Acquiring and Exploiting Persistency of Propargyl Radicals: Novel Paradigms

Article abstract of DOI:10.1021/acs.organomet.6b00435

Three complementary methods for altering an intrinsic nature of propargyl radicals, from transient to persistent, were developed by fine-tuning the bulkiness and degree of substitution around the secondary and tertiary propargylic carbons, as well as by sterically enhancing a π-bonded Co₂(CO)₆ metal core. The latter was employed, as a mechanistic tool, for precluding an acetylene-allene rearrangement, stabilizing propargyl cations, and creating a steric hindrance that could provide for said transition from transient to persistent propargyl radicals. A window of opportunities was identified wherein the steric bulkiness in propargyl radicals remains below the persistency threshold , providing good to excellent stereoselectivities in radical dimerization reactions (d,l 62-100%). Along with the persistency threshold for tertiary propargyl radicals (278.2 ?³), two different thresholds for persistency in secondary propargyl radicals were established - 306.5 and 576.0 ?³ - dependent upon the molecular architecture and the nature of the substituents populating the radical centers. Three alternative molecular platforms were designed to exploit a newly acquired dichotomy in allylic radicals (α-persistent-γ-transient) and trichotomy in pentadienyl radicals (α-persistent-γ-transient-?-transient), providing access to molecular assemblies with contiguous 4°-4°, 4°-3°, and 3°-3° carbon atoms.

Full text of DOI:10.1021/acs.organomet.6b00435

Article
pubs.acs.org/Organometallics
Acquiring and Exploiting Persistency of Propargyl Radicals: Novel
Paradigms
Gagik G. Melikyan,* Ryan Davis, and Samantha Cappuccino
Department of Chemistry and Biochemistry, California State University Northridge, Northridge, California 91330-8262, United
States
ABSTRACT: Three complementary methods for altering an intrinsic nature of propargyl
radicals, from transient to persistent, were developed by fine-tuning the bulkiness and
degree of substitution around the secondary and tertiary propargylic carbons, as well as by
sterically enhancing a π-bonded Co (CO) metal core. The latter was employed, as a
2
6
mechanistic tool, for precluding an acetylene−allene rearrangement, stabilizing propargyl
cations, and creating a steric hindrance that could provide for said transition from transient
to persistent propargyl radicals. A window of opportunities was identified wherein the steric
bulkiness in propargyl radicals remains below the “persistency threshold”, providing good
to excellent stereoselectivities in radical dimerization reactions (d,l 62−100%). Along with
3
the persistency threshold for tertiary propargyl radicals (278.2 Å ), two different thresholds
3
for persistency in secondary propargyl radicals were established306.5 and 576.0 Å 
dependent upon the molecular architecture and the nature of the substituents populating
the radical centers. Three alternative molecular platforms were designed to exploit a newly
acquired dichotomy in allylic radicals (α-persistent-γ-transient) and trichotomy in pentadienyl radicals (α-persistent-γ-transient-ε-
transient), providing access to molecular assemblies with contiguous 4°−4°, 4°−3°, and 3°−3° carbon atoms.
INTRODUCTION
■
Organic radicals are odd-electron, highly reactive species
undergoing a wide range of chemical reactionscoupling,
addition, disproportionation, eliminationat nearly diffusion-
1
2
controlled rates. A steric factor was recognized early on as a
key structural parameter that can effectively hinder intermo-
lecular interactions and convert transient radicals into persistent
3
,4
Figure 1.
