Ruthenium-catalyzed hydrohydroxyalkylation of acrylates with diols and α-hydroxycarbonyl compounds to form spiro- and α-methylene-γ- butyrolactones

Article abstract of DOI:10.1021/ja410533y

Under the conditions of ruthenium(0)-catalyzed hydrohydroxyalkylation, vicinal diols 1a-1l and methyl acrylate 2a are converted to the corresponding lactones 3a-3l in good to excellent yield. The reactions of methyl acrylate 2a with hydrobenzoin 1f, benzoin didehydro-1f, and benzil tetradehydro-1f form the same lactone 3f product, demonstrating that this process may be deployed in a redox level-independent manner. A variety of substituted acrylic esters 2a-2h participate in spirolactone formation, as illustrated in the conversion of N-benzyl-3-hydroxyoxindole 1o to cycloadducts 4a-4h. Hydrohydroxyalkylation of hydroxyl-substituted methacrylate 2i with diols 1b, 1f, 1j, and 1l forms α-exo-methylene-γ-butyrolactones 5b, 5f, 5j, and 5l in moderate to good yield. A catalytic cycle involving 1,2-dicarbonyl-acrylate oxidative coupling to form oxaruthenacyclic intermediates is postulated. A catalytically competent mononuclear ruthenium(II) complex was characterized by single-crystal X-ray diffraction. The influence of electronic effects on regioselectivity in reactions of nonsymmetric diols was probed using para-substituted 1-phenyl-1,2-propanediols 1g, 1m, and 1n and density functional theory calculations.

Full text of DOI:10.1021/ja410533y

Article
pubs.acs.org/JACS
Ruthenium-Catalyzed Hydrohydroxyalkylation of Acrylates with
Diols and α‑Hydroxycarbonyl Compounds To Form Spiro- and
α‑Methylene-γ-butyrolactones
Emma L. McInturff, Jeffrey Mowat, Andrew R. Waldeck, and Michael J. Krische*
Department of Chemistry and Biochemistry, University of Texas at Austin, Austin, Texas 78712, United States
S
* Supporting Information
ABSTRACT: Under the conditions of ruthenium(0)-catalyzed hydro-
hydroxyalkylation, vicinal diols 1a−1l and methyl acrylate 2a are
converted to the corresponding lactones 3a−3l in good to excellent yield.
The reactions of methyl acrylate 2a with hydrobenzoin 1f, benzoin
didehydro-1f, and benzil tetradehydro-1f form the same lactone 3f
product, demonstrating that this process may be deployed in a redox
level-independent manner. A variety of substituted acrylic esters 2a−2h
participate in spirolactone formation, as illustrated in the conversion of
N-benzyl-3-hydroxyoxindole 1o to cycloadducts 4a−4h. Hydrohydrox-
yalkylation of hydroxyl-substituted methacrylate 2i with diols 1b, 1f, 1j, and 1l forms α-exo-methylene-γ-butyrolactones 5b, 5f, 5j,
and 5l in moderate to good yield. A catalytic cycle involving 1,2-dicarbonyl−acrylate oxidative coupling to form oxaruthenacyclic
intermediates is postulated. A catalytically competent mononuclear ruthenium(II) complex was characterized by single-crystal X-
ray diffraction. The influence of electronic effects on regioselectivity in reactions of nonsymmetric diols was probed using para-
substituted 1-phenyl-1,2-propanediols 1g, 1m, and 1n and density functional theory calculations.
oxidative coupling pathways in Pauson−Khand reactions of
1,2-diones,5 suggested the feasibility of hydrohydroxyalkylations
by way of oxidative coupling−secondary alcohol transfer
hydrogenation pathways.
INTRODUCTION
■
Our laboratory has developed ruthenium and iridium “hydro-
hydroxyalkylations” wherein hydrogen transfer from primary
alcohols to π-unsaturated reactants generates organometal−
aldehyde pairs that combine to form products of carbonyl
addition.1−3 Such C−C bond-forming transfer hydrogenations
may be viewed as alternatives to classical carbonyl additions, for
which discrete alcohol-to-aldehyde oxidation and use of
premetallated C-nucleophiles are often required. To expand
the scope of this emerging family of C−C bond formations, the
development of corresponding secondary alcohol-mediated
hydrohydroxyalkylations was undertaken. However, our initial
efforts to promote hydrohydroxyalkylations with secondary
alcohols using previously developed ruthenium2 and iridium3
catalysts resulted in conventional transfer hydrogenation to
form ketone products. Products of C−C coupling were not
observed.
