Enantioselective preparation of 8-oxabicyclo[3.2.1]octane derivatives via asymmetric [3+2]-cycloaddition of platinum-containing carbonyl ylides with vinyl ethers

Article abstract of DOI:10.1021/ja102391t

A catalytic asymmetric synthesis of 8-oxabicyclo[3.2.1]octane derivatives was achieved through the [3+2]-cycloaddition of the platinum-containing carbonyl ylides generated from acyclic γ,δ-ynones on treatment with 10 mol % of PtCl₂-Walphos and

Full text of DOI:10.1021/ja102391t

Published on Web 06/14/2010
Enantioselective Preparation of 8-Oxabicyclo[3.2.1]octane Derivatives via
Asymmetric [3+2]-Cycloaddition of Platinum-Containing Carbonyl Ylides with
Vinyl Ethers
Kento Ishida, Hiroyuki Kusama, and Nobuharu Iwasawa*
Department of Chemistry, Tokyo Institute of Technology, O-okayama, Meguro-ku, Tokyo 152-8551, Japan
Received March 22, 2010; E-mail: niwasawa@chem.titech.ac.jp
Table 1. Reaction of 1a (R1 ) Ph, R2 ) Me) with Benzyl Vinyl
Platinum(II)- or gold(I)-catalyzed electrophilic activation of alkynes
Ether in the Presence of Platinum(II)-Phosphine Complexes
has attracted much attention as an efficient method to facilitate atom-
economical construction of complex molecules.1 Asymmetric versions
entry
Catalyst
Solvent
Time
4a
5a
of these reactions would be highly attractive; however, there are only
a few successful reports of asymmetric enyne cyclizations2 and
asymmetric reactions of carbene complexes generated by isomerization
of propargyl esters.3 Herein, we report a platinum-catalyzed enanti-
oselective preparation of synthetically useful 8-oxabicyclo[3.2.1]octane
derivatives via an asymmetric [3+2]-cycloaddition reaction of a
platinum-containing carbonyl ylide as a new type of asymmetric
reaction based on the electrophilic activation of alkynes.
1
2
PtCl2
toluene
CH2Cl2
3 days
3.5 h
trace
45%
74%
cis-PtCl2(PPh3)2
AgSbF6 (1: 1)
cis-PtCl2(m-tol3)2
AgSbF6 (1: 1)
cis-PtCl2(PPh3)2
AgSbF6 (1: 2)
10%a
3
4
CH2Cl2
CH2Cl2
1.5 h
2 h
92%
16%
8%
-
a Obtained as a hydrolyzed ketone.
of alkynes by a monocationic platinum-bisphosphine complex
depicted as [PtCl(phosphine)2]+ is quite rare,11 while some enyne
cyclizations catalyzed by dicationic platinum-bisphosphine complexes
were reported.2a,b,8a
Scheme 1
Then, we examined various chiral phosphines under the cationic
conditions and found that the reaction with (R)-BINAP, (R)-SEGPHOS,
(S,S)-DIOP, and Josiphos 6 gave the product 4a with low enantiose-
lectivity along with a small amount of the bicyclic enol ether 5a (ee’s
were not determined) (Table 2).12 On the other hand, when Walphos
Table 2. Screening of Chiral Bisphosphinea
4a
5a
Yield
(%)b
Ee
(%)c
Yield
(%)d
entry
Bisphosphine
Time
Recently, we reported that treatment of acyclic γ,δ-ynones 1 with
a catalytic amount of platinum(II) chloride in the presence of vinyl
ethers gave 8-oxabicyclo[3.2.1]octane derivatives 54c through the
novel bifunctional reactive species, platinum-containing carbonyl
ylides 2 (Scheme 1).4-6 The high utility of the product, 5,7
prompted us to develop an asymmetric version of this reaction.
