Enantioselective diene cyclization/hydrosilylation catalyzed by optically active palladium bisoxazoline and pyridineoxazoline complexes

Article abstract of DOI:10.1021/jo0003192

A 1:1 mixture of (N-N)Pd(Me)Cl [N-N = (S,S)-4,4'-dibenzyl-4,5,4',5'- tetrahydro-2,2'-bisoxazoline] (S,S-4a) and NaBAr₄ [Ar = 3,5-C₆H₃(CF₃)₂] (5 mol %) catalyzed the asymmetric cyclization/hydrosilylation of dimethyl diallylmalonate (2) and triethylsilane at -30 °C for 48 h to form an 8.1:1 mixture of the silylated carbocycle (S,S)-trans-1,1-dicarbomethoxy-4-methyl- 3-[(triethylsilyl)methyl]cyclopentane (S,S-3) (95% de, 72% ee) and dimethyl 3,4-dimethylcyclopentane-1,1-dicarboxylate (S,S-6) in 64% combined yield. In comparison, a 1:1 mixture of the palladium pyridineoxazoline complex (N- N)Pd(Me)Cl [N-N = (R)-(+)-4-isopropyl-2-(2-pyridinyl)-2-oxazoline] (R-5b) and NaBAr₄ (5 mol %) catalyzed the asymmetric cyclization/hydrosilylation of 2 and triethylsilane at -32 °C for 24 h to form carbocycle S,S-3 in 82% yield (>95% de, 87% ee) as the exclusive product. Asymmetric diene cyclization catalyzed by complex R-5b was compatible with a range of functional groups and produced carbocycles with up to 91% ee. The procedure also tolerated substitution at a terminal olefinic position and at the allylic position of the diene.

Full text of DOI:10.1021/jo0003192

3836
J . Org. Chem. 2000, 65, 3836-3845
En a n tioselective Dien e Cycliza tion /Hyd r osilyla tion Ca ta lyzed by
Op tica lly Active P a lla d iu m Bisoxa zolin e a n d P yr id in e-Oxa zolin e
Com p lexes
Nicholas S. Perch, Tao Pei, and Ross A. Widenhoefer*
Duke University, P. M. Gross Chemical Laboratory, Durham, North Carolina 27708-0346
Received March 22, 2000
A 1:1 mixture of (N-N)Pd(Me)Cl [N-N ) (S,S)-4,4′-dibenzyl-4,5,4′,5′-tetrahydro-2,2′-bisoxazoline]
(S,S-4a ) and NaBAr4 [Ar ) 3,5-C6H3(CF3)2] (5 mol %) catalyzed the asymmetric cyclization/
hydrosilylation of dimethyl diallylmalonate (2) and triethylsilane at -30 °C for 48 h to form an
8.1:1 mixture of the silylated carbocycle (S,S)-trans-1,1-dicarbomethoxy-4-methyl-3-[(triethylsilyl)-
methyl]cyclopentane (S,S-3) (95% de, 72% ee) and dimethyl 3,4-dimethylcyclopentane-1,1-dicar-
boxylate (S,S-6) in 64% combined yield. In comparison, a 1:1 mixture of the palladium pyridine-
oxazoline complex (N-N)Pd(Me)Cl [N-N ) (R)-(+)-4-isopropyl-2-(2-pyridinyl)-2-oxazoline] (R-5b)
and NaBAr4 (5 mol %) catalyzed the asymmetric cyclization/hydrosilylation of 2 and triethylsilane
at -32 °C for 24 h to form carbocycle S,S-3 in 82% yield (>95% de, 87% ee) as the exclusive product.
Asymmetric diene cyclization catalyzed by complex R-5b was compatible with a range of functional
groups and produced carbocycles with up to 91% ee. The procedure also tolerated substitution at
a terminal olefinic position and at the allylic position of the diene.
In tr od u ction
ee and 95% ee has been achieved in the nickel-catalyzed
cross-coupling of aryl bromides and Grignard reagents.11
The application of asymmetric C-C bond formation to
the synthesis of cyclic compounds is of particular impor-
tance due to the prevalence of carbocycles in biologically
active and naturally occurring molecules.12 However,
examples of highly enantioselective transition metal-
catalyzed annulation procedures remain limited. A no-
table example is the palladium-catalyzed asymmetric
intramolecular Heck reaction which has been applied
extensively to the synthesis of complex functionalized
carbocycles.13 In addition, rhodium14 and cobalt15 bispho-
sphine complexes catalyze the asymmetric [4 + 2] cy-
cloisomerization of unactivated dienynes and trienes with
excellent selectivity (98% ee). Cationic Rh(I) bisphosphine
complexes catalyze the asymmetric intramolecular hy-
droacylation of 4-pentenals with 90-99% ee.16 Tita-
nium(II) metallocene complexes and palladium phosphine
complexes catalyze the asymmetric cyclocarbonylation17
and cycloisomerization,18 respectively, of 1,6-enynes with
75-95% ee. Rhodium-catalyzed asymmetric intramolecu-
lar cyclopropanation19 and C-H insertion20 of diazoac-
etates also generate carbocycles with high enantioselec-
tivity.
Asymmetric C-C bond formation remains of central
importance in organic synthesis due to the pronounced
tendency of naturally occurring compounds to display
optical activity and due to the increasingly stringent
requirements concerning the optical purity of pharma-
ceuticals. A particularly appealing and successful ap-
proach toward asymmetric C-C bond formation is via
catalysis employing optically active transition metal
complexes.1,2 For example, copper3-5 and rhodium6 com-
plexes catalyze the cyclopropanation of olefins with high
(98%) enantioselectivity. Optically active palladium com-
plexes catalyze the asymmetric nucleophilic displacement
of allylic acetates7 and the asymmetric coupling of aryl
triflates and cyclic enol ethers8 with good enantioselec-
tivity. Platinum9 and rhodium10 phosphine complexes
catalyze the hydroformylation of olefins with up to 98%
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10.1021/jo0003192 CCC: $19.00 © 2000 American Chemical Society
Published on Web 05/20/2000

Enantioselective Diene Cyclization/Hydrosilylation
J . Org. Chem., Vol. 65, No. 12, 2000 3837
Sch em e 1
Cyclization/hydrosilylation is emerging as a potential
route toward the synthesis of functionalized carbocycles.
For example, nickel21 and rhodium22 complexes catalyze
the cyclization/hydrosilylation of 1,7-diynes and 1,6-
enynes, respectively. Similarly, lanthanide metallocene
complexes catalyze the cyclization/hydrosilylation of both
dienes and enynes.23 We have recently reported the
cyclization/hydrosilylation of functionalized 1,6- and 1,7-
dienes catalyzed by cationic palladium complexes such
-
as (phen)PdMe(OEt2)+ BAr4 [phen ) 1,10-phenanthro-
line; Ar ) 3,5-C6H3(CF3)2] (1).24-27 For example, reaction
of dimethyl diallylmalonate (2) and triethylsilane cata-
lyzed by 1 at 0 °C for 5 min led to the isolation of the
trans-silylated cyclopentane 3 in 93% yield (98% trans)
(Scheme 1).24
In contrast to the effective cyclization/hydrosilylation
procedures described above, asymmetric cyclization/hy-
drosilylation has not been reported. However, the high
activity and exceptional diastereoselectivity realized in
palladium-catalyzed diene cyclization/hydrosilylation
pointed to the potential of palladium-catalyzed asym-
metric cyclization/hydrosilylation. Here we provide a
detailed report on the employment of optically active
palladium bisoxazoline and pyridine-oxazoline com-
plexes as catalysts for the asymmetric cyclization/hy-
drosilylation of functionalized dienes.28
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Resu lts a n d Discu ssion
Syn th esis of P a lla d iu m P r eca ta lysts. In our previ-
ous studies, in situ generation of cationic complex 1 via
halide abstraction from (phen)Pd(Me)Cl with NaBAr4 [Ar
) 3,5-C6H3(CF3)2] was found superior to the generation
of 1 via protonation of (phen)PdMe2 with HBAr4.25
Therefore, optically active palladium methyl chloride
complexes were employed as precatalysts in this study.
The requisite palladium bisoxazoline complexes 4a -d
(Table 1, entries 1-4) and palladium pyridine-oxazoline
complexes 5a -l (Table 1, entries 5-16) were prepared
by reaction of the appropriate ligand with (COD)Pd(Me)-
Cl in CH2Cl2 at room temperature. Evaporation of solvent
and trituration with ether gave the desired complexes
as off-white or pale yellow solids which were character-
ized by spectroscopy and elemental analysis except R-5d
and S-5i, which could not be isolated free from ligand
and were characterized by spectroscopy (Table 1, entries
1
8 and 13). H NMR spectroscopy of pyridine-oxazoline
complexes 5 revealed the presence of a single stereoiso-
mer in solution. Difference NOE spectroscopy of the
isopropyl-substituted complex (N-N)Pd(Me)Cl [N-N )
(R)-4-i-Pr-2-(2-pyridinyl)-2-oxazoline) (R-5b) established
the cis relationship between the oxazoline ring and the
palladium methyl group.
I. Cycliza tion /Hyd r osilyla tion Ca ta lyzed by P a l-
la d iu m Bisoxa zolin e Com p lexes. We initially targeted
optically active palladium bisoxazoline complexes 4 as
catalysts for asymmetric diene cyclization/hydrosilylation
due to their availability4,29 and due to the wealth of
asymmetric transformations which utilize these ligands.
