Diols, α-Ketols, and Diones as 22π Components in [2+2+2] Cycloadditions of 1,6-Diynes via Ruthenium(0)-Catalyzed Transfer Hydrogenation

Article abstract of DOI:10.1021/jacs.6b11746

The first use of vicinal diols, ketols, or diones as 2_2π components in metal-catalyzed [2+2+2] cycloaddition is described. Using ruthenium(0) catalysts, 1,6-diynes form ruthenacyclopentadienes that engage transient diones in successive carbonyl addition. Transfer hydrogenolysis of the resulting ruthenium(II) diolate mediated by the diol or ketol reactant releases the cycloadduct with regeneration of ruthenium(0) and the requisite dione.

Full text of DOI:10.1021/jacs.6b11746

Communication
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Diols, α‑Ketols, and Diones as 22π Components in [2+2+2]
Cycloadditions of 1,6-Diynes via Ruthenium(0)-Catalyzed Transfer
Hydrogenation
Hiroki Sato,† Matthias Bender,† Weijie Chen, and Michael J. Krische*
Department of Chemistry, University of Texas at Austin, Austin, Texas 78712, United States
S
* Supporting Information
ABSTRACT: The first use of vicinal diols, ketols, or
diones as 22π components in metal-catalyzed [2+2+2]
cycloaddition is described. Using ruthenium(0) catalysts,
1,6-diynes form ruthenacyclopentadienes that engage
transient diones in successive carbonyl addition. Transfer
hydrogenolysis of the resulting ruthenium(II) diolate
mediated by the diol or ketol reactant releases the
cycloadduct with regeneration of ruthenium(0) and the
requisite dione.
etal-catalyzed [2+2+2] cycloadditions of π-unsaturated
M
reactants enable convergent construction of (poly)cyclic
compounds.1 Transformations of this type typically proceed
through catalytic mechanisms wherein low-valent metal centers
mediate π-bond oxidative coupling to form high-valent
metallacyclopentadienes, which upon π-bond insertion−reduc-
tive elimination deliver cycloadducts and regenerate the catalyst
(Figure 1, eq 1). The use of carbonyl compounds,2 including
carbon dioxide,3 as 22π components in metal-catalyzed [2+2+2]
cycloaddition is well established.1−3 Here, carbonyl insertion is
followed by C−O reductive elimination to form pyrans.2,3 To
our knowledge, mechanisms involving capture of the transient
metallacyclopentadiene through an exo-type carbonyl addition
to form hydroxy-substituted cycloadducts have not been
described.1−3
As part of a broad program focused on the development of
carbonyl reductive couplings via catalytic hydrogenation,4 we
imagined a pathway for 1,6-diyne-1,2-dione [2+2+2] cyclo-
addition involving hydrogen auto-transfer from a diol reactant
(Figure 1, eq 2). Specifically, ruthenium(0)-mediated 1,6-diyne
oxidative coupling would provide a ruthenacyclopentadiene
complex that participates in successive carbonyl addition with a
1,2-dione to form a ruthenium(II) diolate. Diol- or ketol-
mediated transfer hydrogenolysis of the diolate regenerates
zerovalent ruthenium and ketol or dione, with release of
cycloadduct to close the catalytic cycle (Figure 1, bottom). In
this Communication, we report the first examples of such
transfer hydrogenative [2+2+2] cycloadditions.5
To explore the feasibility of transfer hydrogenative [2+2+2]
cycloaddition, racemic trans-cyclohexanediol 1b (100 mol%)
and 1,6-diyne 2a (200 mol%) were exposed to various
ruthenium(0) catalysts generated in situ through the combina-
tion of Ru3(CO)12 (2 mol%) and various phosphine ligands
(Scheme 1) . In the course of these optimization experiments,
trace quantities of the desired product of [2+2+2] cyclo-
Figure 1. Top: Classical vs transfer hydrogenative [2+2+2] cyclo-
addition using 1,2-diols as 22π components. Bottom: General catalytic
mechanism.
addition 3a were observed when dppe was used as ligand.
Carboxylic acid co-catalysts enhance rate and conversion in
mechanistically related C−C couplings by accelerating the
hydrogenolysis6 or transfer hydrogenolysis5b of metallacyclic
intermediates. The use of 1-adamantanecarboxylic acid (6 mol
%) as a co-catalyst under otherwise identical conditions led to
the formation of cycloadduct 3b in 92% yield with complete
levels of syn-diastereoselectivity.
To assess the generality of this process, these conditions were
applied to the [2+2+2] cycloaddition of 1,6-diyne 2a with diols
1a−1i (Table 1). As illustrated by the formation of cyclo-
adducts 3a−3c, 5-, 6-, and 7-membered cycloalkanediols 1a−1c
Received: November 13, 2016
© XXXX American Chemical Society
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DOI: 10.1021/jacs.6b11746
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Journal of the American Chemical Society
Communication
asymmetric induction. Finally, acyclic vicinal diols, 2,3-butane-
diol 1h and the diol 1i derived from methyl oleate, are
converted to cycloadducts 3h and 3i.
