Do, Korea, 446-712
dsunglee@uic.edu
Received May 18, 2011
ABSTRACT
Relief of the ring strain of medium-sized rings promotes a regioselective allylic transposition of a CÀO bond when catalyzed by rhenium oxide.
Through the allylic transposition, eight-membered cyclic silyl ethers undergo ring contraction to the corresponding six-membered siloxacycles.
The Re(VII)-catalyzed1 allylic [1,3]-transposition2 of
allylic alcohols and their silyl ether derivatives originally
reported by Osborn is a powerful synthetic tool. The utility
of this transformation, however, is significantly limited by
the formation of an equilibrium mixture of regioisomeric
products due to its reversibility. Recently, several ap-
proaches to control the regioselectivity have been devel-
oped. Grubbs et al. utilized electronic biasing elements
such as conjugation and steric pressure around the allylic
alcohol moiety (eq 1).3 By taking advantage of the
(Z)-vinylboronate moiety tethered to the reaction center,
Lee et al. achieved excellent regiochemical control through
a Lewis acidÀbase interaction between the boronate and
the rearranged silyl ether moieties (eq 2).4 Recently, Za-
karian et al. implemented a ketalization-based trapping
strategy by which the most thermodynamicallly favorable
benzylidene acetals of syn-1,3-diols were efficiently gener-
ated (eq 3).5 With our continued interest in regioselective
allylic transposition, webecameintriguedby the possibility
of using ring strain as the regioselectivity controlling
element (eq 4).
† University of Illinois at Chicago.
‡ Samsung Electronics Co., LTD.
(1) (a) Bellemin-Laponnaz, S.; Gisie, H.; Le Ny, J. P.; Osborn, J. A.
Angew. Chem., Int. Ed. 1997, 36, 976–978. (b) Bellemin-Laponnaz, S.; Le
Ny, J. P.; Dedieu, A. Chem.;Eur. J. 1999, 5, 57–64. (c) Bellemin-
Laponnaz, S.; Gisie, H.; Le Ny, J. P.; Osborn, J. A. Tetrahedron Lett.
2000, 41, 1549–1552.
(2) (a) Takai, K.; Nozaki, H.; Oshima, K.; Okazoe, T.; Matsubara, S.
Bull. Chem. Soc. Jpn. 1985, 58, 844–849. (b) Narasaka, K.; Kusama, H.;
Hayashi, Y. Tetrahedron 1992, 48, 2059–2068. (c) Gordon, M. S.;
Jensen, J. H.; Espenson, J. H.; Jacob, J. Organometallics 1998, 17,
1835–1840. (d) Wang, G.; Jimtaisong, A.; Luck, R. L. Organometallics
2004, 23, 4522–4525. For a review, see: (e) Le Ny, J.-P.; Bellemin-
Laponnaz, S. C. R. Chimie 2002, 5, 217–224.
(3) (a) Morrill, C.; Grubbs, R. H. J. Am. Chem. Soc. 2005, 127, 2842–
2843. (b) Morrill, C.; Beutner, G. L.; Grubbs, R. H. J. Org. Chem. 2006,
71, 7813–7825.
(4) (a) Hansen, E. C.; Lee, D. J. Am. Chem. Soc. 2006, 128, 8142–
8143. (b) Yun, S. Y.; Hansen, E. C.; Volchkov, I.; Cho, E. J.; Lo, W. Y.;
Lee, D. Angew. Chem., Int. Ed. 2010, 49, 4261–4263.
(5) Herrmann, A. T.; Saito, T.; Stivala, C. E.; Tom, J.; Zakarian, A.
J. Am. Chem. Soc. 2010, 132, 5962–5963.
r
10.1021/ol2013473
Published on Web 06/07/2011
2011 American Chemical Society

To examine the new allylic transposition concept, we
required an economic10 access to eight-membered siloxa-
cycles. This needwas easilyaddressedby anintramolecular
allyl transferÀalcoholysis of silylalkynes11 (Scheme 1)
followed by ring-closing metathesis (RCM)12 of corre-
sponding silyl ethers 1. Considering the ring strain of
siloxadienes 2, a negative factor for its formation via
RCM but a prerequisite for the subsequent allylic trans-
position to 3, the presence of an extra double bond in the
form of a vinylsilyl moiety in the siloxacycle platform 2 is
critical for its formation and ring contraction.