species. Such an increase in steric hindrance can be achieved
by introducing bulky substituents into a close vicinity to the
radical center. The drawback of this approach is that the bulky
groups introduced into the molecule, such as a phenyl, tert-
centerthe degree of substitution, nature, and bulkiness of
substituentsthat would allow for dimerization to occur as an
activated, not diffusion-controlled process and for stereo-
selectivities to be effectively controlled by the steric factors. In
other words, we wanted to exploit a narrow window of
opportunity for achieving high stereoselectivities in dimeriza-
tion reactions of organometallic radicals before the requisite
species would turn persistent. Second, achieving persistency
3
,4
butyl, or isopropyl group, are covalently bonded to the
carbon framework and are not intended to be removable or to
act as auxiliary groups. In this account, we developed a
conceptually different strategy for converting organic transient
radicals into their persistent counterparts by attaching a bulky,
π-bonded, and removable metal core to the unsaturated
functionality in proradical substrates. In particular, propargyl
radical A was chosen as the transient organic species, and a
7
with respect to the dimerization reaction between bulky metal-
5
,6
complexed propargyl radicals would allow for studying the
intermolecular radical additions to the activated double bonds,
a synthetic area that remains scarcely studied because of the
competing self-coupling reactions. Third, with an α-radical
center made persistent, an introduction of the conjugated
double bonds would allow for projecting a radical center away
from the metal coordination site and studying dimerization
reactions at the remote locations, such as γ- or ε-carbon atoms
Co (CO) cluster was selected as a bulky auxiliary group that
2
6
could potentially convert propargyl radicals into persistent
species B (Figure 1). Thus, the main task was to experimentally
determine whether the said metal cluster in combination with
other determinants, i.e. a degree of substitution (1°, 2°, 3°) of
1
2
the α radical center (R , R = H, Alk, Ar) and the bulkiness of
an axial ligand L (CO, PR ), could provide sufficient steric
3
protection that would make propargyl radicals increasingly
resistant to dimerization. The transition at issuefrom
transiency to persistencycould serve six different objectives
pertaining to synthetic, analytical, and fundamental chemistry.
The first was to identify the composition of the α radical
(
C and D; Figure 1). Fourth, projecting a radical center into the
Received: May 31, 2016
©
XXXX American Chemical Society
A
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Figure 2.
predefined, select locations in the carbon chain (γ, ε, η, ι, or λ
depending upon the number of alternating double bonds, from
one to five) represents a novel, convenient method for
selectively generating radicals in highly conjugated yne-polyene
systems. Fifth, making an α position to the metal core
persistent would allow for probing and determining the largest
number of the double bonds that could be involved in the
radical site projection or the largest distance over which the
actual reaction center could travel in the course of the radical
reaction. Sixth, an ability to reversibly make propargyl radicals
resistant to dimerization would allow in unsymmetrical bis-
propargyl systems introduction of a persistent−transient
dichotomy providing for selective participation of the propargyl
triads in radical carbon−carbon bond-forming reactions.
propargyl alcohols 1 with HBF4 and isolation of cobalt-
stabilized propargyl cations 2, followed by reduction to the
respective propargyl radicals 3 and subsequent dimerization to
11a,b,g,h
1,5-alkadiynes 4 (Scheme 1). The second protocol
was
a
Scheme 1
RESULTS AND DISCUSSION
■
a
1
2
R , R = H, alkyl, aryl, naphthyl, alkenyl, alkynyl, alkoxy.
In an all-carbon environment, organic radicals undergo
dimerization reactions either in a stereorandom manner or
with low to moderate stereoselectivities that in turn are
dependent upon the size of the substituents around the reaction
site, as well as radical generation methods, temperature,
physical state, and reaction conditions. The formation of
the radical C−C bonds occurs stereorandomly also in the
larger, unsaturated organometallic radicals π-bonded to
specifically developed to avoid the use of strong acids, such as
HBF , thus making the reaction sequence benign to acid-
4
sensitive functionalities (Scheme 2). In particular, the requisite
methyl propargyl ethers 5 were treated with triflic anhydride at
low temperatures to convert to ionic triflates 6, with the latter
being reducible with cobaltocene, a 19e− reducing agent.