Ruthenium(0) catalysts derived from Ru3(CO)12 and
phosphine ligands were found to promote the C−C coupling
of α-hydroxy esters and amides to isoprene and myrcene to
furnish products of prenylation and geranylation, respectively
(Figure 1, top).6a,b More recently, a mechanistically related
ruthenium(0)-catalyzed [4+2] cycloaddition of vicinal diols via
successive hydrohydroxyalkylation of dienes was developed
(Figure 1, middle).6c Here, we report that ruthenium(0)-
catalyzed hydrohydroxyalkylation of acrylates with vicinal diols
or their more highly oxidized congeners delivers spiro- and α-
methylene-γ-butyrolactones, structural motifs that are ubiq-
uitous in nature (Figure 1, bottom).7
It was postulated that secondary alcohols that form vicinal
dicarbonyl compounds upon dehydrogenation, for example, α-
hydroxy esters or vicinal cycloalkane diols, should engage more
readily in carbonyl addition or oxidative coupling pathways en
route to products of C−C coupling. However, this enhanced
reactivity also renders vicinal dicarbonyl compounds more
susceptible to reduction. Hence, if dehydrogenation is
reversible, the short lifetime of the transient vicinal dicarbonyl
might impede C−C coupling pathways. In view of this issue, we
were inspired by recent reports of Ru3(CO)12-catalyzed
aminations of 1,2-diols4a,b and α-hydroxy amides,4c which
occur via reductive amination of transient vicinal dicarbonyl
species. This result, along with Chatani’s observation of
RESEARCH DESIGN AND METHODS
■
It was reasoned that ruthenium(0)-catalyzed hydrohydrox-
yalkylation of acrylates with vicinal diols would provide
transient oxaruthenacycles that would spontaneously cyclize
to form lactone products (Figure 1, bottom). This method
would complement alternate approaches to spirocyclic γ-
butyrolactones,7a which include cationic rearrangements of
epoxides8 and bromonium ions,9 Stetter-type reactions,10
oxidative dearomatization,11 C−H hydroxylation of carboxylic
Received: September 4, 2013
© XXXX American Chemical Society
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Table 1. Selected Optimization Experiments in the
Ruthenium-Catalyzed C−C Coupling of Diol 1b and Methyl
a
Acrylate 2a
time
(h)
T
(°C)
yield
(%)
entry ligand
additive
2a (mol%)
1
BIPY
−
−
−
−
−
−
−
−
−
300
300
300
300
200
400
500
300
300
300
300
300
300
300
300
20
20
20
20
20
20
20
20
20
20
20
4
140
140
140
140
140
140
140
130
150
140
140
140
140
120
140
trace
trace
trace
76
2
Phen
3
PCy3
4
DPPP
DPPP
DPPP
DPPP
DPPP
DPPP
DPPP
DPPP
DPPP
DPPP
DPPP
DPPP
5
56
6
88
7
79
8
33
9
69
10
11
12
13
14
15
benzoic acid
C10H15CO2H
C10H15CO2H
C10H15CO2H
C10H15CO2H
C10H15CO2H
93
96
73
8
83
20
20
62
b
Figure 1. Ruthenium(0)-catalyzed hydrohydroxyalkylations.
55
a
Cited yields are of material isolated by silica gel chromatography.
b
acids,12 reductive cyclizations of α,β-unsaturated esters onto
ketones,13 Pauson−Khand-type reactions of olefins with vicinal
diones,5 and the 2-(alkoxycarbonyl)allylation of carbonyl
compounds.14
C10H15CO2H refers to 1-adamantanecarboxylic acid. 0.5 mol%
Ru3(CO)12. See Supporting Information for further experimental
details.
Table 2. Ruthenium(0)-Catalyzed Hydrohydroxyalkylation
To probe the feasibility of the proposed transformation,
racemic trans-1,2-cyclohexane diol 1b was exposed to methyl
acrylate 2a (300 mol%) in the presence of Ru3(CO)12 (2 mol
%) and various nitrogen or phosphorus containing ligands. It
was found that the ruthenium catalyst modified by DPPP (6
mol%) was uniquely effective, providing the desired spirolac-
tone 3b in 76% yield (Table 1, entry 4). Although increased
loadings of methyl acrylate 2a were found to improve the
isolated yield of spirolactone 3b (Table 1, entries 6 and 7),
enhancing the intrinsic reaction efficiency so as to minimize the
loading of methyl acrylate 2a was preferred. As further variation
of the reaction parameters, including temperature (Table 1,
entries 8 and 9), did not avail further improvement, carboxylic
acid additives, which are known to co-catalyze hydrogenolysis
of oxa- and azametallacycles, were evaluated.15 Using 1-
adamantanecarboxylic acid (10 mol%) as a cocatalyst, the
isolated yield of spirolactone 3b was increased from 76% to
96% (Table 1, entries 4 and 11).
