Successive C-C coupling of dienes to vicinally dioxygenated hydrocarbons: Ruthenium catalyzed [4 + 2] cycloaddition across the diol, hydroxycarbonyl, or dione oxidation levels

Article abstract of DOI:10.1021/ja400691t

The ruthenium(0) catalyst generated from Ru₃(CO)₁₂ and tricyclohexylphosphine or BIPHEP promotes successive C-C coupling of dienes to vicinally dioxygenated hydrocarbons across the diol, hydroxyketone, and dione oxidation levels to form products of [4 + 2] cycloaddition. A mechanism involving diene-carbonyl oxidative coupling followed by intramolecular carbonyl addition from the resulting allylruthenium intermediate is postulated.

Full text of DOI:10.1021/ja400691t

Communication
pubs.acs.org/JACS
Successive C−C Coupling of Dienes to Vicinally Dioxygenated
Hydrocarbons: Ruthenium Catalyzed [4 + 2] Cycloaddition
across the Diol, Hydroxycarbonyl, or Dione Oxidation Levels
Laina M. Geary, Ben W. Glasspoole, Mary M. Kim, and Michael J. Krische*
University of Texas at Austin, Department of Chemistry and Biochemistry, Austin, Texas 78712, United States
S
* Supporting Information
ABSTRACT: The ruthenium(0) catalyst generated from
Ru3(CO)12 and tricyclohexylphosphine or BIPHEP promotes
successive C−C coupling of dienes to vicinally dioxygenated
hydrocarbons across the diol, hydroxyketone, and dione
oxidation levels to form products of [4 + 2] cycloaddition. A
mechanism involving diene-carbonyl oxidative coupling
followed by intramolecular carbonyl addition from the
resulting allylruthenium intermediate is postulated.
icinal diols are ubiquitous in Nature and are of interest vis-a-
̀
V
vis biomass conversion,1,2 yet there exist no examples of
their direct catalytic C−C coupling. We have developed a broad
family of transformations wherein hydrogen transfer between
alcohols and π-unsaturated reactants produces organometal−
carbonyl pairs that combine to form products of addition.3 In the
course of these studies, a ruthenium(0) catalyst recently was
identified that promotes alcohol C−C coupling through an
alternate mechanism, wherein alcohol dehydrogenation drives
carbonyl-diene oxidative coupling to form metallacyclic intermedi-
ates, as illustrated in couplings of α-hydroxy esters to isoprene or
myrcene to form products of prenylation or geranylation,
respectively.4 It was posited that the allylruthenium species arising
transiently upon diene-carbonyl oxidative coupling might be
intercepted via allylruthenation onto a tethered carbonyl moiety to
form products of cycloaddition, suggesting the feasibility of utilizing
diols as partners for C−C coupling. Here, we report that vicinal diols
and their more highly oxidized forms (hydroxyketones and diones)
engage in [4 + 2] cycloaddition with a diverse range of conjugated
dienes, constituting a powerful, new cycloaddition that may be con-
ducted in reductive, redox-neutral, or oxidative modes (Figure 1).5,6
Following the mechanism postulated above, the phenethyl diol 1a
was exposed to isoprene 4b in the presence of substoichiometric
quantities of Ru3(CO)12 and tricyclohexylphosphine, PCy3, at130°C
in toluene solvent. Remarkably, the product of cycloaddition 5a was
obtained in 78% isolated yield as a 6:1 mixture of regioisomers.
Whereas PCy3 was the preferred ligand for terminal 1,2-diols 1a−1b,
a screen of phosphine ligands revealed that the chelating
phosphine ligand BIPHEP, 2,2′-bis(diphenylphosphino)-
1,1′-biphenyl, was better for internal 1,2-diols 1c−1h. For
internal diols 1c−1h, cis- or trans-diastereomers react with
equal facility (Table 1).