Methodologically, an adopted criterion for radicals to be
categorized as transient in nature was the rate of dimerization
reaction for radicals 3, forming respective dimeric products 4 at
reasonable rates, in good to excellent yields (Scheme 3). In
contrast, with the substituents R and R increasing in size, and
creating more steric crowding α to the metal core, radicals 3
could become persistent, thus surrendering their ability to
dimerize and resorting instead to an H atom abstraction
reaction as the only mechanistic pathway allowing for
conversion to stable end products (HAA 7). It is also
conceivable that the certain combinations of α substituents
1
,8
12
9
,10
transition metals, such as Mo, Fe, Cr, and Co
(domain 1,
Figure 2). Increasing the steric hindrance around the reaction
site in organic radicals can preserve their transiency, while
exhibiting a certain level of stereoselectivity (domain 2, Figure
1
2
2
). The secondary α-alkyl, α-phenyl radicals represent one of
the first examples of successful stereodifferentiation, albeit
moderate, with α-Me and α-Et radicals dimerizing stereo-
randomly (d,l:meso 1:1), while α-t-Bu radicals exhibit
preference for the d,l configuration (d,l:meso 62:38). The
qualitative change is observed when the cumulative bulkiness of
substituents achieves some critical levels sufficient for
persistency, with organic radicals becoming kinetically stable
monomeric species which either are not susceptible to radical
8a
1
2
R and R could make propargyl cations 2 persistent toward
reduction, especially with a reducing agent such as cobalto-
1
,3,4
12
3
coupling reactions or dimerize reversibly
). In the purely organic setting, a combination of three phenyl
(domain 3, Figure
cene; the latter is relatively large in size (V = 199.6 Å ) and
comparable with requisite metal complexes (e.g., HC
2
3
groups, three tert-butyl groups, or select combinations thereof
CCH(OH)PhCo (CO) V = 327.6 Å ). TLC and NMR
2
6
4
makes radicals persistent. At the inception of this project, no
monitoring of those cations would reveal the absence of radical
dimers 4 and HAA products 7, with the unreacted cations being
quantitatively converted to methyl propargyl ethers 5 by
methanol quenching (Scheme 3).
In the search for secondary persistent propargyl radicals, we
studied dimerization reactions of propargyl radicals 8−17, in
which the triple bonds were protected with bulky Co (CO)
moieties (group I, Figure 3). The primary locale for varying
requisite structures was an α carbon atom with substituents
ranging from alkyl (8, n = 0−2, 6) to phenyl (9−14) to
naphthyl (15, 16) to alkynyl (17) groups. In all those cases, the
dimerization at issue was observed under a variety of
experimental protocols, including the isolation of respective
cations and their reduction with either zinc or cobaltocene
(Scheme 1) or an in situ generation of respective propargyl
triflates with triflic anhydride and a subsequent low-temper-
examples on persistent π-bonded organometallic radicals have
ever been reported (domain 3, Figure 2).
5
,9,10
Therefore, the
main goal was to probe dimerization reactions of cobalt-
complexed propargyl radicals by gradually increasing the
bulkiness and degree of substitution at the α carbon atom in
order to achieve the said persistency and find the threshold
between domains 2 and 3, with the higher end of the former
being the most suitable for achieving diastereoselectivity in
radical C−C bond formation reactions and with the lower end
of the latter being the most suitable for exploiting a newly
acquired persistency.
2
6
Alternative experimental protocols were developed for
conducting radical dimerization reactions and assessing the
transiency vs persistency of Co (CO) -complexed propargyl
2
6
11a−g
radicals. The first protocol
involves treatment of π-bonded
B
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a
Scheme 2
a
1
2
R , R = H, alkyl, aryl, naphthyl, alkenyl, alkynyl, alkoxy.
a
Scheme 3
a
1
2
R , R = H, alkyl, aryl, naphthyl, alkenyl, alkynyl, alkoxy.
3
2
ature reduction with cobaltocene (Scheme 2). The formation of
respective radical dimers such as 4 (Scheme 3) was observed in
good to high yields (45−75%) with predominant formation of
into two distinct categories: i.e., 2°/sp (8) and 3°/sp (9−16).
The third category, 2°/sp, is represented by α-alkynyl propargyl
radicals 17 which dimerize with an excellent regioselectivity, α
to the metal core, and form d,l-1,1,2,2-tetraethynylethanes with
1
1a
d,l diastereomers (63−98%).
