Catalytic intramolecular formal [3 + 2] cycloaddition for the synthesis of benzobicyclo[4.3.0] compounds

Article abstract of DOI:10.1021/jo9001917

In the presence of 20 mol % of tributylphosphine, tert-butyl carbonate substrate 3a undergoes smoothly an intramolecular formal [3 + 2] cycloaddition reaction at room temperature to give benzobicyclo[4.3.0] compounds in 99% yield with a 19/81 ratio of 2a

Full text of DOI:10.1021/jo9001917

Catalytic Intramolecular Formal [3 + 2] Cycloaddition for the
Synthesis of Benzobicyclo[4.3.0] Compounds
Xun Han,† Long-Wu Ye,† Xiu-Li Sun, and Yong Tang*
State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, Chinese
Academy of Sciences, 354 Fenglin Lu, Shanghai 200032, China
tangy@mail.sioc.ac.cn
ReceiVed January 30, 2009
In the presence of 20 mol % of tributylphosphine, tert-butyl carbonate substrate 3a undergoes smoothly
an intramolecular formal [3 + 2] cycloaddition reaction at room temperature to give benzobicyclo[4.3.0]
compounds in 99% yield with a 19/81 ratio of 2a and 2a′. The mechanism of the isomerization of the
product 2a into 2a′ has been investigated in detail. On the basis of this mechanism, two strategies, using
20 mol % of triphenylphosphine or 10 mol % of tributylphosphine in the presence of 20 mol % of
Ti(OiPr)4, have been established for the selective construction of benzobicyclo[4.3.0] compounds. Under
neutral conditions, the reactions of compounds 3a-g afford benzobicyclo[4.3.0] compounds 2a-g with
high selectivities in good to excellent yields. In addition, R-methyl R,ꢀ-unsaturated ester 3h also works
well to give the corresponding product 2h with one quaternary carbon center in 99% yield under neutral
and room temperature conditions.
Introduction
Recently, elegant works on the catalytic asymmetric versions
have also been reported.4-8 In a previous study on ylide
chemistry,9 we documented that cyclization precursor allylic
bromides 1 underwent readily a formal [3 + 2] cycloaddition
at 80 °C in the presence of PPh3 and base, affording benzobi-
cyclo[4.3.0] compounds diastereoselectively in good to excellent
yields (Scheme 1).10 Under neutral conditions at room temper-
ature, very recently, we found that triphenylphosphine initiates
the same formal [3 + 2] cycloaddition of the corresponding
tert-butyl carbonate substrates 3 smoothly to give 2 in a
Recently, much attention has been paid to tandem ylide
reactions for the construction of cyclic and heterocyclic
compounds.1-8 For instance, Lu and his co-workers reported a
phosphorus ylide cyclization for the synthesis of cyclopentenes
in a number of elegant studies.1 Krische et al. documented the
first intramolecular variant of the cycloaddition.2 Kwon et al.
developed a facile method for the preparation of functionalized
piperidines via [4 + 2] annulation of imines with allenes.3
† Han and Ye made an equal contribution to this paper.
(1) (a) Lu, Z.; Zheng, S.; Zhang, X.; Lu, X. Org. Lett. 2008, 10, 3267. (b)
Lu, X.; Lu, Z.; Zhang, X. Tetrahedron 2006, 62, 457. (c) Du, Y.; Feng, J.; Lu,
X. Org. Lett. 2005, 7, 1987. (d) Du, Y.; Lu, X.; Zhang, C. Angew. Chem., Int.
Ed. 2003, 42, 1035. (e) Du, Y.; Lu, X. J. Org. Chem. 2003, 68, 6463. (f) Lu, C.;
Lu, X. Org. Lett. 2002, 4, 4677. (g) Du, Y.; Lu, X.; Yu, Y. J. Org. Chem. 2002,
67, 8901.
(2) (a) Wang, L.-C.; Ng, S.-S.; Krische, M. J. J. Am. Chem. Soc. 2003, 125,
3682. (b) Wang, L.-C.; Krische, M. J. Angew. Chem., Int. Ed. 2003, 42, 5855.