The allylic transpositionwithmedium-sized ringsystems
involving ring contraction is expected to be regioselective
due totwo mainfactors. First, the endocyclicdoublebonds
in most medium rings are cis-, which would have a sig-
nificant driving force to become a trans-double bond after
the ring contraction. Second, due to their transannular
interactions, the medium-sized rings are generally more
strained than their smaller counterparts. Among medium-
sized rings, the ring contraction of eight-membered rings
to the corresponding six-membered rings would be most
favorable because this transformation would induce more
relief of ring straincomparedtothe process involving other
rings. As a platform for the development of an allylic
transposition strategy, we became interested in a 1,5-dien-
4-ol motif containing a (Z)-trisubstituted double bond for
it is a common structural feature found in many biologi-
cally active natural products including zampanolide,4b,6
bryostatin 1,7 rubifolide,8 and various amphidinolides.9
Herein we describe a successful implementation of the ring
strain-driven allylic transposition employing eight-mem-
bered siloxadienes as an efficient method for the synthesis
of (Z)-trisubstituted vinylsilanes containing a 1,5-dien-4-ol
moiety.
Scheme 1. Ring Contraction of Eight-Membered Siloxacycles
and Their Synthesis
(6) (a) Tanaka, J.; Higa, T. Tetrahedron Lett. 1996, 37, 5535–5538. (b)
Smith, A. B., III; Safonov, I. G.; Corbett, R. M. J. Am. Chem. Soc. 2001,
123, 12426–12427. (c) Smith, A. B., III; Safonov, I. G.; Corbett, R. M.
J. Am. Chem. Soc. 2002, 124, 11102–11113. (d) Hoye, T. R.; Hu, M.
J. Am. Chem. Soc. 2003, 125, 9576–9577. (e) Uenishi, J.; Iwamoto, T.;
Tanaka, J. Org. Lett. 2009, 11, 3262–3265. Dactylolide syntheses: (f)
Smith, A. B., III; Safonov, I. G. Org. Lett. 2002, 4, 635–637. (g) Ding, F.;
Jennings, M. P. Org. Lett. 2005, 7, 2321–2324. (h) Aubele, D. L.; Wan,
S.; Floreancig, P. E. Angew. Chem., Int. Ed. 2005, 44, 3485–3488. (i)
Sanchez, C. C.; Keck, G. E. Org. Lett. 2005, 7, 3053–3056. (j) Louis, I.;
Hungerford, N. L.; Humphries, E. J.; McLeod, M. D. Org. Lett. 2006, 8,
1117–1120.
(7) (a) Pettit, G. R.; Herald, C. L.; Clardy, J.; Arnold, E.; Doubek,
D. L.; Herald, D. L. J. Am. Chem. Soc. 1982, 104, 6846–6848. Bryostatins
syntheses: A comprehensive review: (b) Hale, K. J.; Hummersone, M. G.;
Manaviazar, S.; Frigerio, M. Nat. Prod. Rep. 2002, 19, 413–453. (c)
Kageyama, M.; Tamura, T.; Nantz, M. H.; Roberts, J. C.; Somfai, P.;
Whritenour, D. C.; Masamune, S. J. Am. Chem. Soc. 1990, 112, 7407–7408.
(d) Evans, D. A.; Carter, P. H.; Carreira, E. M.; Prunet, J. A.; Charette,
A. B.; Lautens, M. Angew. Chem., Int. Ed. 1998, 37, 2354–2359. (e) Trost,
B. M.; Dong, G. Nature 2008, 456, 485–488.
Our strategy was first tested with benzyloxymethyl-
substituted silylalkyne (R1 = CH2OBn) and allyl alcohol
(Table 1). An intramolecular allyl transfer reaction driven
by an alcoholysis afforded silyl ether 1a in high yield with
(Z)-stereochemistry (entry 1). Thesilyl ether1awas treated
with Grubbs second-generation catalyst (G-II) for 4 h at
25 °C in CH2Cl2, affording eight-membered siloxacycle 2a
in 96% yield.
