Cobaltocene-induced low-temperature radical coupling reactions in a cobalt-alkyne series

Article abstract of DOI:10.1021/om2006497

A novel method for the low-temperature generation of Co₂(CO) ₆-complexed propargyl radicals is developed. It consists of an in situ preparation of the respective cationic species (-50 to -10 °C) and their rapid reduction with cobaltocene, Cp₂Co, at -50 °C. The optimized experimental protocol is applied to both inter- and intramolecular reactions, affording topologically diverse α-aryl and α-napthyl, d,l- and meso-1,5-hexadiynes and 1,5-cyclodecadiynes. The d,l configuration is the most preferable steric arrangement in intermolecular radical C-C bond-forming reactions (d,l 69-92%), while a reversal of stereoselectivity is observed in intramolecular cyclizations (meso 79%). Under oxidizing conditions (Ce⁴⁺), decomplexation affords d,l-3,4-diaryl- and d,l-3,4-(1-/2-naphthyl)-1,5-hexadiynes in good to excellent yields (47-98%). An enhanced functional tolerance is showcased by introducing peripheral acid-sensitive functionalities, such as benzyloxy and methylenedioxy groups, and carrying out a five-step conversion scheme-from commercial aromatic aldehydes to radical dimers-under nonacidic conditions.

Full text of DOI:10.1021/om2006497

Article
pubs.acs.org/Organometallics
Cobaltocene-Induced Low-Temperature Radical Coupling Reactions
in a Cobalt−Alkyne Series
Gagik G. Melikyan,* Bianca Rivas, Stepan Harutyunyan, Louis Carlson, and Ruth Sepanian
Department of Chemistry and Biochemistry, California State University Northridge, Northridge, California 91330-8262,
United States
S
* Supporting Information
ABSTRACT: A novel method for the low-temperature generation of Co2(CO)6-complexed propargyl radicals is developed. It
consists of an in situ preparation of the respective cationic species (−50 to −10 °C) and their rapid reduction with cobaltocene,
Cp2Co, at −50 °C. The optimized experimental protocol is applied to both inter- and intramolecular reactions, affording
topologically diverse α-aryl and α-napthyl, d,l- and meso-1,5-hexadiynes and 1,5-cyclodecadiynes. The d,l configuration is the
most preferable steric arrangement in intermolecular radical C−C bond-forming reactions (d,l 69−92%), while a reversal of
stereoselectivity is observed in intramolecular cyclizations (meso 79%). Under oxidizing conditions (Ce4+), decomplexation
affords d,l-3,4-diaryl- and d,l-3,4-(1-/2-naphthyl)-1,5-hexadiynes in good to excellent yields (47−98%). An enhanced functional
tolerance is showcased by introducing peripheral acid-sensitive functionalities, such as benzyloxy and methylenedioxy groups, and
carrying out a five-step conversion schemefrom commercial aromatic aldehydes to radical dimersunder nonacidic conditions.
reaction at low temperatures allowed us to achieve a number of
synthetic objectives: in particular, the elimination of the
laborious cation isolation step and minimization of a partial
decomplexation of the triple bonds, while maintaining the
neutrality of the medium. An enhanced functional tolerance
was showcased by engaging the substrates with acid-sensitive
functionalitiesbenzyloxy and methylenedioxylocated on
the periphery of the aromatic nuclei.
INTRODUCTION
■
Recently we reported1 on high-temperature generation of
Co2(CO)6-stabilized propargyl cations under neutral con-
ditions, involving the treatment of the respective methyl
propargyl ethers with triflic or trifluoroacetic anhydrides. In
contrast to the conventional cation generation that utilizes a
variety of Brønsted−Lowry and Lewis acids,2,3 the novel
method could potentially tolerate the acid-sensitive moieties
and functional groups susceptible to protonation. It could also
become a key carbon−carbon bond-forming step in total
syntheses of complex molecular assemblies when an incompat-
ibility of the reagents, or reaction conditions, with peripheral
functionalities may cause unwanted chemical alterations. The
main drawback still remained a relatively high reaction
temperature (83−147 °C), which caused a partial decom-
plexation of radical dimers that, in turn, required a
recomplexation of the crude products.1 Among the disadvan-
tages were also an inherently low atom economy, given the
spontaneous nature of the radical generation reaction (2 equiv
of propargyl substrate → 1 equiv of propargyl radicals),1,4c,e and
the formation of the respective hydrocarbons as side products.1
Herein we report on the novel low-temperature generation of
cobalt-stabilized propargyl cations (−50 to −10 °C) under
neutral conditions and inter- and intramolecular radical
coupling reactions induced by cobaltocene, an external
reducing agent (−50 °C). Carrying out the radical coupling
RESULTS AND DISCUSSION
■
Methyl propargyl ether 1 was synthesized under nonacidic
conditions (Scheme 1) by the condensation of sodium
acetylide with benzaldehyde,5 followed by in situ methylation
of sodium alkoxide with trimethyloxonium tetrafluoroborate
and complexation of the triple bond with dicobalt octacarbon-
yl.6 Developing a three-step sequence that affords the requisite
methyl ethers under nonacidic conditions is of utmost
importance. It allows for the whole synthetic schemefrom
commercially available products to radical dimersto be
carried out without using either Lewis or Brønsted−Lowry acids.
Methyl propargyl ethers were previously synthesizedunder
acidic conditionsfrom the respective Co2(CO)6 propargyl
alcohols by using either HBF4/MeOH (with isolation of
Received: July 19, 2011
Published: February 15, 2012
© 2012 American Chemical Society
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cation isolation step. The existing methods utilize Brønsted−
Lowry acids, such as HBF4, and zinc, as a standard reductant,
the combination of reagents that requires an isolation of the
requisite cations prior to the reduction step.2−4
Scheme 1. Low-Temperature Generation of Propargyl
Cations under Neutral Conditions and a Low-Temperature
Reduction with Cobaltocene
The standardized protocol for generating cobalt-complexed
propargyl cations at low temperatures, under neutral
conditions, was applied to para-substituted alkoxy derivatives
6 (4-OMe) and 7 (4-OBn) (Table 1). The conversion to the
respective propargyl triflates was carried out with Tf2O (2),
followed by reduction with cobaltocene at −50 °C (10 min).
Radical dimers 8 and 9 were formed in good yields (73.3% and
68.6%), both being represented by a mixture of diastereomers
(8, d,l:meso = 72:28; 9, d,l:meso = 69:31). The successful
application of the standardized conditions to substrate 7,
bearing a protecting benzyl group,9 represents experimental
proof that the neutrality of the medium is maintained
throughout the cation generation−reduction steps. The benzyl
group is known to be removable under mild conditions by a
variety of Brønsted−Lowry and Lewis acids (CF3COOH, BF3,
AlCl3),9 and it can hardly “survive” under standard cation
generation conditions, employing HBF4 as an acid.2,3a,4b,e
A methylenedioxy moiety OCH2O9 represents an
alternative acid-sensitive functionality that can hardly maintain
its structural integrity under conventional acid-induced cation
generation protocols.2,3,4b,e To test the scope and applicability
of the low-temperature cation generation method under neutral
conditions, methyl ether 10 was synthesized in three steps from
commercially available benzaldehyde and treated with Tf2O (2)
at −50 °C (Scheme 2). The latter acts as an electrophile,
releasing a triflate anion and forming the highly substituted
oxonium ion 11. The C−O bond heterolysis occurs at −10 °C,
forming propargyl triflate 12, a key cationic intermediate, and
methyl triflate, which provides for a continuous neutrality of the
reaction medium. A rapid reduction with cobaltocene, at −50 °C
(10 min), generates the requisite propargyl radicals 13, which
dimerize, supposedly in a diffusion-controlled step, to 1,5-
hexadiyne 14 (d,l-14:meso-14 = 85:15; d,l-14 46.8%). The
major diastereomer, d,l-14, can be relieved from metal bondage
under oxidative conditions,2a,g thus concluding a five-step
conversion of commercial aromatic aldehyde to a radical
coupling product bearing acid-sensitive functional groups on
the periphery of the aromatic nuclei (Scheme 2).
intermediate cations),1 or BF3/MeOH (without isolation of
intermediate cations).7 The only “nonacidic” protocol, previously
developed by us,1 was less efficient, utilizing a large excess of an
alternative alkylating agent (20 equiv of MeI vs 1.1 equiv of
Me3O+BF4−) and suffering from an extended reaction time
(19 h vs 1.5 h) and a lower overall yield (17.5% vs 28.9%).
An interaction of methyl propargyl ether 1 with triflic
anhydride (2) occurred at low temperatures, albeit at a slow
pace. An optimized experimental protocol included a gradual
elevation of the reaction temperature from −50 to −10 °C,
within 30 min, thus fully converting methyl ether 1 to ionic
propargyl triflate 3 (Scheme 1). Cobaltocene, a 19e reducing
agent,8 was shown by us4h to operate in the T domain different
from that of zinc. The latter is capable of reducing cobalt-
complexed propargyl cations only at 20 °C,4b,e while
cobaltocene, given its reducing power and a good solubility
in CH2Cl2, even at −78 °C, rapidly reduces bis-propargyl
cations to meso-1,5-cyclodecadiynes with an excellent stereo-
selectivity (up to 97%).4h The reduction of propargyl tri-
flate 3 occurred at −50 °C (10 min), forming the requisite
radicals 4, which then underwent intermolecular dimerization
to 1,5-hexadiyne 5 (61.9%; d,l-5:meso-5 = 69:31). The facile
reduction of propargyl triflate 3 with cobaltocene attests to
its presumed ionic nature, since analogous conditions were
employed with propargyl tetrafluoroborates, the intrinsically
ionic compounds.4e,h
The generation of the propargyl cations under neutral
conditions and their reduction with cobaltocene at low
temperatures (−50 °C) allowed us to achieve five synthetic
objectives, while maintaining the neutrality of the medium.