(3) Zhu, X.-F.; Lan, J.; Kwon, O. J. Am. Chem. Soc. 2003, 125, 4716.
(4) Zhu, G.; Chen, Z.; Jiang, Q.; Xiao, D.; Cao, P.; Zhang, X. J. Am. Chem.
Soc. 1997, 119, 3836.
(5) (a) Wilson, J. E.; Fu, G. C. Angew. Chem., Int. Ed. 2006, 45, 1426. (b)
Wurz, R. P.; Fu, G. C. J. Am. Chem. Soc. 2005, 127, 12234.
(6) Cowen, B. J.; Miller, S. J. J. Am. Chem. Soc. 2007, 129, 10988.
(7) Sriramurthy, V.; Barcan, G. A.; Kwon, O. J. Am. Chem. Soc. 2007, 129,
12928.
(9) For reviews, see: (a) Sun, X.-L.; Tang, Y. Acc. Chem. Res. 2008, 41,
937. (b) Ye, S.; Tang, Y.; Sun, X.-L. Synlett 2005, 2720. For recent examples,
see: (c) Wang, Q.-G.; Deng, X.-M.; Zhu, B.-H.; Ye, L.-W.; Sun, X.-L.; Li, C.-
Y.; Zhu, C.-Y.; Shen, Q.; Tang, Y. J. Am. Chem. Soc. 2008, 130, 5408. (d) Li,
C.-Y.; Wang, X.-B.; Sun, X.-L.; Tang, Y.; Zheng, J.-C.; Xu, Z.-H.; Zhou, Y.-
G.; Dai, L.-X. J. Am. Chem. Soc. 2007, 129, 1494. (e) Ye, L.-W.; Sun, X.-L.;
Li, C.-Y.; Tang, Y. J. Org. Chem. 2007, 72, 1335. (f) Deng, X.-M.; Cai, P.; Ye,
S.; Sun, X.-L.; Liao, W.-W.; Li, K.; Tang, Y.; Wu, Y.-D.; Dai, L.-X. J. Am.
Chem. Soc. 2006, 128, 9730. (g) Ye, L.-W.; Sun, X.-L.; Zhu, C.-Y.; Tang, Y.
Org. Lett. 2006, 8, 3853. (h) Zheng, J.-C.; Liao, W.-W.; Tang, Y.; Sun, X.-L.;
Dai, L.-X. J. Am. Chem. Soc. 2005, 127, 12222. (i) Liao, W.-W.; Deng, X.-M.;
Tang, Y. Chem. Commun. 2004, 1516. (j) Liao, W.-W.; Li, K.; Tang, Y. J. Am.
Chem. Soc. 2003, 125, 13030. (k) Ye, S.; Huang, Z.-Z.; Xia, C.-A.; Tang, Y.;
Dai, L.-X. J. Am. Chem. Soc. 2002, 124, 2432.
(10) (a) Ye, L.-W.; Sun, X.-L.; Wang, Q.-G.; Tang, Y. Angew. Chem., Int.
Ed. 2007, 46, 5951. (b) Ye, L.-W.; Han, X.; Sun, X.-L.; Tang, Y. Tetrahedron
2008, 64, 1487.
(8) Fang, Y.-Q.; Jacobsen, E. N. J. Am. Chem. Soc. 2008, 130, 5660.
3394 J. Org. Chem. 2009, 74, 3394–3397
10.1021/jo9001917 CCC: $40.75 2009 American Chemical Society
Published on Web 04/02/2009

Synthesis of Benzobicyclo[4.3.0] Compounds
SCHEME 1. Base Effects for Phosphine-Catalyzed Formal [3 + 2] Cycloaddition
SCHEME 2. Possible Reaction Intermediate
SCHEME 3. Effects of Phosphine Catalysts on the [3 + 2]
Cycloaddition
selectivity of >95/5. Furthermore, the reaction proves phosphine-
dependent.Comparedwithtriphenylphosphine,tributylphosphine11,12
can accelerate the reaction greatly but gave a mixture of 2 and
2′ with a ratio of 19/81 as the products, in which most of 2 is
isomerized into 2′. In this paper, results with the OBoc derivative
3 will be presented.
