Carbon-carbon bond formation in palladium(II)-catalyzed allylic oxidation: A novel oxidative carbocyclization of allene-substituted olefins

Article abstract of DOI:10.1021/ja029505a

A new efficient palladium(II)-catalyzed oxidative carbocyclization has been developed. It was found that allene-substituted olefins 1 cyclized in the presence of 1 mol % Pd(O₂CCF₃)₂ and p-benzoquinone (2 equiv) to give bic

Full text of DOI:10.1021/ja029505a

Published on Web 04/29/2003
Carbon-Carbon Bond Formation in Palladium(II)-Catalyzed Allylic Oxidation:
A Novel Oxidative Carbocyclization of Allene-Substituted Olefins
Johan Franze´n and Jan-E. Ba¨ckvall*
Department of Organic Chemistry, Arrhenius Laboratory, Stockholm UniVersity, SE-106 91 Stockholm, Sweden
Received November 27, 2002; E-mail: jeb@organ.su.se
Table 1. Palladium(II)-Catalyzed Oxidative Carbocyclization of
Functionalizations of C-H bonds are important processes that
Allene-Substituted Olefins 1a
have attracted considerable attention recently.1 A special case is
the activation of allylic C-H bonds, and there are many reports in
the literature on metal-mediated allylic oxidations.2-5 Most of these
reactions, however, proceed with moderate selectivity and often
with the use of stoichiometric amounts of the metal. A few examples
of catalytic allylic oxidations are known, and these include
palladium- and copper-catalyzed allylic acyloxylation to give allylic
esters.3,4 Allylic oxidations involving carbon-carbon bond forma-
tion are scarce and are only known with the use of stoichiometric
amounts of metal.6 For example, it is known that palladium(II)
complexes can cleave allylic C-H bonds to give (π-allyl)palladium
complexes.7 Activation of these π-allyl complexes by phosphine
ligands and subsequent nucleophilic attack by a stabilized carbanion
lead to C-C bond formation in the allylic position.6,8 The
requirement of stoichiometric amounts of metal limits the synthetic
utility of these reactions.
We have recently been involved in palladium-catalyzed reactions
with allenes.9,10 In the present study, we have found that allene-
substituted olefins 1 cyclize oxidatively in the presence of catalytic
amounts of Pd(O2CCF3)2 to give 2 (Scheme 1). This is the first
example of an allylic oxidation leading to carbon-carbon bond
formation employing catalytic amounts of palladium(II).11
Scheme 1
The requisite starting materials 1 were readily obtained from the
corresponding allylic acetates 3. A Pd(0)-catalyzed allylic substitu-
tion of the acetate with sodium dimethyl malonate to give 4 follow-
ed by reaction with bromoallene 5 furnished 1a-g (Scheme 2).
Scheme 2 a
a Unless otherwise noted, 1, Pd(O2CCF3)2 (1 mol %), and BQ (2 equiv)
were dissolved in THF (5 mL/mmol) and refluxed for 4 h. b 6 h of reflux
a (a) NaH, (MeO2C)2CH2, Pd(OAc)2, PPh3, THF, reflux; (b) NaH, 5,
THF, reflux.
was required for full conversion. c 12 h of reflux was required for full
conversion. d Refluxing toluene and Pd(OAc)2 (2 mol %) were used.
Treatment of allene-substituted olefins 1a-d with 1 mol % Pd-
(O2CCF3)2 and 2 equiv of p-benzoquinone (BQ) in refluxing THF
for 4-6 h gave 2a-d in good to high yields (entries 1-4, Table
1). The dependence of the substrate ring size on the outcome of
the cyclization was investigated (entries 5-7, Table 1). The five-
membered ring (1e) cyclized to give a mixture of isomers 2e and
2e′. The formation of 2e′ can be explained by a Pd(II)-catalyzed
isomerization of 2e.
isomer in 82% yield. The stereochemistry of 2f was unambiguously
assigned by NOE measurements. When the ring size was further
increased to an eight-membered ring 1g, the cis-fused ring system
was again obtained as the only product. The acyclic substrate 1h
gave triene 2h. Interestingly, allylic pivalate trans-1i, in which the
allenic moiety and the ester function are trans to one another, under-
went oxidative cyclization in refluxing toluene with Pd(OAc)2 as the
catalyst to give vinylic pivalate 2i.12 On the other hand, the isomeric
substrate cis-1i, with the pivalate and the allenic moiety cis to one
another, cyclized to give 2a. The latter reaction is not an oxidation
reaction but formally an elimination of pivalic acid with cyclization.
In contrast to the five- and six-memebered ring substrates 1a-
e, which all gave the cis-fused ring systems, the seven-membered
ring substrate 1f afforded the trans-fused ring system 2f as a single
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10.1021/ja029505a CCC: $25.00 © 2003 American Chemical Society

