Platinum-catalyzed intramolecular hydroalkoxylation of γ- and δ-hydroxy olefins to form cyclic ethers

Article abstract of DOI:10.1021/ja0477773

Reaction of 2,2-diphenyl-4-penten-1-ol with a catalytic mixture of [PtCl₂(H₂C=CH₂)]₂ (1 mol %) and P(4-C₆H₄CF₃)₃ (2 mol %) at 70 °C for 24 h led to the isolation of 2-

Full text of DOI:10.1021/ja0477773

Published on Web 07/16/2004
Platinum-Catalyzed Intramolecular Hydroalkoxylation of γ- and δ-Hydroxy
Olefins to Form Cyclic Ethers
Hua Qian, Xiaoqing Han, and Ross A. Widenhoefer*
P. M. Gross Chemical Laboratory, Duke UniVersity, Durham, North Carolina 27708-0346
Received April 17, 2004; E-mail: rwidenho@chem.duke.edu
Table 1. Effect of Solvent and Phosphine on the
Platinum-Catalyzed Hydroalkoxylation of 2 Catalyzed by
[PtCl2(H2CdCH2)]2 (1)
The prevalence of saturated oxygen heterocycles in both naturally
occurring and biologically active molecules1 including the aceto-
genins and polyether antibiotics has fueled interest in the develop-
ment of new and efficient methods for the synthesis of cyclic
ethers.2 A particularly attractive approach to the synthesis of cyclic
ethers is via the intramolecular addition of the O-H bond of an
alcohol across the CdC bond of a pendant olefin. Although olefin
hydroalkoxylation is catalyzed by Brønsted acids, such approaches
are of limited synthetic utility.2,3 Rather, selective olefin hydro-
alkoxylation typically requires employment of a stoichiometric
amount of an often toxic electrophile followed by reduction with
an activated metal or metal hydride reagent in a separate step.2,4
Transition metal catalysis represents a potential means to achieve
selective olefin hydroalkoxylation under mild conditions. However,
efficient catalytic hydroalkoxylation has been achieved only in the
cases of CtC5 and activated CdC bonds such as allenes,6 1,3-
dienes,7 and Michael acceptors.8-11 Here we report a mild and
efficient platinum-catalyzed protocol for the intramolecular hy-
droalkoxylation of unactivated γ- and δ-hydroxy olefins.
entry
PR
3
temp (°C)
solvent
yield (%)
1
2
3
4
5
6
7
8
9
10
11
12
13
none
PPh3
PPh3
PPh3
PPh3
PPh3
P(4-C6H4OMe)3
P(4-C6H4Cl)3
P(4-C6H4CF3)3
P(4-C6H4CF3)3
P[3,5-C6H3(CF3)2]3
P(OCH3)3
80
80
80
80
80
70
70
70
70
70
70
70
70
dioxane
dioxane
CCl4
12a,b
42a,c
12a
32a
65a
70a
60d
68d
82d
78d,e
49d
45d
76d
C2H4Cl2
C2H2Cl4
C2H2Cl4
C2H2Cl4
C2H2Cl4
C2H2Cl4
C2H2Cl4
C2H2Cl4
C2H2Cl4
C2H2Cl4
P(2-furyl)3
Simple platinum(II) complexes including [PtCl2(H2CdCH2)]2 (1)
catalyze the hydroalkylation,12 hydroarylation,13 and hydroamina-
tion14 of unactivated olefins. On the basis of these examples, we
considered that 1 might also catalyze the hydroalkoxylation of
unactivated olefins. Unfortunately, the procedures optimized for
C-C12,13 and C-N14 bond formation proved largely ineffective for
the conversion of 2,2-diphenyl-4-penten-1-ol (2) to 2-methyl-4,4-
diphenyltetrahydrofuran (3) (Table 1, entries 1 and 2).15 Therefore,
the efficiency of the platinum-catalyzed conversion of 2 to 3 was
optimized as a function of solvent and phosphine (Table 1). From
these experiments, an effective protocol was identified; reaction
of 2 with a catalytic mixture of 1 (2.5 mol %) and P(4-C6H4CF3)3
(5 mol %) in Cl2CHCHCl2 at 70 °C for 24 h led to the isolation of
3 in 82% yield as a single regioisomer (Table 1, entry 9).16 Effective
conversion of 2 to 3 was also realized with 1% catalyst loading
(Table 1, entry 10).
a GC yield versus internal standard. b 10 mol % of 1 employed. c 5 mol
% of 1 and 10 mol % PPh3 employed. d Isolated yield of g95% pure
material. e 1 mol % of 1 and 2 mol % phosphine employed.
Scheme 1
Platinum-catalyzed hydroalkoxylation of γ-hydroxy olefins toler-
ated substitution at the R, â, and γ-carbon atoms and at the internal
and cis and trans terminal olefinic positions (Table 2, entries 1-15).
Platinum-catalyzed hydroalkoxylation tolerated a number of func-
tional groups including pivaloate and acetate esters, amides, silyl
and benzyl ethers, and pendant hydroxyl and olefinic groups (Table
2, entries 3-9). The efficiency and regioselectivity of hydroalkoxyl-
ation was sensitive to terminal olefinic substitution. For example,
whereas 5-methyl-2,2-diphenyl-4-hexen-1-ol underwent 6-endo
cyclization in high yield, (Z)-2,2-diphenyl-4-hepten-1-ol underwent
5-exo cyclization in moderate yield (Table 2, entries 10 and 11).15
In comparison, Pt-catalyzed cyclization of (E)-2,2-diphenyl-4-
hexen-1-ol led to the isolation of a 3.6:1 mixture of five- and six-
membered heterocycles in 63% combined yield (Table 2, entry 12).
Platinum-catalyzed hydroalkoxylation was also applicable to the
synthesis of fused- and spirobicyclic ethers (Table 2, entries 13-
15) and was effective for the hydroalkoxylation of δ-hydroxy olefins
to form substituted tetrahydropyran derivatives (Table 2, entries
16-19).
Both the regio- and stereoselectivity of platinum-catalyzed
hydroalkoxylation parallels the selectivity observed for the oxy-
mercuration/reduction of γ- and δ-hydroxy olefins,2 which suggests
that C-O bond formation occurs by a similar mechanism in both
processes. On the basis of this analogy and by analogy to the
mechanism established for the platinum-catalyzed cyclization of
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J. AM. CHEM. SOC. 2004, 126, 9536-9537
10.1021/ja0477773 CCC: $27.50 © 2004 American Chemical Society