In an α-methoxyphenyl
1
1a
11i
series, relocation of the substituent along the periphery of
the aromatic nucleus (10, 4-OMe; 11, 3-OMe; 12, 2-OMe) did
not provide for a noticeable level of persistency despite a close
proximity of the 2-OMe group to the radical center (Zn, 61−
high diastereoselectivities (82−93%). Given the topology of
1,4-alkadiynes, the only locale available to the structural
variations are γ,γ′-acetylenic termini. In particular, a bulky
substituent in the γ′ position could potentially affect the course
of the reaction, given its demonstrated ability for inducing a
7
0%; Cp Co, 52−63%). Introducing a larger naphthyl group α
2
11f
to the radical center (15, 16) did not impede the dimerization
reaction with zinc as a reducing agent (Zn, 49−58%), although
the yields were systematically lower in the case of a bulky and
homogeneous reductant (Cp Co, 22−32%).
crystallographic analyses indicated that d,l dimers derived
1,3-steric induction. Introducing duplicate TMS and phenyl
groups in the γ and γ′ positions did not provide persistency,
with the latter (γ = Ph, γ′ = Ph) affording higher yields and
enhanced stereoselectivity in the formation of the respective
α,α dimers. Arranged in group II are propargyl radicals 18−
20 (Figure 3), which contain the α-alkoxy groups and can
1
1h
An X-ray
2
11i
1
1a−c
11h
from α-Ph
(9) and α-2-naphthyl radicals (16)
are
3
conformationally similar with flat aromatic rings positioned
gauche to each other. Given the planarity of aromatic nuclei,
and a lack of conformational constraints in place, it was
concluded that any further increase in size, or the number of
aromatic rings, could hardly lead to a desired level of
persistency. Quantitatively, an experimentally established
transiency for secondary propargyl radicals 8−16 is best
expressed by the total bulkiness around the radical centers
sterically mimic 2° propargyl radicals with sp -hybridized α-
11j
carbon atoms such as 8. Requisite radicals were generated
from the respective acetals according to the Tf O−Cp Co
2
2
11h
protocol
that provides for an in situ generation of ionic
propargyl triflates and their low-temperature reduction with
cobaltocene (−50 °C). While an absolute volume of the
substituent in the α-position was gradually increasing (V
= 72.2 Å ), radicals 18−20 were
able to maintain transiency and to form 3,4-dialkoxy-1,5-
alkadiynes in moderate yields and with high d,l diastereose-
Quantitatively, given the calculated
volume of the cobalt−alkyne core, the total volume of both
=
OMe
3
3
3
35.4 Å , V = 53.8 Å , V
OEt
OiPr
3
that varies within the range of 227−377 Å . Other determinants
to consider are the degree of substitution of the carbon atom
directly attached to the radical center (2°, 3°, 4°) and its
hybridization state. Accordingly, radicals 8−16 can be separated
11j
lectivity (83−92%).
C
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Figure 3.
Scheme 4
substituents in the pseudo 2° propargyl radicals 18−20 fell
complex 22 was synthesized in two steps (condensation/
complexation) and then converted to the requisite cation 23
3
13
within the range of 262−299 Å .
α Quaternary Carbon Induced Persistency of the
Secondary Propargyl Radical. In propargyl radical 21, a
degree of substitution of the α substituent was further elevated,
moving from tertiary toward quaternary carbon atoms (group
III, Figure 3). To probe this class of propargyl radicals, cobalt
by a low-temperature treatment with HBF (Scheme 4).
4
11
Reduction with cobaltocene was carried out at −50 °C to
initiate a radical reaction, and then the reaction mixture was
treated with methanol in order to retrieve any unreacted cation
23. A careful examination of the crude mixture by means of
D
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Scheme 5
NMR spectroscopy indicated that an in situ generation of
radical 24 did take place, although no detectable amounts of
dimeric product 25 were present. Instead, the HAA product 26
was isolated (10.5%) along with Me ether 27 (52.4%), a
solvolysis product of the unreacted cation 23 (Scheme 4).