First, we avoided the high temperatures (83−147 °C) that are
typical for the spontaneous generation of radicals carried out in
the absence of the external reducing agent.1 Second, we proved
that cobalt-complexed propargyl triflates are propargyl cation
mimics due to the high polarizability of the carbon−triflate
bond located α to the metal core. Third, we enhanced the atom
economy with respect to the spontaneous radical reactions, for
which 2 equiv of cobalt-complexed propargyl cations is required
for generation of 1 equiv of the requisite propargyl radicals.4c,e
Fourth, we minimized the partial decomplexation of the triple
bonds, a known deficiency in high-temperature processes that,
in turn, requires a recomplexation of the respective mono
complexes.1,4e,g Fifth, we achieved a long sought after
compatibility between the cation generation conditions and a
reducing agent that would potentially eliminate the laborious
To further expand the scope of the reaction, an intra-
molecular variant was explored in order to develop access to 1,5-
cyclodecadiynes10 with acid-sensitive moieties located on the
periphery of the aromatic rings. Given the structural proximity
to the cytotoxic enediynes,11 radical cyclization products can
provide a novel carbon framework in the development of
the new generation of nontoxic prodrugs12 for cancer treat-
ment. Dimethyl ether 15 was synthesized from the respective
bis alcohol4f by treatment with methanol in the presence of
BF3·Me2O.7 The interaction with a 2-fold excess of Tf2O (2),
within an optimized −50 to −10 °C temperature range,
followed by reduction with a 4-fold excess of cobaltocene
afforded 1,5-cyclodecadiyne 16 (56.7%), with the meso
diastereomer being predominantly formed (d,l-16:meso-16 =
21:79). For comparison, zinc-induced cyclizations4f yielded 1,5-
cyclodecadiynes with lower yields (28.7−43.3%) and featured a
reversed stereoselectivity: i.e., predominant formation of the
respective d,l diastereomers (d,l 54−80%).
An optimized protocol for α-phenyl propargyl cation
generation and its in situ reduction was further expanded to
include topologically diverse α-naphthyl substrates (Table 1;
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Table 1. Low-Temperature, Cobaltocene-Induced Inter- and Intramolecular Radical Coupling Reactions
a
b
c
Chromatographically separable. Chromatographically inseparable. Only major d,l diastereomers were decomplexed with ceric ammonium nitrate
unless indicated otherwise. 1,5-Cyclodecadiyne with a diastereomeric ratio of 67:33 (Zn reduction)4f was used as a substrate in the decomplexation
reaction. Reduction of the isolated propargyl cations with Zn.
d
e
entries 6 and 8). Thus, 1- and 2-naphthyl group containing
ethers 17 and 18 were converted to the respective dimeric
products 19 and 20, each represented by a mixture of
stereoisomers (19, d,l:meso = 81:19; 20, d,l:meso = 92:8). An
increased bulkiness of the α substituent (PCModel, v9.1: ΔV =
V(C6H6) − V(C10H8) = 56 Å3) did not interfere with the
formation of a C−C bond; to the contrary, the diastereo-
selectivities observed are systematically higher than that with a
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Scheme 2. “Survival” of an Acetal Protection Group
much smaller α-phenyl group (5, d,l:meso = 69:31). A higher
level of diastereoselection observed with the 2-naphthyl
substrate 18 indicates that the orientation of converging
propargyl radicals is dependent upon the substitution pattern
(1-naphthyl vs 2-naphthyl) and, attendant with it, the disparity
in the steric hindrance. An impact of the reducing agent was
probed by using an alternative dimerization procedure4b,e,j,k
that includes an isolation of the respective propargyl cations
and their subsequent reduction with zinc. Curiously, for
1-naphthyl-substituted methyl ether 17, d,l diastereoselectivity
was improved (19: Zn, d,l:meso = 87:13; Cp2Co, d,l:meso =
81:19; Table 1, entries 6 and 7), while for 2-naphthyl derivative
18, a significant decline in diastereoselection was detected (20:
Zn, d,l:meso = 74:26; Cp2Co, d,l:meso = 92:8; Table 1, entries 8
and 9). An impact of the reducing agent upon the stereo-
selectivity was previously observed by us4e in cross-coupling
radical reactions, with Cp2Co systematically favoring a meso
configuration. To what extent the observed disparity can be
attributed to the solubility of the reducing agents in methylene
chloride (hetero- vs homogeneous) still remains to be seen.
However, the experimental data on hand allow us to conclude
that Co2(CO)6-complexed propargyl radicals are not kinetically
independent, and the conformational and rotational flexibilities
depend upon the structure and composition of the intermediate
radical ion species.
The diastereoselectivity of radical coupling reactions was
determined by using the diagnostic value of acetylenic protons
in NMR spectra:4a,b,e,k in meso diastereomers, respective signals
are shifted upfield, up to 1.25 ppm, due to the spatial proximity
to the centroid of the aromatic ring (HC, d,l, 5.83−6.33
ppm; meso, 4.69−5.06 ppm). The same disposition of the
acetylenic protons was observed in benzyloxy and methyl-
enedioxy derivatives 9 and 14, with the respective signals in
meso diastereomers being shifted upfield, on average, by
1.18 ppm (HC, d,l, 6.28−6.29 ppm; meso, 5.01−5.20
ppm). The replacement of α-phenyl groups with much larger
1- and 2-naphthyl moieties substantially affected the chemical
shifts of acetylenic and methyne hydrogens, to the extent that a
correlation with previously reported data4 did not allow for
an unambiguous stereochemical assignment. In the case of
α-phenyl derivatives such as 5, the chemical shifts of methyne
hydrogens do not have any diagnostic value because of the
close proximity of the respective signals in d,l and meso
diastereomers (4.33 and 4.38 ppm; Δδ = 0.05 ppm). With a
1-naphthyl group introduced α to the metal core (19), methyne
hydrogens drastically shift downfield, by 1.33 ppm, for one of
the diastereomers, creating a significant gap (Δδ = 0.87 ppm)
between the respective proton resonances in opposite stereo-
isomers. Both acetylenic and methyne hydrogen signals were
found outside the established ranges of chemical shifts, with the
topology of the naphthyl group (1 vs 2) being another
contributing, and complicating, factor. To unambiguously
establish the relative configurations of naphthyl dimers, the
structure of the major stereoisomer, as d,l-20, was determined
by X-ray crystallography (Figure 1).13 The diagnostic methyne
hydrogensH15 and H16are positioned anti to each other
(θH15−C15−C16−H16 = 170.8°), by arranging the bulky cobalt
alkyne moieties in an ideally gauche fashion (θC14−C15−C16−C17
=
62.1°). The acetylenic hydrogens are forced into close
proximity to each other (H13−H18 = 2.31 Å), with the
nonbonding distance slightly exceeding the sum of VdW radii
(2.20 Å14). This is the reason why introducing any γ substi-
tuents at the acetylenic termini (t-Bu,4k Ph,4e Et4j) resulted in
substantial conformational changes, positioning the cobalt
alkyne units anti to each other. Metal coresCo2C2repre-
sent the tetrahedra with a skew geometry where the angles
between Co−Co and C−C triple bonds significantly deviate
from the perpendicular arrangement (70.4, 69.2°).2 Other
noteworthy structural features of d,l-20 include (a) an
essentially undistorted linearity of alkyne moieties (H13−C13−
C14−C15 = 0.1°, C16−C17−C18−H18 = 2.9°), (b) a bent geom-
etry2 for coordinated alkyne units (H13−C13−C14 = 135.1°,
C13−C14−C15 = 145.4°, H13−C13−C14 = 136.2°, C16−C17−
C18 = 142.2°), reflecting a substantial rehybridization of acetyl-
enic carbons and strong back-bonding from the cobalt carbonyl
moiety, and (c) a lengthened coordinated C−C triple bond
(C13−C14 = 1.32 Å vs ∼1.21 Å for free ligand) attendant with
complexation to the transition metal.2
An oxidative decomplexation with cerium(IV) ammonium
nitrate2a,g was carried out for major d,l diastereomers (d,l-5, d,
l-8, d,l-9, d,l-14, d,l-19, d,l-20), or an inseparable stereoisomeric
mixture derived from the intramolecular cyclization reaction
(d,l-16 + meso-16). Metal-free organic products 21−27 were
obtained in good to excellent yields (up to 98%), mostly in an
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Figure 1. ORTEP diagram of d,l-[μ,η2-3,4-bis(2′-naphthyl)-1,5-hexadiyne]bis(dicobalt hexacarbonyl) (20). Selected bond distances (Å), interatomic
distances (Å), and bond and torsion angles (deg): H18−H13 = 2.31, C13−C14 = 1.32, C14−C15 = 1.53, C15−C16 = 1.50, Co1−Co2 = 2.47,
H13−C13−C14 = 135.1, C13−C14−C15 = 145.4, H18−C18−C17 = 136.2, C16−C17−C18 = 142.2, C13−C14−Co1−Co2 = 70.4, C17−C18−
Co3−Co4 = 69.2, H16−C16−C15−H15 = 170.8, H13−C13−C14−C15 = 0.1, C16−C17−C18−H18 = 2.9, C29−C16−C15−C14 = 47.3, C14−
C15−C16−C17 = 62.1, C19−C15−C16−C29 = 47.3.
isomerically pure d,l form (Table 1). The relative configuration
for naphthyl derivative d,l-27 was established by X-ray
crystallography (Figure 2).13 Conformationally, the X-ray
structure of d,l-27 represents a striking departure from that of
its metal-clustered counterpart d,l-20. The latter positioned
bulky cobalt alkyne units and 2-naphthyl groups gauche to each
other, with internal hydrogen atoms exhibiting only a slight
deviation from an expected value (θH15−C15−C16−H16 = 170.8°).