of Methyl Acrylate 2a with Diols 1a−1l to Form Lactones
a
3a−3l
Optimal conditions identified for formation of spirolactone
3b were applied to the C−C coupling of cyclic and acyclic diols
1a−1l and methyl acrylate 2a. The corresponding lactones 3a−
3l were generated in good to excellent yield (Table 2). Both cis-
and trans-diols react with equal efficiency. As illustrated in the
conversion of diols 1a−1d to 3a−3d, five-, six-, seven-, and
eight-membered ring cycloalkanes participate in spirolactone
formation. Acyclic vicinal diols 1e−1h form lactone products
3e−3h. Whereas nonsymmetric diols 1g and 1h are converted
to lactones 3g and 3h with incomplete control of
regioselectivity, the reactions of cyclic diols 1i, 1j, and 1l are
completely regioselective, providing spirolactones 3i, 3j, and 3l
as single constitutional isomers.
a
Cited yields are of material isolated by silica gel chromatography. See
b
Supporting Information for further experimental details. The cis-1,2-
diol was employed. The trans-1,2-diol was employed. A mixture of
cis- and trans-1,2-diols was employed. 2a (400 mol%).
c
d
e
As illustrated in the conversion of hydrobenzoin 1f, benzoin
didehydro-1f, and benzil tetradehydro-1f to lactone 3f, catalytic
C−C coupling may be accomplished in oxidative, redox-neutral,
and reductive modes, respectively (Table 3). For the latter
B
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a
Table 3. Redox Level-Independent Formation of Lactone 3f
Table 4. Ruthenium(0)-Catalyzed Hydrohydroxyalkylation
of Acrylic Esters 2a−2h with N-Benzyl-3-hydroxyoxindole 1o
a
to Form Spirolactones 4a−4h
a
Yields are of material isolated by silica gel chromatography.
C10H15CO2H refers to 1-adamantanecarboxylic acid. See Supporting
Information for further details.
reaction involving benzil tetradehydro-1f, isopropanol (300 mol
%) is employed as terminal reductant. Additionally, it was
found that other vicinally deoxygenated compounds participate
in lactone formation. For example, exposure of α-hydroxy esters
1m and 1n to methyl acrylate 2a under standard reaction
conditions provided the corresponding spirolactones 3m and
3n in 97% and 58% yields, respectively (eq 1).
a
Cited yields are of material isolated by silica gel chromatography. See
Supporting Information for further experimental details.
Table 5. Hydrohydroxyalkylation of Hydroxyl-Substituted
Having explored the scope of the diol and hydroxyester
partners 1a−1n, substituted α,β-unsaturated esters 2a−2h were
investigated. Attempted reactions of esters 2b−2h with diols
1a−1l under standard conditions did not provide products of
C−C coupling. In contrast, the reactions of N-benzyl-3-
hydroxyoxindole 1o with esters 2a−2h proceed in good to
excellent yield to furnish spirooxindole products 4a−4h (Table
4). As illustrated, β-substituted acrylic esters 2b, 2c, 2f, 2g, and
2h provide the corresponding spirolactones 4b, 4c, 4f, 4g, and
4h, respectively, in good to excellent isolated yields as single
diastereomers. Relative stereochemistry was assigned by single-
crystal X-ray diffraction analysis of 4b. The relative stereo-
chemistry of cycloadducts 4c, 4f, 4g, and 4h is assigned in
analogy to 4b. As will be discussed in greater detail, for
cycloadditions of acrylic esters 2a−2h with N-benzyl-3-
hydroxyoxindole 1o, catalytic amounts of potassium tert-
butoxide are required to enforce complete levels of
diastereoselectivity. Finally, it is notable that even β,β-
substituted acrylic ester 2e participates in spirolactone
formation, albeit in moderate yield.
Methacrylate 2i with Diols 1b, 1f, 1j, and 1l to Form α-exo-
a
Methylene-γ-butyrolactones 5b, 5f, 5j, and 5l
a
Yields are of material isolated by silica gel chromatography.
C10H15CO2H refers to 1-adamantanecarboxylic acid. See Supporting
b
c
Information for further details. The cis-1,2-diol was employed. The
d
trans-1,2-diol was employed. A mixture of cis- and trans-1,2-diols was
employed.