The proposed ring contraction was demonstrated by
treatment of 2awith a catalytic amount of Re2O7 (5 mol %,
ether, 25 °C, 3 h), providing siloxene 3a in 49% yield.
Although the yield was marginal, this clearly illustrated the
feasibility of the proposed reaction sequence. The low yield
of the ring contraction is most likely to be the consequence
(8) (a) Williams, D.; Andersen, R. J.; Van Duyne, G. D.; Clardy, J.
ꢀ
J. Org. Chem. 1987, 52, 332–335. (b) Sanchez, M. C.; Ortega, M. J.;
Zubıa, E.; Carballo, J. L. J. Nat. Prod. 2006, 69, 1749–1755. (c)
´
(10) (a) Trost, B. M. Acc. Chem. Res. 2002, 35, 695–705. (b) Trost,
B. M. Angew. Chem., Int. Ed. 1995, 34, 259–281. (c) Trost, B. M. Science
1991, 254, 1471–1477. (d) Wender, P. A.; Bi, F. C.; Gamber, G. G.;
Gosselin, F.; Hubbard, R. D.; Scanio, M. J. C.; Sun, R.; Williams, T. J.;
Zhang, L. Pure Appl. Chem. 2002, 74, 25–31. (e) Wender, P. A.; Miller,
B. L. Nature 2009, 460, 197–201.
(11) Park, S.; Lee, D. J. Am. Chem. Soc. 2006, 128, 10664–10665.
(12) (a) Grubbs, R. H.; Chang, S. Tetrahedron 1998, 54, 4413–4450.
(b) Armstrong, S. K. J. Chem. Soc., Perkin Trans. 1 1998, 371–388. (c)
Blechert, S. Pure Appl. Chem. 1999, 71, 1393–1399. (d) Furstner, A.
Angew. Chem., Int. Ed. 2000, 39, 3012–3043. (e) Handbook of Metath-
esis; Grubbs, R. H., Ed.; Wiley-VCH: Weinheim, Germany, 2003; Vol. 2. (f)
Deiters, A.; Martin, S. F. Chem. Rev. 2004, 104, 2199–2238. (g)
Nicolaou, K. C.; Bulger, P. G.; Sarlah, D. Angew. Chem., Int. Ed.
2005, 44, 4490–4527. For enyne metathesis: (h) Giessert, A. J.; Diver,
S. T. Chem. Rev. 2004, 104, 1317–1382. (i) Poulsen, C. S.; Madsen, R.
Synthesis 2003, 1, 1–18. (j) Mori, M. In Handbook of Metathesis; Grubbs,
R. H., Ed.; Wiley-VCH: Weinheim, Germany, 2003; Vol. 2, pp 176À204.
Marshall, J. A.; Sehon, C. A. J. Org. Chem. 1997, 62, 4313–4320. (d)
Marshall, J. A.; Van Devender, E. A. J. Org. Chem. 2001, 66, 8037–8041.
(e) Roethle, P. A.; Hernandez, P. T.; Trauner, D. Org. Lett. 2006, 8,
5901–5904.
(9) (a) Kobayashi, J.; Ishibashi, M.; Nakamura, H.; Ohizumi, Y.
Tetrahedron Lett. 1986, 27, 5755–5758. (b) Lam, H. W.; Pattenden, G.
Angew. Chem., Int. Ed. 2002, 41, 508–511. (c) Trost, B. M.; Wrobleski,
S. T.; Chisholm, J. D.; Harrington, P. E.; Jung, M. J. Am. Chem. Soc.
2005, 127, 13589–13597. (d) Kobayashi, J.; Ishibashi, M.; Murayama,
T.; Takamatsu, M.; Iwamura, M.; Ohizumi, Y.; Sasaki, T. J. Org. Chem.