The removal of metal cores and, attendant with it, a substantial
steric relief caused the naphthyl rings to spring out to a nearly
ideal anti disposition (θC10−C11−C12−C13 = 173.8°). The triple
do not provide the anchoring points in proximity to the
stereogenic centers, so that the stereochemistry of the head-to-
head coupling products1,5-alkadiynescould be controlled
by auxiliary functional groups, either sterically or electronically.
Even in transition-metal-catalyzed processes (Ti, Ru, Pd),15b−d
isomeric allenes are formed in significant quantities
(45−50%),15b along with poor diastereo- and regioselectivities
and low conversions (∼70%).15c,d The very nature of propargyl
radicalsprone to rearrangement and featuring a low chemo-
selectivitytriggered an interest toward developing their
synthetic equivalents.16 The complexation of the triple bonds
with a Co2(CO)6 protecting group allowed us to preclude an
unwanted acetylene−allene rearrangement, thus providing for
an exclusive formation of head-to-head radical dimers, in a
highly regioselective manner. In addition to this, well-known
ionic transformations of propargyl derivatives, such as Rupe and
Meyer−Schuster rearrangements,17 were not observed in
cobalt-protected propargyl systems, even in the presence of
strong acids. Another advantage of having a bulky protecting
group is its potential ability to favorably affect the stereo-
chemical outcome of radical C−C formation by altering the
orientations of converging propargyl radicals and limiting their
conformational freedoms. It should also be mentioned that
synthesizing propargyl cations under nonacidic conditions has
long been a synthetic challenge. In organometallic chemistry,
a standard protocol involves treatment of transition metal
π-complexed organic derivatives, typically alcohols, with strong
acids, such as H2SO4, HBF4, CF3COOH, HBr, TfOH, TsOH,
and FSO3H. Under these conditions, the existing methods
could be of limited use when applied to larger polyfunctional
bonds retained their steric relationship (θC23−C11−C12−C25
=
67.1°), while the hydrogen atoms, reflecting a decomplexation-
derived conformational change, appear gauche to each other
(d,l-27, θH11−C11−C12−H12 = 60.1°; d,l-20, θH15−C15−C16−H16
=
170.8°).
The novel method for radical C−C bond formation, α to the
metal core, represents a viable approach to the synthesis of
acyclic and cyclic alkadiynes with 1,5-disposition of the triple
bonds. The latter can readily be converted, via conventional
methods, to a variety of classes of organic compounds, such as
1,5-alkadienes, 1,4-/1,6-diketones, cyclopentenes, cyclopente-
nones, cycloalkane-1,2-diols, enediynes, and fused and bridged
carbocycles. It should be emphasized that d,l 3,4-disubstituted
1,5-alkadiynes are not easily accessible by alternative means.15
In a purely “organic” setting, propargyl−propargyl coupling
exhibits a poor regioselectivity due to unwanted acetylene−
allene rearrangement and, attendant with it, the formation of
inseparable mixtures of isomeric dimers (head-to-head, head-to-
tail, tail-to-tail).15a Another drawback is that organic molecules
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converging propargyl radicals containing α-phenyl (A), α-
1-naphthyl (B), and α-2-naphthyl (C) substituents. All three
pre-d,l spatial arrangements place aromatic rings gauche to each
other, with the number of gauche interactions being equal to 2.
A higher d,l diastereoselectivity observed in the presence of α-
naphthyl groups (d,l-19, 81%; d,l-20, 92%), relative to that in α-
phenyl containing substrate (d,l-5, 69%), can be attributed to
the larger size of the naphthyl group. In other words, by
introducing a bulkier substituent α to the metal core, we were
able to achieve a better discrimination between the alternative
spatial arrangements, leading to d,l and meso diastereomers. In
the intramolecular cyclization reaction, an opposite trend was
observed, with the meso diastereomer being the dominant
stereoisomer (Table 1: 16, d,l:meso = 21:79). The alternative
orientations for converging propargyl radicals, designated D
(pre-meso) and E (pre-d,l) (Figure 3), feature three and two
gauche interactions, respectively. With the current level of
understanding of cyclization kinetics, it is difficult to
unambiguously explain why the pre-meso orientation D is
energetically favored, despite the larger number of potentially
destabilizing gauche interactions. Given the reducing power of
cobaltocene, providing for a rapid reduction at temperatures as
low as −50 °C, and its relatively high bulkiness (199.56 Å3)
comparable with that of requisite substrates (e.g., 1 358.72 Å3),
it is conceivable that the cyclizing diradicals are not kinetically
independent species comparable to those in intermolecular
reactions. To the contrary, a one-electron transfer toward
cationoid species can generate diradicals that could remain
associated with oxidized Cp2Co+ species. The latter in turn
could act as counterions and affect, both sterically and confor-
mationally, the converging propargyl radical ions in such a way
that the pre-meso orientation D becomes energetically more
favorable.
Figure 2. ORTEP diagram of d,l-3,4-bis(2′-naphthyl)-1,5-hexadiyne
(27). Selected bond lengths (Å) and torsion angles (deg): C11−C12
= 1.57, H11−C11−C12−H12 = 60.1, C23−C11−C12−C25 = 67.1,
C10−C11−C12−C13 = 173.8.
molecules containing acid-sensitive functionalities. The novel
method substantially enhances the function compatibility of
transition-metal-mediated radical reactions, allowing for
functionalization of propargyl positions, as key steps, in the
multistep synthesis of biologically relevant molecules.
The stereoselectivity observed in low-temperature cobalto-
cene-induced radical coupling reactions indicates that in
intermolecular reactions the d,l configuration is favored for
topologically diverse 1,5-hexadiynes 5, 8, 9, 14, 19, and 20
(Table 1). The level of d,l stereocontrol is dependent upon
the nature and bulkiness of the α substituent, ranging from 69%
to 92%. Figure 3 represents the preferential orientations for
CONCLUSION
■
A novel method for the generation of propargyl triflates at low
temperaturesby interaction of Co2(CO)6-complexed methyl
propargyl ethers with triflic anhydridewas developed. Their
ionic nature, at temperatures as low as −50 °C, was demo-
nstrated by a successful reduction with cobaltocene. The
requisite substrates, metal-complexed methyl propargyl ethers,
can be synthesized under nonacidic conditions, allowing for
the whole schemefrom commercial aromatic aldehydes and
alkynes to 1,5-alkadiynes and 1,5-cyclodecadiynesto be
carried out in an acid-free environment. The compatibility of
Figure 3. Preferential orientations of converging propargyl radicals.
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(5). Under an atmosphere of nitrogen, Tf2O (2; 73 mg, 0.26 mmol)
was added dropwise (11 min) to a solution of methyl ether 1 (108 mg,
0.25 mmol) in dry methylene chloride (4 mL) at −50 °C. The
reaction mixture was brought to −10 °C in 30 min (NMR control),
and then a solution of Cp2Co (49 mg, 0.26 mmol) in dry methylene
chloride (1 mL) was added dropwise at −50 °C. The reaction mixture
was stirred for 10 min, diluted with saturated brine (10 mL), warmed
to 0 °C in 40 min, and then extracted with ether (10 mL), washed with
water (2 × 15 mL), and dried (Na2SO4). By NMR, the crude mixture
contained d,l-5, meso-5, and (HCCCH2Ph)Co2(CO)6 in the ratio of
64, 30, and 6 (d,l-5:meso-5 = 69:31). Organic solvents were evaporated
under reduced pressure, and the residue was fractionated by
preparative TLC (PE:CH2Cl2 = 10:1) to afford d,l-5 and meso-5
(62.1 mg, 61.9%; d,l-5:meso-5 = 68:32). Both diastereomers were fully
characterized in the previous account.4d
the reaction conditions, throughout a five-step synthetic sequ-
ence, with acid-sensitive structural units was successfully
demonstrated by engaging substrates with benzyloxy and
methylenedioxy protecting groups. The latter are textbook
examples of functionalities that are poorly compatible with
strong acids, such as HBF4. It is worth mentioning that the
temperature domain for reduction of propargyl triflates, pre-
viously falling in the range of 20−147 °C,1,4c,g was expanded
toward much lower temperatures, down to −50 °C. A newly
acquired ability to generate cationoid species and form a
carbon−carbon bond at low temperatures, while maintaining
the neutrality of the medium, substantially enhances the syn-
thetic potential of transition-metal-mediated radical chemistry.