The fact that diols 1a−1l did not react with substituted α,β-
unsaturated esters 2b−2h may be due to reversible oxaruthena-
cycle formation. If so, one can envision decorating the enoate
reactant such that the transient metallacyclic intermediate is
captured and driven to product. As the oxaruthenacycle
intermediate may be viewed as a ruthenium enolate (Figure
1, bottom), it was reasoned that the hydroxyl-substituted
methacrylate 2i might engage in E1cB elimination to furnish α-
methylene-γ-butyrolactones. In the event, upon exposure of
diols 1b, 1f, 1j, and 1l to acrylic ester 2i under standard
conditions the α-exo-methylene γ-butyrolactones 5b, 5f, 5j, and
5l, respectively, were formed in moderate yield.14 The modest
yields in the formation of 5b, 5f, 5j, and 5l are, in part,
attributed to reduction of the exocyclic double bond (Table 5).
MECHANISM AND DISCUSSION
■
A plausible general catalytic mechanism for the ruthenium-
catalyzed C−C coupling of cyclohexanediol 1b and methyl
acrylate 2a to form spirolactone 3b is as follows (Scheme 1).
Based on literature precedent, intervention of a discrete,
mononuclear ruthenium(0) complex is anticipated.16 Consis-
tent with this expectation, upon heating a solution of
Ru3(CO)12, DPPP, and 1-adamantanecarboxylic acid, the
mononuclear ruthenium(II) species, Ru(CO)(dppp)-
(C10H15CO2)2 is formed, as established by single-crystal X-ray
diffraction analysis (Figure 2). It should be noted that
Ru(CO)(dppp)(C10H15CO2)2 is a competent precatalyst for
catalytic C−C coupling (eq 2). Oxidative coupling of
C
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ketone dihydro-1b. Upon β-hydride elimination, dihydro-1b or
tetradehydro-1b would be generated, respectively, along with a
ruthenium hydride, which upon O−H reductive elimination
would regenerate ruthenium(0).
Scheme 1. A Plausible General Mechanism for
Ruthenium(0)-Catalyzed Spirolactone Formation as
Illustrated in the Coupling of Diol 1b and Methyl Acrylate
2a
Whereas couplings of methyl acrylate 2a with diols 1a−1l
require an acidic cocatalyst (Table 2), cycloadditions of acrylic
esters 2a−2h with N-benzyl-3-hydroxyoxindole 1o require
catalytic amounts of potassium tert-butoxide to enforce
complete levels of diastereoselectivity. Based on the postulated
mechanism (Scheme 1), one possible interpretation is as
follows. If oxidative coupling is reversible via retro-Michael
addition, complete kinetic stereoselectivity will be eroded if
transfer hydrogenolysis of the metallacycle is not fast.
Deprotonation of N-benzyl-3-hydroxyoxindole 1o may accel-
erate transfer hydrogenolysis with respect to retro-Michael
addition through alkoxide exchange as indicated (Scheme 2).
Scheme 2. Diastereoselection in the Formation of
Spirolactones 4b, 4c, 4f, 4g, and 4h and Potential Effect of
tert-Butoxide
The inversion in regioselectivity observed in the reaction of
diol 1g versus diols 1i and 1j merits discussion. As observed
across numerous carbonyl additions, 1,2-indanedione reacts at
the carbonyl moiety distal to the aromatic ring,21 whereas 1-
phenyl-2,3-propanedione reacts predominantly at the carbonyl
moiety proximal to the aromatic ring.22 Such trends in
regioselectivity are evident in metal-catalyzed transformations,
for example, hydrogenations of 1,2-indanedione and 1-phenyl-
1,2-propanedione.23 Naturally, regioselectivities observed in the
aforementioned carbonyl additions and the present ruthenium-
catalyzed C−C couplings are governed by the interaction of
frontier molecular orbitals. Thus, notwithstanding steric effects,
C−C coupling will occur predominantly at the dione carbonyl
bearing the largest LUMO coefficient. Indeed, as posited by
Hoffmann, the conversion of polarized bis(olefin) complexes to
metallacyclopentanes should occur such that C−C bond
formation occurs at the atom bearing the largest LUMO
coefficient.24
Figure 2. Single-crystal X-ray diffraction data of Ru(CO)(dppp)-
(C10H15CO2)2. Displacement ellipsoids are scaled to the 50%
probability level. Hydrogen atoms have been omitted for clarity.
C10H15CO2H refers to 1-adamantanecarboxylic acid.