For example, copper bisoxazoline complexes catalyze the
asymmetric cyclopropanation of olefins3,4 and the asym-
(21) Tamao, K.; Kobayashi, K.; Ito, Y. J . Am. Chem. Soc. 1989, 111,
6478.
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1994, 35, 8177. (c) Molander, G. A.; Nichols, P. J .; Noll, B. C. J . Org.
Chem. 1998, 63, 2292. (d) Molander, G. A.; Dowdy, E. D.; Schumann,
H. J . Org. Chem. 1998, 63, 3386.
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R. A. J . Am. Chem. Soc. 1999, 121, 6960.
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Org. Chem. 1997, 62, 3375.

3838 J . Org. Chem., Vol. 65, No. 12, 2000
Perch et al.
Ta ble 1. Syn th esis of P a lla d iu m Bisoxa zolin e a n d
Ta ble 2. Asym m etr ic Cycliza tion /Hyd r osilyla tion of 2
Em p loyin g P a lla d iu m Bisoxa zolin e a n d
P yr id in e-Oxa zolin e P r eca ta lysts 4 (5 m ol %) a n d HSiEt3
in CH2Cl2
P yr id in e-Oxa zolin e P r eca ta lysts
temp time
yield
de 3
ee 3
entry precat
(°C)
(h)
3:6a 3 + 6 (%) (%)a
(%)b
1
2
3
4
5
6
S,S-4a
25
0
0.2 4.5:1
70
65
64
69
31
89
92 53 (S,S)
94 68 (S,S)
96 72 (S,S)
>95 37 (R,R)
>95 52 (R,R)
>95 >5 (-)
1
5.5:1
8.1:1
-30 24
25
25 24
25 0.2 35:1
R,R-4b
S,S-4c
R,R-4d
2.5 8.0:1
1:4.4
a
b
Product ratio and de determined by capillary GC. ee deter-
mined by chiral GC.
catalyze the asymmetric Diels-Alder reaction.33 Pal-
ladium-bisoxazoline complexes catalyze the nucleophilic
substitution of allylic acetates with moderate enantiose-
lectivity4,34 and also catalyze the copolymerization of
R-olefins and CO to form highly stereoregular polyke-
tones.35
Reaction of diene 2 and HSiEt3 catalyzed by a 1:1
mixture of the benzyl-substituted precatalyst (N-N)Pd-
(Me)Cl [N-N ) (S,S)-4,4′-dibenzyl-4,5,4′,5′-tetrahydro-
2,2′-bisoxazoline] (S,S-4a ) and NaBAr4 [Ar ) 3,5-C6H3-
(CF3)2] (5 mol %) at room temperature for 15 min led to
isolation of a 4.5:1 mixture of silylated carbocycle (S,S-
3) (92% de, 54% ee) and dimethyl 3,4-dimethylcyclopen-
tane-1,1-dicarboxylate36,37 (S,S-6) (77% de, 35% ee) in 70%
combined yield (Table 2, entry 1).38 Both the chemo- and
stereoselectivity increased with decreasing reaction tem-
perature and at -30 °C, an 8.1:1 mixture of 3:6 was
isolated in 64% yield with 96% de and 72% ee for 3. The
methyl-substituted bisoxazoline precatalysts R,R-4b gave
diminished levels of enantioselectivity relative to S,S-
4a (Table 2, entry 4), while the phenyl-substituted
bisoxazoline precatalyst S,S-4c was inefficient and formed
only traces of carbocycle 3 (∼6%) (Table 2, entry 5).
Relative to palladium phenanthroline catalyst 1, em-
ployment of palladium bisoxazoline catalysts in the
cyclization/hydrosilylation of 2 led to diminished product
yield, sluggish reaction rates, and poor chemoselectivity.
In an effort to probe the role of steric and electronic
effects on the efficiency of bisoxazoline-catalyzed cycliza-
tion/hydrosilylation, the unhindered 5,5-diphenylbisox-
azoline complex R,R-4d was employed as a cyclization
precatalyst. Reaction of 2 and HSiEt3 catalyzed by R,R-
4d led to the isolation of a 35:1 ratio of 3:6 in 89% yield
(>95% de) but with <5% ee (Table 2, entry 6). Compari-
son of this result with those obtained with precatalysts
S,S-4a and R,R-4b indicated that excessive steric crowd-
ing of the coordination plane was detrimental to the
a
b
Previously reported in ref 34. Not isolated free from ligand.
metric aziridination of olefins30 and imines.31 Iridium
bisoxazoline complexes catalyze the asymmetric transfer
hydrogenation of aryl ketones with up to 91% ee4 while
the corresponding rhodium complexes catalyze the hy-
drosilylation of acetophenone with moderate 84% ee.32
Iron, copper, and magnesium bisoxazoline complexes
(33) (a) Corey, E. J .; Imai, N.; Zhang, H. Y. J . Am. Chem. Soc. 1991,
113, 728. (b) Corey, E. J .; Ishihara, K. Tetrahedron Lett. 1992, 33, 6807.
(c) Evans, D. A.; Miller, S. J .; Leckta, T. J . Am. Chem. Soc. 1993, 115,
6460. (d) Evans, D. A.; Murry, J . A.; von Matt, P.; Norcross, R. D.;
Miller, S. J . J . Angew. Chem., Int. Ed. Engl. 1995, 34, 798.
(34) von Matt, P.; Pfaltz, A. Angew. Chem., Int. Ed. Engl. 1993, 32,
566.
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Barnes, D. M. J . Am. Chem. Soc. 1993, 115, 5328.
(31) Hansen, K. B.; Finney, N. S.; J acobsen, E. N. Angew. Chem.,
Int. Ed. Engl. 1995, 34, 676.
(32) Helmchen, G.; Krotz, A.; Ganz, K.-T.; Hansen, D. Synlett, 1991,
257.
(35) Brookhart, M.; Wagner, M. I.; Balavoine, G. G. A.; Haddou, H.
A. J . Am. Chem. Soc. 1994, 116, 3641.
(36) Kuehne, M. E.; Damon, R. E. J . Org. Chem. 1977, 42, 1825.
(37) Curran, D. P.; Shen, W. J . Am. Chem. Soc. 1993, 115, 6051.
(38) The formation of 6 was traced, at least in part, to the presence
of trace amounts of water in the solvent and/or borate salt.

Enantioselective Diene Cyclization/Hydrosilylation
J . Org. Chem., Vol. 65, No. 12, 2000 3839
Ta ble 3. Asym m etr ic Cycliza tion /Hyd r osilyla tion of 2
Em p loyin g P a lla d iu m P yr id in e-Oxa zolin e P r eca ta lysts 5
(5 m ol %) a n d HSiEt3 in CH2Cl2
Ta ble 4. Effect of Solven t a n d Sila n e on th e Cycliza tion /
Hyd r osilya tion of 2 Ca ta lyzed by a 1:1 Mixtu r e of R-5b
a n d Na BAr 4 (5 m ol %) a t -18 °C
entry solvent
silane
HSiEt3
HSiEt3
carbocycle yield (%)
ee (%)
1
DCE
3
3
3
3
7
8
9
86
85
83
96
71
87
38
74 (S,S)a
70 (S,S)a
75 (S,S)a
74 (S,S)a
82 (S,S)a
89 (S,S)d
80 (S,S)d
2
C6H5Cl
3
1,1-DCE HSiEt3
4
CHCl3
CH2Cl2
CH2Cl2
CH2Cl2
HSiEt3
5
HSiMe2Et
HSiMe2t-Bu
HSiMe2Ph
entry precat temp (°C) time (h) yield (%) de (%)a ee (%)b
6b
7b
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
R-5a
R-5a
R-5a
25
-18
-43
-18
-32
-18
-18
-18
-45
-18
-18
-18
-40
-18
-18
-18
0.2
12
81
89
85
89
82
96c
82
96
84
74
91
83c
89c
76
96
88
>95
>95
>95
>95
>95
>95
>95
92
>95
>95
>95
83
66 (S,S)
76 (S,S)
80 (S,S)
84 (S,S)
87 (S,S)
80 (S,S)
49 (S,S)
59 (S,S)
77 (R,R)
77 (R,R)
79 (R,R)
73 (R,R)
91 (R,R)
71 (S,S)
81 (S,S)
83 (S,S)
ee determined by chiral GC. b Reaction run at -40 °C. c 10 mol
a
% catalyst employed. ee determined by 1H NMR spectroscopy.
d
48
12
24
12
12
12
48
12
12
12
48
12
12
12
R-5b
R-5b
R-5c
entry 1). The enantioselectivity of the reaction increased
with decreasing temperature and cyclization of 2 at -43
°C for 48 h gave S,S-3 in 85% yield with 80% ee (Table
3, entries 2, 3). Noteworthy was that the pyridine-
oxazoline catalysts led the opposite sense of asymmetric
induction relative to the bisoxazoline catalysts.
