Asymmetric [3 + 2] cycloaddition of 2,3-butadienoates with electron-deficient olefins catalyzed by novel chiral 2,5-dialkyl-7-phenyl-7-phosphabicyclo[2.2.1]heptanes

Full text of DOI:10.1021/ja9644687

3836
J. Am. Chem. Soc. 1997, 119, 3836-3837
Asymmetric [3 + 2] Cycloaddition of
2,3-Butadienoates with Electron-Deficient Olefins
Catalyzed by Novel Chiral 2,5-Dialkyl-7-phenyl-7-
phosphabicyclo[2.2.1]heptanes
Guoxin Zhu, Zhaogen Chen, Qiongzhong Jiang,
Dengming Xiao, Ping Cao, and Xumu Zhang*
Figure 1.
Department of Chemistry, 152 DaVey Laboratory
The PennsylVania State UniVersity
UniVersity Park, PennsylVania 16802
ReceiVed December 31, 1996
The efficient synthesis of highly functionalized cyclopentane
rings remains an important challenge in organic chemistry.1
Among the reported methods, [3 + 2] cycloaddition has the
advantage of forming multiple bonds although issues of chemo-,
regio-, diastereo-, and enantioselectivity must be resolved if the
process is to achieve useful generality. Transition metal-
catalyzed,2 anionic,3 cationic,4 and free radical mediated5 [3 +
2] cycloadditions have been investigated. Recently, an impor-
tant finding by Lu’s group shows that phosphines can catalyze
a [3 + 2] annulation reaction.6 This novel [3 + 2] approach
involves cycloaddition of electron-deficient olefins with simple
2,3-butadienoates as the three-carbon source. Inspired by this
elegant work, herein we report the first asymmetric version of
this reaction with new chiral monophosphines, 2,5-dialkyl-7-
phenyl-7-phosphabicyclo[2.2.1]heptanes, as catalysts.
Figure 2. Synthesis of chiral monophosphines.
Several chiral monophosphines have been reported in the
literature.7 Most applications of these phosphines were in
formation of asymmetric catalysts with transition metals.7 Some
chiral phosphines have also been used directly as catalysts for
asymmetric reactions.8 Our new chiral phosphines contain a
rigid phosphabicyclic structure (Figure 2). The rigid, fused
bicyclic [2.2.1] structure eliminates the conformational flexibility
associated with the five-membered rings in other chiral phos-
phines (e.g., Duphos and BPE ligands9) and represents a new
motif for chiral ligand design.
The syntheses of chiral monophosphines 7 and 8 are shown
in Figure 2. Halterman10 and Vollhardt11 have previously
prepared chiral cyclopentadiene derivatives from the chiral diols.
Halterman10 has synthesized chiral diols 1 and 2 via Birch
reduction12 followed by asymmetric hydroboration.13 Conver-
sion of the optically pure diols to the corresponding mesylates
proceeded cleanly. Nucleophilic addition of Li2PPh to the chiral
dimesylates 3 and 4 generated the corresponding bicyclic
phosphines, which were trapped by BH3‚THF to form the air-
Figure 3.
stable boron-protected monophosphines 5 and 6, respectively.
Deprotection with a strong acid14 produced the desired products
(7, (1R,2S,4R,5S)-(+)-2,5-dimethyl-7-phenyl-7-phosphabicyclo-
[2.2.1]heptane; 8, (1R,2R,4R,5R)-(+)-2,5-diisopropyl-7-phenyl-
7-phosphabicyclo[2.2.1]heptane) in high yields.
We performed the asymmetric [3 + 2] annulation reaction15
with several known chiral phosphines as catalysts in addition
to 7 and 8 (Figure 3). Table 1 lists the results under different
sets of conditions and with various substrates. Some general
characteristics6 of this reaction include the following: (1) two
regioisomers A and B are formed, but isomer A generally is
preferred (Figure 1); (2) the geometry of the starting electron-
deficient olefins remains unchanged in the cycloaddition reac-
tion.
We screened the asymmetric reaction with the chiral phos-
phines by mixing ethyl 2,3-butadienoate and ethyl acrylate in
benzene with 10 mol % of phosphine at room temperature
(entries 1-5). New phosphines 7-8 are more effective in terms
of both regioselectivity (A:B) and enantioselectivity (% ee of
A) than known phosphines 9-11. The absolute configuration
of product A (entries 1-5) was assigned by correlation with
(1R,3R)-dihydroxymethyl-3-cyclopentane.16 In particular, the
enantioselectivity is much higher with 7 (81% ee, R, entry 1)
than with 10 (6% ee, S, entry 4), which illustrates the
consequences of using a rigid bicyclic [2.2.1] structure rather
than the conformationally more flexible five-membered ring.
