1204

Chemistry Letters Vol.38, No.12 (2009)

Platinum(II)-catalyzed Acetal–Ene Reaction: Easy Access to Homoallylic Ethers
Katsukiyo Miura,1 Hiroyuki Izumi,2 Hidenori Kinoshita,1 Junji Ichikawa,2 and Akira Hosomi2
1
Department of Applied Chemistry, Graduate School of Science and Engineering,
Saitama University, Sakura-ku, Saitama 338-8570
2
Department of Chemistry, Graduate School of Pure and Applied Sciences, University of Tsukuba, Tsukuba 305-8571(Received October 2, 2009; CL-090889; E-mail: kmiura@apc.saitama-u.ac.jp)
Catalytic use of PtCl2 and AgX (X ¼ OTf and SbF6 ) has
been found to eﬀectively promote the intermolecular ene reaction of acetals and the tandem acetalization–ene reaction of aldehydes under solvent-free conditions.

Table 1. Acetal–ene reaction with methylidenecyclohexane(2a)aOMeR

Catalytic ene reactions using simple alkenes provide atomeconomical methods for allylation of carbon electrophiles.1 Unlike allylation reactions using allylmetals, they are not accompanied by metal wastes. The ene reaction of acetals leads to homoallylic ethers, an important class of synthetic intermediates. Theintramolecular acetal–ene reaction is well established as a useful
method for the construction of carbocycles and cyclic ethers;2,3
however, the intermolecular version has been little studied.4–6 In
the course of our study of Pt(II)-catalyzed reactions, we foundthat combined use of PtCl2 and AgX (X ¼ OTf and SbF6 )achieved an eﬃcient annulation of alkenols with aldehydes.7
The reaction mechanism probably involves the formation of oxocarbenium ions by the action of a Lewis acidic Pt(II) species
and subsequent intramolecular ene reaction. We herein describethat the Pt(II) catalysis is eﬀective also in the intermolecular acetal–ene reaction under solvent-free conditions, and that it enables direct conversion of aldehydes into homoallylic ethers bya tandem acetalization–ene reaction.
The reaction of benzaldehyde dimethyl acetal (1a) withmethylidenecyclohexane (2a) was initially selected to optimize
the reaction conditions. Catalytic use of PtCl2 (1 mol %) andAgOTf (2 mol %) in toluene at 60  C gave the desired homoallylic ether 3a in 64% yield (eq 1). Without solvent, the acetal–ene
reaction proceeded more eﬃciently. Both PtCl2 and AgOTf wereessential to the eﬃcient reaction.8 With 4 equivalents of 2a, theyield of 3a was improved to 90%.
Various acetals were subjected to the reaction with 2a(Table 1). Aromatic acetals 1b–1d smoothly underwent theene reaction (Entries 1–3). Use of acetal 1e derived from 4-methoxybenzaldehyde led to an unsuccessful result, which is due todecomposition of the desired product 3e (Entry 4). Aromaticacetal 1f and aliphatic acetal 1g were less reactive to 2a, however, they could be allylated eﬃciently when AgSbF6 was used instead of AgOTf (Entries 5–8). Acetals 1h and 1i were converted
into 3h and 3i in good yield under catalysis by PtCl2 and AgSbF6(Entries 9 and 10).
OMe
Ph

PtCl2 (1 mol%)
AgOTf (2 mol%)+60 °C, 1 hOMe
1aOMe
Ph

2a2a (2 equiv), toluene:
2a (2 equiv), neat:
2a (4 equiv), neat:

3a64%
83%
90%

PtCl2 (1 mol%)AgX (2 mol%)+ 2aneat, 60 °C

OMe

R13Entry

R (1)XTime/h12345678910

4-MeC6 H4 (1b)4-ClC6 H4 (1c)4-FC6 H4 (1d)4-MeOC6 H4 (1e)c4-O2 NC6 H4 (1f)
4-O2 NC6 H4Ph(CH2 )2 (1g)
Ph(CH2 )2n-C8 H17 (1h)c-C6 H11 (1i)

OTf
OTf
OTf
OTf
OTf
SbF6
OTf
SbF6
SbF6
SbF6

1
1
1
1.5
2
1
2
1
1
1.5

Yield/%b (3)87 (3b)82 (3c)76 (3d)53 (3e)42 (3f)78 (3f)26d (3g)
80d (3g)
83 (3h)85 (3i)aConditions: 1 (1.00 mmol), 2a (4.00 mmol), PtCl2 (0.01 mmol),AgX (0.02 mmol), 60  C. b Isolated yield. c At 40  C. d Determinedby GC.