For this purpose, we first examined the reactivity of platinum-
phosphine complexes; however, the low electrophilicity of the
model complex, cis-PtCl2(PPh3)2, resulted in recovery of the starting
materials. We then thought of using cationic platinum(II)-phosphine
complexes2a-e,8 generated by treatment of platinum(II) chloride-
phosphine complexes with a silver salt. As expected, the reaction
proceeded smoothly at room temperature on treatment of acyclic γ,δ-
ynone 1a (R1 ) Ph, R2 ) Me) with 10 mol % of cis-PtCl2(PPh3)2
associated with 10 mol % AgSbF6 in the presence of excess benzyl
vinyl ether (5 equiv) (Table 1, entry 2), and more importantly, the
bicyclic alkene 4a, the product formed through a 1,2-hydrogen shift
of the carbene intermediate 3a,9 was obtained in 45% yield as a single
diastereomer, while the hydrolyzed ketone of the product 5a formed
by using PtCl2 was obtained in only 10% yield as a minor product.
Furthermore, the reaction with cis-PtCl2[P(m-tol)3]2 afforded 4a in
higher yield and selectivity (entry 3).10 Use of 2 equiv (20 mol %) of
AgSbF6 resulted in polymerization of the vinyl ether (entry 4). It should
also be noted that the reaction was significantly accelerated compared
to the reaction of PtCl2. To our knowledge, the electrophilic activation
1e
2
(R)-BINAP
(R)-SEGPHOS
(S, S)-DIOP
Josiphos 6
Walphos 7a
Walphos 7b
Walphos 7c
Walphos 7d
Walphos 7d
Walphos 7d
Walphos 7e
7.5 h
25 h
3 h
22 h
rt-reflux
20.5 h
rt-reflux
21.5 h
21.5 h
16.5 h
21.5 h
21
33
67
50
-
31
trace
49
57
70
30
4 (+)
18 (+)
4 (-)
10 (-)
-
87 (-)
-
91 (-)
91 (-)
91 (-)
77 (-)
17
detected
3e
4
31
16
-
-
-
-
-
-
-
5
6
7
8
9e
10e f
,
11
a Reactions were performed by addition of AgSbF6 (10 mol %) to a
mixture of ynone 1a, benzyl vinyl ether (5 equiv), PtCl2(cod) (10 mol
%), and bisphosphine (10 mol %) at RT. b Isolated yield. c Determined
by chiral HPLC analysis (CHIRALPAK AD-H, 0.5 mL/min, 2-propanol/
hexane ) 1/99) d NMR yield. e Isolated PtCl2(bisphosphine) complex
was used instead of PtCl2(cod) and bisphosphine. f 10 equiv of benzyl
vinyl ether were used.
9
8842 J. AM. CHEM. SOC. 2010, 132, 8842–8843
10.1021/ja102391t  2010 American Chemical Society

C O M M U N I C A T I O N S
cationic platinum-phosphine complex [PtCl(7d)]+. To our knowl-
edge, this is the first report of the catalytic enantioselective
cycloaddition of metal-containing zwitterionic intermediates gener-
ated from alk-4-yn-1-ones.
Table 3. Generality of the Reaction
Acknowledgment. This research was partly supported by a
Grant-in-Aid for Scientific Research from Ministry of Education,
Culture, Sports, Science and Technology of Japan. K.I. has been
granted a Research Fellowship of the Japan Society for the
Promotion of Science for Young Scientists.
entry
R1
R2
R3
Time
Yield(%)a/Ee(%)b
1
2
3
Ph
Me
Me
Me
Me
Me
Me
Me
Me
Bu
Bn
Bn
Bn
Bn
TIPS
Bn
PMB
Bn
Bn
Bn
16.5 h
9 h
70/91(-)
70/91(-)
79/89(-)
80/91(-)
68/94(-)
89/90(-)
69/91(-)
83/93(-)
50/96(-)
51/97(-)
65/97(-)
p-Me-C6H4
p-CF3-C6H4
CH2CH2Ph
CH2CH2Ph
i-Pr
21 h
11 h
43 h
17 h
46 h
8 h
26 h
9 h
48 h
4
Supporting Information Available: Preparative methods and
spectral and analytical data of all new materials (PDF). This material
is available free of charge via the Internet at http://pubs.acs.org.
5c
6
7d
8
i-Pr
(CH2)3OTIPS
CH2CH2Ph
Ph
9e
10f
References
CH2OBn
CHdCH2
11c g
Ph
TIPS
,
(1) For recent reviews, see: (a) Jime´nez-Nu´n˜ez, E.; Echavarren, A. M. Chem.
Commun. 2007, 333–346. (b) Chianese, A. R.; Lee, S. J.; Gagne´, M. R.