Results and Discussion
TABLE 1. PBu3-Promoted Isomerizationa
Modification of the Intramolecular [3 + 2] Cycloaddition
and Isomerization Mechanisms of 2a. Since the reaction of
bromide 1 with triphenylphosphine was very slow, the [3 + 2]
cycloaddition shown in Scheme 1 was conducted at 80 °C.
Considering that tert-butyl carbonate substrate 3 might also
furnish a similar intermediate of this annulation in the presence
of tributylphosphine (Scheme 2),1d,10a our further efforts focused
on the improvement of the annulation by employing 3 as
substrates. In the presence of 20 mol % of tributylphosphine,
to our delight, it was found that the reaction of tert-butyl
carbonate substrate 3a underwent smoothly the same intramo-
lecular annulation under neutral conditions and 99% yield was
obtained at room temperature in 2 h. Unfortunately, the product
was obtained as a mixture of 2a and the isomerized product
2a′ with a ratio of 19/81 (eq 1).
reaction times (h) )
24
83/17 79/21 78/22 57/43 24/76
2a/2a′ tBuOHb 83/17 82/18 80/20 72/28 25/75
entry
additive
0
2
6
72
1
2
2a/2a′
a Conditions: PBu3 (10.1 mg, 20 mol %), 2a (80.7 mg, 0.25 mmol) in
toluene (2.5 mL), rt. The ratio was determined by 1H NMR. b 1.0 equiv
t
of BuOH was added.
the fact that the intramolecular annulation took 2 h to give
products 2a and 2a′ with a ratio of 19/81 in 99% yield (eq 1).
Considering that the annulation reaction in eq 1 will release
t
1.0 equiv of BuOH that might act as a proton shuttle to
accelerate the isomerization, 1.0 equiv of tBuOH was added to
a mixture of 2a and tributylphosphine in toluene. However, it
almost did not speed up the isomerization (entry 2, Table 1).
These results suggested that 2a′ was formed only partially
through PBu3-promoted isomerization from 2a and there is
another decisive pathway to govern this isomerization.
To inhibit the isomerization of product 2a and to make the
current reaction useful, we investigated the mechanism of the
isomerization in detail. Initially, an isomerization proceeded
through phosphine-initiated Michael addition/proton transfer/
elimination was proposed as depicted in Scheme 3 (path A).
However, it was found that the PBu3-catalyzed isomerization
reaction proceeded very slowly under the reaction conditions.
In the presence of 20 mol % of tributylphosphine, for example,
it would take 72 h to switch the molar ratio of 2a and 2a′ from
83/17 to 24/76 (entry 1, Table 1), which sharply contrasts with
In our previous study, we found that base could accelerate
the isomerization of 2a to 2a′.10b In this annulation, the initial
step is the attack of phosphine to tert-butyl carbonate, which
t
will produce 1.0 equiv of BuO- (eq 2). It is envisioned that
t
the in situ generated BuO- will result in the isomerization of
2a to 2a′ (path B in Scheme 3). To demonstrate this assumption,
20 mol % of Ti(OiPr)4 was added to the reaction mixture to
reduce the trends of the isomerization by modulating the
t
concentration of BuO-. We are pleased to find that the molar
(11) For reviews on phosphine-mediated annulation reaction, please see: (a)
Ye, L.-W.; Zhou, J.; Tang, Y. Chem. Soc. ReV. 2008, 37, 1140. (b) Denmark,
S. E.; Beutner, G. L. Angew. Chem., Int. Ed. 2008, 47, 1560. (c) Nair, V.; Menon,
R. S.; Sreekanth, A. R.; Abhilash, N.; Biji, A. T. Acc. Chem. Res. 2006, 39,
520. (d) Lu, X.; Du, Y.; Lu, C. Pure Appl. Chem. 2005, 77, 1985. (e) Methot,
J. L.; Roush, W. R. AdV. Synth. Catal. 2004, 346, 1035. (f) Lu, X.; Zhang, C.;
Xu, Z. Acc. Chem. Res. 2001, 34, 535.
