Palladacycle-catalyzed highly efficient kinetic resolution of 1-hydroxy-2-aryl-1,2-dihydronaphthalenes via dehydration reaction

Article abstract of DOI:10.1021/ol801946e

(Chemical Equation Presented) Palladacycles showed their high efficiency in the kinetic resolution of 1-hydroxy-2-aryl-1,2-dihydronaphthalenes via dehydration, providing optically active products in high yields and high ee with an S factor up to 26. The superiority of a benzylic-substituted palladacycle in asymmetric induction was also demonstrated.

Full text of DOI:10.1021/ol801946e

ORGANIC
LETTERS
2008
Vol. 10, No. 23
5337-5340
Palladacycle-Catalyzed Highly Efficient
Kinetic Resolution of
1-Hydroxy-2-aryl-1,2-dihydronaphthalenes
via Dehydration Reaction
Ting-Ke Zhang,† Dong-Liang Mo,‡ Li-Xin Dai,‡ and Xue-Long Hou*,†,‡
State Key Laboratory of Organometallic Chemistry and Shanghai-Hong Kong Joint
Laboratory in Chemical Synthesis, Shanghai Institute of Organic Chemistry,
Chinese Academy of Sciences, 354 Feng Lin Road, Shanghai 200032, China
xlhou@mail.sioc.ac.cn
Received August 20, 2008
ABSTRACT
Palladacycles showed their high efficiency in the kinetic resolution of 1-hydroxy-2-aryl-1,2-dihydronaphthalenes via dehydration, providing
optically active products in high yields and high ee with an S factor up to 26. The superiority of a benzylic-substituted palladacycle in asymmetric
induction was also demonstrated.
Palladacycles as readily available, air- and moisture-
tolerant, highly active catalysts have attracted more
attention over the years.1 Many different types of palla-
dacycles have been synthesized and have shown their
usefulness in a variety of reactions. However, in many
cases, palladacycles serve as catalyst precursors only,1d
and asymmetric catalysis has only been realized in a few
examples,2,3 even though chiral palladacycles were used.4,5
A great challenge still remains regarding the applications of
palladacycles as efficient catalysts in asymmetric cataly-
sis.
(2) (a) Navarro, R.; Urriolabeitia, E. P.; Cativiela, C.; Diaz-de-Villegas,
M. D.; López, M. P.; Alonso, E. J. Mol. Catal. A: Chem. 1996, 105, 111.
(b) Leung, P. H.; Ng, K.-H.; Li, Y. X.; White, A. J. P.; Williams, D. J.
Chem. Commun. 1999, 2435. (c) Anderson, C. E.; Overman, L. E. J. Am.
Chem. Soc. 2003, 125, 12412. (d) Moyano, A.; Rosol, M.; Moreno, R. M.;
Lo´pez, C.; Maestro, M. A. Angew. Chem., Int. Ed. 2005, 44, 1865. (e)
Anderson, C. E.; Donde, Y.; Douglas, C. J.; Overman, L. E. J. Org. Chem.
2005, 70, 648. (f) Weiss, M. E.; Fischer, D. F.; Xin, Z.-q.; Jautze, S.;
Schweizer, W. B.; Peters, R. Angew. Chem., Int. Ed. 2006, 45, 5694. (g)
Jautze, S.; Seiler, P.; Peters, R. Angew. Chem., Int. Ed. 2007, 46, 1260. (h)
Fischer, D. F.; Xin, Z.-q.; Peters, R. Angew. Chem., Int. Ed. 2007, 46, 7704.
† Shanghai-Hong Kong Joint Laboratory in Chemical Synthesis.
‡ State Key Laboratory of Organometallic Chemistry.
(1) For some reviews, see: (a) Herrmann, W. A.; Bo¨hm, V. P. W.;
Reisinger, C. P. J. Organomet. Chem. 1999, 576, 23. (b) Bedford, R. B.
Chem. Commun. 2003, 1787. (c) van der Boom, M. E.; Milstein, D. Chem.
ReV. 2003, 103, 1759. (d) Farina, V. AdV. Synth. Catal. 2004, 346, 1553.
(e) Dupont, J.; Consorti, C. S.; Spencer, J. Chem. ReV. 2005, 105, 2527.
(i) Nomura, H.; Richards, C. J. Chem.sEur. J. 2007, 13, 10216
.
10.1021/ol801946e CCC: $40.75
Published on Web 11/04/2008
2008 American Chemical Society

