Gold-catalyzed synthesis of bicyclo[3.2.0]heptenes via a formal [3+2]/[2+2]-annulation of allylsilane with 4-methoxybut-2-yn1-ols

Article abstract of DOI:10.1002/adsc.201000201

This work reports the novel gold-catalyzed [3+ 2]/[2+2]-annulation of allylsilane with Amethoxybut-2-yn-l-ols that yields highly strained bicyclo[3.2.0]heptene products efficiently and stereoselectively.

Full text of DOI:10.1002/adsc.201000201

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DOI: 10.1002/adsc.201000201
Gold-Catalyzed Synthesis of Bicyclo
ACHTUNGTRENNUNG
[3+2]/
ACHTUNGTRENNUNG
1-ols
Chun-Yao Yang,a Chiou-Dong Wang,a Shu-Fan Tian,a and Rai-Shung Liua,*
a
Department of Chemistry, National Tsing-Hua University, Hsinchu, Taiwan, Republic of China
Fax : (+886)-3-571-1082; e-mail: rsliu@mx.nthu.edu.tw
Received: March 15, 2010; Revised: May 10, 2010; Published online: June 30, 2010
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/adsc.201000201.
Abstract: This work reports the novel gold-cata-
lyzed [3+2]/
methoxybut-2-yn-1-ols that yields highly strained
bicyclo[3.2.0]heptene products efficiently and ste-
ACHTUNGTRENNUNG[2+2]-annulation of allylsilane with 4-
ACHTUNGTRENNUNG
reoselectively.
Keywords:
ACHTUNGTRENNUNG
allylsilanes;
annulation;
bicyclo-
Scheme 1. Natural products containing the bicyclo-
AHCTUNGERTG[NNUN 3.2.0]heptane skeleton.
of their marked activities in propargyl substitutions.[9]
As shown in entries 1–3, AuCl3 and PPh3AuCl/
AgSbF6 led to exclusive recovery of starting 1a
Metal-catalyzed cycloadditions or annulations are whereas PtCl2 gave messy products. The desired bicy-
powerful tools in organic synthesis. Allylsilanes are clic compound 2a was formed in 76% yield with
particularly appealing and serve as three-carbon PPh3AuCl/AgNTf2 (entry 4), whereas PPh3AuCl/
building units for the construction of various carbo- AgSbF6 and AgNTf2 alone gave 2a inefficiently (0–
or heterocyclic frameworks through versatile Lewis 10%). As the formation of compound 2a requires
acid-mediated [3+2]-, [3+3]- and [3+4]-annulations allylsilane in two equimolar proportions, we increased
with aldehydes, ketones, imines and enones.[1,2] Re- the allylsilane in three- and four-fold proportions,
ported reactions of such types generally gave cyclized giving 2a in up to 81% and 90% yields, respectively
products incorporating one ring. We recently report- (entries 7 and 8). The catalytic annulation of
ed[3] gold- and platinum-catalyzed annulations of allyl- PPh3AuCl/AgNTf2 became less active in other sol-
silanes with oxabicyclic benzenes, oxodienes and oxo- vents including nitromethane and 1,4-dioxane, from
ACHTUNGTRENNUNG
alkynes,[4] which are efficient to construct new bicyclic which we obtained 2a in only 14–16% yields with
frameworks with high stereocontrol, thereby increas- complete consumption of starting 1a (entries 9 and
ing the molecular complexity of the products.[5] 10).
Herein, we report the synthesis of highly strained
Table 2 shows the effects of the two oxy groups
bicyclo[3.2.0]heptenes through catalytic annulations (OX and OY) on the efficiencies of the annulation.
ACHTUNGTRENNUNG
of allylsilanes with readily available 4-methoxybut-2- We prepared analogous substrates 3a–3e with altera-
yn-1-ols that serve as a four-carbon building unit.[6] tions of the substituents at the C(1)-oxy OY=OMe,
Notably, this bicyclic framework is present in various OAc and OMOM (MOM=methoxymethyl) and the
natural compounds including repraesentin F, kelsoene C(4)-oxy OX=OH, OMOM; the results are given in
and sulcatine G (Scheme 1).[7,8]
Table 2. Although most of these substrates were also
Table 1 shows the optimum conditions involving as active as the parent species 1a, their corresponding
various gold catalysts (5 mol%) to implement the an- yields (51–70%) of desired 2a were somewhat dimin-