To challenge this hypothesis, a series of para-substituted 1-
phenyl-1,2-propanediols 1g, 1m, and 1n were prepared and
subjected to standard conditions for spirolactone formation (eq
3). For the para-methoxy-substituted diol 3m, the electro-
tetradehydro-1b and methyl acrylate 2a forms oxaruthenacycle
I,5,6 which is anticipated to reside as the O-bound haptomer.17
The requisite dione tetradehydro-1b likely arises through
Ru3(CO)12-catalyzed oxidation of cyclohexanediol 1b employ-
ing methyl acrylate 2a as the hydrogen acceptor.18−20
Protonation of oxaruthenacycle I15 by cyclohexanediol 1b or
didehydro-1b may be slow compared to protonation of
oxaruthenacycle I by 1-adamantanecarboxylic acid to form
ruthenium carboxylate II, which lactonizes to form the
spirocycle 3b. The resulting ruthenium(II) complex III may
engage in substitution with cyclohexanediol 1b or α-hydroxy
philicity of the resulting dione at the carbonyl moiety proximal
to the arene is attenuated and the proportion of regioisomer
derived from C−C coupling to this position decreases.
D
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Conversely, for the 1,2-dione derived from the para-
carbomethoxy-substituted diol 3n, the electrophilicity of the
carbonyl moiety proximal to the arene is now augmented and
the proportion of regioisomer derived from C−C coupling to
this position increases. To more quantitatively correlate
regioselectivity with the magnitude of the respective dione
LUMO coefficients, density functional theory (DFT) calcu-
lations were used to evaluate the dione LUMO coefficients.
Although these data correspond to the diones in the ground
state, and not the ruthenium bound diones that would be
evident in the transition state, the observed trends are in
alignment with the experimental results. That is, while the
LUMO coefficients are always larger at the carbonyl moiety
proximal to the arene, the proportion of regioisomers derived
from coupling to the carbonyl moiety distal to the arene
increases as the difference between the LUMO coefficients
become smaller. Notably, indane diol 1i engages in completely
regioselective coupling, and the corresponding dione 5i is
predicted to have the smallest difference between the LUMO
coefficients (Table 6).
B(OMe)3, InCl3, ZnI2, MgCl2). Here, only small quantities of
the spirolactone were obtained along with recovered starting
materials (eq 5).
CONCLUSIONS
■
In summary, we report a convergent synthesis of γ-
butyrolactones, including spiro- and α-methylene-γ-butyrolac-
tones, through the ruthenium(0)-catalyzed C−C coupling of
vicinal diols and acrylic esters. As demonstrated in the reactions
of methyl acrylate 2a with hydrobenzoin 1f, benzoin didehydro-
1f, and benzil tetradehydro-1f, such transformations can be
conducted in a redox level-independent manner. As shown in
the conversion of α-hydroxy esters 1m and 1n to lactones 3m
and 3n, respectively, the reaction is applicable to other vicinally
dioxygenated systems. Additionally, diverse α,β-unsaturated
esters 2a−2h participate in spirolactone formation to form
cycloadducts 4a−4h. A catalytically competent ruthenium(II)
complex, Ru(CO)(dppp)(C10H15CO2)2, was characterized by
single-crystal X-ray diffraction, and the influence of electronic
effects on regioselectivity in reactions of nonsymmetric diols
was probed experimentally and computationally. Future studies
will focus on the development of related atom-efficient C−C
couplings that result in formal alcohol C−H functionalization.
Table 6. Magnitude of Dione LUMO Coefficients
Determined by DFT Calculations Correlate to
a
Regioselectivity
EXPERIMENTAL SECTION
■
General Experimental Procedure for Hydrohydroxyalkyla-
tion of Methyl Acrylate with Diol 1b. To a resealable pressure tube
(13 × 100 mm) equipped with a magnetic stir bar were added trans-
1,2-cyclohexanediol 1b (35 mg, 0.30 mmol), Ru3(CO)12 (3.8 mg,
0.006 mmol, 2 mol%), 1,3-bis(diphenylphosphino)propane (7.4 mg,
0.018 mmol, 6 mol%), and 1-adamantanecarboxylic acid (5.4 mg, 0.03
mmol, 10 mol%). The tube was sealed with a rubber septum and
purged with argon. Methyl acrylate 2a (81 μL, 0.90 mmol, 300 mol%)
and m-xylenes (0.22 mL) were added. The rubber septum was
replaced with a screw cap. The mixture was heated at 140 °C (oil bath
temperature) for 20 h, at which point the reaction mixture was allowed
to cool to ambient temperature. The reaction mixture was
concentrated, and the residue was subjected to flash column
chromatography (SiO2; hexanes:ethyl acetate = 1:1) to furnish the
title compound (48.4 mg, 0.29 mmol, 96%) as a clear yellow oil.