On the other hand, the kinetic resolution is a powerful
tool in gaining optically active molecules from racemic
starting materials.6,7 Enormous advances, especially in the
use of chiral transition-metal complexes as catalysts, have
been made over the years. High efficiency regarding ee value
and yield of one enantiomer as product has been realized in
many reactions using a kinetic resolution strategy. Ring-
opening reactions of epoxides7a,b,r and aziridines,7c epoxi-
dation and dihydroxylation of alkenes,7d-f acylation,7g
oxidative transfer hydrogenation,7h Baeyer-Villiger reac-
tion,7i hydrogenation of alkenes and imines,7j,k ring-closing
metathesis,7l Pd-catalyzed allylic alkylation,7m,n cyclopro-
panation using diazoesters,7o alcoholysis of anhydrides,7p 1,4-
conjugated addition,7q and cycloaddition reaction7r are among
the most general types of reactions used in kinetic resolution.
However, few reports achieved kinetic resolution via dehy-
dration reaction of alcohols though it is a very common type
of reaction in organic synthesis.8 Furthermore, there are no
reports of using palladacycles as catalysts in kinetic resolu-
tion.
Based upon the above results, we deduced that there should
be a kinetic resolution process for 3a. The fact that the
During our program aimed at the applications of pallada-
cycles in organic synthesis, we have reported highly catalytic
activity of chiral benzylic-substituted ligands,5 and the
catalytic effciency of related palladacycles has also been
revealed in hydrophenylation and ring-opening reactions of
oxa-bicyclic alkenes with ArCH2ZnBr.5d In the latter case,
the palladacycle should be the real catalyst,5d though the
products were racemic. However, moderate ee for the ring-
opening product was afforded when phenylboronic acid was
the reagent using palladacycle 5 as catalyst.5e In addition,
we also observed kinetic resolution phenomenon. In this
paper, we report the kinetic resolution of 1-hydroxy-2-aryl-
1,2-dihydronaphthalenes via dehydration catalyzed by pal-
ladacycle with high efficiency, providing the products in high
ee.
Figure 1. Structure of palladacycles.
reaction of racemic 3a with 1.0 equiv of Cs2CO3 in the
presence of 5 mol % of palladacycle 5 in MeOH provided
optically active 3a in 19% yield and in 11% ee accompanied
by 4a in 67% yield confirmed it. Control experiments
revealed that strong bases only, such as KOH, Cs2CO3,
Table 1. Optimization of Kinetic Resolution of 1,2-cis-3a
Catalyzed by Palladacyclesa
First we investigated the reaction of oxabicyclic alkene
1a with PhB(OH)2 2a using palladacycle 5 as catalyst (eq
1). It was found that the ee value of the product varied
depending on the reaction time. Ring-opening product 3a
was provided in 23% yield and in 33% ee when the reaction
ran for 40 min. The yield increased to 98% while the ee
value remained 33% if the reaction time was 1.5 h. However,
the ee value increased to 41% but the yield decreased to
86% and naphthylene 4a was separated in 12% yield if the
reaction time was prolonged to 2 h. When the reaction ran
for 3 h, 3a was afforded in 52% yield and in 84% ee
accompanied by 40% yield of 4a. Ring-opening product 3a
in 97% ee was obtained if the reaction time was 4 h, but the
yield was reduced to 45% while 4a was provided in 48%
yield. No 3a was found, and only 4a was separated in 90%
yield if the reaction ran for 12 h.
product, 3a
4a
entry palladacycle
base
Et3N
Et3N
Et3N
Et3N
Et3N
Et3N
Et3N
yield (%)b ee (%)c yield (%)b
1
5
31
52
18
37
90
40
46
38
42
26
0
94
5
99
94
0
88
14
5
98
98
62
47
70
56
4
55
54
58
56
72
95
2
6
7
8
3d
4
5
9
6
7
8
9
10
11
12
8
Et3N
i-Pr2NEt
DABCO
pyridine
10
11
8
8
a Molar ratio of 3a/base/palladacycle ) 1.0:0.5:0.05, reaction time: 4 h.
b Isolated yield. c Determined by chiral HPLC. d Run for 10 h.
K2CO3, and KF, caused dehydration of 3a to give rise to 4a
in almost quantitative yields, while no reaction took place if
palladacycle 5 or a weak base, such as Et3N, pyridine, and
i-Pr2NEt, was used solely.
Investigations on the influence of palladacycles and base
on the reaction (Table 1) showed that the structure of the
5338
Org. Lett., Vol. 10, No. 23, 2008