R-5d d
S-5e
S-5f
S-5g
S,S-5h
S-5id
S-5id
R,R-5j
R,R-5k
R-5l
91
Effect of Ca ta lyst Str u ctu r e. The enantioselectivity
of cyclization/hydrosilylation of 2 with HSiEt3 was probed
as a function of the substituent at the 4-position of the
oxazoline ring. Precatalysts possessing a primary alkyl
substituent such as an i-Bu (S-5f) or cyclohexylmethyl
(S-5g) formed carbocycle 3 in good yield with 77-79%
ee, comparable to precatalyst R-5a (Table 3, entries 9,
10). Precatalysts substituted with a secondary alkyl
group such as i-Pr (R-5b), s-Bu (S,S-5h ), or Cy (R-5c)
led to improved enantioselectivity (82-87% ee) while
maintaining good chemical yield (Table 3, entries 4-6,
11). The tert-butyl precatalyst (S-5i) provided even higher
levels of enantioselectivity (91% ee), but suffered from
diminished chemo- and diastereoselectivity (Table 3,
entry 13). Precatalysts which possessed a 4-phenyl (R-
5d ), sulfide (R-5e), or a methoxymethyl group (R,R-5j)
led to lower levels of enantioselectivity than did the
precatalysts substituted with an alkyl group of compa-
rable steric bulk (Table 3, entries 7, 8, 14). Substitution
on the pyridine ring of the palladium pyridine-oxazoline
complex had little effect on the efficiency or enantiose-
lectivity of cyclization/hydrosilylation (Table 3, entries 15,
16).
>95
>95
>95
a
b
Product ratio and de determined by GC. ee Determined by
chiral GC. c Product contained traces (∼5% of 6). Generated in
d
situ from reaction of (COD)Pd(Me)Cl and ligand.
efficiency of cyclization. However, this comparison also
revealed that a substituent adjacent to the oxazoline
nitrogen atom was required for asymmetric induction.
II. Cycliza tion /Hyd r osilyla tion Ca ta lyzed by P a l-
la d iu m P yr id in e-Oxa zolin e Com p lexes. Palladium
pyridine-oxazoline complexes are both relatively un-
crowded and possess a chiral center adjacent to the
oxazoline nitrogen atom. As a result, these complexes
were targeted as catalysts for asymmetric cyclization/
hydrosilylation. However, a potential problem associated
with the pyridine-oxazoline ligand is the formation of
multiple diastereomeric transition states in the stereo-
chemical determining step due to the low C1-symmetry
of the ligand. Perhaps because of this, examples of highly
enantioselective catalytic transformations which employ
pyridine-oxazoline ligands remain scarce. These ex-
amples are limited to the rhodium-catalyzed hydrosily-
lation of acetophenone which generated silylated alcohols
with up to 94% ee39 and to the copper-catalyzed asym-
metric phenylation of 1,2-diols which formed phenols
with low (e50% ee) selectivity.40
Despite the low symmetry of the pyridine-oxazoline
ligand, employment of palladium pyridine-oxazoline
complexes as catalysts for asymmetric diene cyclization/
hydrosilylation led to the formation of silylated car-
bocycles with higher yield and improved chemo-, diaste-
reo-, and enantioselectivity relative to the bisoxazoline
complexes (Table 3). For example, reaction of diene 2 and
HSiEt3 catalyzed by a 1:1 mixture of the methyl-
substituted complex (N-N)Pd(Me)Cl [N-N ) (R)-(+)-4-
Me-2-(2-pyridinyl)-2-oxazoline] (R-5a ) at room tempera-
ture for 10 min led to the isolation of S,S-3 in 81% yield
(>95% de, 66% ee) as the exclusive product (Table 3,
Effect of Solven t a n d Sila n e. The efficiency and
enantioselectivity of cyclization/hydrosilylation was then
probed as a function of solvent and silane employing
isopropyl-substituted precatalyst R-5b. In general, ef-
ficient cyclization/hydrosilylation required a chlorinated
solvent such as CHCl3, 1,1-dichloroethane, 1,2-dichloro-
ethane, or chlorobenzene although employment of these
solvents led to diminished enantioselectivity relative to
CH2Cl2 (Table 4, entries 1-4). In addition, trialkylsilanes
such as HSiMe2Et and HSiMe2CMe3 reacted with 2 to
form carbocycles 7 and 8 with good yield and selectivity
(Table 4, entries 5, 6). The enantioselectivity appeared
to increase with the increasing steric bulk of the silane
in the order HSiMe2Et (82% ee) < HSiEt3 (84-87% ee)
< HSiMe2CMe3 (89% ee). In contrast, reaction of 2 and
HSiMe2Ph required 10% catalyst loading and formed
carbocycle 9 in moderate yield (38%, 80% ee) (Table 4,
entry 7). The concentration of the ligand or of the silane
had no significant effect on the efficiency or enantiose-
lectivity of cyclization/hydrosilylation.
(39) (a) Nishiyama, H.; Sakaguchi, H.; Nakamura, T.; Horihata, M.;
Kondo, M.; Itoh, K. Organometallics 1989, 8, 846. (b) Brunner, H.;
Oberman, U. Chem. Ber. 1989, 122, 499. (c) Brunner, H.; Brandl, P.
J . Organomet. Chem. 1990, 390, C81. (d) Brunner, H.; Brandl, P.
Tetrahedron: Asymm. 1991, 2, 919.
(40) Brunner, H.; Obermann, U.; Wimmer, P. Organometallics 1989,
8, 821.

3840 J . Org. Chem., Vol. 65, No. 12, 2000
Perch et al.
Ta ble 5. Asym m etr ic Cycliza tion /Hyd r osilyla tion of 1,6-Dien es Em p loyin g a 1:1 Mixtu r e of R-5b a n d Na BAr 4 (5 m ol %)
in CH2Cl2
a
b
d
Reaction times: -18 °C, 12 h; -40 °C, 48 h. Yield refers to isolated material of >95% purity. c de determined by GC. ee determined
by chiral GC. e ee determined by 1H NMR spectroscopy. f 10 mol % catalyst employed. Product isolated as the corresponding
dicarbomethoxy derivative. ee of major diastereomer.
g
h
Scop e of Asym m etr ic Cycliza tion /Hyd r osilyla -
tion . The scope of asymmetric cyclization/hydrosilylation
was probed with respect to the diene employing HSiEt3
and R-5b (Table 5). Efficient asymmetric cyclization/
hydrosilylation required a homoallylic ester, ether, ke-
tone, or acetoxy group, similar to the requirements for
cyclization with achiral catalyst 1.25 For example, diesters
10-12, diethers 13 and 14, protected diols 15 and 16,
and monoesters 17 and 18 reacted with HSiEt3 to form
carbocycles 19-27 in good yield and with good enanti-
oselectivity (Table 5, entries 1-10). Although complex
R-5b catalyzed the cyclization/hydrosilylation of diallyl-
trifluoroacetamide (28) to form the corresponding pyr-
rolidine 29 in good yield, enantioselectivity was low
(Table 5, entry 11). The enantioselectivity of cyclization
appeared to roughly parallel the steric bulk of the
homoallylic substituents of the diene, which is presum-
ably related to the ease of cyclization (Thorpe-Ingold).41
For example, the enantioselectivity of cyclization/hydrosi-
lylation increased in the order COCF3 (33% ee) < (CH2-
OMe)2 (72% ee) < (CO2Me)2 (84-87% ee) < (CH2CO2-
CMe3)2 (91% ee).
Asymmetric cyclization/hydrosilylation also tolerated
limited substitution at the allylic and terminal olefinic
positions. Cyclization/hydrosilylation of these substrates
displayed excellent regioselectivity for delivery of the
silane to the less-hindered olefin, as was observed with
the achiral phenanthroline catalyst 1.25 For example,
dienes substituted at a terminal olefinic carbon atom with
a methyl (30) or butyl (31) group underwent asymmetric
cyclization/hydrosilylation in high yield to form car-
bocycles 32 and 33 with g85% ee although diastereose-
lectivity was somewhat diminished relative to unsubsti-
tuted dienes (Table 5, entries 12 and 13). The procedure
also tolerated a terminal phenyl group (34) to form
carbocycle 35 although considerably lower enantioselec-
tivity was achieved (Table 5, entry 14). In a similar
manner, 4,4-dicarbomethoxy-3,3-dimethyl-1,6-heptadiene
(36), which possesses gem-dimethyl substitution at a
(41) (a) DeTar, D. F.; Luthra, N. P. J . Am. Chem. Soc. 1980, 102,
4505. (b) Kirby, A. J . Adv. Phys. Org. Chem. 1980, 17, 208. (c) Eliel,
E. L. Stereochemistry of Carbon Compounds; McGraw-Hill: New York,
1962; pp 197-202. (d) Schore, N. E. in Comprehensive Organic
Synthesis; Trost, B. M., Fleming, I., Eds.; Pergamon: Oxford, 1991;
Vol. 5, p 1037.

Enantioselective Diene Cyclization/Hydrosilylation
J . Org. Chem., Vol. 65, No. 12, 2000 3841
Sch em e 2
Sch em e 3
single allylic carbon atom underwent cyclization/hydrosi-
lylation to form 37 in high yield and with good stereo-
selectivity (Table 5, entry 15).
S,S-6 as determined by both optical rotation and chiral
1H NMR spectroscopy employing Eu(hfc)3. Carbocycles
3, 7, and 8 generated from precatalyst R-5b were also
assigned the S,S-configuration due to the similar shifts
of these carbocycles relative to S,S-9 in the chiral 1H
NMR spectra.