1990, 55, 3421–3423. (e) Va, P.; Roush, W. R. J. Am. Chem. Soc. 2006,
128, 15960–15961. (f) Kim, C. H.; An, H. J.; Shin, W. K.; Yu, W.; Woo,
S. K.; Jung, S. K.; Lee, E. Angew. Chem., Int. Ed. 2006, 45, 8019–8021.
(g) Kobayashi, J.; Sato, M.; Ishibashi, M. J. Org. Chem. 1993, 58, 2645–
2646. (h) Barbazanges, M.; Meyer, C.; Cossy, J. Org. Lett. 1993, 10,
4489–4492. (i) Kubota, T.; Tsuda, M.; Kobayashi, J. Tetrahedron Lett.
€
€
2000, 41, 713–716. (j) Furstner, A.; Larionov, O.; Flugge, S. Angew.
Chem., Int. Ed. 2007, 46, 5545–5548.
Org. Lett., Vol. 13, No. 13, 2011
3531

Re2O7 (5 mol %, ether, 25 °C, 10 min) provided six-
membered siloxenes 3b and 3c in good yields with trans-
stereochemistry of the newly generated double bond.
Under these reaction conditions, the TBS-group of the
primary alcohol was cleaved (entry 3); yet, diphenylsilyl
group migration from the secondary alcohol moiety to the
primary one was not observed. Compounds 3d and 3e were
obtained similarly from metoxymethyl-substituted silylalk-
yne (R1 = CH2OMe) and secondary allylic alcohols
(entries 4 and 5).
Table 1. Synthesis of Functionalized (Z)-Trisubstituted Vinyl-
silanes
The generality of the sequence was further examined with
a variety of substrates including allylic alcohols bearing
aromatic substituents, tertiary allylic alcohols, and pro-
pargylic alcohols. Influence of the substituent on the silylalk-
yne moiety was also examined. Allyl transferÀalcoholysis
with propargylic alcohols afforded vinylsilanes 1f and 1g,
which were subsequently ring closed to give compounds 2f
and 2g (entries 6 and 7). Although the ring-closing enyne
metathesis of silyl ethers 1f and 1g required longer reaction
times and an ethylene environment,13 eight-membered si-
loxacycles containing a 1,4-diene moiety were formed with-
out difficulty albeit the yield of 2g is marginal. The rhenium
oxide catalyzed allylic transposition of 2f afforded siloxene 3f
with high efficiency. However, the allylic transposition of 2g
provided a mixture of 3g and an aromatized byproduct,
which should be the result of methanol elimination. Not
surprisingly, tertiary allylic and secondary benzylic alcohols
were not compatible with the allyl transfer conditions as
opposed to nonallylic tertiary and secondary allylic
alcohols.11 Probably, this is due to the formation of relatively
stable allylic and benzylic cations from the starting alcohols
or the products thereof.
Changing the nature of the substituent on the silylalkyne
significantly affected the efficiency of both the gold-cata-
lyzed allyl transfer reaction and RCM (entries 8À11). As
opposed to the substrates with alkoxymethyl substituents,
those with a simple methyl group showed slower allyl
transfer and diminished RCM yields. Yet, under reopti-
mized reaction conditions,13 (Z)-vinylsilanes 1hÀk were
obtained in good yields and stereoselectivity. RCM of
these silyl ethers required a high reaction temperature
(85 °C, toluene) and provided mixtures of the desired
eight-membered cyclic siloxadiene together with a varying
amount of the five-membered siloxene.14,15 The ring con-
traction of siloxadienes 2hÀk under standard conditions
afforded siloxenes 3hÀk in good yields.
The chirality transfer during allylic transposition
was examined with substrates 2l and 2m obtained from
(S)-1-octen-3-ol (ee > 95%) and (S)-3-pentyne-2-ol
(ee > 99%16), respectively (Scheme 2). The chiral
HPLC analysis of the desilylated alcohol derived from
a 5 mol % of catalyst was used. b Isolated yield. c Isolated yield overall
for 2 steps. d NMR ratio of eight- and five-membered siloxacycles.
e Combined yield of 3g and aromatized product.
(13) See Supporting Information for details.
of generating the thermodynamically less favorable term-
inal alkene from the internal one in the starting material.