C O M M U N I C A T I O N S
If an additional olefin was placed in the allenic side chain, or if
two methyl groups were placed in the allylic position, the cyclization
was completely inhibited under the present reaction conditions.
To gain further insight into the mechanism of the cyclization of
1 to 2, deuterated compounds trans-1a-d1 and cis-1f-d1 were pre-
pared.13 Oxidation of trans-1a-d1 and cis-1f-d1 by BQ in the presence
of catalytic amounts of Pd(O2CCF3)2 gave cis-2a-d1 and trans-2f-
d1, respectively, with complete retention of deuterium (Scheme 3).
In summary, we have found that allene-substituted olefins
undergo an oxidative cyclization, in good to excellent yields, in
the presence of Pd(O2CCF3)2 as catalyst and p-benzoquinone as
the stoichiometric oxidant. The fact that the catalyst loading can
be as low as 1 mol % and that the starting materials are readily
accessible makes this oxidation attractive in organic synthesis.
Acknowledgment. Financial support from the Swedish Research
Council and the Swedish Foundation for Strategic Research is
gratefully acknowledged.
Scheme 3
Supporting Information Available: Experimental procedures and
characterizations for products 1a, 2a, deuterated compounds trans-1a-
d1, cis-2a-d1, cis-1f-d1, trans-2f-d1, and spectral data for all new
compounds (PDF). This material is available free of charge via the
Internet at http://pubs.acs.org.
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At least two mechanisms can be considered for these palladium-
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Scheme 4) with palladium syn to the pending allene followed by
nucleophilic attack on palladium by the allene14 (A) and subsequent
insertion would give B. Subsequent syn â-hydride elimination
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Scheme 4
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reaction, and the starting material was recovered. Attempts to cyclize 1i
with Pd(O2CCF3)2/BQ in refluxing toluene resulted in a complex mixture
of unidentified products.
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catalyzed NaBD4 reduction of the corresponding allylic trifluoroacetate
(see Supporting Information).
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intermediate followed by elimination of a proton, rather than an oxidative
allylic C-H abstraction. However, both pathways would lead to the same
intermediate A.
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analogous mechanisms but with palladium on the opposite side of
the ring as the pendant allene.
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bond cleavage and â-elimination are syn-selective processes.
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membered ring. However, formation of 2h from 1h is only
consistent with the first proposal, involving intermediates A and
B. Furthermore, when 1a and 6 were allowed to react in a
competitive reaction, only 1a was converted to 2a, whereas 6
remained unreacted (Scheme 5).17 This suggests that a pathway
Scheme 5
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via (π-allyl)palladium intermediate C (Scheme 4) is less likely.
However, another interpretation is that the cyclohexene double bond
is not forming a favorable chelate in 6 required to give (π-allyl)-
palladium intermediate C (cf. trans-1a-d1 f C, Scheme 4).
(17) Compounds 1a and 6 would be able to form the same (π-allyl)palladium
intermediate and should in that case both cyclize to give 2a.
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