LUMO coefficient
experimental isomeric
dione
A
B
Δ(A − B)
ratio (A:B)
5i, indane
dione
−0.12189
−0.10896
0.013
1:>20
5m, R =
OMe
−0.13750
−0.11802
0.019
1.3:1
5g, R = H
−0.13943
−0.13353
−0.11213
−0.09587
0.027
0.038
4:1
5n, R =
CO2Me
10:1
a
DFT calculations were carried out with QChem 4.0 using the B3LYP
hybrid functional and 6-311G(d,p) basis set.
To further challenge the veracity of the proposed oxidative
coupling mechanism, several control experiments were
performed. To evaluate the possibility of a mechanistic pathway
involving conventional Michael addition, benzoin didehydro-1f
was converted to the methyl ether O-Me-didehydro-1f and
subjected to standard conditions for ruthenium(0)-catalyzed
lactone formation, however, no reaction was observed and the
starting materials were recovered unchanged (eq 4). Addition-
ASSOCIATED CONTENT
■
S
* Supporting Information
Experimental procedures and spectroscopic data for all new
compounds (1H NMR, 13C NMR, IR, HRMS), including NMR
spectra; single-crystal X-ray diffraction data (CIF files) for
spirolactone 4b and the ruthenium complex Ru(CO)(dppp)-
(C10H15CO2)2. This material is available free of charge via the
Internet at http://pubs.acs.org.
AUTHOR INFORMATION
■
Corresponding Author
mkrische@mail.utexas.edu
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
The Robert A. Welch Foundation (F-0038) and the NIH-
NIGMS (RO1-GM069445) are acknowledged for partial
support of this research. Prof. Eric Anslyn and Brette Chapin
are acknowledged for kindly conducting DFT calculations.
ally, hydroxyketone didehydro-1j was subjected to methyl
acrylate 2a in the presence of various Lewis acids (RuCl3,
E
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Angew. Chem., Int. Ed. 2011, 50, 5331. (b) Bigi, M. A.; Reed, S. A.;
White, M. C. Nature Chem. 2011, 3, 216.
(13) For a recent review on spirolactone formation via reductive
cyclization of α,β-unsaturated esters onto ketones, see: Streuff, J.
Synthesis 2013, 281.
(14) For synthesis of α-methylene-γ-butyrolactones via carbonyl 2-
(alkoxycarbonyl)allylation, see: Montgomery, T. P.; Hassan, A.; Park,
B. Y.; Krische, M. J. J. Am. Chem. Soc. 2012, 134, 11100 and references
cited therein.
(15) Ngai, M.-Y.; Barchuk, A.; Krische, M. J. J. Am. Chem. Soc. 2007,
129, 280 and references cited therein.
REFERENCES
■
(1) For selected reviews on the direct redox-triggered C−C coupling
of alcohols, see: (a) Bower, J. F.; Krische, M. J. Top. Organomet. Chem.
2011, 43, 107. (b) Hassan, A.; Krische, M. J. Org. Proc. Res. Devel.
2011, 15, 1236. (c) Moran, J.; Krische, M. J. Pure Appl. Chem. 2012,
84, 1729.
(2) For selected examples of ruthenium(II)-catalyzed C−C couplings
of primary alcohols, see: (a) Shibahara, F.; Bower, J. F.; Krische, M. J.
J. Am. Chem. Soc. 2008, 130, 6338. (b) Patman, R. L.; Williams, V. M.;
Bower, J. F.; Krische, M. J. Angew. Chem., Int. Ed. 2008, 47, 5220.
(c) Shibahara, F.; Bower, J. F.; Krische, M. J. J. Am. Chem. Soc. 2008,
130, 14120. (d) Zbieg, J. R.; McInturff, E. L.; Krische, M. J. Org. Lett.
2010, 12, 2514. (e) Zbieg, J. R.; McInturff, E. L.; Leung, J. C.; Krische,
M. J. J. Am. Chem. Soc. 2011, 133, 1141. (f) Zbieg, J. R.; Yamaguchi, E.;
McInturff, E. L.; Krische, M. J. Science 2012, 336, 324. (g) McInturff,
E. L.; Yamaguchi, E.; Krische, M. J. J. Am. Chem. Soc. 2012, 134, 20628.
(3) For selected examples of iridium-catalyzed C−C couplings of
primary alcohols, see: (a) Bower, J. F.; Skucas, E.; Patman, R. L.;
Krische, M. J. J. Am. Chem. Soc. 2007, 129, 15134. (b) Bower, J. F.;
Patman, R. L.; Krische, M. J. Org. Lett. 2008, 10, 1033. (c) Han, S. B.;
Kim, I. S.; Han, H.; Krische, M. J. J. Am. Chem. Soc. 2009, 131, 6916.