Deter m in a tion of Absolu te Con figu r a tion . Diene
2 was treated with dimethylphenylsilane in the presence
of R-5b/NaBAr4 (5 mol %) at room temperature for 2 h
to form carbocycle S,S-9. Carbocycle S,S-9 was then
oxidized with mercuric acetate and peracetic acid42 to
form 1,1-dicarbomethoxy-3-methyl-4-(hydroxylmethyl)-
cyclopentane (S,S-38) in 30% yield (92% de, 66% ee) from
2. Alcohol 38 was mesylated (MsCl/py) and then reduced
with sodium iodide, zinc, and water43 to give S,S-6 in 85%
yield from 38 (Scheme 2). An authentic sample of S,S-6
(57% de, 62% ee) was synthesized in four steps from
(R,R)-2,3-dimethylsuccinic acid44 employing a procedure
similar to that developed by Kuehne (Scheme 2).35 The
absolute configuration of S,S-6 obtained from precatalyst
R-5b was identical to that of the authentic sample of
Mech a n istic Hyp oth eses. We propose a mechanism
for palladium-catalyzed asymmetric diene cyclization/
hydrosilylation analogous to that postulated for diene
cyclization/hydrosilylation catalyzed by palladium phenan-
throline complex 1 (Scheme 3).25 Coordination of one
olefin of the diene to the palladium silyl intermediate I
would form the palladium silyl olefin complex II. Sub-
sequent â-migratory insertion of the olefin into the Pd-
Si bond could form the palladium-alkyl intermediate III.
Coordination of the pendant olefin followed by â-migra-
tory insertion of the olefin into the Pd-C bond of IV
would form palladium cyclopentylmethyl intermediate V.
The conversion of IV to V is significant as this step both
forms the C-C bond and sets the trans stereochemistry
of the carbocycle. Reaction of V with free triethylsilane
could then release the carbocycle and regenerate the
palladium-silyl intermediate I (Scheme 3).
(42) (a) Fleming, I.; Henning, R.; Plaut, H. J . Chem. Soc., Chem.
Commun. 1984, 29. (b) Fleming, I.; Sanderson, P. E. J . Tetrahedron
Lett. 1987, 28, 4229. (c) J ones, G. R.; Landais, Y. Tetrahedron 1996,
52, 7599.
(43) Kocovsky, P.; Cerny, V. Coll. Czech. Chem. Commun. 1979, 44,
246.
In the palladium-catalyzed hydrosilylation of unfunc-
(44) McCasland, G. E.; Proskow, S. J . Am. Chem. Soc. 1956, 78,
5646.
tionalized olefins, both intermolecular olefin coordination

3842 J . Org. Chem., Vol. 65, No. 12, 2000
Perch et al.
Sch em e 4
to I and â-migratory insertion of the olefin into the Pd-
Si bond is rapid and reversible.45 However, in the case
of cyclization/hydrosilylation catalyzed by palladium
pyridine-oxazoline complexes, coordination of the pen-
dant olefin of intermediate III to form IV would fill the
coordination site required for â-silyl elimination and may
therefore render C-Si bond formation irreversible. Under
these conditions, enantioselectivity would be determined
by the selectivity of olefin insertion into the Pd-Si bond
of II to form III (Scheme 3). Olefin coordination to the
R-pyridine-oxazoline palladium intermediate I-A could
potentially form eight diastereomeric palladium silyl
olefin complexes II (Scheme 4). However, a cis arrange-
ment of the prochiral olefin and the oxazoline ring is
presumably required to account for the high levels of
asymmetric induction observed experimentally and the
terminal end of the olefin must be directed toward the
silane to account for the regioselectivity of insertion.46
Of the two diastereomers which meet these requirements
(II-A and II-B), intermediate II-A should undergo inser-
tion at a higher rate than does II-B as the oxazoline and
olefinic substituents are directed toward opposite faces
of the coordination plane in the transition state for
insertion (Scheme 4). Subsequent trans-cyclization of
III-A followed by metathesis would then form the S,S-
carbocycle, in accord with experimental observations.
Cyclization/hydrosilylation employing bisoxazoline pre-
catalysts S,S-4a and R,R-4b led the opposite sense of
asymmetric induction relative to the pyridine-oxazoline
catalysts.47 This reversal in enantioselectivity most likely
results from a change in the stereochemical determining
step. As one possibility, the distal oxazoline substituent
of (R,R)-bisoxazoline alkyl intermediates III-C and III-D
may hinder coordination of the pendant olefin and render
C-Si bond formation reversible (Scheme 5). Under these
conditions, enantioselectivity will be determined by the
selectivity of either C-C bond formation (IV f V)
(Scheme 5). Of the two possible diastereomeric alkyl
olefin intermediates IV-C and IV-D, intermediate IV-C
should be of higher energy due to steric interaction
between the alkyl(trialkylsilyl) group and the proximal
oxazoline substituent. Because the transition states for
both formation and consumption of intermediates IV-C
and IV-D should closely resemble the corresponding
intermediate, IV-D should be both formed and consumed
faster than IV-C, ultimately leading to preferential
formation of the R,R-carbocycle, as was observed experi-
mentally.
Con clu sion s
Optically active palladium bisoxazoline complexes 4
catalyze the cyclization/hydrosilylation of dimethyl dial-
lylmalonate (2) and triethylsilane to form mixtures of
silylated carbocycle 3 and carbocycle 6 in moderate yield
and with up to 72% ee for 3. Optically active, palladium
pyridine-oxazoline complexes 5 catalyze the asymmetric
cyclization/hydrosilylation of 2 and HSiEt3 to form 3 as
the exclusive product in good yield and with up to 87%
ee. The latter procedure was applied to the asymmetric
cyclization/hydrosilylation of a range of functionalized
dienes including those with olefinic and allylic substitu-
tion. The enantioselectivity of cyclization/hydrosilylation
roughly paralleled the steric bulk of the homoallylic
substituents and ranged from 33% ee for cyclization of
diallyltrifluoroacetamide (28) to 91% ee for the cycliza-
tion/hydrosilylation of 4,4-bis(trimethylacetoxymethyl)-
1,6-heptadiene (16). A number of silanes were employed
in the cyclization/hydrosilylation procedure although
dimethylphenylsilane was not particularly efficient. Be-
cause of this latter limitation, further studies will be
directed toward the identification of effective silanes for
asymmetric cyclization/hydrosilylation which undergo
oxidative cleavage under mild conditions.
(45) LaPoint, A. M.; Rix, F. C.; Brookhart, M. J . Am. Chem. Soc.
1997, 119, 906.
(46) The C-C bond of the olefin must lie in the coordination plane
for â-migratory insertion to occur through a concerted four-centered
transition state.
(47) Although bisoxazoline catalyst S,S-4c led to the opposite sense
of asymmetric induction relative to bisoxazoline catalysts S,S-4a and
R,R-4b, use of catalyst S,S-4c led to formation of only traces (∼6%) of
silylated carbocycle.
Exp er im en ta l Section
Gen er a l Meth od s. All reactions were performed under an
atmosphere of nitrogen employing standard Schlenk tech-
niques. NMR spectra were obtained in CDCl3 at 300 MHz for

Enantioselective Diene Cyclization/Hydrosilylation
J . Org. Chem., Vol. 65, No. 12, 2000 3843
Sch em e 5
1H and 75 MHz for 13C unless otherwise noted. Routine gas
chromatography was performed on a Hewlett-Packard 5890
gas chromatograph equipped with a 25 m poly(dimethylsilox-
ane) capillary column. Chiral gas chromatography was per-
Hz, 1 H), 3.15 (dd, J ) 3.2, 14.0 Hz, 1 H), 3.02 (dd, J ) 8.4,
14.0 Hz, 1 H), 2.79 (dd, J ) 8.4, 13.6 Hz, 1 H), 1.07 (s, 3 H).
13C{1H} NMR (CD2Cl2): δ 161.1, 158.5, 136.9, 135.8, 130.8,
130.6, 129.9, 129.7, 128.4, 128.0, 77.3, 77.2, 66.3, 64.9, 40.5,
40.0, -6.8. Anal. Calcd (found) for C21H23N2O2PdCl: H, 4.86
(4.71); C, 52.94 (52.88).
formed on
a
20 m × 0.25 mm Chiraldex G-TA column
(Advanced Separation Technologies). Flash chromatography
was performed employing 200-400 mesh silica gel (EM).
Elemental analyses were performed by E+R Microanalytical
Laboratories (Parsippany, NJ ). Methylene chloride, dichloro-
ethane, chloroform, and chlorobenzene were distilled from
CaH2 under nitrogen. Ether and THF were distilled from Na/
benzophenone under nitrogen. N,N-Dimethylformamide (Al-
drich, anhydrous) was used as received.
[(S,S)-2,2′-Meth ylen ebis(4-ph en yl-2-oxazolin e)]P d(Me)-
1
Cl (S,S-4c). Off-white solid. H NMR (400 MHz): δ 7.30 (m,
8 H), 7.12 (m, 2 H), 5.80 (m, 1 H), 5.29 (m, 1 H), 4.66 (dt, J )
3.7, 8.6 Hz, 2 H), 4.49 (dd, J ) 4.6, 8.8 Hz, 1 H), 4.31 (dd, J )
4.0, 8.4 Hz, 1 H), 3.83, 3.70 (ABquartet, J ) 20.7 Hz, 2 H),
0.22 (s, 3 H). 13C{1H} NMR (100 MHz): δ 167.7, 163.9, 142.3,
141.3, 130.0, 129.5, 129.3, 128.8, 127.9, 126.6, 77.9, 77.6, 70.3,
68.1, 28.4, -4.3. Anal. Calcd (found) for C20H21N2OPdCl: H,
4.58 (4.48); C, 51.94 (52.01).