ratio of produced 2a and 2a′ was improved from 19/81 to 91/9
in the presence of 20 mol % of Ti(OiPr)4 (entry 1 vs. entry 2,
Table 2). The ratio was further improved to 98/2 when the
tributylphosphine loading decreased from 20 mol % to 10 mol
% (entry 3, Table 2). All of these results indicated clearly
J. Org. Chem. Vol. 74, No. 9, 2009 3395

Han et al.
TABLE 2. Effects of Additive and Catalyst on the Annulationa
SCHEME 4. Synthesis of Substrates 3a-f and 3ha
entry
catalyst (mol %)
additive (mol %)
yield (%)b
2a/2a′c
1
2
3
4
PBu3 (20)
PBu3 (20)
PBu3 (10)
PPh3 (20)
99
99
95
95
19/81
91/9
98/2
95/5
Ti(iOPr) (20)
Ti(iOPr) (20)
a Conditions: 3a (110 mg, 0.25 mmol) in toluene (2.5 mL), rt,
c
a Reagents and conditions: (a) BrCH2CHdC(R3)CO2R1, NaH, DMF, rt,
56-88%. (b) CH2dCHCOR2, DABCO or quinuclidine, rt, 29-71%. (c)
(Boc)2O, DMAP, CH2Cl2rt, 45-70%.
0.25-32 h. b Isolated yield. Determined by H NMR.
1
product 2a′, is formed through both paths A and B as shown in
Scheme 3 and path B is dominant.
The tert-butyl carbonate 3g was synthesized by cross-
metathesis between 2-but-3-enylbenzaldehyde and acrylic acid
methyl ester by using 2.5 mol % of the second-generation
Grubbs catalyst,17 followed by similar Baylis-Hillman reac-
tion18 and esterification as described in Scheme 5.
As shown in Table 3, under the optimal conditions, products
2a-g were obtained as major ones with excellent selectivities.
The substituents, such as Cl, Br, and OMe, on the benzene ring
had slight effects on the yields (entries 1-7, Table 3). All of
the substrates examined gave high to excellent yields. Notice-
ably, the diastereoselectivity of the current reaction is excellent
and only one diastereomer was observed in all cases described
in Table 3.
By using 20 mol % of PPh3 as the catalyst, benzobicy-
clo[4.3.0] compounds 2a-g could also be synthesized as major
products with excellent diastereoselectivities in good to excellent
yields, as shown in Table 4. The substituents on the benzene
ring had also a slight effect on the yields (entries 1-7, Table
4). In addition, the reaction could also be performed well when
10 mol % of PPh3 was used as catalyst (entry 1, Table 4). Thus,
the present reaction provided a facile and an efficient method
for the synthesis of functionalized benzobicyclo[4.3.0] com-
pounds in a high-yielding and stereocontrolled manner.
In addition, by using 20 mol % of tributylphosphine as
catalyst, R-methyl R,ꢀ-unsaturated ester tert-butyl carbonate
substrate 3h could also furnish the corresponding benzobicy-
clo[4.3.0] compound 2h with a quaternary carbon as the product
(eq 3). It is worth noting that, under this neutral and room
temperature condition, the reaction yield was greatly improved
compared with that of the bromide substrate in our previous
report (99% vs. 78%).10b
On the basis of above mechanistic discussions, it is envisioned
that the isomerization could also be blocked by employing
weakly nucleophilic arylphosphine as catalyst to reduce the
t
generation rates of BuO-. As we have speculated, using 20
13
mol % of PPh3 as catalyst and without the addition of
Ti(OiPr)4, the annulation also proceeded well to give benzobi-
cyclo[4.3.0] compounds 2a and 2a′ with a ratio of 95/5 under
similar reaction conditions (entry 4, Table 2).