(d) Zbieg, J. R.; Fukuzumi, T.; Krische, M. J. Adv. Synth. Catal. 2010,
352, 2416. (e) Moran, J.; Preetz, A.; Mesch, R. A.; Krische, M. J.
Nature Chem. 2011, 3, 287. (f) Geary, L. M.; Woo, S. K.; Leung, J. C.;
Krische, M. J. Angew. Chem., Int. Ed. 2012, 51, 2972.
(16) Ru3(CO)12 reacts with dppe in benzene solvent to provide
Ru(CO)3(dppe): Sanchez-Delgado, R. A.; Bradley, J. S.; Wilkinson, G.
J. Chem. Soc., Dalton Trans. 1976, 399.
(17) For an O-bound nickel enolate derived via intramolecular enal−
alkyne oxidative coupling, see: Amarasinghe, K. K. D.; Chowdhury, S.
K.; Heeg, M. J.; Montgomery, J. Organometallics 2001, 20, 370.
(18) For Ru3(CO)12-catalyzed oxidation of alcohols employing
olefins and alkynes as hydrogen acceptors, see: (a) Blum, Y.; Reshef,
D.; Shvo, Y. Tetrahedron Lett. 1981, 22, 1541. (b) Shvo, Y.; Blum, Y.;
Reshef, D.; Menzin, M. J. Organomet. Chem. 1982, 226, C21.
(c) Meijer, R. H.; Ligthart, G. B. W. L.; Meuldijk, J.; Vekemans, J.
A. J. M; Hulshof, L. A.; Mills, A. M.; Kooijman, H.; Spek, A. L.
Tetrahedron 2004, 60, 1065.
(19) For mechanistically related Ru3(CO)12-catalyzed transfer
hydrogenation of ketones mediated by isopropanol, see: Johnson, T.
C.; Totty, W. G.; Wills, M. Org. Lett. 2012, 14, 5230.
(20) For mechanistically related Ru3(CO)12-catalyzed secondary
alcohol amination via alcohol-mediated hydrogen transfer, see:
(a) Baehn, S.; Tillack, A.; Imm, S.; Mevius, K.; Michalik, D.;
Hollmann, D.; Neubert, L.; Beller, M. ChemSusChem 2009, 2, 551.
(4) For Ru3(CO)12-catalyzed secondary alcohol amination via
alcohol-mediated hydrogen transfer, see: (a) Bahn, S.; Tillack, A.;
Imm, S.; Mevius, K.; Michalik, D.; Hollmann, D.; Neubert, L.; Beller,
M. ChemSusChem 2009, 2, 551. (b) Pingen, D.; Muller, C.; Vogt, D.
̈
Angew. Chem., Int. Ed. 2010, 49, 8130. (c) Zhang, M.; Imm, S.; Bahn,
S.; Neumann, H.; Beller, M. Angew. Chem., Int. Ed. 2011, 50, 11197.
(5) (a) Chatani, N.; Tobisu, M.; Asaumi, T.; Fukumoto, Y.; Murai, S.
J. Am. Chem. Soc. 1999, 121, 7160. (b) Tobisu, M.; Chatani, N.;
Asaumi, T.; Amako, K.; Ie, Y.; Fukumoto, Y.; Murai, S. J. Am. Chem.
Soc. 2000, 122, 12663.
(6) For ruthenium(0)-catalyzed C−C couplings of secondary
alcohols, see: (a) Leung, J. C.; Geary, L. M.; Chen, T.-Y.; Zbieg, J.
R.; Krische, M. J. J. Am. Chem. Soc. 2012, 134, 15700. (b) Chen, T.-Y.;
Krische, M. J. Org. Lett. 2013, 15, 2994. (c) Geary, L. M.; Glasspoole,
B. W.; Kim, M. M.; Krische, M. J. J. Am. Chem. Soc. 2013, 135, 3796.
(7) For reviews of γ-butyrolactone and α-methylene-γ-butyrolac-
tones, respectively, see: (a) Bartoli, A.; Rodier, F.; Commeiras, L.;
Parrain, J.-L.; Chouraqui, G. Nat. Prod. Rep. 2011, 28, 763. (b) Kitson,
R. R. A.; Millemaggi, A.; Taylor, R. J. K. Angew. Chem., Int. Ed. 2009,
48, 9426.
(b) Pingen, D.; Muller, C.; Vogt, D. Angew. Chem., Int. Ed. 2010, 49,
̈
8130. (c) Zhang, M.; Imm, S.; Bahn, S.; Neumann, H.; Beller, M.