Silanes (Aldrich) were distilled from CaH2 under nitrogen.
Dimethyl diallylmalonate, (S,S)-4,4′-dibenzyl-2,2′-bis(2-oxazo-
line), (S,S)-2,2′-methylenebis(4-phenyl-2-oxazoline) (Fluka),
dimethyl malonate, and (()-2,3-dimethylsuccinic acid (Aldrich)
were used as received. The remaining bisoxazoline ligands
were prepared employing published procedures.29 Pyridine-
oxazoline ligands were prepared employing the method of Bolm
(see Supporting Information).48 Dienes 10,49 13,50 17,25 18,51
28,25 34,25 and 3625 were prepared by known procedures; the
syntheses of the remaining dienes is included in the Support-
ing Information. NaB[3,5-C6H3(CF3)2]4 was prepared by known
procedures.52 (COD)PdMeCl was prepared by known proce-
dures and stored under inert atmosphere at -30 °C.53 Car-
bocycles 8, 9, 19, 22, 26, 29, 32, and 37 have been previously
characterized.25
P r eca ta lysts. [(S,S)-4,4′-Diben zyl-2,2′-bis(2-oxa zolin e)]-
P d (Me)Cl (S,S-4a ). A solution of (COD)PdMeCl (200 mg, 0.75
mmol) and (S,S)-4,4′-dibenzyl-2,2′-bis(2-oxazoline) (260 mg,
0.82 mmol) in CH2Cl2 (5 mL) was stirred at room temperature
for 15 min to form a bright yellow solution. Evaporation of
solvent and trituration with ether gave a yellow solid which
was dried under a flow of nitrogen to yield S,S-4a (284 mg,
80%). 1H NMR (CD2Cl2): δ 7.29-7.36 (m, 10 H), 4.53-4.69
(m, 5 H), 4.45 (dd, J ) 7.2, 8.8 Hz, 1 H), 3.47 (dd, J ) 3.6, 14.0
[(R,R)-5,5′-Dip h en yl-2,2′-bis(oxa zolin e)]P d (Me)Cl (R,R-
4d ). Yellow solid. 1H NMR (400 MHz): δ 7.437 (m, 10 H), 6.07
(dt, J ) 4.8, 9.98 Hz, 1 H), 5.96 (t, J ) 9.8 Hz, 1 H), 4.43 (m,
2 H), 4.09 (dd, J ) 9.1, 16.2 Hz, 2 H), 4.01 (dd, J ) 9.2, 15.2
Hz, 1 H), 1.03 (s, 3 H). 13C{1H} NMR (100 MHz): δ 131.1,
130.8, 130.3, 130.2, 129.8, 129.6, 127.5, 127.5, 88.6, 88.5, 59.5,
59.0, -7.0. Anal. Calcd (found) for C19H19N2OPdCl: H, 4.27
(4.32); C, 50.89 (51.12).
[(R)-(+)-4-Meth yl-2-(2-p yr id in yl)-2-oxa zolin e]P d (Me)-
1
Cl (R-5a ). Yellow solid. H NMR (400 MHz): δ 8.96 (m, 1 H),
7.93 (m, 1 H), 7.72 (m, 1 H), 7.61 (m, 1 H), 4.89 (t, J ) 8.4 Hz,
1 H), 4.48 (t, J ) 8.8 Hz, 2 H), 1.38 (d, J ) 6.4 Hz, 3 H), 0.96
(s, 3 H). 13C{1H} NMR (100 MHz): δ 167.6, 148.8, 142.2, 137.8,
128.0, 122.86, 77.2, 58.3, 20.6, -10.0. Anal. Calcd (found) for
C
10H13N2OPdCl: H, 4.11 (4.10); C, 37.64 (37.76).
[(R)-(+)-4-Isopr opyl-2-(2-pyr idin yl)-2-oxazolin e]P d(Me)-
1
Cl (R-5b). Pale yellow solid. H NMR: δ 8.97 (d, J ) 5.5 Hz,
1 H), 7.94 (dt, J ) 1.7, 7.8 Hz, 1 H), 7.70 (d, J ) 7.7 Hz, 1 H),
7.60 (ddd, J ) 1.2, 5.0, 7.6 Hz, 1 H), 4.71 (m, 2 H), 4.35 (m, 1
H), 2.27 (doublet of septets, J ) 3.3, 7.0 Hz, 1 H), 0.95 (s, 3
H), 0.93 (d, J ) 7.0 Hz, 3 H), 0.79 (d, J ) 6.8 Hz, 3 H). 13C-
{1H} NMR: δ 168.4, 149.6, 142.9, 138.8, 129.0, 123.9, 71.8,
68.0, 29.8, 19.1, 14.3, -9.0. Anal. Calcd (found) for C12H17N2-
OPdCl: H, 4.94 (4.72); C, 41.52 (41.45).
(48) Bolm, C.; Weickhardt, K.; Zehnder, M.; Ranff, T. Chem. Ber.
1991, 124, 1173.
(49) Oppliger, M.; Schwyzer, R. Helv. Chim. Acta 1977, 60, 43.
(50) Luker, T.; Whitby, R. J .; Webster, M. J . Organomet. Chem.
1995, 492, 53.
(51) Riggi, I. De.; Nouguier, R.; Surzur, J . M.; Lesueur, C.; Bertrand,
M. Bull. Soc. Chim. Fr. 1993, 130, 229.
(52) Brookhart, M.; Grant, B.; Volpe, A. F. Organometallics 1992,
11, 3920.
Str u ctu r a l Deter m in a tion of R-5b by NOE. Irradiation
of H1 gave a 20.5% enhancement of the signal for H2.
Irradiation of H5 gave an 8.8% enhancement for H6, a 2.2%
enhancement for H4, and a 3.4% enhancement for H3. Irradia-
tion of H3 gave a 9.1% enhancement for H6 and a 15.9%
enhancement for H5.
(53) Ru¨lke, R. E.; Ernsting, J . M.; Spek, A. L.; Elsevier: C. J .; van
Leeuwen, P. W. N. M.; Vrieze, K. Inorg. Chem. 1993, 32, 5769.

3844 J . Org. Chem., Vol. 65, No. 12, 2000
Perch et al.
(d, J ) 5.3 Hz, 1 H), 8.25 (t, J ) 0.9 Hz, 1 H), 8.05 (dd, J )
1.5, 5.3 Hz, 1 H), 4.70 (m, 2 H), 4.47 (dd, J ) 7.9, 9.1 Hz, 1 H),
4.33 (m, 1 H), 4.14 (m, 2 H), 2.29 (m, 1 H), 1.83 (m, 1 H), 1.01
(d, J ) 6.8 Hz, 3 H), 1.00 (s, 3 H), 0.94 (d, J ) 7.0 Hz, 3 H),
0.92 (d, J ) 6.7 Hz, 3 H), 0.80 (d, J ) 6.9 Hz, 3 H). 13C{1H}
NMR (100 MHz): δ 168.2, 160.1, 150.1, 143.1, 138.1, 127.1,
122.5, 73.5, 71.7, 71.5, 68.1, 33.0, 29.7, 19.1, 19.0, 18.5, 14.2,
-8.6. Anal. Calcd (found) for C18H26N3O2PdCl: H, 5.72 (5.72);
C, 47.18 (47.12); N, 9.17 (9.08).
R -5b
[(R)-4-Cycloh exyl-2-(2-p yr id in yl)-2-oxa zolin e]P d (Me)-
Cl (R-5c). Pale yellow solid. 1H NMR (400 MHz): δ 9.03 (ddd,
J ) 0.9, 1.7, 5.0 Hz, 1 H), 7.93 (dt, J ) 1.7, 7.7 Hz, 1 H), 7.71
(dt, J ) 1.0, 7.7 Hz, 1 H), 7.63 (ddd, J ) 1.3, 5.0, 7.7 Hz, 1 H),
4.76 (dd, J ) 4.8, 9.2 Hz, 1 H), 4.63 (t, J ) 9.4 Hz, 1 H), 4.26
(m, 1 H), 1.98-1.87 (m, 1 H), 1.81-0.83 (m, 10 H), 0.99 (s, 3
H). 13C{1H} NMR (100 MHz): δ 168.3, 149.7, 142.9, 138.7,
128.9, 123.8, 72.4, 67.6, 39.8, 29.6, 26.4, 26.3, 25.6, 24.7, -8.9.
Anal. Calcd (found) for C14H21N2OPdCl: H, 5.47 (5.42); C, 46.53
(46.44); N, 7.23 (7.13).
[(R)-4-Isop r op yl-2-isoq u in olin yl-2-oxa zolin e]P d (Me)-
1
Cl (R-5l). Bright yellow powder. H NMR (400 MHz): δ 9.10
(d, J ) 5.8 Hz, 1 H), 8.87 (d, J ) 8.5 Hz, 1 H), 7.99 (d, J ) 5.8
Hz, 1 H), 7.93 (d, J ) 7.9 Hz, 1 H), 7.78 (m, 2 H), 4.87 (m, 2
H), 4.40 (ddd, J ) 3.3, 5.2, 9.4 Hz, 1 H), 2.38 (m, 1 H), 1.05
(s,3 H), 1.00 (d, J ) 7.1 Hz, 3 H), 0.84 (d, J ) 6.9 Hz, 3). 13C-
{1H} NMR (100 MHz): δ 170.1, 141.5, 141.4, 137.5, 131.9,
130.2, 127.9, 126.9, 125.6, 70.0, 67.0, 29.8, 19.0, 14.3, -8.1.