Reaction Scope. The generality of this intramolecular an-
nualtion reaction was studied by investigating a variety of R,ꢀ-
unsaturated carbonyl compounds. Substrates 3a-f and 3h are
readily accessible from the corresponding salicylaldehydes, as
shown in Scheme 4. γ-Bromocrotonate reacted with the sali-
cylaldehydes,14 followed by the Baylis-Hillman reaction15 and
esterification with di-tert-butyl dicarbonate,16 affording the
corresponding cyclization precursors tert-butyl carbonate 3a-f
and 3h.
(12) For recent examples on phosphine-mediated annulation reaction, please
see: (a) Zheng, S.; Lu, X. Org. Lett. 2008, 10, 4481. (b) Creech, G. S.; Kwon,
O. Org. Lett. 2008, 10, 429. (c) Tran, Y. S.; Kwon, O. J. Am. Chem. Soc. 2007,
129, 12632. (d) Castellano, S.; Fiji, H. D. G.; Kinderman, S. S.; Watanabe, M.;
de Leon, P.; Tamanoi, F.; Kwon, O. J. Am. Chem. Soc. 2007, 129, 5843. (e)
Xia, Y.; Liang, Y.; Chen, Y.; Wang, M.; Jiao, L.; Huang, F.; Liu, S.; Li, Y.;
Yu, Z.-X. J. Am. Chem. Soc. 2007, 129, 3470. (f) Gabillet, S.; Lecercle´, D.;
Loreau, O.; Carboni, M.; De´zard, S.; Gomis, J.-M.; Taran, F. Org. Lett. 2007,
9, 3925. (g) Henry, C. E.; Kwon, O. Org. Lett. 2007, 9, 3069. (h) McDougal,
N. T.; Schaus, S. E. Angew. Chem., Int. Ed. 2006, 45, 3117. (i) Dudding, T.;
Kwon, O.; Mercier, E. Org. Lett. 2006, 8, 3643. (j) Krafft, M. E.; Wright, J. A.
Chem. Commun. 2006, 2977. (k) Thalji, R. K.; Roush, W. R. J. Am. Chem. Soc.
2005, 127, 16778. (l) Krafft, M. E.; Haxell, T. F. N. J. Am. Chem. Soc. 2005,
127, 10168. (m) Krafft, M. E.; Seibert, K. A.; Haxell, T. F. N.; Hirosawa, C.
Chem. Commun. 2005, 5772. (n) Tran, Y. S.; Kwon, O. Org. Lett. 2005, 7,
4289. (o) Zhu, X.-F.; Schaffner, A.-P.; Li, R. C.; Kwon, O. Org. Lett. 2005, 7,
2977. (p) Zhu, X.-F.; Henry, C. E.; Wang, J.; Dudding, T.; Kwon, O. Org. Lett.
2005, 7, 1387. (q) Jung, C.-K.; Wang, J.-C.; Krische, M. J. J. Am. Chem. Soc.
2004, 126, 4118.
Conclusions
In summary, we have developed a phosphine-catalyzed
intramolecular ylide annulation under neutral conditions at room
temperature. The isomerization mechanism of product 2 under
the reaction conditions is studied. On the basis of this mecha-
nism, we established two strategies for the efficient construction
of benzobicyclo[4.3.0] compounds 2. In addition, we also
reported a phosphine-catalyzed ylide annulation for the facile
(13) For details about the phosphines we tested, please see the Supporting
Information.
(14) (a) Aurrecoechea, J. M.; Lo´pez, B.; Ferna´ndez, A.; Arrieta, A.; Coss´ıo,
F. P. J. Org. Chem. 1997, 62, 1125. (b) Mori, K.; Tanaka, T. I.; Honda, H.;
Yamamoto, I. Tetrahedron 1983, 39, 2303.