C O M M U N I C A T I O N S
Table 2. Hydroalkoxylation of γ- and δ-hydroxy Olefins (2.0 M)
Catalyzed by a Mixture of [PtCl2(H2C)CH2)]2 (1) (1 mol %) and
P(4-C6H4CF3)3 (2 mol %) in Cl2CHCHCl2 at 70 °C for 16-48 h
zwitterion II (Scheme 1). Although a number of pathways can be
envisioned for proton transfer, we favor a mechanism involving
ionization to form a contact or solvent-separated ion pair (III),
followed by protonolysis of the Pt-C bond (Scheme 1). A similar
proton-transfer pathway has been proposed for the Wacker oxida-
tion17 and would obviate the need to break a strong Pt-Cl bond
prior to protonolysis.
In summary, we have developed a mild and efficient platinum-
catalyzed protocol for the hydroalkoxylation of γ- and δ-hydroxy
olefins. Our current efforts are directed toward expanding the scope
and improving the efficiency of platinum-catalyzed olefin hy-
droalkoxylation.
Acknowledgment is made to the NSF (CHE-03-04994) for
support of this research. R.W. thanks the Camille and Henry
Dreyfus Foundation and GlaxoSmithKline for unrestricted financial
assistance.
Supporting Information Available: Experimental procedures and
spectroscopic data for products. This material is available free of charge
via the Internet at http://pubs.acs.org.
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a Isolated product of >95% purity. b Reaction time ) 64 h. c 0.5 mol %
1 and 1 mol % P(4-C6H4CF3)3 employed. d Reaction temperature ) 80 °C.
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hydroxyl group on the platinum-complexed olefin of I to form
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