Anal. Calcd (found) for C16H19N2OPdCl: H, 4.82 (4.68); C, 48.38
(48.00); N, 7.05 (6.78).
[(R)-4-P h en yl-2-(2-p yr id in yl)-2-oxa zolin e]P d (Me)Cl(R-
5d ). H NMR (400 MHz): δ 8.99 (d, J ) 4.7 Hz, 1 H), 7.96 (t,
1
J ) 7.7 Hz, 1 H), 7.81 (d, J ) 7.7 Hz, 1 H), 7.64 (br t, J ) 6.2
Hz, 1 H), 7.29 (m, 5 H), 5.48 (dd, J ) 6.7, 10.8 Hz, 1 H), 5.21
(dd, J ) 10.2, 10.8 Hz, 1 H), 4.64 (dd, J ) 7.0, 9.7 Hz, 1 H),
0.63 (s, 3 H). 13C{1H} NMR (100 MHz): δ 169.7, 149.8, 142,8,
139.2, 138.7, 129.3, 129.2, 129.0, 126.8, 124.1, 79.4, 67.0, -7.9.
[(S)-4-Meth ylm er ca p tom eth yl-2-(2-p yr id in yl)-2-oxa zo-
Gen er a l P r oced u r e for Cycliza t ion /Hyd r osilyla t ion .
Methylene chloride (10 mL) was added via syringe to a mixture
of the diene (0.60 mmol), (N-N)PdMeCl (7 mg, 2.2 × 10-3
mmol) and NaB[3,5-C6H3(CF3)2]4 (24 mg, 2.3 × 10-3 mmol) at
-20 °C. Silane (300 µL) was added via syringe and the
resulting solution was stirred at -18 °C for 12 h. Solvent and
excess silane were evaporated under vacuum, and the oily
residue was chromatographed on silica gel to give the car-
bocycle as a colorless oil. Carbocycles which possessed carbo-
tert-butoxy groups (Table 5, entries 1 and 2) were isolated as
the corresponding carbomethoxy derivatives employing the
following procedure: A solution of the crude di-tert-butoxy
carbocycle (∼0.40 mmol) and H2SO4 (10 drops) in MeOH (5
mL) was heated at 60 °C for 12 h. Ether (10 mL) and aqueous
NaHCO3 (10 mL) were added, the layers were separated, and
the aqueous layer was extracted with ether (2 × 10 mL). The
combined organic layers were dried and evaporated under
vacuum, and the residue was chromatographed (hexane:EtOAc
) 24:1) to give the pure dicarbomethoxy carbocycle.
Dim eth yl tr a n s-4-Meth yl-3-[(d im eth yleth ylsilyl)m eth -
yl]cyclop en ta n e-1,1-d ica r boxyla te (7). 1H NMR: δ 3.66 (s,
6 H), 2.52 (dd, 1 H, J ) 6.6, 13.5), 2.46 (dd, 1 H, J ) 6.6, 13.5),
1.61 (dd, 2 H, J ) 10.8, 12.9), 1.39 (m, 2 H), 0.90 (d, J ) 6.0,
3 H), 0.87 (t, J ) 7.8 Hz, 3 H), 0.82 (dd, J ) 2.1, 14.4, Hz, 1
H), 0.44 (q, J ) 7.8 Hz, 2 H), 0.23 (dd, J ) 10.8, 14.4 Hz, 1 H),
-0.06 (s, 6 H). 13C{1H} NMR: δ 172.7, 57.4, 51.9, 51.8, 42.9,
42.8, 42.1, 41.4, 17.7, 16.5, 6.7, 6.6, -3.7, -3.9. IR (neat, cm-1):
1738 (CdO). HRMS (CI) calcd (found) for C15H29SiO4 (MH+):
301.1835 (301.1848).
Diben zyl tr a n s-4-Meth yl-3-(tr ieth ylsilylm eth yl)cyclo-
p en ta n e-1,1-d ica r boxyla te (20). 1H NMR: δ 7.30-7.22 (m,
10 H), 5.08 (m, 4 H), 2.58 (dd, J ) 6.8, 13.4 Hz, 1 H), 2.50 (dd,
J ) 7.0, 13.6 Hz, 1 H), 1.69 (ddd, J ) 6.6, 10.7, 13.4 Hz, 2 H),
1.45 (m 2 H), 0.93 (d, J ) 6.2 Hz, 3 H), 0.89 (t, J ) 7.8 Hz, 9
H), 0.47 (q, J ) 7.8 Hz, 6 H), 0.24 (dd, J ) 11.0 Hz, 14.6 Hz,
1 H). 13C{1H} NMR: δ 172.8, 135.9, 128.7, 128.4, 128.2, 128.1,
67.2, 58.6, 44.0, 43.5, 43.1, 42.3, 17.5, 14.9, 7.7, 4.0. Anal. Calcd
(found) for C29H40SiO4: H, 8.39 (8.56); C, 72.46 (72.44).
Diisop r op yl tr a n s-4-Meth yl-3-(tr ieth ylsilylm eth yl)cy-
clop en ta n e-1,1-d ica r boxyla te (21). 1H NMR: δ 5.13 (septet,
J ) 6.2 Hz, 1 H), 5.12 (septet, J ) 6.2 Hz, 1 H), 2.64 (dd, J )
6.7, 13.3 Hz, 1 H), 2.55 (dd, J ) 6.7, 13.2 Hz, 1 H), 1.74 (ddd,
J ) 6.0, 10.7, 13.3 Hz, 2 H), 1.60-1.48 (m, 2 H), 1.32 (d, J )
6.2 Hz, 12 H), 1.07 (d, J ) 5.1 Hz, 3 H), 1.04 (t, J ) 7.9 Hz, 9
H), 0.97 (dd, J ) 2.2, 11.4 Hz, 1 H), 0.63 (q, J ) 7.9 Hz, 6 H),
0.39 (dd, J ) 11.0, 14.6 Hz, 1 H). 13C{1H} NMR: δ 172.7, 68.6,
58.5, 43.9, 43.4, 43.0, 42.1, 21.7, 17.5, 14.9, 7.6, 4.0. Anal. Calcd
(found) for C21H40SiO4: H, 10.48 (10.39); C, 66.58 (66.42).
1,1-Bis(b en zyloxylm et h yl)-4-m et h yl-3-(t r iet h ylsilyl-
m eth yl)cyclop en ta n e (23). 1H NMR: δ 7.30 (m, 10 H), 4.50
(m, 4 H), 3.30 (m, 4 H), 1.85 (dd, J ) 6.5, 12.9 Hz, 1 H), 1.76
(dd, J ) 6.7, 13.2 Hz, 1 H), 1.2-1.1 (m, 2 H), 0.91 (t, J ) 8.0
Hz, 9 H), 0.90 (d, J ) 5.4 Hz, 3 H), 0.45 (q, J ) 8.0 Hz, 6 H),
0.18 (dd, J ) 10.9, 14.5 Hz, 1 H). 13C{1H} NMR: δ 139.3, 128.5,
127.6, 127.5, 75.7, 73.3, 45.6, 43.6, 43.1, 42.4, 41.6, 18.0, 15.3,
7.8, 4.2. HRMS (CI) calcd (found) for C29H44SiO2 (M+): 452.3111
(452.3127).
1
lin e]P d (Me)Cl (S-5e). Yellow powder. H NMR (400 MHz):
δ 9.02 (br d, J ) 4.1 Hz, 1 H), 7.96 (dt, J ) 1.4, 7.9 Hz, 1 H),
7.78 (d, J ) 7.7 Hz, 1 H), 7.66 (br s, 1 H), 4.87 (br s, 2 H), 4.59
(br s, 1 H), 2.98 (b, 1 H), 2.63 (br s, 1 H), 2.24 (br s, 3 H), 0.96
(s, 3 H). 13C NMR was not obtained due to excessive broaden-
ing of the resonances which was also observed in the H NMR
spectrum. Anal. Calcd (found) for C11H15N2OSPdCl: H, 4.14
(4.30); C, 36.18 (36.27).
1
[(S)-4-(2-Isobu tyl)-2-(2-p yr id in yl)-2-oxa zolin e]P d (Me)-
Cl (S-5f). Yellow powder. 1H NMR (400 MHz): δ 8.95 (m, 1
H), 7.93 (m, 1 H), 7.71 (m, 1 H), 7.61 (m, 1 H), 4.87 (m, 1 H),
4.60 (m, 1 H), 4.35 (m, 1 H), 1.81 (m, 1 H), 1.64 (m, 1 H), 1.41
(m, 1 H), 0.95 (d, J ) 3.0 Hz, 6 H), 0.94 (s, 3 H). 13C{1H} NMR
(100 MHz): δ 167.5, 148.8, 142.1, 137.8, 128.0, 122.8, 61.2,
43.0, 24.7, 22.9, 20.8, -9.6. Anal. Calcd (found) for C13H19N2-
OPdCl: H, 5.30 (5.40); C, 43.23 (43.33).