Thus, radical 24 is the first persistent secondary propargyl radical
agent. The fact that the cation 23 exhibited an unexpected
compatibility with cobaltocene shows that both entities cannot
communicate effectively due to their steric bulkiness, topology,
and probably an unfavorable electronic distribution in redox
components.
Axial Ligand Induced Persistency of the Secondary
Propargyl Radical. Introducing a phosphorus ligand into a
cobalt core represents an alternative strategy for making
propargyl radicals persistent (group IV, Figure 3). Two
different topologies were tested by replacing carbon monoxide
with trimethylphosphine and triphenylphosphine in α-alkoxy
and α-phenyl derivatives 28 and 29, respectively (Figure 3).
The most attractive feature of this approach is that the
structural alteration to the carbon framework, intended by
design to control the kinetic stability of propargyl radicals, is
3
ever reported (Vtotal = 306.5 Å ). It proves that there is not a
single determinant of the persistency of the propargyl radicals.
Along with the cumulative bulkiness determined by the
substituents directly attached to the radical center, a degree
of substitution of the β carbon atom (2°, 3°, 4°) appears to be
as critical: radical 20 with an α OiPr group is sterically similar to
3
radical 24 with a t-Bu substituent (V = 72.2 Å vs V = 79.9
OiPr
tBu
3
Å ), but there is a profound difference in their behavior
transient vs persistentdue to the fact that radical 24 contains
the quaternary carbon atom directly attached to the radical
center. Attendant with it is another parameter that can be
identified as an additional determinant: type of hybridization of
the β atom directly attached to the α radical center. The
1
4
not introduced in the π-bonded ligand but into the metal core
15
that can be oxidatively removed after the radical reaction,
11j
releasing an organic product. In the propargyl acetal series,
trimethylphosphine was tested in an α-OEt-substituted
3
persistency of radical 24 shows that an sp hybridization with
propargyl radical, expecting that a much larger phosphorus
3
3
the local tetrahedral geometry is more efficient in impeding
ligand (VPMe3 = 94.6 Å ; V = 33.8 Å ) might block an α
CO
2
dimerization than a flat geometry of the sp -hybridized carbon
carbon atom and impede a dimerization reaction. Under the
atoms, in either phenyl (9−14) or naphthyl (15, 16)
substituents. The kinetic stability of radical 24 also indicates
that the scope of persistency can be expanded by introducing
structural homologues of the tert-butyl group with the larger
11h,j
standard conditions,
dimerization did in fact occur,
providing access to 3,4-diethoxy-1,5-hexadiynes with an
enhanced diastereoselectivity (d,l 93%). These data indicated
that the combination of an alkoxy group in an α position and a
number of carbon atoms, such as CR (R = Et, Pr, Bu) as well
3
PMe group in an axial position (28, Figure 3) did not provide
3
as main-group elements bulkier than carbon itself (Si, Ge, Sn,
Pb). The formation of Me ether 27 as the main product (Me
ether 27, 52.4%; HAA 26, 10.5%) suggests that the cation 23 is
the first Co (CO) -complexed propargyl cation persistent to
for the critical level of steric hindrance that is needed for radical
persistency. Sterically, substrate 29 (Figure 3) represents
enhancements in two dimensions: i.e., a larger α substituent
2
6
3
3
(
VPh = 91.5 Å ; V = 53.8 Å ) and a larger axial ligand (V
OEt PPh
3
reduction with cobaltocene. This phenomenon has never been
3
3
=
291.7 Å ; V
= 94.6 Å ). A triphenylphosphine ligand was
PMe
3
observed in radical dimerizations of the metal-complexed
5
,9−11
propargyl radicals.
