A new asymmetric wacker-type cyclization and tandem cyclization promoted by Pd(II)-spiro bis(isoxazoline) catalyst

Full text of DOI:10.1021/ja005920w

J. Am. Chem. Soc. 2001, 123, 2907-2908
A New Asymmetric Wacker-Type Cyclization and
2907
Tandem Cyclization Promoted by Pd(II)-Spiro
Bis(isoxazoline) Catalyst
Figure 1. Spiro bis(isoxazoline) ligands (SPRIXs).
Midori A. Arai, Minori Kuraishi, Takayoshi Arai, and
Hiroaki Sasai*
Table 1. Catalytic Asymmetric Wacker-type Cyclizationa
The Institute of Scientific and Industrial Research (ISIR)
Osaka UniVersity, Mihogaoka
Ibaraki, Osaka 567-0047, Japan
ReceiVed December 23, 2000
The Pd(II)-catalyzed selective oxidative transformations of
alkenes have evolved into a highly useful methodology in
synthetic organic chemistry.1 The intramolecular version of the
Wacker reaction, employing oxygen-containing nucleophiles, can
provide various heterocyclic compounds.2 Although catalytic
asymmetric Wacker-type cyclizations of o-allylphenols have been
reported,3,4 no report has yet been made on alkenyl alcohols as
starting materials. In this paper we report a new catalytic
asymmetric Wacker-type cyclization of alkenyl alcohols promoted
by chiral Pd(II)-spiro bis(isoxazoline) catalysts. Further, we also
describe a new catalytic asymmetric tandem cyclization via an
oxy-palladation, which gives a unique bicyclic ether compound
in one step with up to 95% ee.
a All reactions were carried out using in situ prepared catalyst by
mixing Pd(OCOCF3)2 and SPRIX in CH2Cl2 at room temperature for
2 h. b Reaction was quenched after all of the starting material had been
consumed. c Determined by chiral HPLC after conversion to the
corresponding p-nitrobenzoyl ester. d Directly determined by chiral
HPLC.
We previously reported the first design and synthesis of the
novel spiro bis(isoxazoline) ligands (SPRIXs), which have a chiral
spiro skeleton and two isoxazoline rings (Figure 1).5,6 In view of
the good affinity of SPRIXs for Pd(II) and the stability of SPRIXs
under the oxidative condition, we envisioned the use of SPRIXs
in Wacker-type cyclization. A catalyst system based on (M,S,S)-
H-SPRIX (1a) and Pd(OCOCF3)2 promoted the asymmetric
Wacker-type cyclization of alkenyl alcohol 2a in the presence of
p-bezoquinone in CH2Cl2 to give 6-endo cyclized product 3a in
83% yield in 41% ee (Table 1, entry 1).7-10 The 6-endo-
regioselectivity would be attributed to the stability of the
intermediary carbocation. Compared to use of the other two
diastereomers of SPRIXs, the use of 1a showed the highest
catalytic activity and ee.11 Moreover, the bulkiness of substituents
on (M,S,S)-SPRIX affected enantioselectivity of products,12 and
by use of 1d, 3a was obtained in 70% yield in 70% ee (Table 1,
entry 4). To our knowledge, this is the first report of the catalytic
asymmetric Wacker-type cyclization of alkenyl alcohols.
Figure 2. X-ray structure of Pd(OCOCF3)2-1d.
It is notable that the use of known asymmetric catalysts such
as Pd(OCOCF3)2-(S,S)-ip-boxax,4 Pd(OCOCF3)2-BINAP, Pd-
(OCOCF3)2-bis(oxazolinyl)propane,13,14 and [(3,2,10-η3-pinene)-
3
PdOAc]2 did not promote the reaction of 2 to give 3. Mono-
dentate oxazoline ligands15 gave racemic products (40-50%).16
In an effort to clarify the active catalytic species of this reaction,
we succeeded in obtaining a single crystal of the Pd-1d complex.