Angew. Chem., Int. Ed. 2007, 46, 4042–4059. (c) Fu¨rstner, A.; Davies,
P. W. Angew. Chem., Int. Ed. 2007, 46, 3410–3449. (d) Shen, H. C.
Tetrahedron 2008, 64, 3885–3903. (e) Sohel, S.; Md., A.; Liu, R.-S. Chem.
Soc. ReV. 2009, 38, 2269–2281. (f) Fu¨rstner, A. Chem. Soc. ReV. 2009,
38, 3208–3221.
(2) For examples of platinum- or gold-catalyzed asymmetric enyne cyclizations,
see: (a) Charruault, L.; Michelet, V.; Taras, R.; Gladiali, S.; Geneˆt, J.-P.
Chem. Commun. 2004, 850–851. (b) Toullec, P. Y.; Chao, C.-M.; Chen,
Q.; Gladiali, S.; Geneˆt, J.-P.; Michelet, V. AdV. Synth. Catal. 2008, 350,
2401–2408. (c) Brissy, D.; Skander, M.; Retailleau, P.; Frison, G.; Marinetti,
A. Organometallics 2009, 28, 140–151. (d) Brissy, D.; Skander, M.; Jullien,
H.; Retailleau, P.; Marinetti, A. Org. Lett. 2009, 11, 2137–2139. (e) Mun˜oz,
M. P.; Adrio, J.; Carretero, J. C.; Echavarren, A. M. Organometallics 2005,
24, 1293–1300. (f) Chao, C.-M.; Vitale, M. R.; Toullec, P. Y.; Geneˆt, J.-
P.; Michelet, V. Chem.sEur. J. 2009, 15, 1319–1323. (g) Chao, C.-M.;
Beltrami, D.; Toullec, P. Y.; Michelet, V. Chem. Commun. 2009, 6988–
6990.
(3) (a) Watson, I. D. G.; Ritter, S.; Toste, F. D. J. Am. Chem. Soc. 2009, 131,
2056–2057. (b) Uemura, M.; Watson, I. D. G.; Katsukawa, M.; Toste, F. D.
J. Am. Chem. Soc. 2009, 131, 3464–3465. (c) Johansson, M. J.; Gorin,
D. J.; Staben, S. T.; Toste, F. D. J. Am. Chem. Soc. 2005, 127, 18002–
18003.
(4) (a) Kusama, H.; Funami, H.; Takaya, J.; Iwasawa, N. Org. Lett. 2004, 6,
605–608. (b) Kusama, H.; Funami, H.; Iwasawa, N. Synthesis 2007, 2014–
2024. (c) Kusama, H.; Ishida, K.; Funami, H.; Iwasawa, N. Angew. Chem.,
Int. Ed. 2008, 47, 4903–4905.
(5) For other examples of cycloaddition of metal-containing zwitterionic
intermediates, see: (a) Oh, C. H.; Lee, J. H.; Lee, S. M.; Yi, H. J.; Hong,
C. S. Chem.sEur. J. 2009, 15, 71–74. (b) Li, G.; Huang, X.; Zhang, L.
J. Am. Chem. Soc. 2008, 130, 6944–6945. (c) Hsu, Y.-C.; Ting, C.-M.;
Liu, R.-S. J. Am. Chem. Soc. 2009, 131, 2090–2091. (d) Shu, X.-Z.; Zhao,
S.-C.; Ji, K.-G.; Zheng, Z.-J.; Liu, X.-Y.; Liang, Y.-M. Eur. J. Org. Chem.
2009, 117–122. (e) Hojo, D.; Noguchi, K.; Tanaka, K. Angew. Chem., Int.
Ed. 2009, 48, 8129–8132.
(6) For reviews of cycloaddition reaction of metal-containing zwitterionic
intermediates, see: (a) Kusama, H.; Iwasawa, N. Chem. Lett. 2006, 35,
1082–1087. (b) Asao, N. Synlett 2006, 1645–1656.