palladacycle has a great impact on the efficiency of resolu-
tion. Among palladacycles we screened (Figure 1), benzylic-
substituted palladacycles 5 and 8 demonstrated their supe-
riority (entries 1 and 4), providing optically active 3a in 31%
yield with 94% ee accompanied by 62% yield of 4a and
37% yield of 3a with 94% ee and 56% of 4a, respectively.
However, palladacycle 6 with a tertiary butyl group as
substituent on the oxazoline ring gave only 5% ee (entry 2),
which reflects the relationship between the substituents at
benzylic and oxazoline ring.5b Excellent ee was obtained
using palladacycle dimer 7, but the yield of 3a was only
18% (entry 3). Lower ee was given using pincer complex 9
(entry 5) and palladacycle 11 derived from chiral benzyl-
amine (entry 7). Dihydronaphthalene 3a was recovered in
40% yield with 88% ee using Overman’s palladacycle 10
(entry 6). The P-containing palladacycle 12 gave 3a in 38%
yield with only 5% ee (entry 8). The properties of the base
also influence the reaction. A better result was afforded when
i-Pr2NEt was used as the base, providing 3a in 42% yield
with 98% ee (entry 9 vs entry 4). Stronger base DABCO
gave a lower yield of 3a, though with high ee (entry 10),
and weak base pyridine did not allow the reaction to proceed
(entry 11). A screen of common solvents showed that MeOH
should be the choice.
to provide optically active 3 with the yields ranging from
35 to 43% and with high ee value ranging from 84-99%.
The reactions showed high efficiency, and the S factor was
between 9 and 26.9 Reaction of 3 with phenyl and naphthyl
substituents afforded enantiomeric enriched products 3 with
higher S values (entries 1 and 7). The presence of a
substituent at the meta and para positions of the phenyl ring,
whatever its electronic property, has no great influence on
the S value. All reactions of 3 with 3- and 4-substituted
phenyl ring gave optically active 3 with similar S values
(entries 2-5). However, dihydronaphthalene 3f with a
substituent at the ortho position of 2-aryl gave optically active
product 3f with a slightly higher S value (entry 6). Substit-
uents on the dihydronaphthalene ring did not affect the
efficiency of the reaction. Substituted 3i-k afforded corre-
sponding products with high S values (entries 9-11). It is
worth noting that dihydronaphthalene 3h with PhCHdCH
as substituent was also a suitable substrate, giving product
with a lower S value (entry 8). The absolute configuration
of 3a was determined as (1S,2R) by comparing its optical
rotation and HPLC trace with that reported by Lautens.10
The reaction of phenylethynyl-substituted dihydronaph-
thalene 3l also provided optically active 3l in 54% yield by
using palladecycle 8 as catalyst and PhNHMe as base.
Though the ee value was only 17%, it represents the first
example of asymmetric synthesis of phenylacetyl-substituted
dihydronaphthalene (eq 2).11 Again, the choice of base is
important, and the reaction provided a complex mixture if
stronger base Et3N or i-Pr2NEt was used.
The substrate scope of the reaction was evaluated using
optimized conditions (Table 2). Using palladacycle 8 as
Table 2. Kinetic Resolution of Various Substratesa
product, 3
4
No dehydration product was detected when racemic trans-
3a12 was treated under the optimized conditions, which
suggests that the dehydration might proceed via an E2
elimination mechanism.13
In conclusion, highly efficient kinetic resolution via
dehydration using chiral palladacycles was realized, which
represents an alternative method for kinetic resolution and
entry
3,Ar
a, Ph
yield %b
ee %c
Sf
yield %b
1
42
38
41
35
43
38
40
40
41
38
38
98
91
86
99
86
99
99
84
92
97
99
26
15
12
16
13
20
24
9
56
59
56
58
55
58
55
58
57
60
47
2
b, 3-ClC6H4
c, 3-MeOC6H4
d, 4-MeOC6H4
e, 4-CF3C6H4
f, 2-MeC6H4
g, 1-naphthyl
h, PhCH)CH
i, phenyl
3d
4
5
6e
7e
8
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10
11
14
16
20
j, phenyl
k, 4-MeOC6H4
a Reaction conditions: 3/iPr2NEt/8 ) 1.0:0.5:0.05. b Isolated yield.
c Determined by chiral HPLC. d Et3N as base. e Run for 10 h. f Calculated
by the equation: ln[(1 - C)(1 - ee)]/ln[(1 - C)(1 + ee)].6a
(5) (a) Hou, X. L.; Dong, D. X.; Yuan, K. Tetrahedron: Asymmetry
2004, 15, 2189. (b) Wu, W. Q.; Peng, Q.; Dong, D. X.; Hou, X. L.; Wu,
Y. D. J. Am. Chem. Soc. 2008, 130, 9717. (c) Yuan, K.; Zhang, T.-K.;
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aryl-1,2-dihydronaphthalen-1-ols 3 were suitable substrates
Org. Lett., Vol. 10, No. 23, 2008
5339

demonstrates the superiority of benzylic substituted palla-
dacycle 8 in asymmetric induction. These results also provide
a useful index for designing new catalyst systems. Investiga-
tions on the detailed mechanism and applications of palla-
dacycles in asymmetric catalysis as well as the kinetic
resolution via dehydration are in progress.
Acknowledgment. This work was financially supported
by the Major Basic Research Development Program
(2006CB806100), National Natural Sciences Foundation of
China (20532050, 20672130), Chinese Academy of Science,
Croucher Foundation of Hong Kong, and Shanghai Com-
mittee of Science and Technology. T.-K.Z. gratefully thanks
the Croucher Foundation of Hong Kong for a studentship.
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Supporting Information Available: General procedure
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data for 3 and 4. This material is available free of charge
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