(15) Roush, W. R.; Brown1, B. B. J. Org. Chem. 1993, 58, 2151.
(16) Erent, D.; Keinan, E. J. Am. Chem. Soc. 1988, 110, 4356.
3396 J. Org. Chem. Vol. 74, No. 9, 2009

Synthesis of Benzobicyclo[4.3.0] Compounds
SCHEME 5. Synthesis of Substrate 3g
TABLE 3. Tributylphosphine-Catalyzed Highly Diastereoselective
Synthesis of Benzobicyclo[4.3.0] Compounds 2a
mg, 0.050 mmol) and tributylphosphine (5.1 mg, 0.025 mmol) at
room temperature. The resulting mixture was further stirred for 1 h.
After the reaction was complete, the mixture was filtered rapidly
through a funnel with a thin layer of silica gel and eluted with
ethyl acetate (50 mL). Next 20% aqueous H2O2 (0.3 mL) solution
was added and the resultant mixture was stirred for another 2 h at
room temperature, then saturated Na2SO3 (0.5 mL) was added. After
the resulting mixture was stirred for 1 h, the residue was dried over
Na2SO4, filtered, and concentrated. The crude product was purified
by flash chromatography on silica gel to afford the desired products
entry
3
R
R1
R2
X
2 (2/2′)b
yield (%)c
1
2
3
4
5
6
7
3a
3b
3c
3d
3e
3f
4-Cl
4-Cl
4-Br
H
2-OMe
4-Br
H
Me
Et
OMe
OEt
OMe
OMe
OMe
Me
O
O
O
O
O
O
C
2a (>97/3)
2b (>97/3)
2c (>97/3)
2d (>95/5)
2e (93/7)
2f (>98/2)
2g (>97/3)
99
99
99
94
75
95
93
Me
Me
Me
Me
Me
1
2a as white solid. Mp 82-83 °C; yield 80 mg (99%); H NMR
(300 MHz, CDCl3, TMS) δ 7.56 (d, J ) 2.1 Hz, 1H), 7.05 (dd, J
) 8.7 and 2.4 Hz, 1H), 6.80-6.77 (m, 2H), 4.40-4.31 (m, 2H),
4.05-3.97 (m, 2H), 3.81 (s, 3H), 3.78 (s, 3H), 3.23-3.16 (m, 1H);
13C NMR (75 MHz, CDCl3) δ 172.3, 164.8, 153.6, 141.2, 139.8,
129.7, 127.7, 126.4, 125.3, 119.1, 66.2, 52.4, 52.0, 50.6, 43.4, 42.2.
IR V/cm-1 2982 (m), 2935 (m), 1734 (s), 1714 (s), 1628 (m), 1485
(m), 1242 (m), 821 (m), 735 (m), 639 (m); MS (ESI, positive mode,
m/z) 377 (M + MeOH + Na+), 345 (M + Na+); HRMS (EI) calcd
for C16H15O5Cl (M+) 322.0608, found 322.0607.
3g
OMe
a Reagents and conditions: PBu3 (5.1 mg, 10 mol %), Ti(OiPr)4 (14.2
mg, 20 mol %), 3 (0.25 mmol) in toluene (2.5 mL), rt, 1-2.5 h.
b
Determined by 300 MHz H NMR. c Isolated yield for 2 + 2′.
1
TABLE 4. Triphenylphosphine-Catalyzed Highly
Diastereoselective Synthesis of Benzobicyclo[4.3.0] Compounds 2a
Representative Procedure for the PPh3-Catalyzed Synthesis of
Benzobicyclo[4.3.0] Compounds 2: Preparation of 8-Chloro-
3,3a,4,9b-tetrahydrocyclopenta[c]chromene-1,3-dicarboxylic Acid
Dimethyl Ester 2a. To a solution of substrate 3a (110 mg, 0.25
mmol) in toluene (2.5 mL) was added triphenylphosphine (13.1
mg, 0.050 mmol). The resulting mixture was stirred at room
temperature for 32 h. After the reaction was complete, the mixture
was filtered rapidly through a funnel with a thin layer of silica gel
and eluted with ethyl acetate. The filtrate was concentrated and
the residue was purified by chromatography on silica gel to afford
the desired product 2a in 95% yield (76.3 mg).