In particular, this method can now be used, as a key step, in
targeted synthesis of larger organic assemblies wherein the
compatibility of reaction conditions and reagents with periph-
eral functionalities becomes pivotal.
d,l- and meso-[μ,η2-3,4-Bis(4′-methoxyphenyl)-1,5-
hexadiyne]bis(dicobalt hexacarbonyl) (8). According to protocol
B, methyl ether 61 (116 mg, 0.25 mmol), Tf2O (2, 73 mg, 0.26 mmol),
and Cp2Co (49 mg, 0.26 mmol) afforded the crude mixture,
containing, by NMR, d,l-8, meso-8, and [HCCCH2C6H4(4-OMe)]-
Co2(CO)6 in the ratio of 69:28:3 (d,l-8:meso-8 = 72:28). Organic
solvents were evaporated under reduced pressure, and the residue was
fractionated by preparative TLC (PE:E = 20:1) to yield d,l-8 and meso-
8 (79 mg, 73.3%; d,l-8:meso-8 = 74:26). Both diastereomers were fully
characterized in the previous account.4b
EXPERIMENTAL SECTION
■
All manipulations of air-sensitive materials were carried out in flame-
dried Schlenk-type glassware on a dual-manifold Schlenk line
interfaced to a vacuum line. Argon and nitrogen (Airgas, ultrahigh
purity) were dried by passing through a Drierite tube (Hammond). All
solvents were distilled before use under dry nitrogen over appropriate
drying agents (ether, THF, from sodium benzophenone ketyl;
CH2Cl2, from CaH2; benzene, from sodium). All reagents were pur-
chased from Sigma-Aldrich and Acros and used as received. Co2(CO)8
and Ce(NH4)2(NO3)4 were purchased from Strem. NMR solvents
[μ,η2-3-(4′-Benzyloxyphenyl)-3-methoxy-1-propyne]-
dicobalt Hexacarbonyl (7). [μ,η2-1-(4′-Benzyloxyphenyl)-2-pro-
pyn-1-ol]dicobalt Hexacarbonyl. Under an atmosphere of nitrogen, a
solution of 4-benzyloxybenzaldehyde (2.12 g, 10.0 mmol) in dry THF
(10 mL) was added dropwise (10 min) to a suspension of sodium
acetylide (4.0 g, 18% w/w in xylene; 0.72 g, 15 mmol) in dry THF (30 mL)
at −50 °C. Upon addition, the reaction mixture was stirred for 5 min,
warmed to 20 °C, and then stirred for 6 h (TLC monitoring).
Degassed saturated aqueous ammonium chloride (40 mL) was added
at 0 °C, the crude mixture was diluted with water (50 mL), and then
ether (150 mL), and the ethereal layer was separated. The aqueous
layer was extracted with ether (5 × 50 mL), and the combined ethereal
fractions were dried (Na2SO4). Under reduced pressure, crude alcohol
(2.38 g, 10 mmol; assuming 100% yield) was stripped of organic
solvents, redissolved in ether (100 mL), and added dropwise (20 min)
to a solution of dicobalt octacarbonyl (3.76 g, 11 mmol) in dry ether
(100 mL) under a flow of nitrogen. The reaction mixture was stirred at
20 °C for 2 h (TLC control), concentrated under reduced pressure,
and fractionated on the silica gel column (75 g, PE:E = 5:1) to afford
[HCCCH(OH)C6H4(4′-OBn)]Co2(CO)6 (1.49 g, 28.4% yield) as
red crystals. An analytical sample was obtained with preparative TLC
(PE:B = 1:1). Mp: 70−72 °C (sealed capillary; dried by coevaporation
with benzene, 3 × 1 mL). TLC (PE:E = 3:1): Rf 0.35. 1H NMR (400
MHz, CDCl3): δ 2.25 (1H, d, OH, J = 3.6), 5.07 (2H, s, OCH2Ph),
5.86 (1H, d, CH), 6.06 (1H, s, HC), 6.96 (2H, d, aromatic H, J =
8.8), 7.30−7.44 (7H, m, aromatic H). MS-HR-TOF: calcd for
C22H13O7Co2 (M − OH)+ 506.9320, found 506.9323.
Methylation Step (Protocol C): HBF4/MeOH. Under an atmosphere
of nitrogen, HBF4·Me2O (804 mg, 6.0 mmol) was added dropwise
in four equal portions to a solution of [HCCCH(OH)C6H4-
(4′-OBn)]Co2(CO)6 (786 mg, 1.5 mmol) in dry ether (35 mL) at
−20 °C. Introduction of each portion took 3 min, and the reaction mixture
was stirred for 5 min after each addition. The cation was allowed to settle,
and the ethereal layer was removed. At −20 °C, dry ether (20 mL)
was added along the inner wall of the flask, stirring was resumed for
5 min, the cation was allowed to settle, and the ethereal layer was
removed. The washing was repeated once with an additional portion of
dry ether (20 mL). The residual amount of ether was removed under
reduced pressure, and the cation was suspended in dry ether (20 mL)
at −20 °C. Dry methanol (1 mL) was then added dropwise (3 min)
to the reaction mixture, which was stirred for 5 min at −20 °C and
then for 1.5 h at 20 °C (TLC control). The reaction mixture was
diluted with water (15 mL) and ether (5 mL). The ethereal layer was
washed with water (2 × 15 mL), dried over molecular sieves (4 Å),
and evaporated to dryness to yield 7 (689 mg, 85.4% yield) as a red
were supplied by Cambridge Isotope Laboratories. H and 13C NMR
1
spectra were recorded on a Bruker DRX-400 (1H, 400 MHz) spectro-
meter. Chemical shifts were referenced to internal solvent resonances
and are reported relative to tetramethylsilane. Spin−spin coupling
constants (J) are given in hertz. Elemental analyses were performed by
Columbia Analytical Services (Kelso, WA). Melting temperatures
(uncorrected) were measured on a Mel-Temp II (Laboratory Devices)
apparatus and Optimelt Automated Meltemp. Silica Gel S735-1
(60−100 mesh; Fisher) was used for flash column chromatography.
Analytical and preparative TLC analyses (PTLC) were conducted on
silica gel 60 F254 (EM Science; aluminum sheets) and silica gel 60
PF254 (EM Science; w/gypsum, 20 × 20 cm), respectively. Eluents are
ether (E), petroleum ether (PE), pentane (P), and benzene (B). Mass
spectra were run at the Regional Center on Mass Spectroscopy, UC
Riverside, Riverside, CA (FAB, ZAB-SE; CI-NH3, 7070EHF; Micro-
mass; TOF Agilent 6210 LCTOF instrument with a Multimode
source).
Synthesis of Methyl Propargyl Ethers under Nonacidic
Conditions (Protocol A): (μ,η2-1-Methoxy-1-phenyl-2-
propyne)dicobalt Hexacarbonyl (1). Under an atmosphere of
nitrogen, at −50 °C, a solution of benzaldehyde (212 mg, 2 mmol) in
dry THF (8 mL) was added dropwise (15 min) to a suspension of
sodium acetylide (106 mg, 2.2 mmol; 587 mg, 18% suspension in
xylene) in dry THF (12 mL), and the reaction mixture was stirred for
4 h at 20 °C. Trimethyloxonium tetrafluoroborate (326 mg, 2.2 mmol)
was added at −20 °C, in one portion, and the reaction mixture was
stirred for 1.5 h at −20 °C (TLC control). The mixture was quenched
with water (25 mL) at −20 °C, the aqueous layer was extracted with
ether (3 × 20 mL), and the combined ethereal fractions were dried
(Na2SO4). Upon concentration under reduced pressure (1/3 v/v),
under an atmosphere of nitrogen, the crude methyl ether (292 mg,
2 mmol; assuming 100% yield) was added dropwise (25 min) to a
solution of dicobalt octacarbonyl (1.64 g, 4.8 mmol) in dry ether
(40 mL). The reaction mixture was stirred for 4 h at 20 °C, concen-
trated under reduced pressure, and fractionated on a silica gel column
(132 g, PE) to give 1 (250 mg, 28.9% over three steps). Spectral and
physicochemical data are analogous with those reported earlier.4a
Low-Temperature Generation and Cp2Co Reduction of
Co2(CO)6-Complexed Cations (Protocol B): d,l- and meso-
(μ,η2-3,4-Diphenyl-1,5-hexadiyne)bis(dicobalt hexacarbonyl)
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Article
solid. Mp: 66−68 °C (sealed capillary; dried by coevaporation with
benzene, 3 × 1 mL). TLC (PE:E = 5:1): Rf 0.48. 1H NMR (400 MHz,
CDCl3): δ 3.44 (3H, s, OMe), 5.08 (2H, s, OCH2Ph), 5.25 (1H, s,
CH), 6.03 (1H, s, HC), 6.98 (2H, spl d, aromatic H, J = 8.8), 7.28−
7.46 (7H, m, aromatic H). 13C NMR (100 MHz, CDCl3): δ 57.4, 70.3,
72.3, 83.4, 99.0, 115.1, 127.6, 127.7, 128.1, 128.7, 134.9, 137.2, 158.9,
199.5. MS-HR-TOF: calcd for C24H19O9Co2 (M + OMe)− 568.9699,
found 568.9682.
137.5, 146.6, 147.6 (aromatic C), 199.0, 200.1 (CO). HR-MS ESI/
APCI: calcd for C33H17O17Co4 [M + MeO]− 920.7799, found
920.7780.
[μ,η2-1,10-Dimethoxy-1,10-bis(4′-methoxyphenyl)-2,8-
decadiyne]bis(dicobalt hexacarbonyl) (15). According to proto-
col D, [(4′-OMeC6H4CH(OH)CC(CH2)4CCCH(OH))C6H4(4′-
OMe)][Co2(CO)6]24f (570 mg, 0.6 mmol), methanol (0.5 mL), and
BF3·Me2O (342 mg, 3 mmol) afforded, after chromatographic isola-
tion on a silica gel column (150 g; PE:E = 10:1), bis methyl ether 15
(326 mg, 55.6%) as dark red crystals. Mp: 72−87 °C (sealed capillary;
dried by coevaporation with benzene, 3 × 1 mL). TLC (PE:E = 7:1):
d,l- and meso-[μ,η2-3,4-Bis(4′-benzyloxyphenyl)-1,5-
hexadiyne]bis(dicobalt hexacarbonyl) (9). According to protocol
B, methyl ether 7 (135 mg, 0.25 mmol), Tf2O (2; 73 mg, 0.26 mmol),
and Cp2Co (49 mg, 0.26 mmol) afforded the crude mixture, con-
taining, by NMR, d,l-9 and meso-9 in a ratio of 69:31. Organic
solvents were evaporated under reduced pressure, and the residue was
fractionated by column chromatography (Florisil, 40 g; PE:E = 20:1)
followed by preparative TLC (2 plates; PE:CH2Cl2:E = 10:1:0.5) to
afford d,l-9 and meso-9 (87.0 mg, 68.6%; d,l-9:meso-9 = 69:31). Indi-
vidual diastereomers were isolated on a Florisil column (P:B = 2:1)
under anaerobic conditions, with d,l-9 being repurified by preparative
TLC (P:B = 5:1).