The X-ray crystallographic analysis of this single crystal revealed
that 1d coordinated to Pd with two nitrogen atoms (Figure 2).17
Using these single crystals, Wacker-type cyclization of 2b gave
the product 3b in 80% yield in 69% ee, which was comparable
to the result using in situ-prepared catalysis (Table 1, entry 5).18
Having developed the Wacker-type cyclization of alkenyl
alcohol, we focused on a Pd-catalyzed asymmetric tandem
(1) (a) Feringa, B. L. Transition Metals for Organic Synthesis; Beller, M.,
Bolm, C., Eds.; Wiley-VCH: Weinheim, 1998; Vol. 2, p 307. (b) Tuji, J.
Palladium Reagents and Catalysts; John Wiley and Sons: Chichester, 1995;
p 19.
(2) (a) Hosokawa, T.; Murahashi, S.-I. Heterocycles 1992, 33, 1079. (b)
Hegedus, L. S. Organometallics in Synthesis; Schlosser, M., Ed.; John Wiley
and Sons: Chichester, 1994; p 383.
(3) Hosokawa, T.; Okuda, C.; Murahashi, S.-I. J. Org. Chem. 1985, 50,
1282 and references therein.
(4) Uozumi, Y.; Kyota, H.; Kato, K.; Ogasawara, M.; Hayashi, T. J. Org.
Chem. 1999, 64, 1620 and references therein.
(5) Arai, M. A.; Arai, T.; Sasai, H. Org. Lett. 1999, 1, 1795.
(6) SPRIX is an abbreviation of spiro bis(isoxazoline).
(7) The combinations of (M,S,S)-H-SPRIX and Pd-salts other than Pd-
(OCOCF3)2 (e.g., Pd(OAc)2, Pd(CH3CN)4(BF4)2, PdCl2, PdCl2-AgOTf) resulted
in low yield.
(8) As solvent effects: CH3CN (86%, 39% ee), MeOH (41%, 36% ee),
THF (35%, 27% ee), toluene (45%, 36% ee).
(13) Corey, E. J.; Imai, N.; Zhang, H.-Y. J. Am. Chem. Soc. 1991, 113,
728.
(14) Evans, D. A.; Woerpel, K. A.; Hinman, M. M.; Faul, M. M. J. Am.
Chem. Soc. 1991, 113, 726.
(9) Four equivalents of p-benzoquinone were used for a smooth reaction.
(10) The use of Cu(OAc)2 and O2 system: 43%, 27% ee, after 48 h.
(11) (M,R,R)-H-SPRIX (30%, 3% ee, after 30 h) and (M,S,R)-H-SPRIX
(74%, 22% ee, after 28 h).
(12) Substituted SPRIXs (1b-d) were readily synthesized in a manner
similar to that of 1a. Experimental details are provided in the Supporting
Information. Enantiomerically pure SPRIXs were obtained by chiral stationary
phase column chromatography (DAICEL CHIRALPAK AD (φ 2 cm × 25
cm)).
(15) Ikeda, S.; Cui, D.-M.; Sato, Y. J. Am. Chem. Soc. 1999, 121, 4712.
(16) For the results with known Pd-catalysts, see Supporting Information.
The reaction with 15 mol % Pd(OCOCF3)2 without chiral ligand gave racemic
3a in 63% after 14 h.
(17) Crystal data: orthorhombic; space group P212121; a ) 15.310(3) Å,
b ) 24.61(1) Å, c ) 8.283(3) Å; V ) 3120(1) Å3, Z ) 4; Mo KR radiation
(-75 °C); R ) 0.049, Rw ) 0.050.
(18) Decomposition of 1d was not observed on NMR under the reaction
process.
10.1021/ja005920w CCC: $20.00 © 2001 American Chemical Society
Published on Web 03/06/2001

2908 J. Am. Chem. Soc., Vol. 123, No. 12, 2001
Communications to the Editor
Table 2. The Pd-Catalyzed Asymmetric Tandem Cyclization via
the Oxy-palladation
Scheme 1. Plausible Mechanism of Tandem Cyclization via
the Oxy-palladation
a Pd catalyst was prepared in situ by mixing Pd(OCOCF3)2 and 1d
(Pd:1d 1:1.2) at room temperature for 2 h. b Reaction was quenched
after all of compound 4 had been consumed. c Total yield of Wacker-
type cyclization products.
cyclization via oxy-palladation using a Pd-SPRIX catalyst.