Preparation of 8-Chloro-3-methyl-3,3a,4,9b-tetrahydrocyclo-
penta[c]chromene-1,3-dicarboxylic Acid Diethyl Ester 2h..10b To
a solution of substrate 3h (121 mg, 0.25 mmol) in toluene (2.5
mL) was added tributylphosphine (10.1 mg, 0.050 mmol). The
resulting mixture was stirred at room temperature for 2 h. After
the reaction was complete, the mixture was filtered rapidly through
a funnel with a thin layer of silica gel and eluted with ethyl acetate.
The filtrate was concentrated and the residue was purified by
chromatography on silica gel to afford 90.5 mg (99%) of the desired
product 2h. 1H NMR (300 MHz, CDCl3, TMS) δ 7.62 (d, J ) 2.1
Hz, 1H), 7.03 (dd, J ) 9.0 and 2.4 Hz, 1H), 6.74 (t, J ) 8.7 Hz,
2H), 4.46-4.14 (m, 7H), 3.08 (dt, J ) 8.4 and 3.0 Hz, 1H), 1.41
(s, 3H), 1.36 (t, J ) 7.2 Hz, 3H), 1.29 (t, J ) 7.2 Hz, 3H).
entry
3
R
R1
R2
X
2 (2/2′)b
yield (%)c
1
2
3
4
5
6
7
3a
3b
3c
3d
3e
3f
4-Cl
4-Cl
4-Br
H
2-OMe
4-Br
H
Me
Et
OMe
OEt
OMe
OMe
OMe
Me
O
O
O
O
O
O
C
2a (>95/5)
2b (>95/5)
2c (>95/5)
2d (94/6)
2e (93/7)
2f (>96/4)
2g (93/7)
95 (90)d
99
99
86
82
Me
Me
Me
Me
Me
93
78
3g
OMe
a Reagents and conditions: PPh3 (13.1 mg, 20 mol %), 3 (0.25 mmol)
b
1
in toluene (2.5 mL), rt, 32-120 h. Determined by 300 MHz H NMR.
c Isolated yield for 2 + 2′. d 10 mol % of PPh3 was used.
preparation of benzobicyclo[4.3.0] compound with one quater-
nary carbon center in excellent yield. The simple procedure,
mild conditions, high diastereoselectivity, excellent yields, and
metal-free catalyzed processes make this method potentially
useful in organic synthesis. Further investigations into the
synthetic application of the current reaction and the development
of its asymmetric version are in progress in our laboratory.
Acknowledgement. We are grateful for the financial support
from the Natural Sciences Foundation of China (Nos. 20821002
and 20672131), the Major State Basic Research Development
Program (Grant No. 2006CB806105), the Chinese Academy of
Sciences, and the Science and Technology Commission of
Shanghai Municipality.
Experimental Section
Representative Procedure for the Tributylphosphine-Catalyzed
Synthesis of Benzobicyclo[4.3.0] Compounds 2: Preparation of
8-Chloro-3,3a,4,9b-tetrahydrocyclopenta[c]chromene-1,3-dicar-
boxylic Acid Dimethyl Ester 2a. To a solution of substrate 3a (110
mg, 0.25 mmol) in toluene (2.5 mL) was added Ti(OiPr)4 (14.2
Supporting Information Available: General synthetic pro-
cedures and characterization and spectral data for key com-
pounds. This material is available free of charge via the Internet
at http://pubs.acs.org.
(17) (a) Chatterjee, A. K.; Choi, T.-L.; Sanders, D. P.; Grubbs, R. H. J. Am.
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Grubbs, R. H. J. Am. Chem. Soc. 2000, 122, 3783.
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JO9001917
J. Org. Chem. Vol. 74, No. 9, 2009 3397