nulation of allylsilane with 4-phenyl-4-methoxybut-2- ished, whereas compound 3b (X=MOM, Y=H) was
yn-1-ol (1a) in dichloromethane (DCM) at 258C; we found to be inactive under the same conditions.
selected gold complexes for activity screening because
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Chun-Yao Yang et al.
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Table 1. Optinum conditions for the synthesis of bicycloACTHNUTRGNEU[GN 3.2.0]heptenes.
[a]
[b]
[1a]=0.10M.
Product yields are reported after chromatography on a silica column.
On the basis of the preceding data, we prepared applicable to substrates 1j–1n bearing various para-
various 4-methoxybut-2-yn-1-ols 1b–1q to assess the phenyl substituents, with the methoxy (entry 10)
generality of this formal [3+2]/ACHTUNGTRENN[UNG 2+2]-annulation; the being more effective than methyl, fluoro, chloro and
resulting bicyclo[3.2.0]heptene products 2b–5q were bromo analogues (entries 9, 11–13). This trend con-
ACHTUNGTRENNUNG
obtained in satisfactory yields (>65%) and diastereo- forms to our expectation that an electron-rich ben-
selectivities (dr >10:1) in most cases, as specified in zene facilitates a gold-catalyzed propargyl substitu-
Table 3 (entries 1–16). Product analysis confirms that tion. For compounds 1o and 1p bearing a 2-thienyl
the C(1)–C(3) and C(7) carbon skeletons of the re- and a 2-naphthyl groups, their annulations with allylsi-
sulting products 2b–5q originated from the starting 4- lane gave the desired carbocycles 2o and 2p in 53%
methoxybut-2-yne-1,4-diols 1b–1q. This new annula- and 76% yields, respectively (entries 14 and 15). A
tion is applicable to substrates 1b–1h bearing various similar annulation of substrate 1q occurred with an in-
R groups (R=H, Me, i-Bu, i-Pr, cyclohexyl, t-Bu and itial allylation preferably at the propargyl carbon ad-
Bn); the corresponding products 2b–2h were obtained jacent to the p-methoxyphenyl rather than the phenyl
in 65–91% yields (entries 1–7). This gold catalysis is group (entry 16), giving the desired 4q and methoxy
derivative 5q in 53% and 36% yield, respectively.
Scheme 2 shows the deuterium-labeling experi-
Table 2. Effects of oxy groups on gold-catalyzed annulation.
ments to elucidate the reaction mechanism. We pre-
pared d1-1r bearing 100% deuterium content at the
C(4)-methoxy group; its gold annulation with allylsi-
lane provided d1-2r bearing the same deuterium con-
tent at the C(2)-carbon, indicative of a 1,2-hydrogen
shift. We prepared also a diastereomeric mixture of
species 1i bearing a (R)-configuration at the C(2)-
carbon, but the reaction gave annulation product 2i in
racemic form through a complete loss of the chirality
at the C(7)-Me carbon. More importantly, the same
gold-catalyzed allylation on substarte 1b for a brief
time (1 h) gave alcohol 6a in 21% yield, together with
desired 2b (56%) and unreacted 1b (14%). Alcohol
6a was completely transformed into 2b with the same
gold catalyst.
[a]
[3a–e]=0.10M, allylTMS (4 equiv.), CH2Cl2.
Product yields are reported after chromatography on a
[b]
On the basis of deuterium-labeling experiments
and the isolation of intermediate 6a, we propose the
silica column.
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Gold-Catalyzed Synthesis of BicycloACTHNUTRGNENG[U 3.2.0]heptenes via a Formal [3+2]/ACHUTNGTREN[NUGN 2+2]-Annulation
Table 3. Reaction scope for the synthesis of bicycloACTHUNRTGNEUNG[3.2.0]heptenes.
[a]
[b]
[1b–q]=0.10M, CH2Cl2.
Product yields are reported after chromatography on a silica column.
Scheme 2. Control experiments for mechanistic elucidation.
mechanism in Scheme 3 involving an initial progargyl that is again activated by the same gold catalyst to
substitution catalyzed by PPh3AuNTf2.[9] This substitu- give cyclopropyl gold-carbenoid species B according