The scope of alkenes was next examined. The reaction of 1awith 1-decene did not occur at all. In contrast, 2-methyl-1-heptene (2b) reacted with acetals 1a and 1h to aﬀord the corresponding ene products as mixtures of regio- and stereo-isomers (eq 2).
Thus gem-disubstituted alkenes, which are more electron-richthan monosubstituted alkenes, showed high reactivity toward
the ene reaction. 1-Methylcyclohexene (2c), a trisubstitutedalkene, was also reactive enough for the ene reaction with 1a(eq 3).
Under the standard conditions, the reaction of 1a with methylstyrene (2d) gave the ene product 8a in moderate yield
OMe
R

PtCl2 (1 mol%)AgX (2 mol%)
+

BuOMe

ð2Þ

neat, 60 °C

2b

1OMe

OMe
Bu +R

R
4a, 71% (E : Z = 73:27)
R = Ph, X = OTf, 6 h:
R = n -C8H17, X = SbF6, 1 h: 4b, 72% (E : Z = 70:30)+Ph5a, 4%5b, 6%

ð3Þ

neat, 60 °C, 0.7 h

OMe
1aBu

PtCl2 (1 mol%)
AgSbF6 (2 mol%)OMeð1ÞOMeOMe

2cPh

OMe+ Ph

6, 54% (dr = 66:34)

Copyright Ó 2009 The Chemical Society of Japan7, 2%

Chemistry Letters Vol.38, No.12 (2009)

1205

Table 2. Reaction of -methylstyrene (2d)aPtCl2 (1 mol%)
AgOTf (2 mol%)OMe+
R

Table 3. Tandem acetalization–ene reactiona

1+Ph

OMe

toluene

R2d+

MeO

RPhPh
8a (R = Ph), 8b (R = n -C8H17)

OMe
Ph1Temp/ CTime/h1b23d4561a1a1h1a1a1a6060603030300.50.50.33
1312PhOMeGC yield/%
89106171 (70)c(73)c1333
721612—6153
1162
69—
93995

Conditions: 1 (1.00 or 3.00 mmol), 2a (4 equiv), PtCl2(1 mol %), AgOTf (2 mol %), toluene (1 mL/1 mmol of 1).
b
Without toluene. c Isolated yield. d AgSbF6 was used instead ofAgOTf.

(Entry 1 in Table 2). Diether 9 and methyl ether 10 were formed
as by-products. Use of toluene as solvent improved the yield of8a (Entry 2). A similar result was obtained in the reaction of 1h(Entry 3). Interestingly, the reaction of 1a with 2d at 30  C for
1 h gave 9 predominantly (Entry 4). The molar ratios of 8a and
10 to 9 increased with the reaction time (Entries 5 and 6). After
12 h the yield of 8a reached 72%. This observation is indicativeof the formation of 8a from 9. Indeed, 9 was partially converted
into 8a under catalysis by PtCl2 and AgOTf (eq 4). The presenceof 2d was eﬀective in the elimination of methanol from 9.
PtCl2 (1 mol%), AgOTf (2 mol%)
9 + 8a + 10

toluene, 30 °C

Without 2d:
76%
With 2d (1 equiv): 34%

11%
50%

ð4Þ

24%

The present reaction probably involves the formation of an
oxocarbenium ion 11 (Scheme 1). The Lewis acidic Pt(II) species generated from PtCl2 and AgX would promote the C–O
bond cleavage of 1.8 The allylation of 11 with alkene 2 can proceed by a concerted or stepwise path. The latter path consists ofthe formation of a cationic adduct 12 and its deprotonation.
Judging from the formation of 9 and its elimination to 8a, the reaction of 2d would take the stepwise path. The preference for thestepwise path is likely due to the cation-stabilizing eﬀect of thephenyl group.
Pt (II)OMe − Pt OMeOMe

211− H+concerted

R1OMe

R1
R2R

R1

2R2stepwiseOMe

R1R2R
121234567810aRneat, 60 °C

H

Entry+9

EntryOMeHC(OR1)3 + 2a− H+Pt OMe

MeO

R1 = HR2 = PhROMePh9Scheme 1. Plausible mechanisms for the acetal–ene reaction.