(7) Hartung, I. V.; Hoffmann, H. M. R. Angew. Chem., Int. Ed. 2004, 43, 1934–
1949.
a Isolated yield. b Determined by chiral HPLC analysis (see
Supporting Information). c 5 equiv of triisopropylsilyl vinyl ether were
used. d 1.5 equiv of 4-methoxybenzyl vinyl ether and 5 mol % of
catalysts were used. e 5 was obtained as a hydrolyzed ketone in 27%
yield. f Hydrolyzed ketone of 5 and an isomer of 4 were obtained in
17% and 13% yield, respectively. g Product was isolated as an alcohol
by deprotection of the silyl group.
was employed, the product 4a was obtained with good enantioselec-
tivity as a single diastereomer. Further screening of Walphos ligands
revealed that the use of Walphos 7d gave the product 4a in 49% yield
and 91% ee.13 Furthermore, the use of the isolated PtCl2-7d complex
and 10 equiv of vinyl ether increased the yield of 4a to 70% without
lowering the enantioselectivity.
The generality of this asymmetric reaction is summarized in Table
3. Ynones bearing various aryl or alkyl groups as R1 gave the
corresponding products 4 in good yields and mostly in over 90% ee’s.
4-Methoxybenzyl vinyl ether could be used as dipolarophiles to give
the desired product 4 bearing a PMBO group which can easily be
deprotected selectively in the presence of an olefin moiety. Further-
more, triisopropylsilyl vinyl ether could be used as a dipolarophile to
give the product 4 with higher enantioselectivity. The reactions of
ynones bearing butyl, benzyloxymethyl, and vinyl group as the alkyne
substituent R2 afforded the desired bicyclic alkenes 4 in lower yield
but with higher enantioselectivity. In most cases, 4 were obtained as
a single diastereomer bearing the alkoxy group in the exo orientation.
It should be noted that the products, 8-oxabicyclo[3.2.1]octane
derivatives equipped with several functional groups, are useful
intermediates not only for the synthesis of related natural products
containing this basic skeleton, such as (-)-englerin A14 and cortista-
tin,15 but also for the preparation of a variety of valuable functionalized
cyclic compounds through manipulation of the functional groups.
Finally, the reaction was successfully applied to the intramo-
lecular cycloaddition. Thus, treatment of an enynone 8 with 10 mol
% of the catalyst gave the desired tricyclic oxacycle 9 in 90% ee
in high yield (eq 1).
(8) (a) Oi, S.; Tsukamoto, I.; Miyano, S.; Inoue, Y. Organometallics 2001,
20, 3704–3709. (b) Cucciolito, M. E.; D’Amora, A.; Vitagliano, A.
Organometallics 2005, 24, 3359–3361. (c) Han, X.; Widenhoefer, R. A.
Org. Lett. 2006, 8, 3801–3804. (d) Feducia, J. A.; Campbell, A. N.; Doherty,
M. Q.; Gagne´, M. R. J. Am. Chem. Soc. 2006, 128, 13290–13297.
(9) We reported that a 1,2-hydrogen shift of the carbene intermediate 3 occurred
in the reaction of ynones bearing an alkyl or an alkoxy group at the
propargylic position with platinum(II) chloride. See ref 4c.
(10) We believe both electronic and steric parameters of the ligand influence
the reaction pathway. Examination of other ligands suggests that bulkier
ligands favor a 1,2-hydrogen shift product. Details will be reported in due
course.
(11) For example of the electrophilic activation of alkenes by monocationic
platinum-bisphosphine complex, see ref 8c.
(12) The [3+2]-cycloaddition reaction was thought to proceed in a stepwise
manner beginning with the nucleophilic addition of the vinyl ether to the
oxonium carbon, which was apart from the chiral ligand on platinum.
(13) The absolute configuration of 4a was determined by X-ray crystal structure
analysis of the corresponding dibromide. (see Supporting Information).
(14) Nicolaou, K. C.; Kang, Q.; Ng, S. Y.; Chen, D. Y.-K. J. Am. Chem. Soc.
2010, 132, 8219-8222, and references therein.
(15) Nicolaou, K. C.; Peng, X.-S.; Sun, Y.-P.; Polet, D.; Zou, B.; Lim, C. S.;
Chen, D. Y.-K. J. Am. Chem. Soc. 2009, 131, 10587–10597, and references
therein.
In summary, we have developed the enantioselective synthesis
of potentially useful 8-oxabicyclo[3.2.1]octane derivatives 4 by a
simple treatment of acyclic γ,δ-ynones 1 and vinyl ethers with a
JA102391T
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