Changing the size of the ester group in the electron-deficient
olefin alters the enantioselectivity. With phosphine 7, the
enantioselectivity increases as the size of the ester increases
(1) For a review, see: Hudlicky, T.; Price, J. D. Chem. ReV. 1989, 89,
1467.
(2) For reviews, see: (a) Trost, B. M. Angew. Chem., Int. Ed. Engl. 1986,
25, 1. (b) Lautens, M.; Klute, W.; Tam, W. Chem. ReV. 1996, 96, 49 and
references cited therein.
(3) Beak, P.; Burg, D. A. J. Org. Chem. 1989, 54, 647 and references
cited therein.
(4) Danheiser, R. L.; Carini, D. J.; Fink, D. M.; Basak, A. Tetrahedron
1983, 39, 935.
(5) Feldman, K. S.; Romanelli, A. L.; Ruckle, R. E., Jr.; Miller, F. M. J.
Am. Chem. Soc. 1988, 110, 3300.
(6) Zhang, C.; Lu, X. J. Org. Chem. 1995, 60, 2906.
(7) Hamada, Y.; Seto, N.; Ohmori, H.; Hatano, K. Tetrahedron Lett. 1996,
37, 7565 and references cited therein.
(8) Vedejs, E.; Dangulis, O.; Diver, S. T. J. Org. Chem. 1996, 61, 430.
(9) (a) Burk, M. J. J. Am. Chem. Soc. 1991, 113, 8518. (b) Burk, M. J.;
Feaster, J. E.; Nugent, W. A.; Harlow, R. L. J. Am. Chem. Soc. 1993, 115,
10125.
(10) (a) Chen, Z.; Eriks, K.; Halterman, R. L. Organometallics 1991,
10, 3449. (b) Halterman, R. L.; Chen, Z.; Khan, M. Organometallics 1996,
15, 3957.
(11) Halterman, R. L.; Vollhardt, K. P. C.; Welker, M. E.; Blaser, D.;
Boese, R. J. Am. Chem. Soc. 1987, 109, 8105.
(12) Kwart, H.; Conley, R. A. J. Org. Chem. 1973, 38, 2011.
(13) Brown, H. C.; Jadhav, P. K.; Mandal, A. K. J. Org. Chem. 1982,
47, 5074.
i
t
(entry 1, Et, 81% ee; entry 6, Bu, 86% ee; entry 7, Bu, 89%
(14) McKinstry, L.; Livinghouse, T. Tetrahedron 1995, 51, 7655.
(15) For an example of asymmetric [3 + 2] cycloaddition, see:
Yamamoto, A.; Ito, Y.; Hayashi, T. Tetrahedron Lett. 1989, 30, 375.
(16) (a) Richter, W. J.; Richter, B. Isr. J. Chem. 1976, 15, 57. (b) Birch,
S. F.; Dean, R. A. J. Chem. Soc. 1953, 2477. The detailed procedure is
reported in the Supporting Information.
S0002-7863(96)04468-X CCC: $14.00 © 1997 American Chemical Society

Communications to the Editor
J. Am. Chem. Soc., Vol. 119, No. 16, 1997 3837
Table 1. Phosphine-Catalyzed Asymmetric [3 + 2] Cycloadditiona
entry
phosphine
E
R1
R2
R3
solvent
T (°C)e
yield (%)
A:Bb
% ee of Ab
configc
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15d
16d
7
8
9
10
11
7
7
7
8
8
8
8
7
8
8
8
COOEt
COOEt
COOEt
COOEt
COOEt
COOiBu
COOtBu
COOtBu
COOMe
COOiBu
COOiBu
COOtBu
COOEt
COOEt
COOEt
COOMe
Et
Et
Et
Et
Et
Et
Et
Et
Et
Et
Et
Et
tBu
tBu
Et
Et
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
benzene
benzene
benzene
benzene
benzene
benzene
benzene
toluene
benzene
benzene
toluene
benzene
benzene
benzene
toluene
benzene
rt
rt
rt
rt
rt
rt
rt
0
rt
rt
0
rt
rt
rt
0
66
76
80
83
33
46
69
42
87
92
88
75
13
84
49
84
95:5
97:3
80:20
72:29
73:27
100:0
95:5
97:3
96:4
100:0
100:0
95:5
81
81
56
6
(-) R
(-) R
(+) S
(+) S
(-) R
(-) R
(-) R
(-) R
(-) R
(-) R
(-) R
(-) R
(-) R
(-) R
(+)
12
86
89
93
79
88
93
88
89
69
79
36
97:3
94:6
COOEt
H
COOMe
rt
(-)
a The reaction was carried out under N2 with a chiral phosphine (10 mol %), 2,3-butadienoate (100 mol %), and electron deficient olefins (1000
mol %). b A:B and % ee were measured by GC with â and γ-DEX columns. c The absolute configuration was determined by comparing the optical
rotation with the literature value.16 d Olefins (200 mol %) were used. e rt ) room temperature.