In contrast, given the very nature of
introduced in cobalt complex 30 according to the literature
12
16
cobaltocene as a powerful one-electron reducing agent, the
reaction times are usually measured in minutes, even at
temperatures as low as −78 °C.
protocol that involves treatment of the requisite alcohol 31
with an equimolar amount of the phosphorus ligand at elevated
temperatures (Scheme 5). The formation of the cation 32 was
substantially facilitated due to the powerful stabilizing effect of
11a,b,d,g,j
Thus, the strategy
adopted by us (Scheme 3) allows for differentiating between
the cation persistency toward reduction and radical persistency
toward dimerization. In other words, two determinants for the
successful radical generation are the cumulative bulkiness
around the cationic center and the volume of the reducing
16
the axial ligand. Reduction with zinc to generate radical 33
1
5
was followed by decomplexation with Ce(NH ) (NO ) and
4
2
3 6
1
3b
reverse complexation with Co (CO) .
This reaction
2
8
sequence allowed for release of the products of the initial
E
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Scheme 6
Scheme 7
radical reaction (34, 35) from chiral metal bondages and
subsequent complexation of organic dimer 36 and HAA
product 37 to form the easily identifiable bis-cluster 38 (3%)
and HAA product 39 (2%). The very fact that both products
were formed in trace amounts is indicative of the fact that
radical 33 acquired a long sought after persistency due to the
interrogate their structural requirements toward the bulkiness
of α substituents. Two types of tertiary radicals, 40 and 41,
were probed (group V, Figure 3) along with the structurally
related pseudo-3° propargyl radical 42 (group VI, Figure 3). Of
particular interest was the simplest tertiary propargyl radical 43,
containing an unsubstituted acetylenic terminus and α,α-methyl
groups directly attached to the radical center (Scheme 6).
Cobalt complex 44 was synthesized from the commercially
available tertiary alcohol by complexation with dicobalt
11k
close proximity of the bulky axial ligand (PPh ) to the radical
3
center that effectively blocked the convergence of radical
species. It is noteworthy that the treatment of the crude radical
mixture with methanol did not form any detectable amounts of
the respective Me ether, [(HCC)CH(OMe)Ph]-
13b
5,11
and then treatment with HBF4
octacarbonyl
to form
tertiary propargyl cation 45. Its reduction with cobaltocene was
carried out at −50 °C with the crude mixture being treated with
methanol to trap any unreacted tertiary cation 45. A careful
NMR examination of the crude mixture showed that no radical
dimer 46 was formed, with HAA product 47 (52.0%) and Me
ether 48 (11.5%) being two major products. These data
indicate that intermediate 43 represents the smallest persistent
1
1k
Co (CO) , thus attesting to the fact that the reduction did
2
6
indeed take place and it was not impeded by the substrate
topology. Thus, introducing an axial ligand in the cobalt core
represents a facile method for making the transient secondary
propargyl radicals persistent, with the chiral metal cluster acting
as a removable molecular template. In quantitative terms, the3
3
tertiary propargyl radical with a cumulative volume of 278.2 Å .
threshold for achieving persistency is equal to 576.0 Å
3
3
This value can serve as a lowest reference point in designing the
persistent tertiary radicals with the alternative all-carbon or
heteroatom-containing substituents. Thus, the steric threshold
was exceeded in an α-methyl α-ethyl tertiary propargyl alcohol
(type 41, γ′-Ph; Figure 3), which failed to dimerize, affording
(
V(
(226.6 Å ) − V (33.8 Å ) + V (91.5
HCC)CH
2
Co
2
(CO)
6
CO
Ph
3
3
Å ) + V
(291.7 Å )). For comparison, in secondary
PPh
3
propargyl radicals carrying an α tert-butyl group, such as 24,
3
the total volume required for persistency was only 306.5 Å ,
11j
indicating that there are two different thresholds for persistency in
secondary propargyl radicals dependent upon the molecular
architecture and the nature of the substituents around the radical
center.
Persistent Tertiary Propargyl Radicals. Having devel-
oped two methods for achieving persistency in secondary
propargyl radicals, we turned to tertiary radicals in order to
the respective HAA product (34.0%) and Me ether (8.3%).