tion is expected to give 1,5-enyne intermediate A[10,11] to a well established gold-catalyzed cycloisomeriza-
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Chun-Yao Yang et al.
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Scheme 3. A proposed mechanism for [3+2]/ACHTNUTRGNEUNG[2+2] annulation.
Scheme 4. Preliminary results with alterations of allylsilanes and substrates.
tion route. This gold carbenoid species further forms tively. One the basis of experimental data, we propose
alcohol C through a 1,2-hydride shift that is supported that this tandem catalysis begins with an initial prop-
by deuterium labeling. We envisage that, in the pres- argylation, followed by a 1,6-enyne cycloisomeriza-
ence of gold catalyst, alcohol C undergoes a subse- tion, and ends with a carbocation-induced ring expan-
quent ionization to form carbocation D that is infer- sion of a cyclopropyl ring; all three steps are imple-
red from the complete loss of the chirality in the mented by PPh3AuNTf2 alone. This new catalysis
transformation of a diastereomeric mixture of chiral highlights a rapid access to molecular complexity with
1i to racemic 2i. This cationic intermediate undergoes readily available starting reagents.
a cyclopropyl expansion to give tertiary cation E that
ultimately reacts with allylsilane to give desired prod-
uct 2c together with regeneration of the catalyst
PPh3Au+.
Experimental Section
Scheme 4 shows our preliminary results with altera-
tions of the allylsilanes and 4-methoxybut-2-yn-1-ol
substrates. For substrate 1b, gold-catalyzed annulation
with crotylsilane failed to proceed, but the use of 2-
General Procedure for Synthesis of 2a.
A
CH2Cl2 (2.0 mL) solution of ClAuPPh3 (8.6 mg,
0.0175 mmol) and AgNTf2 (6.7 mg, 0.0175 mmol) was stirred
methylallylsilane gave a 75% yield of 1,3,5-trisubsti- at 258C for 10 min before addition of a CH2Cl2 solution
(1.5 mL) of 1a (81 mg, 0.35 mmol) and allylsilane (0.22 mL,
1.40 mmol), and the mixture was stirred for 6 h. The result-
ing solution was filtered through a celite bed, and eluted
through a silica gel column (ethyl acetate-hexane, 1:50) to
tuted benzene 7 (75% yield) via a 6-endo-dig cycliza-
tion of hypothetic intermediate F. For alcohol 8, we
observed a distinct allylation reaction that proceeded
through an SN2’ pathway, giving species G initially
that underwent a subsequent oxacyclization to deliver
2,5-dihydrofuran 9 in 36% yield.
give compound 2a as
(0.315 mmol, 90%). IR (neat): n=3080, 1961, 1850, 1665,
810 cmÀ1 1H NMR (400 MHz, CDCl3): d=7.49–7.44 (m,
a colorless oil; yield: 84 mg
;
In summary, we report novel gold-catalyzed [3+2]/ACHTUNG-
2H), 7.33–7.29 (m, 2H), 7.23–7.20 (m, 1H), 6.06 (s, 1H),
5.78–5.68 (m, 1H), 5.02–4.92 (m, 2H), 2.84 (ddd, J=16.0,
7.6, 2.4 Hz, 1H), 2.46–2.34 (m, 3H), 2.31–2.20 (m, 3H),
TRENNUNG
ACHTUNGTRENNUNG[3.2.0]heptene products efficiently and stereoselec- 1.45–1.36 (m, 1H), 1.28–1.20 (m, 3H), 1.85–1.10 (m, 3H),
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Adv. Synth. Catal. 2010, 352, 1605 – 1609

Gold-Catalyzed Synthesis of BicycloACTHNUTRGNENG[U 3.2.0]heptenes via a Formal [3+2]/ACHUTNGTREN[NUGN 2+2]-Annulation
0.85 (t, J=6.8 Hz, 3H); 13C NMR (100 MHz, CDCl3): d=
143.0, 137.0, 135.5, 129.2, 128.2, 127.0, 125.9, 116.0, 60.0,
44.6, 43.8, 40.5, 37.0, 31.6, 31.2, 29.8, 22.8, 14.1; HR-MS:
m/z=266.2035, calcd. for C20H26: 266.2035.
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Acknowledgements
The authors thank National Science Council, Taiwan for sup-
port this work.
[6] Derivatives of 2-butyne-1,4-diols were previously used
in gold-catalyzed cyclization without external nucleo-
philes, see: A. Buzas, F. Istrate, F. Gagosz, Org. Lett.
2006, 8, 1957.
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