Angew. Chem., Int. Ed. 2011, 50, 11197.
(21) 1,2-Indanedione reacts with nucleophiles exclusively at the
carbonyl moiety distal to the aromatic ring. For selected examples, see:
(a) Fatiadi, A. J. Synthesis 1978, 165. (b) Petrovskaia, O.; Taylor, B.
M.; Hauze, D. B.; Carroll, P. J.; Joullie, M. M. J. Org. Chem. 2001, 66,
7666 and references cited therein. (c) Vanden Eynden, M. J.;
Kunchithapatham, K.; Stambuli, J. P. J. Org. Chem. 2010, 75, 8542.
(22) 1-Phenyl-2,3-propanedione reacts with nucleophiles predom-
inantly at the carbonyl moiety proximal to the aromatic ring,
suggesting the LUMO coefficient is largest at this position. For
selected examples, see: (a) Inaba, S-i.; Rieke, R. D. Synthesis 1984, 844.
(b) Nishigaichi, Y.; Orimi, T.; Takuwa, A. J. Organomet. Chem. 2009,
694, 3837. (c) Dhondi, P. K.; Carberry, P.; Choi, L, B.; Chisholm, J. D.
J. Org. Chem. 2007, 72, 9590. (d) Ramachandran, P. V.; Rudd, M. T.;
Burghardt, T. E.; Reddy, M. V. R. J. Org. Chem. 2003, 68, 9310.
(e) Gewald, R.; Kira, M.; Sakurai, H. Synthesis 1996, 111. (f) Kang, S.-
K.; Baik, T.-G.; Jiao, Z.-H. Synth. Commun. 2002, 32, 75.
(8) For selected examples of spirolactone formation via epoxide ring
opening, see: (a) Yokoyama, T.; Izui, N. Bull. Chem. Soc. Jpn. 1965, 38,
1501. (b) Faraj, H.; Claire, M.; Rondot, A.; Aumelas, A.; Auzou, G. J.
Chem. Soc., Perkin Trans. 1 1990, 3045. (c) Eipert, M.; Maichle-
Mossmer, C.; Maier, M. E. Tetrahedron 2003, 59, 7949. (d) Fujioka,
H.; Matsuda, S.; Horai, M.; Fujii, E.; Morishita, M.; Nishiguchi, N.;
Hata, K.; Kita, Y. Chem.Eur. J. 2007, 13, 5238.
(23) (a) Busygin, I.; Rosenholm, M.; Toukoniitty, E.; Murzin, D. Y.;
Leino, R. Catal. Lett. 2007, 117, 91. (b) Langvik, O.; Maki-Arvela, P.;
Aho, A.; Saloranta, T.; Murzin, D. Y.; Leino, R. Catal. Lett. 2013, 143,
142. (c) Nieminen, V.; Taskinen, A.; Hotokka, M.; Murzin, D. Y. J.
Catal. 2007, 245, 228.
(9) For selected examples of spirolactone formation via bromonium
ion intermediates, see: (a) Mandal, A. K.; Jawalkar, D. G. Tetrahedron.
Lett. 1986, 27, 99. (b) Mandal, A. K.; Jawalkar, D. G. J. Org. Chem.
1989, 54, 2364.
(24) Stockis, A.; Hoffmann, R. J. Am. Chem. Soc. 1980, 102, 2952.
(10) For selected examples of spirolactone formation via N-
heterocyclic carbene-catalyzed Stetter-type reactions, see: (a) Burstein,
C.; Glorius, F. Angew. Chem., Int. Ed. 2004, 43, 6205. (b) Ye, W.; Cai,
G.; Zhuang, Z.; Jia, X.; Zhai, H. Org. Lett. 2005, 7, 3769.
(11) For selected examples of spirolactone formation via oxidative
dearomatization, see: (a) Tamura, Y.; Yakura, T.; Haruta, J.; Kita, Y. J.
Org. Chem. 1987, 52, 3927. (b) Cox, C.; Danishefsky, S. J. Org. Lett.
2000, 2, 3493. (c) Uyanik, M.; Yasui, T.; Ishihara, K. Tetrahedron
2010, 66, 5841. (d) Dohi, T.; Takenaga, N.; Nakae, T.; Toyoda, Y.;
Yamasaki, M.; Shiro, M.; Fujioka, H.; Maruyama, A.; Kita, Y. J. Am.
Chem. Soc. 2013, 135, 4558.
(12) For selected examples of spirolactone formation via C−H
hydroxylation, see: (a) Uyanik, M.; Suzuki, D.; Yasui, T.; Ishihara, K.
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