Scheme 1
Figure 4.
A detailed mechanism of this reaction has not been rigorously
proven. Scheme 1 shows Lu’s proposed mechanism.6
A
catalytic amount of the phosphine acts as a nucleophilic trigger.18
Formation of cyclic intermediates 14A and 14B is the key step
for asymmetric induction. The stereochemistry of the starting
E and Z olefins is preserved in the products, which provides
suggestive evidence that this reaction proceeds through a
concerted mechanism.19 Based on this model, we offer a
mechanistic rationale for the high asymmetric induction with 7
and 8 (Figure 4). The R groups from 7 and 8 can effectively
block the “bottom” face of the allylic carbanion 12/13, and this
shielding forces the electron-deficient olefins to approach from
the “top” face. The electron-withdrawing olefins approach with
the endo orientation as shown in Figure 4. The Z olefins (e.g.,
diethyl maleate) show a similar degree of selectivity as do the
acrylates, while E olefins (e.g., dimethyl fumarate) introduce
large groups around the sterically crowded C1 center. It is
possible that the lower enantioselectivity obtained with E olefins
is due to this disfavored interaction between COOEt and
substituents of E olefins.
ee). A similar trend was observed with phosphine 8 (entries 2,
9-10, and 12). Upon cooling the reaction to 0 °C in toluene,
up to 93% ee of A was obtained with phosphines 7 and 8 with
excellent regioselectivity (entries 8 and 11). Increasing the size
of the ester moiety in the 2,3-butadienoates, however, has
different effects on the product ee with phosphine 7 (entry 1,
t
Et, 81% ee; entry 13, Bu, 89% ee) or 8 (entry 2, Et, 81% ee;
t
entry 14, Bu, 69% ee). A second major difference between
catalysis by 7 or 8 is in the yield of products. The conversion
to the desired products is generally higher with 8 than with 7
(e.g., entries 6-8 vs entries 9-12). With diethyl maleate (entry
15) and dimethyl fumarate (entry 16) as substrates, single cis
and trans products were obtained with 8, respectively. While
the % ee of the cis product (entry 15, 79% ee) is slightly lower
than the result with ethyl acrylate (entry 2, 81% ee), the trans
product has much lower optical purity (entry 16, 36% ee). For
two-atom species17 other than acrylates, we have studied
acrylonitrile and methyl vinyl ketone as substrates. With ethyl
2,3-butadienoate as the three-atom species and 7 as the catalyst,
48% ee of A, A/B (97/3) and 94% yield were obtained with
acrylonitrile while 27% ee of A, A/B (81/19) and 33% yield
were achieved with methyl vinyl ketone.
In conclusion, we have developed a new family of chiral
phosphines with a unique fused bicyclic [2.2.1] ring structure.
A [3 + 2] cycloaddition between 2,3-butadienoates and electron-
deficient olefins catalyzed by these chiral monophosphines gives
cyclopentene products with excellent regioselectivity and enan-
tioselectivity. This method is a potentially powerful tool for
the synthesis of chiral cyclopentanoids.
Acknowledgment. This work was supported by a Camille and
Henry Dreyfus New Faculty Award, an ONR young investigator award,
a DuPont Young Faculty Award, Amoco, and Hoechst Celanese
Corporation. This work is dedicated to Professor Xiyan Lu for his
encouragement throughout the project. We thank Supelco for the gift
of a γ-DEX 225 GC column and Professor Ray Funk for helpful
suggestions.
(17) Substrates such as â-substituted enones do not work because 2,3-
butadienoates are better acceptors and dimerization of 2,3-butadienoates
occurs (see ref 6).
(18) Trost, B. M.; Li, C.-J. J. Am. Chem. Soc. 1994, 116, 3167 and
references cited therein.
(19) A stepwise mechanism was suggested for a related [3 + 2]
cyclization reaction: Padwa, A.; Yeske, P. E. J. Am. Chem. Soc. 1988,
110, 1617.
Supporting Information Available: Spectroscopic data for com-
pounds 5-8 and experimental details (7 pages). See any current
masthead page for ordering and Internet access instructions.
JA9644687