1
Rf 0.45. H NMR (400 MHz, CDCl3): δ 1.72 (4H, m, 2CH2), 2.73
(4H, m, 2CH2), 3.41 (6H, s, OMe), 3.81 (6H, s, OMe), 5.26 (2H, s,
CH), 6.92 (4H, d, aromatic H, J = 8.4), 7.30 (4H, d, aromatic H). 13C
NMR (100 MHz, CDCl3): δ 31.68, 33.42 (C4, C5, C6, C7), 55.30,
57.12 (OMe), 83.48 (C1, C10), 98.11, 100.00 (C2, C3, C8, C9),
113.92, 127.41, 134.02, 159.55 (aromatic C), 199.70 (CO). MS TOF:
m/z calcd for C38H30O16ClCo4 [M + Cl]− 1012.8556, found 1012.8584.
Anal. Found: C, 46.65; H, 3.22. Calcd for C38H30O16Co4: C, 46.65;
H, 3.09.
d,l- and meso-[μ,η2-3,4-Bis(4′-methoxyphenyl)-1,5-
cyclodecadiyne]bis(dicobalt hexacarbonyl) (16). According to
protocol B, bis methyl ether 15 (98 mg, 0.1 mmol), Tf2O (2; 62 mg,
0.22 mmol), and Cp2Co (76 mg, 0.4 mmol) afforded the crude
mixture, containing, by NMR, d,l-16 and meso-16 in a ratio of 21:79.
Organic solvents were evaporated under reduced pressure, and the
residue was fractionated by preparative TLC (2 plates; PE:E = 10:1) to
afford d,l-16 and meso-16 (52 mg, 56.7%; d,l-16:meso-16 = 18:82).
Both diastereomers were fully characterized in the previous account.4f
[μ,η2-3-Methoxy-3-(1′-naphthyl)-1-propyne]dicobalt Hexa-
carbonyl (17) (Protocol E). Under an atmosphere of nitrogen,
1-naphthaldehyde (1.03 g, 6.63 mmol) in dry THF (5 mL) was added
dropwise (5 min) to a suspension of sodium acetylide (350 mg, 7.29
mmol; 1.94 g, 18% suspension in xylene) in dry THF (20 mL) at
−50 °C. The reaction mixture was stirred for 4 h at 20 °C and then
was quenched with water (25 mL). An aqueous layer was extracted
with ether (3 × 20 mL), and the combined ethereal fractions were
dried (Na2SO4). Under an atmosphere of nitrogen, a solution of crude
HCCCH(OH)(1-naphthyl) (1.21 g, 6.63 mmol; assuming 100%
yield) in dry ether (20 mL) was added dropwise (25 min) to a solution
of dicobalt octacarbonyl (2.38 g, 6.96 mmol) in dry ether (20 mL).
The reaction mixture was stirred for 3 h at 20 °C, concentrated under
reduced pressure, and fractionated on a silica gel column (230 g;
PE:E = 15:1) to afford [HCCCH(OH)(1-naphthyl)]Co2(CO)6
(746 mg, 24.1%) as a red oil. Under an atmosphere of nitrogen, at
0 °C, methanol (2 mL) and BF3·Me2O (912 mg, 8.0 mmol) were
added to a solution of alcohol (746 mg, 1.59 mmol) in dry methylene
chloride (10 mL). The reaction mixture was stirred for 2 h at 0 °C,
poured into saturated aqueous NaHCO3 (20 mL), and extracted with
ether (3 × 20 mL). The combined organic fractions were dried
(MgSO4) and then evaporated to dryness to afford 17 (704 mg,
d,l-9: red crystals. Tdec = 118.4−123.8 °C (sealed capillary; dried by
coevaporation with benzene, 3 × 1 mL). TLC (P:B = 2:1): Rf 0.38. 1H
NMR (400 MHz, CDCl3): δ 4.30 (2H, s, HC), 4.97 (4H, s, OCH2Ph),
6.28 (2H, s, HC), 6.78 (4H, d, 3′-H, 5′-H, J = 8.8), 7.00 (2H, d,
2′-H, 6′-H, J = 8.4), 7.28−7.39 (10H, m, aromatic H). 13C NMR (100
MHz, CDCl3): δ 54.2, 70.2, 77.0, 102.5, 114.8, 127.6, 128.0, 128.6,
129.9, 136.2, 137.2, 157.9, 199.1, 200.2. HR-MS ESI/APCI: calcd for
C44H26O14KCo4 MK+ 1052.8288, found 1052.8260.
meso-9: red solid. Tdec 133.2−137.8 °C (sealed capillary; dried by
coevaporation with benzene, 3 × 1 mL). TLC (P:B = 2:1): Rf 0.63.
1H NMR (400 MHz, CDCl3): δ 4.31 (2H, s, HC), 5.01 (2H, s,
HC), 5.15 (4H, s, OCH2Ph), 6.97−7.51 (18H, m, aromatic H).
HR-MS ESI/APCI: calcd for C44H26O14KCo4 1052.8288, found
1052.8274.
Synthesis of Methyl Propargyl Ethers under Acidic
Conditions (Protocol D): [μ,η2-3-Methoxy-3-(3′,4′-methylene-
dioxyphenyl)-1-propyne]dicobalt Hexacarbonyl (10). Under an
atmosphere of nitrogen, at 0 °C, methanol (0.5 mL) and BF3·Me2O
(166 mg, 1.46 mmol) were added to a solution of [HC
CCH(OH)C6H3(3′,4′-OCH2O)]Co2(CO)6 (270 mg, 0.584 mmol)
in dry methylene chloride (3 mL). The reaction mixture was stirred for
1 h at 0 °C, poured into saturated aqueous NaHCO3 (10 mL), and
extracted with methylene chloride (3 × 10 mL). The combined
organic fractions were dried (MgSO4), concentrated under reduced
pressure, and chromatographed on a silica gel column (60 g; PE:E =
10:1) to afford 10 (228 mg, 82.0%) as red crystals. Mp: 44−46 °C
(sealed capillary; dried by coevaporation with benzene, 3 × 1 mL).
1
TLC (PE:E = 10:1): Rf 0.42. H NMR (400 MHz, CDCl3): δ 3.43
(3H, s, OMe), 5.19 (1H, m, CH), 5.95 (2H, AB spectrum, CH2,
JH(A)−H(B) = 1.4), 6.02 (1H, d, HC, J = 1.2), 6.79 (1H, dd, 5′-H, J =
8.0, J = 0.4), 6.85 (1H, ddd, 6′-H, J = 2.0, 0.4), 6.90 (1H, dt, 2′-H, J =
2.0, 0.4). MS TOF FD+: m/z calcd for C17H10O9Co2 [M+] 475.8983,
found 475.8983. Anal. Found: C, 42.63; H, 2.16. Calcd for
C17H10O9Co2: C, 42.88; H, 2.12.
1
91.9%) as a dark red oil. TLC (PE:E = 10:1): Rf 0.59. H NMR
(400 MHz, CDCl3): δ 3.55 (3H, s, OMe), 5.89 (1H, s, CH), 6.01 (1H, s,
HC), 7.47−7.55 (2H, m, aromatic H), 7.56−7.61 (1H, m, aromatic H),
7.69 (1H, d, aromatic H, J = 7.2), 7.81 (1H, d, aromatic H, J = 8.4),
7.89 (1H, dd, aromatic H, J = 8.2, J = 0.6), 8.16 (1H, d, aromatic H, J =
8.4). 13C NMR (100 MHz, CDCl3): δ 57.4 (OMe), 71.9 (CH), 80.9,
97.8 (HCC), 123.1, 123.4, 125.4, 125.6, 125.9, 128.4, 128.9, 130.3,
134.0, 137.4 (aromatic C), 199.0, 199.5 (CO). MS TOF EI: m/z
calcd for C21H15O8Co2 [M + MeO]− 512.9436, found 512.9428. MS
TOF FD+: m/z M+ 482. Anal. Found: C, 49.59; H, 2.89. Calcd for
C20H12O7Co2: C, 49.82; H, 2.51.
d,l- and meso-[μ,η2-3,4-Bis(3′,4′-methylenedioxyphenyl)-1,5-
hexadiyne]bis(dicobalt hexacarbonyl) (14). According to proto-
col B, methyl ether 10 (119 mg, 0.25 mmol), Tf2O (2; 73 mg, 0.26
mmol), and Cp2Co (49 mg, 0.26 mmol) afforded the crude mixture,
containing, by NMR, d,l-14 and meso-14 in a ratio of 85:15. The
reaction mixture was treated with dicobalt octacarbonyl (13 mg,
0.0375 mmol; 20 °C, 2 h), and organic solvents were evaporated under
reduced pressure. The residue was fractionated by preparative TLC
(PE:CH2Cl2:E = 18:1:0.5); repurification by preparative TLC afforded
d,l-14 (PE:E = 10:1; 2 runs; 52.1 mg, 46.8%).
d,l- and meso-[μ,η2-3,4-Bis(1′-naphthyl)-1,5-hexadiyne]bis-
(dicobalt hexacarbonyl) (19). (a). Zn-Mediated, Two-Step
Dimerization Reaction (Protocol F). Under an atmosphere of
nitrogen, at −20 °C, a solution of HBF4·Me2O (201 mg, 1.5 mmol)
was added dropwise to a solution of methyl ether 17 (121 mg,
0.25 mmol) in dry pentane (10 mL). The reaction mixture was stirred
for 5 min at −20 °C and then for an additional 1.5 h at 0 °C. The cation
was washed with dry pentane (3 × 20 mL) at −30 °C, the residual
d,l-14: red crystals. Tdec = 117−120 °C (sealed capillary; dried by
coevaporation with benzene, 3 × 1 mL). TLC (PE:E = 10:1): Rf 0.25.