[(S)-4-Cycloh exylm eth yl-2-(2-p yr id in yl)-2-oxa zolin e]-
P d (Me)Cl (S-5g). Yellow powder. 1H NMR (400 MHz): δ 9.00
(dd, J ) 0.3, 4.6 Hz, 1 H), 7.93 (dt, J 1.6, 7.7 Hz, 1 H), 7.71 (d,
J ) 7.3 Hz, 1 H), 7.61 (ddd, J ) 1.2, 5.1, 7.7 Hz, 1 H), 4.81 (t,
J ) 8.9 Hz, 1 H), 4.59 (dd, J ) 5.0, 8.7 Hz, 1 H), 4.34 (m, 1 H),
1.89 (m, 1 H), 1.77-1.58 (m, 5 H), 1.39-0.85 (m, 7 H), 0.96 (s,
3 H). 13C{1H} NMR (100 MHz): δ 168.3, 149.7, 143.1, 138.7,
128.9, 123.6, 61.6, 42.6, 35.0, 34.4, 32.5, 26.4, 26.1, -8.7. Anal.
Calcd (found) for C16H23N2OPdCl: H, 5.78 (5.83); C, 47.90
(48.14); N, 6.98 (6.91).
[(S,S)-4-sec-Bu tyl-2-(2-p yr id in yl)-2-oxa zolin e]P d (Me)-
Cl (S,S-5h ). Yellow powder. 1H NMR: δ 9.05 (dq, J ) 5.1, 0.9
Hz, 1 H), 7.96 (dt, J ) 7.5, 1.8 Hz, 1 H), 7.73 (d, J ) 7.8 Hz,
1 H), 7.65 (ddd, J ) 1.2, 5.1, 7.8 Hz, 1 H), 4.67 (m, 2 H), 4.44
(ddd, J ) 3.0, 6.0, 9.0 Hz, 1 H), 2.08 (m, 1 H), 1.27 (m, 2 H),
0.99 (s, 3H), 0.97 (t, J ) 7.5 Hz, 3 H), 0.79 (d, J ) 6.9 Hz, 3
H). 13C{1H} NMR: δ 168.5, 149.8, 143.0, 138.8, 129.0, 123.9,
71.8, 66.6, 36.6, 26.6, 12.2, 12.1, -8.9. Anal. Calcd (found) for
C
13H19N2OPdCl: H, 5.30 (5.38), C, 43.23 (43.59); N, 7.76 (7.65).
[(S)-4-ter t-Bu t yl-2-(2-p yr id in yl)-2-oxa zolin e]P d (Me)-
1
Cl (S-5i). H NMR: δ 9.02 (d, J ) 4.8 Hz, 1 H), 8.04 (dt, J )
1.3, 7.6 Hz, 1 H), 7.96 (d, J ) 1.4 Hz, 1 H), 7.64 (ddd, J ) 1.2,
3.8, 7.7 Hz, 1 H), 4.86 (dd, J ) 2.9, 9.4 Hz, 1 H), 4.04 (dd, J )
2.9, 9.0 Hz, 1 H), 1.00 (s, 9 H); 0.97 (s, 3 H). 13C{1H} NMR: δ
149.7, 142.7, 138.5, 128.8, 123.7, 73.2, 70.5, 35.5, 25.7, -5.4.
[(R,R)-4-(Met h oxym et h yl)-5-p h en yl-2-(2-p yr id in yl)-2-
oxa zolin e]P d (Me)Cl (R,R-5j). Yellow powder. 1H NMR (400
MHz): δ 9.07 (br d, J ) 6.0 Hz, 1 H), 7.96 (dt, J ) 1.5, 7.9 Hz,
1 H), 7.81 (br d, J ) 7.7 Hz, 1 H), 7.67 (ddd, J ) 1.4, 5.1, 8.3
Hz, 1 H), 7.40 (m, 3 H), 7.30 (m, 2 H), 5.97 (d, J ) 5.3 Hz, 1
H), 4.35 (m, 1 H), 3.69 (m, 2 H), 3.43 (s, 3 H), 0.95 (s, 3 H).
13C{1H} NMR (100 MHz): δ 169.1, 149.9, 142.8 138.8, 137.8,
129.9, 129.5, 129.3, 126.1, 124.1, 87.9, 87.8, 72.2, 70.7, 70.6,
59.5, -9.2.
{2,4-Bis[2-((R)-4-isop r op yl-2-oxa zolin yl)]p yr id in e}P d -
(Me)Cl (R,R-5k ). Yellow powder. 1H NMR (400 MHz): δ 9.08

Enantioselective Diene Cyclization/Hydrosilylation
J . Org. Chem., Vol. 65, No. 12, 2000 3845
1,1-Bis(a cetoxym eth yl)-3-(tr ieth ylsilylm eth yl)-4-m eth -
ylcyclop en ta n e (24). H NMR: δ 3.90 (s, 4 H), 2.04 (s, 6 H),
gave a 4:1 mixture of (R,R)-2,3-dimethylsuccinic acid (62% ee)
and meso-2,3-dimethylsuccinic acid which was used without
further purification. The optically enriched 2,3-dimethylsuc-
cinic was first esterified (MeOH/H2SO4/Na2SO4, reflux, 12 h)
to give 2,3-dimethylsuccinic acid dimethyl ester in 91% yield
as a pale yellow oil. The diester was reduced (LiAlH4, ether,
25 °C, 12 h) to give 2,3-dimethylbutane-1,4-diol in 91% yield
as a pale yellow oil. PPh3Br2 (23.6 g, 55.8 mmol) was added to
a solution of the diol (2.20 g, 18.6 mmol) in DMF (60 mL), and
the resulting mixture was stirred overnight at room temper-
ature, quenched with water, and extracted with ether. Workup
and chromatography (pentane:ether ) 15:1) gave 2,3-dimethyl-
1,4-dibromobutane as a colorless oil (1.73 g, 38%). Dimethyl
malonate (0.40 mL, 3.5 mmol) and the dibromide (0.74 g, 3.0
mmol) were added sequentially to a solution of NaOMe (0.45
g, 8.0 mmol) in DMF (35 mL) at room temperature, and the
mixture was heated at 115 °C for 36 h. Workup and chroma-
tography (hexane:ether ) 12:1) gave (S,S)-6 (57% de, 62% ee)
(70 mg, 11%) as a colorless oil.
1
1.74 (m, 2 H), 1.10 (m, 1 H), 1.05 (m, 2 H), 1.02 (m, 1 H), 0.90
(t, J ) 8.1 Hz, 9 H), 0.49 (q, J ) 7.8 Hz, 6 H), 0.20 (dd, J )
3.6, 10.8 Hz, 1 H). CH-CH3 protons obscured. 13C{1H} NMR:
δ 171.0, 105.6, 77.4, 77.0, 76.6, 68.2, 65.3, 43.1, 20.7, 20.6, 3.7.
IR (neat, cm-1): 1745 (CdO). HRMS (CI) calcd (found) for
C
19H36SiO4 (MH+): 357.2461 (357.2461). Anal. Calcd (found)
for C19H36SiO4: H, 10.18 (9.87); C, 64.00 (64.91).
1,1-Bis(tr im eth yla cetoxym eth yl)-4-m eth yl-3-(tr ieth yl-
1
silylm eth yl)cyclop en ta n e (25). H NMR: δ 3.89 (m, 4 H),
1.80 (dd, J ) 6.7, 13.2 Hz, 1 H), 1.71 (dd, J ) 6.5, 13.1 Hz, 1
H). 1.5-1.3 (m, 2 H), 1.18 (s, 18 H), 1.00 (m, 2 H), 0.93 (d, J
) 6.0 Hz, 3 H), 0.90 (t, J ) 7.8 Hz, 9 H), 0.47 (q, J ) 7.9 Hz,
6 H), 0.20 (dd, J ) 11.1, 14.6 Hz, 1 H). 13C{1H} NMR: δ 178.5,
68.4, 43.9, 43.6, 41.8, 40.8, 39.0, 27.3, 17.8, 15.1, 7.6, 4.0. Anal.
Calcd (found) for C25H48SiO4: H, 10.98 (11.13); C, 68.13 (68.02).
1-Ca r b om et h oxy-4-m et h yl-1-p h en yl-3-(t r iet h ylsilyl-
m eth yl)cyclop en ta n e (27). 1H NMR: δ 7.17-6.98 (m, 5 H),
3.42 (s, 3 H), [2.74 (dd, J ) 5.1, 11.7 Hz), 2.40 (d, J ) 7.8 Hz),
2:3, 2 H], 2.24-2.05 (m, 2 H), 1.39-1.31 (m, 2 H), [0.83 (d, J
) 6.6 Hz), 0.80 (d, J ) 5.4 Hz), 2:3, 3 H], 0.75 (t, J ) 8.1 Hz,
9 H), [0.36 (q, J ) 7.8 Hz), 0.35 (q, J ) 7.8 Hz), 6 H], 0.13 (dd,
J ) 10.8, 14.7 Hz, 1 H). 13C{1H} NMR: δ 177.2, 144.9, [128.3,
126.3 (2:3)], 57.2, 52.1, [44.7, 44.0 (3:2)], [43.9, 43.8 (2:3)], [43.7,
43.2 (3:2)], [19.5, 18.9 (3:2)], [16.0, 15.0 (2:3)], 7.9, 3.9. IR (neat,
cm-1): 1731 (CdO). Anal. Calcd (found) for C19H36O4Si: H,
9.89 (9.68); C, 72.78 (72.67).