Figure 1. Cycloaddition of vicinally dioxygenated hydrocarbons
through interception of an allylruthenium intermediate.
is tolerated at any position of the diene. For the dimethyl substituted
butadienes 4e−4g, good to excellent yields of cycloadducts 5l−5o,
respectively, are obtained. For the terminally disubstituted diene 4h,
2,4-hexadiene, substantial olefin isomerization in advance of
cycloaddition is observed (Table 2). Indeed, Ru3(CO)12
catalyzed olefin isomerization has been documented.7 This
phenomenon is advantageous in terms of recruiting non-
conjugated dienes as partners for cycloaddition. For example,
rac-cyclohexanediol 1f was reacted with the nonconjugated
diene iso-4g (eq 1). Remarkably, iso-4g and 4g produce
cycloadduct 5n with roughly equal facility.
The cycloadditions of diols 1a−1h are oxidative processes
wherein excess diene presumably serves as the hydrogen
acceptor (Tables 1 and 2). The feasibility of cycloaddition
from more highly oxidized congeners of diols 1a−1d and 1f were
evaluated in reactions with isoprene 4b (Table 3). In the event,
exposure of the α-hydroxycarbonyl compounds 2a−2d and 2f to
standard conditions employing substoichiometric quantities of
Ru3(CO)12 and either PCy3 or BIPHEP as a ligand provided
the cycloadducts 5a−5d and 5f in good to excellent yield.
The scope of the diene partner is illustrated in cycloadditions of
rac-cyclohexanediol 1f. Butadiene 4a and a range of substituted
dienes 4b−4h participate in the ruthenium catalyzed cycloaddition
to furnish decalins 5f, 5i−5o in excellent yield. A single substituent
Received: January 21, 2013
© XXXX American Chemical Society
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Table 1. Ruthenium Catalyzed [4 + 2] Cycloaddition of
Isoprene 4b with Diols 1a−1h
Table 3. Ruthenium Catalyzed [4 + 2] Cycloaddition of
Isoprene 4b with Vicinally Dioxygenated Hydrocarbons
1a−1d, 1f, 2a−2d, 2f, and 3a−3d, 3f
a
a
a
b
Yields are of material isolated by silica gel chromatography. PCy3
c
(12 mol %). 150 °C. See Supporting Information for further details
and structural assignments.
Table 2. Ruthenium Catalyzed [4 + 2] Cycloaddition of
a
rac-Cyclohexanediol 1f with Dienes 4a−4h
a
b
Yields are of material isolated by silica gel chromatography. PCy3
c
d
(12 mol %). BIPHEP (6 mol %). RuH2CO(PPh3)3 (6 mol %),
BIPHEP (6 mol %). 150 °C. See Supporting Information for further
e
details and structural assignments.
A general catalytic mechanism has been proposed, as illustrated
in the cycloaddition of rac-cyclohexanediol 1f and isoprene 4b
(Scheme 1). It is well established that exposure of Ru3(CO)12 to
chelating phosphine ligands provides complexes of the type
Ru(CO)3(diphosphine).9 Hence, intervention of a discrete,
monometallic catalyst is anticipated. The Ru3(CO)12 catalyzed
oxidation of alcohols employing olefins and alkynes as hydrogen
acceptors has been described.10,11 Further, mechanistically related
Ru3(CO)12 catalyzed secondary alcohol aminations involving
dehydrogenation of 1,2-diols12a and α-hydroxy esters12c are
known. These data suggest the present Ru3(CO)12−phosphine
catalyst system is capable of converting 1,2-diol 1f to the hydro-
xyketone 2f and, ultimately, the corresponding 1,2-dione 3f using
diene 4b as the hydrogen acceptor.10 The diol rac-1f, which is
introduced as the isomerically pure trans-stereoisomer, appears as
a mixture of cis- and trans-diastereomers when recovered from the
reaction mixture, suggesting dehydrogenation of 1f is reversible.