Encouraged by this observation, eight-membered silox-
adienes2band 2c were synthesized via the same but one-pot
reaction without isolating intermediates (entries 2 and 3).
Gratifyingly, after purification, treatment of 2b and 2c with
(14) It is unusual to observe this five-membered ring product because
RCM of vinylsilanes is known to be difficult with a Grubbs catalyst. (a)
Denmark, S. E.; Yang, S.-M. Org. Lett. 2001, 3, 1749–1752. (b) Denmark,
S. E.; Yang, S.-M. Tetrahedron 2004, 60, 9695–9708.
(15) We surmise that the five-membered ring formation is most likely
the consequence of direct RCM of the acyclic precursors because
resubjection of the eight-membered siloxacycle to the reaction condi-
tions did not provide any five-membered ring product.
3532
Org. Lett., Vol. 13, No. 13, 2011

siloxene 3l and Mosher’s ester analysis of the desily-
lated alcohol from 3m showed that the stereochemical
integrity of the allylic alcohol was lost to some extent.
Scheme 3. Plausible Mechanism for Silyl-Directed Allylic
Transposition/Ring Contraction
Scheme 2. Chirality Transfer in [1,3]-Transposition
while an electron-donating substituent should facilitate
formation of ion pairs via an allyl cation intermediate.
In conclusion, we have developed a novel allylic
transposition reaction that relies on the relief of ring
strain. Through this process, eight-membered ring si-
loxadienes undergo a ring contraction to the corre-
sponding six-membered siloxenes bearing an endo-
cyclic double bond and an alkenyl substituent. The
orchestrated use of three metal-catalyzed reactions, an
intramolecular allyl transfer of silyl alkynes to set the
(Z)-stereochemistry of vinylsilyl moiety, RCM to form
the eight-membered ring, and a silyl-directed allylic
transposition/ring contraction, constitutes an efficient
entry to functionalized (Z)-trisubstituted vinylsilanes.
Application of this synthetic method to natural product
syntheses will be reported in due course.
When the reaction was carried out at room temperature,
3l and 3m were obtained in 79% and 76% ee, respectively.
The degree of racemization for Re2O7 catalyzed allylic
transposition depends on the reaction time, and thus a
prolonged reaction time resulted in low ee values.
Based on the allylic transposition of 2l and 2m, it is
reasonable to consider that there are two distinctive me-
chanisms for the allylic transposition catalyzed by rhenium
oxide (Scheme 3). Upon activation of the SiÀO bond with
rhenium oxide, σ-bond metathesis takes place, which then
undergoes an allylic transposition via a [3,3]-sigmatropic
rearrangement or ion-pair formation.
The product of the concerted [3,3]-sigmatropic rearran-
gement pathway should be enantiomerically enriched with
high ee value. On the other hand, due to the highly Lewis
acidic nature of Re2O7, the allylic transposition may
partially occur via an allylic cation intermediate generating
a product with low or no ee value.3,4 The extent of the two
manifolds of allylic transposition alsodepends on the steric
and electronic nature of substituents R1 and R2. An
electron-withdrawing R1 should favor a concerted process
Acknowledgment. Financial support for this work from
UIC is greatly acknowledged. We are grateful to Mr. Furong
Sun of the University of Illinois at UrbanaÀChampaign for
high resolution mass spectrometry data.
(16) This compound was obtained by kinetic resolution of its race-
mate with Novozym. For Novozym resolution, see: (a) Burgess, K.;
Jennings, L. D. J. Am. Chem. Soc. 1990, 112, 7434–7436. (b) Burgess, K.;
Jennings, L. D. J. Am. Chem. Soc. 1991, 113, 6129–6139. (c) Xu, D.; Lib,
Z.; Ma, S. Tetrahedron Lett. 2003, 44, 6343–6346. (d) Xu, D.; Lib, Z.;
Ma, S. Tetrahedron: Asymmetry 2003, 14, 3657–3666.
Supporting Information Available. Experimental pro-
cedures and spectroscopic data for all new compounds.
This material is available free of charge via the Internet at
http://pubs.acs.org.
Org. Lett., Vol. 13, No. 13, 2011
3533