1H NMR (400 MHz, CDCl3): δ 4.18 (2H, s, CH), 5.87 (4H, AB
spectrum, OCH2O, J = 1.2), 6.29 (2H, s, HC), 6.53−6.67 (6H, m,
aromatic H). 13C NMR (100 MHz, CDCl3): δ 54.3 (CH), 77.3
(HCC), 101.1 (OCH2O), 102.1 (HCC), 108.2, 109.1, 122.4,
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amount of pentane was removed under reduced pressure, and the
precipitate was dissolved in dry methylene chloride (10 mL) at
−20 °C. The reaction mixture was treated with zinc (650 mg,
10 mmol), stirred for 5 min at −20 °C, and then the temperature was
raised to 20 °C, and zinc was mechanically scraped from the walls of
the flask. The reaction mixture was stirred for 20 min at 20 °C (TLC
control), and zinc was filtered off on a short bed of Florisil (1 in.). The
crude mixture (NMR: d,l-19:meso-19 = 87:13) was fractionated on a
silica gel column (40 g; PE) to afford a mixture of d,l-19 and meso-19
(55 mg, 48.8%). The individual diastereomers were isolated by
preparative TLC (PE:CH2Cl2 = 5:1; two runs) to afford d,l-19 (42 mg,
37.3%) and meso-19 (6 mg, 5.3%).
d,l-19: dark red solid. Tdec = 137−145 °C (sealed capillary; dried by
coevaporation with benzene, 3 × 1 mL). TLC (PE:CH2Cl2 = 3:1): Rf
0.44. 1H NMR (400 MHz, CDCl3): δ 5.66 (2H, s, 2CH), 6.51 (2H, s,
HC), 7.07 (2H, dd, aromatic H, J = 7.6, J = 8.4), 7.39−7.48 (4H, m,
aromatic H), 7.51−7.58 (4H, m, aromatic H), 7.69 (2H, d, aromatic
H, J = 8.4), 8.11 (2H, d, aromatic H, J = 8.4). 13C NMR (100 MHz,
CDCl3): δ 46.9 (CH), 77.5, 101.4 (CC), 121.8, 124.6, 124.9, 125.2,
126.2, 127.3, 129.0, 131.0, 133.5, 139.6 (aromatic C), 198.3, 200.1
(CO). MS TOF EI: m/z calcd for C39H21O13Co4 [M + MeO]−
932.8316, found 932.8325. MS TOF FD+: m/z M+ 902. Anal. Found:
C, 50.57; H, 2.51. Calcd for C38H18O12Co4: C, 50.58; H, 2.01.
meso-19: dark red solid. Tdec = 124−133 °C (sealed capillary; dried
by coevaporation with benzene, 3 × 1 mL). TLC (PE:CH2Cl2 = 5:1):
Rf 0.53. 1H NMR (400 MHz, CDCl3): δ 4.79 (2H, s, 2CH), 5.78 (2H,
was fractionated on a silica gel column (20 g; PE:E = 15:1) to yield a
mixture of d,l-20 and meso-20 (65 mg, 57.5%; d,l-20:meso-20 = 75:25).
The individual diastereomers were isolated by preparative TLC
(PE:E = 10:1) to afford d,l-20 (50 mg, 44.1%) and meso-20
(10 mg, 8.5%).
d,l-20: dark red solid. Tdec = 127−135 °C (sealed capillary; dried by
coevaporation with benzene, 3 × 1 mL). TLC (PE:E = 5:1): Rf 0.64.
1H NMR (400 MHz, CDCl3): δ 4.68 (2H, s, 2CH), 6.38 (2H, s,
HC), 7.30−7.40 (6H, m, aromatic H), 7.54−7.73 (8H, m, aromatic
H). 13C NMR (100 MHz, CDCl3): δ 54.4 (CH), 77.0, 101.6 (CC),
125.4, 125.8, 127.4, 127.5, 127.9, 132.3, 132.9, 140.6 (aromatic C),
198.6, 199.8 (CO). MS TOF EI: m/z calcd for C39H21O13Co4 [M +
MeO]− 932.8316, found 932.8278. MS TOF FD+: m/z M+ 902. Anal.
Found: C, 51.12; H, 2.27. Calcd for C38H18O12Co4: C, 50.58; H, 2.01.
Single crystals suitable for X-ray structure analysis (Figure 1) were
obtained by ethanol vapor diffusion into a solution of d,l-20 in pentane
and methylene chloride (5:1, v/v) at 0 °C (1 day).
meso-20: dark red solid. Tdec = 165−170 °C (sealed capillary; dried
by coevaporation with benzene, 3 × 1 mL). TLC (PE:E = 5:1): Rf
0.68. 1H NMR (400 MHz, CDCl3): δ 4.69−4.87 (2H, m, 2CH),
4.89−5.08 (2H, m, HC), 7.53−8.10 (16H, m, arom H). MS TOF
EI: m/z calcd for C39H21O13Co4 [M + MeO]− 932.8316, found
932.8271.
(b). Cp2Co-Mediated Dimerization Reaction (Protocol B).
According to protocol B, methyl ether 18 (121 mg, 0.25 mmol),
Tf2O (2; 92 mg, 0.325 mmol; stirred for 2 h at −10 °C), and Cp2Co
(142 mg, 0.75 mmol; stirred for 2 h at −30 °C) afforded, upon partial
recomplexation with Co2(CO)8 (13 mg, 0.0375 mmol; ether, 13 mL)
and fractionation by preparative TLC (PE:CH2Cl2 = 10:1; two plates,
two runs), d,l-20 (33 mg, 29.2%) and meso-20 (3 mg, 2.7%; re-
purification by preparative TLC, PE:CH2Cl2 = 20:1). The mass ratio
of d,l-20 and meso-20 was equal to 92:8.
s, HC), 7.60 (4H, m, aromatic H), 7.70 (2H, t, aromatic H, Jav
=
7.8), 7.83 (2H, d, aromatic H, J = 7.2), 7.98 (4H, dd, aromatic H, J =
8.0, J = 10.0), 8.23 (2H, d, aromatic H, J = 8.0). MS TOF EI: m/z
calcd for C39H21O13Co4 [M + MeO]− 932.8316, found 932.8273. MS
TOF FD+: m/z M+ 902. Anal. Found: C, 50.67; H, 3.14. Calcd for
C38H18O12Co4: C, 50.58; H, 2.01.
(b). Cp2Co-Mediated Dimerization Reaction (Protocol B).
According to protocol B, methyl ether 17 (121 mg, 0.25 mmol),
Tf2O (2; 92 mg, 0.325 mmol; stirred for 2 h at −10 °C), and Cp2Co
(71 mg, 0.375 mmol; stirred for 2 h at −30 °C) afforded the crude
mixture, containing, by NMR, d,l-19 and meso-19 in the ratio of 81:19.
Fractionation by column chromatography (SiO2, 54 g; PE:E = 100:1),
yielded d,l-19 (25 mg, 22.2%) and [HCCCH2(1-naphthyl)]-
Co2(CO)6 (7 mg, 6.2%; repurification by preparative TLC, pentane).
[HCCCH2(1-Naphthyl)]Co2(CO)6: dark red oil. TLC (PE:E =
d,l-3,4-Bis(4′-benzyloxyphenyl)-1,5-hexadiyne (23) (Proto-
col G). Under an atmosphere of nitrogen, a solution of degassed
Ce(NH4)2(NO3)6 (121 mg, 0.22 mmol) in acetone (5 mL) was added
to a solution of d,l-9 (20 mg, 0.02 mmol) in acetone (5 mL) at −78 °C.
The reaction mixture was warmed to −30 °C, stirred for 1 h (TLC
control), cooled to −78 °C, and quenched with degassed saturated
NaCl solution (5 mL). The reaction mixture was then diluted with
water (10 mL), warmed to 20 °C, and extracted with ether (5 × 20 mL).
The combined ethereal layers were concentrated to about one-
fifth of their original volume and dried over molecular sieves
(4 Å). The molecular sieves were filtered off, the ethereal layer was
evaporated to dryness, and the residual tan powder was washed with
pentane (5 × 5 mL). The residual pentane was removed under redu-
ced pressure, and product was coevaporated with benzene (5 mL) to
give d,l-23 (8.7 mg, 98.4%) as an off-white powder. Mp: 153−154 °C
(with partial decomposition; sealed capillary; dried by coevaporation
1
15:1): Rf 0.57. H NMR (400 MHz, CDCl3): δ 4.58 (2H, s, CH2),
5.97 (1H, s, HC), 7.39 −7.47 (2H, m, aromatic H), 7.52 (1H, td,
aromatic H, J = 8.0, J = 1.2), 7.58 (1H, td, aromatic H, J = 6.8, J = 1.2),
7.79 (1H, t, aromatic H, J = 5.2), 7.88 (1H, d, aromatic H, J = 7.6),
8.10 (1H, d, aromatic H, J = 8.4). MS TOF FD+: M+ 452.