Deter m in a tion of En a n tiom er ic Excess. The enantio-
meric excess of carbocycles 3, 6, 7, 8, 22, and 29 was
determined by chiral GC. The enantiomeric excess of 9, 19,
26, 27, 32, 33, 34, and 37 was determined by 1H NMR
spectroscopy employing Eu(hfc)3 as a chiral shift reagent.
Carbocycle 20 was converted to 3 by transesterification
(MeOH, H2SO4, reflux, 48 h) and analyzed by chiral GC.
Carbocycle 21 was converted to 3 by saponification (NaOMe,
MeOH, H2O, reflux, 12 h) followed by esterification (MeOH,
H2SO4, reflux, 12 h) and analyzed by chiral GC. Carbocycle
23 was hydrogenated (10% Pd/C, 1 atm H2, 25 °C, 4 h)54 to
give 1,1-bis(hydroxymethyl)-4-methyl-3-[(triethylsilyl)methyl]-
cyclopentane (40), converted to 1,1-bis(trifluoroacetoxymethyl)-
3-[(triethylsilyl)methyl]-4-methylcyclopentane (41) [(CF3CO)2O,
NEt3, CH2Cl2, 25 °C, 30 min],55 and analyzed by chiral GC.
Carbocycle 24 was hydrolyzed (K2CO3, MeOH, 25 °C, 2 h) to
form 40,56 converted to 41, and analyzed by chiral GC.
Carbocycle 25 was also hydrolyzed (KOH, MeOH/H2O, reflux,
2 h)57 to form 40, converted to 41, and analyzed by chiral GC.
F or 40: 1H NMR: δ 3.55 (m, 4 H), 2.62 (br s, 2 H), 1.76 (dd,
J ) 6.9, 12.9 Hz, 1 H), 1.71 (dd, J ) 6.7, 12.4 Hz, 1 H), 1.4-
1.2 (m, 4 H), 0.92 (d, J ) 6.1 Hz, 3 H), 0.90 (t, J ) 8.1 Hz, 9
H), 0.49 (q, J ) 7.9 Hz, 6 H), 0.20 (dd, J ) 11.1, 14.6 Hz, 1 H),
one Et3Si-CH2 proton obscured. 13C{1H}NMR: δ 70.2, 70.0,
46.2, 43.2, 42.7, 41.4, 40.5, 17.8, 15.2, 7.6, 4.0. HRMS (CI) calcd
(found) for C15H33SiO2 (MH+): 273.2250 (273.2241).
Dim eth yl tr a n s-4-P en tyl-3-(tr ieth ylsilylm eth yl)cyclo-
1
p en ta n e-1,1-d ica r boxyla te (33). H NMR: δ 3.69 (s, 6 H),
2.53 (td, J ) 5.9, 12.9 Hz, 2 H), 1.7-1.2 (m, 12 H), 0.91 (t, J
) 7.9 Hz, 9 H), 0.86 (t, J ) 7.0 Hz, 3 H), 0.51 (q, J ) 8.0 Hz,
6 H), 0.27 (dd, J ) 11.0 Hz, 14.6 Hz, 1 H). 13C{1H} NMR: δ
173.6, 58.5, 52.8, 49.2, 43.0, 42.0, 40.2, 33.4, 32.4, 28.1, 22.9,
15.3, 14.3, 7.7, 4.1. Anal. Calcd (found) for C21H40SiO4: H,
10.48 (10.66); C, 65.58 (65.60).
P r ep a r a tion of S,S-6 fr om S,S-9. A solution of 2 (1.06 g,
5 mmol), HSiMe2Ph (2.05 g, 15 mmol), NaBAr4 (444 mg, 0.5
mmol), and R-5b (174 mg, 0.5 mmol) in DCE (60 mL) was
stirred at room temperature for 2 h. Volatile material was
evaporated, and the residue was dissolved (hexane:EtOAc )
30:1), filtered through a plug of silica gel, and concentrated to
give S,S-9 (1.43 g, ∼75%) which was ∼90% pure by GC
analysis. Crude S,S-9 was then oxidized as previously de-
scribed25 to form pure 1,1-dicarbomethoxy-3-methyl-4-(hy-
droxylmethyl)cyclopentane (S,S-38) (340 mg, 30% from 2). A
solution of S,S-38 (1.30 g, 5.65 mmol) in pyridine (12 mL) was
treated with methanesulfonyl chloride (2.63 mL, 34.0 mmol)
at 0 °C and stirred for 2.5 h. Workup and chromatography
(hexane:EtOAc ) 10:1) gave 1,1-dicarbomethoxy-3-methyl-4-
(methanesulfonoxy)methylcyclopentane (S,S-39) (1.48 g, 85%)
as a colorless oil. Sodium iodide (1.40 g, 9.4 mmol), zinc powder
(1.40 g, 22 mmol), and water (0.5 mL, 28 mmol) were added
sequentially to a solution of S,S-39 (1.48 g, 4.8 mmol) in 1,2-
dimethoxyethane (15 mL), and the mixture was refluxed
overnight.43 The resulting suspension was diluted with ether
and filtered, and the filtrate was washed with 1 N HCl,
saturated aqueous NaHCO3, 10% aqueous sodium thiosulfate,
and water, dried (Na2SO4), and concentrated under vacuum
to give S,S-6 (0.98 g, 100%) as a colorless oil.
1
F or 41: H NMR: δ 4.21 (m, 4 H), 1.85 (dd, J ) 6.8, 13.6
Hz, 1 H), 1.80 (dd, J ) 6.8, 13.7 Hz, 1 H), 1.53-1.36 (m, 2 H),
1.07 (ddd, J ) 8.4, 11.0, 13.6 Hz, 2 H), 0.96 (d, J ) 6.1 Hz, 3
H), 0.91 (t, J ) 8.0 Hz, 9 H), 0.48 (q, J ) 8.0 Hz, 6 H), 0.23
(dd, J ) 11.0, 14.7 Hz, 1 H). 13C{1H} NMR: δ 157.7 (q, J ) 43
Hz), 114.8 (q, J ) 285 Hz), 71.4, 71.3, 43.9, 43.6, 43.2, 41.4,
40.5, 17.5, 15.2, 7.5, 4.1. Anal. Calcd (found) for C19H30
SiF6O4: H, 6.51 (6.22); C, 49.13 (48.94).
-
Ack n ow led gm en t is made to the National Institutes
of Health (GM59830-01) and the donors of the Petro-
leum Research Fund (33131-G1), administered by the
American Chemical Society, for support of this research.
R.W. thanks the Camille and Henry Dreyfus Foundation
and DuPont for new faculty awards and the Alfred P.
Sloan Foundation for a research fellowship. We thank
Dr. B. Krzyzanowska for synthesizing dienes 30 and 31.
F or 39: 1H NMR: δ 4.25 (dd, J ) 4.8, 9.9 Hz, 1 H), 4.11
(dd, J ) 6.9, 9.9 Hz, 1 H), 3.72 (d, J ) 1.7 Hz, 6 H), 3.02 (s, 3
H), 2.53 (m, 2 H), 2.08 (dd, J ) 9.4, 13.8 Hz, 1 H), 1.96 (m, 1
H), 1.83 (m, 2 H), 1.05 (d, J ) 6.2 Hz, 3 H). 13C{1H}NMR: δ
173.0, 172.9, 71.4, 58.8, 53.2, 46.0, 42.8, 37.7, 36.8, 18.5. IR
Su p p or tin g In for m a tion Ava ila ble: Experimental pro-
cedures, spectroscopic and analytical data for the synthesis of
new pyridine-oxazoline ligands and new dienes. This material
is available free of charge via the Internet at http://pubs.acs.org.
(neat, cm-1): 1730 (CdO). HRMS (CI) calcd (found) for C11H17
-
SO6 (M+-OCH3): 277.0746 (277.0742).
F or 6: 1H NMR: δ 3.70 (s, 6 H), 2.51 (dd, J ) 6.6, 13.6 Hz,
2 H), 1.72 (dd, J ) 10.8, 13.6 Hz, 2 H), 1.47 (m, 2 H), 0.96 (d,
J ) 6.0 Hz, 6 H). 13C{1H}NMR: δ 173.8, 58.4, 52.9, 43.2, 42.0,
17.6.
J O0003192
P r ep a r a tion of (S,S)-6 fr om (R,R)-2,3-Dim eth ylsu c-
cin ic Acid . An authentic sample of S,S-6 was synthesized
employing a procedure similar to that developed by Kuehne.36
Resolution of a mixture of rac- and meso-2,3-dimethylsuccinic
acid with L-Brucine according to the method of McCasland44
(54) Heathcock, C. H.; Ratcliffe, R. J . Am. Chem. Soc. 1971, 93, 1746.
(55) Lardon, A.; Reichstein, T. Helv. Chim. Acta 1954, 37, 443.
(56) Plattner, J . J .; Gless, R. D.; Rapoport, H. J . Am. Chem. Soc.
1972, 94, 8613.
(57) Ogilvie, K. K.; Iwacha, D. J . Tetrahedron Lett. 1973, 317.