Scheme 1. Selected Optimization Experiments in the
[2+2+2] Cycloaddition of 1,6-Diyne 2a with
Cyclohexanediol 1b
a
In a further evaluation of the reaction scope, 1,6-diynes 2a−
2i were exposed to cyclopentanediol 1a under standard
conditions (Table 2). As demonstrated by the reaction of
Table 2. Survey of Diynes 2a−2i in Ruthenium(0)-Catalyzed
a
Transfer Hydrogenative [2+2+2] Cycloaddition
a
Yields of material isolated by silica gel chromatography. AdCO2H
refers to 1-adamantanecarboxylic acid. PCy3 = tricyclohexylphosphine.
dppe = bis-(diphenylphosphino)ethane. See Supporting Information
for further experimental details.
Table 1. Survey of Diols 1a−1i in Ruthenium(0)-Catalyzed
a
Transfer Hydrogenative [2+2+2] Cycloaddition
a
Yields of material isolated by silica gel chromatography. See
b
Supporting Information for further experimental details. 120 °C.
c
24 h.
diyne 2b to form 3j, pre-organization via geminal substitution
of the diyne partner is not required for efficient cycloaddition.7
The formation of cycloadducts 3k and 3l from diynes 2c and
2d, respectively, establishes the tolerance of both O- and N-
tethers. Compatibility of substituents at the acetylenic terminus
beyond phenyl moieties is illustrated by the cycloaddition of
diynes 2e−2h to form adducts 3m−3p. Finally, generation of
the benzimidazole-containing cycloadduct 3q establishes
compatibility with Lewis-basic N-heterocycles. 1,6-Diynes that
are unsubstituted at the acetylenic terminus and 1,7-diynes do
not engage in efficient cycloaddition under these initially
developed conditions.
Cycloaddition is postulated to occur through a general
catalytic mechanism involving successive dehydrogenation of
the diol reactant to form a transient α-ketol and, ultimately, the
vicinal dione partner that is required for oxidative coupling
(Figure 1). Thus, in addition to diols, α-ketols and vicinal
a
Yields of material isolated by silica gel chromatography. See
b
Supporting Information for further experimental details. THF (1.0
M).
participate in cycloaddition. Tolerance of adjacent π-unsatura-
tion is demonstrated by the conversion of indanediol 1d,
cyclohexenediol 1e, and acenaphthalenediol 1f to cycloadducts
3d−3f, respectively. Notably, the transient dione derived from
cyclohexenediol 1e undergoes cycloaddition more rapidly than
tautomerization to form the corresponding catechol. Diol 1g,
which incorporates a pre-existing stereogenic center, engages in
cycloaddition to form 3g with serviceable levels of 1,2-
B
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Journal of the American Chemical Society
Communication
diones should be viable reactants. Whereas the cycloaddition of
diols is an oxidative transformation for which excess diyne likely
serves as hydrogen acceptor, the cycloaddition of α-ketols is
redox-neutral, and the cycloaddition of vicinal diones is
reductive. To demonstrate that the present cycloaddition may
be conducted in oxidative, redox-neutral, and reductive modes,
the reactions of diol 1f, α-ketol dehydro-1f, and vicinal dione
didehydro-1f were explored (Scheme 2). Standard conditions
Scheme 3. Stoichiometric Reaction of Diynes 2c and 2a with
Ru3(CO)12 To Form Ru-Complex I and Ru-Complex II
a
Scheme 2. Redox-Level Independent [2+2+2]
Cycloadditions of Diol 1f, α-Ketol dehydro-1f, and Vicinal
a
Dione didehydro-1f
a
Yields of material isolated by silica gel chromatography. See
a
Structure of Ru-complex II as determined by single-crystal X-ray
Supporting Information for further experimental details.
diffraction (H-atoms omitted for clarity). Yields of material isolated by
silica gel chromatography (eq 6) or precipitation (eq 7). Displacement
ellipsoids are scaled to the 50% probability level. See Supporting
Information for crystallographic data and further experimental details.
used for the cycloaddition of diol 1f (Scheme 2, eq 3), when
applied to α-ketol dehydro-1f (Scheme 2, eq 4), led to the
formation of cycloadduct 3f in 80% yield. Reductive cyclo-
addition of vicinal dione didehydro-1f to form 3f also was
possible using 2-propanol as a source of hydrogen under
otherwise standard conditions (Scheme 2, eq 5). Recently, a
variety of oxidative5a,8 and reductive5a,9 cycloaddition reactions
have been reported that provide access to cyclic compounds
from unconventional substrates. To our knowledge, the
conversion of dione didehydro-1f to 3f represents the first
example of a reductive [2+2+2] cycloaddition reaction.1
The proposed general catalytic mechanism (Figure 1) is
corroborated by the following data. As reported by
Yamamoto,10 the stoichiometric reaction of 1,6-diyne 2c with
Ru3(CO)12 in the presence of carbon monoxide delivers the
dinuclear ruthenacyclopentadiene complex, Ru-complex I
(Scheme 3, eq 6). It is reported that exposure of Ru3(CO)12
to dppe in benzene solvent provides the mononuclear complex
Ru(CO)3(dppe).11 As might be anticipated on the basis of
these two observations, we have found that, in the absence of
carbon monoxide, the stoichiometric reaction of 1,6-diyne 2a
with Ru3(CO)12 and dppe provides the mononuclear
ruthenium cyclopentadienone complex, Ru-complex II
(Scheme 3, eq 7).12 Together, these data corroborate diyne
oxidative coupling mediated by a mononuclear ruthenium−
phosphine complex as a key feature of the catalytic
mechanism.13 The addition of metallacyclopentadienes to π-
electrophiles has been demonstrated in rhodium-catalyzed
reductive couplings of acetylene with aldehydes and imines
mediated by elemental hydrogen.6 Finally, carboxylic acid co-
catalyzed transfer hydrogenolysis of oxoruthenacycle inter-
mediates, the final stage of the catalytic mechanism, has been
established in our prior work.5b A model accounting for syn-
diastereoselectivity can be found in the Supporting Information.