[μ,η2-3-Methoxy-3-(2′-naphthyl)-1-propyne]dicobalt Hexa-
carbonyl (18). According to protocol E, 2-naphthaldehyde (1.87 g,
12 mmol; THF, 10 mL), sodium acetylide (634 mg, 13.2 mmol; 3.52 g,
18% suspension in xylene; THF, 40 mL), and dicobalt octacarbonyl
(4.31 g, 12.6 mmol; ether, 40 mL) afforded, upon chromatographic
isolation (silica gel, 250 g; PE:E = 10:1), [HCCCH(OH)-
(2-naphthyl)]Co2(CO)6 (1.13 g, 20.2%) as a red oil. Methylation with
methanol (1 mL) and BF3·Me2O (1.38 g, 12.1 mmol), at 0 °C, yielded
18 (937 mg, 80.4%; 16.2% over three steps) as a dark red solid. Mp:
73−76 °C (sealed capillary; dried by coevaporation with benzene, 3 ×
1
with benzene, 3 × 1 mL). TLC (B): Rf 0.54. H NMR (400 MHz,
CDCl3): δ 2.37 (2H, s, HC), 3.94 (2H, s, CH), 5.05 (4H, s,
OCH2Ph), 6.88 (4H, d, aromatic 3′-H and 5′-H, J = 8.4), 7.19 (4H, d,
aromatic H, J = 8.8), 7.31−7.47 (10H, m, aromatic H). HR-MS ESI/
+
APCI: calcd for C32H30O5 MNH4 460.2277, found 460.2263.
d,l-3,4-Diphenyl-1,5-hexadiyne (21), d,l-3,4-Bis(4′-methoxy-
phenyl)-1,5-hexadiyne (22), and d,l- and meso-3,4-Bis(4′-
methoxyphenyl)-1,5-cyclodecadiyne (25). Decomplexation of d,l-
5, d,l-8, and d,l- and meso-16 was carried out according to protocol G
and described in the previous accounts.1,4f
1
1 mL). TLC (PE:E = 5:1): Rf 0.63. H NMR (400 MHz, CDCl3): δ
3.50 (3H, s, OMe), 5.45 (1H, s, CH), 6.05 (1H, d, HC, J = 0.8),
7.45−7.55 (3H, m, aromatic H), 7.81−7.89 (4H, m, aromatic H). 13C
NMR (100 MHz, CDCl3): δ 57.3 (OCH3), 71.9 (CH), 83.7, 97.8
(CC), 124.0, 125.2, 125.9, 126.2, 127.6, 127.8, 128.2, 128.4, 133.1,
139.4 (aromatic C), 199.2 (CO). MS TOF EI: m/z calcd for
C19H9O7Co2 [M − Me]− 466.9018, found 466.9036. MS TOF FD+:
m/z M+ 482. Anal. Found: C, 49.87; H, 2.53. Calcd for C20H12O7Co2:
C, 49.82; H, 2.51.
d,l-3,4-Bis(3′,4′-methylenedioxyphenyl)-1,5-hexadiyne (24).
According to protocol G, the treatment of d,l-14 (36 mg, 0.04 mmol)
with degassed Ce(NH4)2(NO3)6 (241 mg, 0.44 mmol; −78 °C, 2 h;
0 °C 30 min), followed by purification on a preparative TLC plate
(PE:E = 3:1) afforded d,l-24 (11 mg, 89.0%) as an off-white solid. Mp:
140−141 °C (sealed capillary; dried by coevaporation with benzene,
3 × 1 mL). TLC (PE:E = 3:1): Rf 0.22. 1H NMR (400 MHz, CDCl3):
δ 2.39 (2H, s, HC), 3.89 (2H, s, CH), 5.96 (4H, AB spectrum,
OCH2O, J = 1.4), 6.72 (4H, s, aromatic H), 6.88 (2H, s, aromatic H).
13C NMR (100 MHz, CDCl3): δ 45.4 (CH), 73.6, 83.1 (CCH),
d,l- and meso-[μ,η2-3,4-Bis(2′-naphthyl)-1,5-hexadiyne]bis-
(dicobalt hexacarbonyl) (20). (a). Zn-Mediated, Two-Step
Dimerization Reaction. According to protocol F, HBF4·Me2O (201 mg,
1.5 mmol), methyl ether 18 (121 mg, 0.25 mmol), and zinc (325 mg,
5 mmol) afforded crude 20 (NMR: d,l-20:meso-20 = 74:26), which
101.2 (OCH2O), 108.1, 109.0, 122.0, 132.1, 147.1, 147.6 (aromatic
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Organometallics
Article
C). MS TOF EI+: m/z calcd for C20H14O4 M+ 318.0887, found
318.0897.
Notes
The authors declare no competing financial interest.
d,l-3,4-Bis(1′-naphthyl)-1,5-hexadiyne (26). According to
protocol G, the treatment of d,l-19 (26 mg, 0.029 mmol) with
degassed Ce(NH4)2(NO3)6 (127 mg, 0.232 mmol; −78 °C, 30 min;
−50 °C, 30 min; −30 °C, 30 min), followed by repeated purification
on a preparative TLC plate (PE:CH2Cl2 = 5:1; PE:CH2Cl2 = 10:1)
afforded d,l-26 (4.5 mg, 47.0%) as a light yellow solid. Mp: 133−135 °C
(sealed capillary; dried by coevaporation with benzene, 3 × 1 mL).
ACKNOWLEDGMENTS
■
This material is based upon work supported by the National
Science Foundation under Grant No. CHE-1112129. We are
also greatly indebted to the Office of Graduate Studies,
Research and International Programs, and University Corpo-
ration, California State University Northridge, for their
generous support.
1
TLC (PE:CH2Cl2 = 2:1): Rf 0.47. H NMR (400 MHz, CDCl3): δ
2.47 (2H, d, HC, J = 0.8), 4.95 (2H, s, 2CH), 7.47−7.59 (6H, m,
aromatic H), 7.83 (2H, d, aromatic H, J = 8.4), 7.88−7.96 (2H, m,
aromatic H), 8.03−8.19 (4H, m, aromatic H). 13C NMR (100 MHz,
CDCl3): δ 39.5 (CH), 73.6, 83.2 (CC), 122.3, 125.3, 125.4, 126.1,
126.9, 128.2, 129.1, 130.3, 133.8, 134.5 (aromatic C). MS TOF EI: m/z
calcd for C26H18 M+ 330.1409, found 330.1417.
REFERENCES
■
(1) Melikyan, G. G.; Sepanian, R.; Spencer, R.; Rowe, A.; Toure, P.
Organometallics 2009, 28, 5541.
d,l-3,4-Bis(2′-naphthyl)-1,5-hexadiyne (27). According to
protocol G, the treatment of d,l-20 (40 mg, 0.044 mmol) with
degassed Ce(NH4)2(NO3)6 (193 mg, 0.352 mmol; −78 °C, 30 min;
−50 °C, 1 h), followed by purification on a preparative TLC plate
(activation at 130 °C, 1 h; PE:CH2Cl2 = 10:1; THF extraction)
afforded d,l-27 (9.7 mg, 68.9%) as a light yellow solid. Mp: 143−145 °C
(sealed capillary; dried by coevaporation with benzene, 3 × 1 mL).
(2) (a) Melikyan, G. G.; Nicholas, K. M. In Modern Acetylene
Chemistry; Stang, P. J., Diederich, F., Ed.; VCH: Weinheim, Germany,
1995; Chapter 4. (b) McGlinchey, M. J.; Girard, L.; Ruffolo, R. Coord.
Chem. Rev. 1995, 143, 331. (c) Amouri, H. E.; Gruselle, M. Chem. Rev.
1996, 96, 1077. (d) Went, M. Adv. Organomet. Chem. 1997, 41, 69.
(e) Green, J. R. Curr. Org. Chem. 2001, 5, 809. (f) Muller, T. J. J. Eur. J.
Org. Chem. 2001, 2021. (g) Teobald, B. J. Tetrahedron 2002, 58, 4133.
(h) Omae, I. Appl. Organomet. Chem. 2007, 21, 318.
1
TLC (PE:E = 2:1): Rf 0.64. H NMR (400 MHz, CDCl3): δ 2.453
(1H, d, HC, J = 0.8), 2.457 (1H, d, HC, J = 0.8), 4.33 (2H, s,
2CH), 7.44−7.52 (6H, m, aromatic H), 7.74−7.89 (8H, m, aromatic
H). 13C NMR (100 MHz, CDCl3): δ 45.4 (CH), 73.7, 82.5 (CC),
125.8, 126.0, 126.2, 127.4, 127.5, 127.7, 127.9, 132.6, 133.0, 135.4
(aromatic C). MS TOF EI: m/z calcd for C26H18 M+ 330.1409, found
330.1399. Single crystals suitable for X-ray structure analysis (Figure 2)
were obtained by ethanol vapor diffusion into a solution of d,l-27 in
methylene chloride at 0 °C (2 days).
(3) Representative examples are as follows. HBF4: (a) Varghese, V.;
Saha, M.; Nicholas, K. M. Org. Synth. 1989, 67, 141. BF3: (b) Saha,
M.; Nicholas, K. M. J. Org. Chem. 1984, 49, 417. CF3COOH:
(c) Nicholas, K. M.; Siegel, J. J. Am. Chem. Soc. 1985, 107, 4999.