Tandem reactions, which can form several bonds without isolating
the intermediates, are a useful and important topic of synthetic
chemistry.19 If the alkyl Pd(II) intermediates resulting from an
intramolecular oxy-palladation are trapped by alkenes, the variety
of heterocyclic compounds can be synthesized in a single step.20
In the case of substrate 4, which contains two C-C double bonds,
the Pd(OCOCF3)2-1d catalyst efficiently gave a bicyclic com-
pound 521 as a single diastereomer. The tandem product 5 was
obtained in 95% ee in CH2Cl2, along with dihydropyranes 6 and
7, which were generated by â-elimination (the ratio of
5:6:7 ) 68:5:27) (Table 2, entry 1).21,22
MeOH as a solvent increased the ratio of the bicyclic compound
5, though the ee of 5 was slightly decreased (Table 2, entry 2).
Balancing the factors of yield and ee of 5 led to the use of a
mixed CH2Cl2/MeOH solvent system, which realized good yield
and ee of 5 (Table 2, entries 5 and 6). In the mixed solvent system,
the reaction proceeded with 10 mol % of the catalyst.
formation would afford the bicyclic product 5 via the formation
of a palladacycle 10 or a direct insertion intermediate 12. The
monocyclic products 6 and 7 would be the result of â-elimination
from the intermediates 9 and 11, respectively. When the isolated
monocyclic product, either 6 or 7, was again treated under the
tandem cyclization conditions, 10 was not obtained and the
monocyclic product was recovered without isomerization. This
result would indicate that 5 was produced in a sequential reaction.
The addition of MeOH increased the yield of the tandem product
5, and suppressed the generation of â-elimination product 7. This
effect of MeOH would be responsible for the acceleration of the
reductive elimination from the palladacycle intermediate 10.
In summary, we developed the catalytic asymmetric Wacker-
type cyclization of alkenyl alcohols promoted by a Pd-SPRIX
catalyst. Moreover, we demonstrated the Pd-catalyzed asymmetric
tandem cyclization via the oxy-palladation in up to 95% ee. The
details of the mechanism of the tandem cyclization and its
application to the synthesis of biologically important compounds
are now under investigation.
The plausible mechanism of tandem cyclization is shown in
Scheme 1. Intramolecular nucleophilic attack of the hydroxy group
at the activated C-C double bond of the complex 8 would afford
the alkyl Pd(II) intermediate 9, then another C-C double bond
would coordinate to Pd(II) intramolecularly. Further C-C bond
Acknowledgment. We are grateful to Prof. Uozumi for providing
an intermediate for the (S,S)-ip-boxax. This work was supported by the
Ministry of Education, Science, Sports and Culture, Japan and the Japan
Society for the Promotion of Science (JSPS) for M.A.A. We thank the
technical staff at the Materials Analysis Center of Osaka University.
(19) (a) Tietze, L. F. Chem. ReV. 1996, 96, 115. (b) Bunce, R. A.
Tetrahedron 1995, 51, 13103.
(20) Tandem oxy-palladation and vinylation, see: (a) Larock, R. C.; Lee,
N. H. J. Am. Chem. Soc. 1991, 113, 7815. (b) Semmelhack, M. F.; Epa, W.
R. Tetrahedron Lett. 1993, 34, 7205.
(21) The absolute configurations of the major enantiomers of 5-7 have
not been determined yet. For the determination of the product ratio of 5:6:7,
and for the elucidation of relative configuration of 5 by NOE study, see
Supporting Information.
(22) Without 1d, the Wacker cyclization of 4 proceeded very slowly to
give 6 as the major product.
Supporting Information Available: Detailed experimental proce-
dures and 1H, 13C NMR, NOE, IR, mass spectra, and X-ray crystal-
lographic analysis data for the products (PDF). This material is available
free of charge via the Internet at http://pubs.acs.org.
JA005920W