In summary, adding a broad, new dimension to a
longstanding field,14 we report the first examples of vicinal
diols, ketols, or diones as 22π components in metal-catalyzed
[2+2+2] cycloaddition. The collective data corroborate a
mechanism in which ruthenium(0)-mediated oxidative coupling
of a 1,6-diyne is followed by successive carbonyl addition
between the resulting ruthenacyclopentadiene and a transient
dione. Transfer hydrogenolysis of the resulting ruthenium(II)
diolate releases the cycloadduct, an arene diol, and returns
ruthenium to its zerovalent form with concomitant regener-
ation of the vicinal dicarbonyl partner. Future studies will focus
on the development of related hydrogen-transfer-mediated
cycloadditions, as well as application of the present method-
ology to the synthesis of polycyclic aromatic hydrocarbons.
ASSOCIATED CONTENT
* Supporting Information
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/jacs.6b11746.
■
S
Experimental procedures and spectral data (PDF)
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Journal of the American Chemical Society
Communication
(d) Saxena, A.; Perez, F.; Krische, M. J. Angew. Chem., Int. Ed. 2016,
55, 1493.
Single-crystal X-ray diffraction data for Ru-complex II
(CIF)
Single-crystal X-ray diffraction data for 3a (CIF)
(6) (a) Kong, J.-R.; Krische, M. J. J. Am. Chem. Soc. 2006, 128, 16040.
(b) Skucas, E.; Kong, J.-R.; Krische, M. J. J. Am. Chem. Soc. 2007, 129,
7242. (c) Williams, V. M.; Kong, J.-R.; Ko, B.-J.; Mantri, Y.; Brodbelt,
J. S.; Baik, M.-H.; Krische, M. J. J. Am. Chem. Soc. 2009, 131, 16054.
(7) For reviews on the Thorpe−Ingold effect in metal-catalyzed
cyclizations and cycloadditions, see: (a) Jung, M. E. Synlett 1999, 843.
(b) Jung, M. E.; Piizzi, G. Chem. Rev. 2005, 105, 1735.
AUTHOR INFORMATION
■
Corresponding Author
*mkrische@mail.utexas.edu
(8) For selected examples of oxidative metal-catalyzed cycloadditions,
see: (a) Ueura, K.; Satoh, T.; Miura, M. Org. Lett. 2007, 9, 1407.
(b) Ueura, K.; Satoh, T.; Miura, M. J. Org. Chem. 2007, 72, 5362.
(c) Stuart, D. R.; Bertrand-Laperle, M.; Burgess, K. M. N.; Fagnou, K.
J. Am. Chem. Soc. 2008, 130, 16474. (d) Guimond, N.; Fagnou, K. J.
Am. Chem. Soc. 2009, 131, 12050. (e) Nakao, Y.; Morita, E.; Idei, H.;
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M. C. J. Am. Chem. Soc. 2011, 133, 14892. (g) Ohashi, M.; Takeda, I.;
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2006, 128, 14030. (b) Chang, H.-T.; Jayanth, T. T.; Cheng, C.-H. J.
Am. Chem. Soc. 2007, 129, 4166. (c) Jenkins, A. D.; Herath, A.; Song,
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ORCID
Michael J. Krische: 0000-0001-8418-9709
Author Contributions
†H.S. and M.B. contributed equally to this work.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
The Robert A. Welch Foundation (F-0038) and the NSF
(CHE-1565688) are acknowledged for partial support of this
research. The Japan Student Services Organization (JASSO)
and Graduate Dean’s Prestigious Supplemental Fellowship
(DPFS) and the Deutsche Forschungsgemeinschaft (DFG) are
acknowledged for graduate fellowship (H.S.) and postdoctoral
fellowship (M.B.) support, respectively.
(10) Yamamoto, Y.; Miyabe, Y.; Itoh, K. Eur. J. Inorg. Chem. 2004,
3651.
(11) Sanchez-Delgado, R. A.; Bradley, J. S.; Wilkinson, G. J. Chem.
Soc., Dalton Trans. 1976, 399.
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DOI: 10.1021/jacs.6b11746
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