H2SO4: (d) Top, S.; Jaouen, G. J. Org. Chem. 1981, 46, 78. HBr:
(e) Descoins, C.; Samain, D. Tetr.ahedron Lett. 1976, 745. TiCl4:
(f) Magnus, P.; Pitterna, T. J. Chem. Soc., Chem. Commun. 1991, 541.
Bu2BOTf: (g) Schreiber, S. L.; Klimas, M. T.; Sammakia, T. J. Am.
Chem. Soc. 1987, 109, 5749. MeAl(OR)2: (h) Nakamura, T.; Matsui,
T.; Tanino, K.; Kuwajima, I. J. Org. Chem. 1997, 62, 3032. Me2AlCN:
(i) Stuart, J. G.; Nicholas, K. M. Synthesis 1989, 454. TfOH:
(j) Tanaka, S.; Isobe, M. Tetrahedron 1994, 50, 5633. TsOH:
(k) Hosokawa, S.; Isobe, M. J. Org. Chem. 1999, 64, 37. AgBF4:
(l) Vizniowski, G. S.; Green, J. R.; Breen, T. L.; Dalacu, A. V. J. Org.
Chem. 1995, 60, 7496. FSO3H: (m) Reutov, O. A.; Barinov, I. V.;
Chertkov, V. A.; Sokolov, V. I. J. Organomet. Chem. 1985, 297, C25.
(4) (a) Melikyan, G. G.; Deravakian, A.; Myer, S.; Yadegar, S.;
Hardcastle, K. I.; Ciurash, J.; Toure, P. J. Organomet. Chem. 1999, 578,
68. (b) Melikyan, G. G.; Sepanian, S.; Riahi, B.; Villena, F.; Jerome, J.;
Ahrens, B.; McClain, R.; Matchett, J.; Scanlon, S.; Abrenica, E.;
Paulsen, K.; Hardcastle, K. I. J. Organomet. Chem. 2003, 683, 324.
(c) Melikyan, G. G.; Villena, F.; Sepanian, S.; Pulido, M.; Sarkissian,
H.; Florut, A. Org. Lett. 2003, 5, 3395. (d) Melikyan, G. G.; Villena, F.;
Florut, A.; Sepanian, S.; Sarkissian, H.; Rowe, A.; Toure, P.; Mehta, D.;
Christian, N.; Myer, S.; Miller, D.; Scanlon, S.; Porazik, M.
Organometallics 2006, 25, 4680. (e) Melikyan, G. G.; Floruti, A.;
Devletyan, L.; Toure, P.; Dean, N.; Carlson, L. Organometallics 2007,
26, 3173. (f) Melikyan, G. G.; Wild, C.; Toure, P. Organometallics
2008, 27, 1569. (g) Melikyan, G. G.; Mikailian, B.; Sepanian, R.;
Toure, P. J. Organomet. Chem. 2009, 694, 785. (h) Melikyan, G. G.;
Spencer, R.; Abedi, E. J. Org. Chem. 2009, 74, 8541. (i) Melikyan, G.
G.; Voorhees, E.; Wild, C.; Spencer, R.; Molnar, J. Tetrahedron Lett.
2010, 51, 2287. (j) Melikyan, G. G.; Spencer, R. Tetrahedron 2010, 66,
5321. (k) Melikyan, G. G.; Spencer, R.; Rowe, A. Organometallics
2010, 29, 3556.
X-ray Crystallography of d,l-20 and d,l-27. Suitable crystals of
d,l-20 and d,l-27 were coated with Paratone N oil, suspended in small
fiber loops, and placed in a cooled nitrogen gas stream at 173 K on a
Bruker D8 APEX II CCD sealed-tube diffractometer with graphite-
monochromated Cu Kα (1.541 78 Å) radiation. Data were measured
for each crystal using a series of combinations of ψ and ω scans with
10 s frame exposures and 0.5° frame widths. Data collection, indexing,
and initial cell refinements were all carried out using APEX 213a
software. Frame integration and final cell refinements were done using
SAINT13b software. The structures were solved using direct methods
and difference Fourier techniques (SHELXTL V6.12).13c Hydrogen
atoms were placed in their expected chemical positions using the
HFIX command and were included in the final cycles of least squares
with isotropic Uij values related to the atoms ridden upon, except for
H24 and H26 in d,l-27, which were found in a difference Fourier map
and refined. All non-hydrogen atoms were refined anisotropically for
d,l-27, but only the Co and O atoms were refined anisotropically
for d,l-20. Scattering factors and anomalous dispersion corrections
are taken from ref 13d. Structure solution, refinement, graphics, and
generation of publication materials were performed by using
SHELXTL V6.12 software.
ASSOCIATED CONTENT
■
S
* Supporting Information
CIF files and tables giving crystallographic details, bond
distances and angles, atomic coordinates and equivalent
isotropic displacement parameters, and torsion angles for d,l-20
and d,l-27 and figures giving 1H and 13C NMR spectra of d,l-9,
meso-9, d,l-14, meso-20, d,l-23, d,l-24, d,l-26, and d,l-27. This
material is available free of charge via the Internet at http://
pubs.acs.org.
(5) Brandsma, L.; Verkruijsse, H. D. Synthesis of Acetylenes, Allenes
and Cumulenes: Elsevier: New York, 1981; p 80.
(6) Greenfield, H.; Sternberg, H. W.; Friedel, R. A.; Wotiz, J. H.;
Markby, R.; Wender, I. J. Am. Chem. Soc. 1956, 78, 120.
(7) Olier, C.; Gastaldi, S.; Gil, G.; Bertrand, M. P. Tetrahedron Lett.
2007, 48, 7801.
(8) (a) Tyler, D. R. Acc. Chem. Res. 1991, 24, 325. (b) Zavarine, I. S.;
Kubiak, C. P. Coord. Chem. Rev. 1998, 171, 419. For the X-ray
structure of cobaltocene see: (c) Antipin, M. Yu.; Boese, R.; Augart,
N.; Schmid, G. Struct. Chem. 1993, 4, 91.
AUTHOR INFORMATION
■
Corresponding Author
*E-mail: gagik.melikyan@csun.edu.
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(9) Greene, T. W.; Wuts, P. G. M. Protective Groups in Organic
Synthesis; Wiley: New York, 1999; pp 266−269, 287−288.
(10) (a) Gleiter, R.; Kratz, D.; Schafer, W.; Schehlmann, V. J. Am.
Chem. Soc. 1991, 113, 9258. (b) Haberhauer, G.; Roers, R.; Gleiter, R.
Tetrahedron Lett. 1997, 38, 8679. (c) Semmelhack, M. F.; Gallagher, J.
Tetrahedron Lett. 1993, 4121. (d) Boss, C.; Keese, R. Tetrahedron
1997, 53, 3111. (e) Myers, A. G.; Dragovich, P. S. J. Am. Chem. Soc.
1992, 114, 5859. (f) Klein, M.; Zabel, M.; Bernhardt, G.; Konig, B.
̈
J. Org. Chem. 2003, 68, 9379. (g) Pitsch, W.; Klein, M.; Zabel, M.;
Konig, B. J. Org. Chem. 2002, 67, 6805.
̈
(11) (a) Grissom, J. W.; Gunawardena, G. U.; Klingberg, D.; Huang,
D. Tetrahedron 1996, 52, 6453. (b) Smith, A. L.; Nicolaou, K. C.
J. Med. Chem. 1996, 39, 2103. (c) Basak, A.; Mandal, S.; Bag, S. S.
Chem. Rev. 2003, 103, 4077.
(12) (a) Testa, B.; Mayer, J. M. Hydrolysis in Drug and Prodrug
Metabolism; VHCA, Zurich/Wiley-VCH: Weinheim, Germany, 2003;
p 780. (b) Balant, L. P.; Doelker, E. In Burger’s Medicinal Chemistry
and Drug Discovery; Wolff, M. E., Ed.; Wiley: New York, 1995; p 949.
(13) (a) Bruker APEX 2 SAINT Version 6.45A; Bruker AXS Inc.,
Madison, WI, 2003. (b) Bruker SAINT; Bruker AXS Inc., Madison,
WI. (c) Sheldrick, G. M. A short history of SHELX. Acta Crystallogr.
2008, A64, 112−122. (d) Wilson, A. J. C., Ed. International Tables for
X-ray Crystallography; Kynoch Academic: Dordrecht, The Nether-
lands, 1992; Vol. C, Tables 6.1.1.4 (pp 500−502) and 4.2.6.8 (pp
219−222).
(14) (a) Bondi, A. J. Phys. Chem. 1964, 68, 441. (b) Mantina, M.;
Chamberlin, A. C.; Valero, R.; Cramer, C. J.; Truhlar, D. G. J. Phys.
Chem. A 2009, 113, 5806.
(15) (a) Badanyan, Sh. O.; Voskanyan, M. G.; Chobanyan, Zh. A.
Russ. Chem. Rev. 1981, 50, 1074. (b) Onodera, G.; Nishibayashi, Y.;
Uemura, S. Organometallics 2006, 25, 35. (c) Yang, F.; Zhao, G.; Ding,
Y.; Zhao, Z.; Zheng, Y. Tetrahedron Lett. 2002, 43, 1289. (d) Ogoshi,
S.; Nishiguchi, S.; Tsutsumi, K.; Kurosawa, H. J. Org. Chem. 1995, 60,
4650.
(16) Boutillier, P.; Zard, S. Z. Chem. Commun. 2001, 1304.
(17) Swaminathan, S.; Narayanan, K. V. Chem. Rev. 1971, 71, 429.
1663
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