OR 1R313OMe

9 + 2dPtCl2 (1 mol%)AgX (2 mol%)O

R (13)

R

1XTime/h

Ph (13a)Ph
4-ClC6 H4 (13c)4-O2 NC6 H4 (13f)
Ph(CH2 )2 (13g)n-C8 H17 (13h)n-C8 H17
c-C6 H11 (13i)

Me
Et
Me
Me
Me
Me
Et
Me

OTf
OTf
OTf
SbF6
SbF6
SbF6
SbF6
SbF6

3
31.5
3
1
1
1
1

Yield/%b (3)78 (3a)83 (3j)71 (3c)80 (3f)78 (3g)96 (3h)67 (3k)91 (3i)aConditions: 13 (1.00 mmol), HC(OR1 )3 (1.00 or 1.20 mmol), 2a(4.00 mmol), PtCl2 (0.01 mmol), AgX (0.02 mmol), 60  C. b Isolatedyield.

We further attempted a direct synthesis of homoallylicethers from aldehydes by a tandem acetalization–ene reaction.
We found that orthoformates acted as eﬀective acetalization
agents. Thus the Pt(II)-catalyzed reaction of benzaldehyde(13a), methyl orthoformate, and 2a gave the desired product3a in good yield (Entry 1 in Table 3). Use of ethyl orthoformate
led to ethyl ether 3j (Entry 2). Other aldehydes also underwent
the tandem reaction eﬃciently (Entries 3–8).
In conclusion, we have developed the Pt(II)-catalyzed acetal–ene reaction under solvent-free conditions, which provides
a convenient, green route to homoallylic ethers. More importantly, the Pt(II) catalysis is quite eﬀective in the tandem acetalization–ene reaction of aldehydes.9
References and Notes
1 a) B. B. Snider, in Comprehensive Organic Synthesis, ed. by B. M.
Trost, I. Fleming, Pergamon, Oxford, 1991, Vol. 2, pp. 527–561. b)
D. J. Berrisford, C. Bolm, Angew. Chem., Int. Ed. Engl. 1995, 34,1717. c) K. Mikami, M. Terada, in Comprehensive Asymmetric Catalysis, ed. by E. N. Jacobsen, A. Pfaltz, H. Yamamoto, Springer Verlag,Berlin, 1999, Vol. III, pp. 1143–1174.
2 Reviews: a) B. B. Snider, Acc. Chem. Res. 1980, 13, 426. b) K.
Mikami, M. Shimizu, Chem. Rev. 1992, 92, 1021.
3 a) H. Muratake, M. Natsume, Tetrahedron 2006, 62, 7056. b) T. A.
Blumenkopf, M. Bratz, A. Castañeda, G. C. Look, L. E. Overman,D. Rodriguez, A. S. Thompson, J. Am. Chem. Soc. 1990, 112, 4386.
c) T. A. Blumenkopf, G. C. Look, L. E. Overman, J. Am. Chem.
Soc. 1990, 112, 4399. d) M. L. Melany, G. A. Lock, D. W. Thompson,J. Org. Chem. 1985, 50, 3925.
4 For a pioneering work on acetal–ene reaction, see: T. Mukaiyama, K.
Wariishi, M. Furuya, S. Kobayashi, Chem. Lett. 1989, 1277.
5 a) K. Ishihara, H. Nakamura, H. Yamamoto, Synlett 2000, 1245. b) H.
Nakamura, K. Ishihara, H. Yamamoto, J. Org. Chem. 2002, 67, 5124.
6 Ghosez and co-workers have reported that FeCl3 is an eﬀective catalyst
of intermolecular acetal–ene reaction in CH2 Cl2 . This method is slightly less eﬃcient to the reaction of aromatic acetals and cannot be applied to the reaction with trisubstituted alkenes. A. Ladépêche, E.
Tam, J.-E. Ancel, L. Ghosez, Synthesis 2004, 1375.
7 K. Miura, M. Horiike, G. Inoue, J. Ichikawa, A. Hosomi, Chem. Lett.
2008, 37, 270.
8 TfOH (2 mol %) also promoted the ene reaction of 1a with 2a (1 h, 60%
yield). We cannot neglect the participation of proton catalysis. We appreciate the referee’s suggestion on the reaction mechanism.
9 Supporting Information is available electronically on the CSJ-Journal
Web site, http://www.csj.jp/journals/chem-lett/index.html.

Published on the web (Advance View) November 21, 2009; doi:10.1246/cl.2009.1204