Small quantities of hydroxyketone 2f also can be recovered from
reaction mixtures. Oxidative coupling of 1,2-dione 3f and diene 4b
to form oxametallacycle I finds precedent in the work of Chatani
and Murai on Pauson−Khand type reactions of 1,2-diones13 and
our own work on the prenylation of substituted mandelic esters.4
Protonolytic cleavage of oxametallacycle I by 1f or 2f to form the
allylruthenium complex II triggers intramolecular allylruthenation
to form the ruthenium(II) alkoxide III. Finally, β-hydride
elimination forms ruthenium hydride IV and O−H reductive
elimination delivers the product 5f and returns ruthenium to its
zerovalent form to close the cycle.14
a
b
Yields are of material isolated by silica gel chromatography. 300 mol %
c
d
diene. 150 °C. The same products are generated in the same
distribution using 1,5-hexadiene. See Supporting Information for
further details and structural assignments.
Whereas reactions of α-hydroxycarbonyl compounds 2a−2d and
2f are redox-neutral processes, cycloadditions of the correspond-
ing dicarbonyl compounds 3a−3d and 3f are reductive processes
requiring a stoichiometric hydrogen donor. For such dicarbonyl
reactants, formic acid proved to be most effective reductant, and
use of RuH2CO(PPh3)3 as a precatalyst was advantageous in
certain cases.8 While glyoxals 3a and 3b failed to deliver any
cycloadduct, the vicinal diketones 3c, 3d, and 3f provided the
anticipated products 5c, 5d, and 5f in modest yields. Thus,
ruthenium catalyzed [4 + 2] cycloaddition is achieved from the
diol, hydroxycarbonyl, and dicarbonyl oxidation levels.
B
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Journal of the American Chemical Society
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Scheme 1. Proposed Mechanism and Stereochemical Model for the Cycloaddition of rac-Cyclohexanediol 1f and Isoprene 4b
The assignment of regio- and stereochemistry merit discussion.
Single crystal X-ray diffraction analysis of cycloadduct 5j revealed
the cis-diastereomer. Additionally, the 1H NMR spectral character-
istics of cycloadducts 5i and 5l are consistent with the indicated
meso-stereoisomers, not the corresponding C2-symmetric stereo-
isomers. The stereochemical assignment of other cycloadducts was
made in analogy to compounds 5j, 5i, and 5l. A model accounting
for the observed syn-diastereoselectivity has been postulated, which
involves intramolecular allylruthenation through a boat-like
transition structure. Finally, aromatization of cycloadduct 5a via
acid catalyzed double dehydration enabled the regiochemical
assignment of this cycloadduct (see Supporting Information).
Indeed, a systematic investigation of diol cycloaddition−aromatization
is now underway in our laboratory.
REFERENCES
■
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addition reactions remain highly uncommon.5,6 Here, we report a
powerful and conceptually novel strategy for the [4 + 2] cycloaddition
of dienes with 1,2-diols and their higher vicinally dioxygenated
congeners. This work demonstrates that merged redox-construction
events17 can be exploited in succession to form multiple C−C bonds,
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ASSOCIATED CONTENT
* Supporting Information
■
S
Experimental procedures and spectral data. Single crystal X-ray
diffraction data for compound 5j. This material is available free of
charge via the Internet at http://pubs.acs.org.
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1985, 281, 299. (b) Hilal, H. S.; Khalaf, S.; Jondi, W. J. Organomet. Chem.
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AUTHOR INFORMATION
Corresponding Author
mkrische@mail.utexas.edu
■
Notes
(8) The precatalyst RuH2CO(PPh3)3 may reductively eliminate
elemental hydrogen or transfer hydrogen to the diene to furnish the
zerovalent ruthenium species required for diene-carbonyl oxidative
coupling.
(9) For example, exposure of Ru3(CO)12 to dppe in benzene solvent
provides Ru(CO)3(dppe): Sanchez-Delgado, R. A.; Bradley, J. S.;
Wilkinson, G. J. Chem. Soc., Dalton Trans. 1976, 399.
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
The Robert A. Welch Foundation (F-0038), the NIH-NIGMS
(RO1-GM069445), and the Government of Canada’s Banting
Postdoctoral Fellowship Program (L.M.G.) are acknowledged
for partial support of this research. Firmenich is acknowledged
for unrestricted partial financial support.
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1541. (b) Shvo, Y.; Blum, Y.; Reshef, D.; Menzin, M. J. Organomet.
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D
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