A
pseudo tertiary propargyl radical containing α-methyl and α-
methoxy substituents (type 42, γ′-Ph; Figure 3) also failed to
dimerize, undergoing rapid β scission (46.3%) and H atom
11j
transfer (33.7%) reactions.
Having developed three alternative methods for building the
persistent 2° (two) and 3° (one) propargyl radicals, we
F
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Scheme 8
Scheme 9
designed three topologically diverse molecular platforms to
demonstrate that the newly acquired persistency can be
exploited for controlling the regioselectivity of the radical
reactions and for projecting reaction sites away from the locale
of the initial cation generation. In all cases, the double bond was
used as a molecular vehicle for repositioning the reaction site
toward the periphery of the molecules, in both acyclic and
cyclic settings.
to the metal core was the first attempt to trigger an allylic
rearrangement in the persistent tertiary radical 49(α) and
escape a steric congestion that was builtby designaround a
1
1g
propargyl position (Scheme 7). Alcohol 50 was converted to
cation 51, which was then reduced with zinc to generate the
tertiary radical 49(α). As anticipated, the latter exhibited a
complete persistency with respect to radical dimerization
reactions, forming no detectable amounts of α,α dimer 52.
The presence of a double bond provided for an “escape route”,
rearranging a spin density from the α to γ position within an
Exploiting Persistency I: Projection α to γ in Acyclic
Systems. Chronologically, introducing an isobutenyl group α
G
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allylic triad. The tertiary radical 49(γ) exhibited transiency due
isolation of cation 63 was still complicated by the formation of
pentane-soluble side products supposedly derived from electro-
philic addition reactions across the conjugated double bonds.
Treatment with methanol allowed us to determine that, under
the conditions chosen, alcohol 61 undergoes complete
conversion to cation 63, although its sizable fraction (ca.
to the much lower level of steric hindrance (α-C3°
3
V(
= 292.6 Å ; γ-C3°
HCC)CH
CHCMe
2
Co
2
(CO)
6
+(CHCH
2 3
)+CH
3
VCH2
= 94.3 Å ), thus forming γ,γ dimer 53 in high
2
1
1g
yield (86%). Its decomplexation proceeded smoothly at low
temperatures, yielding the 1,5-diene-1,9-diyne 54 (70%) with
4
3%) could not be precipitated due to a multitude of side
11g,17
contiguous quaternary carbon atoms.
Due to the very
reactions. Reduction of cation 63 with a 2-fold excess of Cp Co
2
design of this reaction, we created the persistent−transient
dichotomy in an allylic system wherein radical 49(α) is made
persistent (due to the presence of a bulky cobalt−alkyne core),
while radical 49(γ) exhibits transiency with said properties
being mutually exclusive and jointly exhaustive.
Exploiting Persistency II: Projection α to γ in Cyclic
Systems. Alcohol 55 represents a cyclic version of its
counterpart 50 wherein the carbon atom, α to the metal
core, is made tertiary, while the ring carbon, γ to the metal core,
remains secondary (Scheme 8). Accordingly, radical 56
at low temperatures (−78 to −20 °C) allowed for an in situ
generation of radical 64, which is trichotomic by design: i.e., an
α radical should exhibit the persistency, while the γ and ε
locations should retain the transiency (persistent−transient−
transient trichotomy). The crude mixture contained γ,ε dimer 65
and γ,γ dimer 66 in a 93:7 ratio, attesting to the high
regioselectivity of the radical coupling reaction (Scheme 9). No
detectable amounts of the respective ε,ε dimer 67 were found
in a careful examination of the NMR spectrum. In addition to
dimeric products, α-HAA 68 was also formed, with the reaction
chemoselectivity being equal to (γ,ε-65 + γ,γ-66):α-HAA 68
74:26. Dimeric products proved to be inseparable by means of
preparative TLC on silica gel at low temperatures (−15 °C;
becomes dichotomous in nature with C (persistent) and
α
C (transient) reaction sites being positioned at both ends of
γ
the allylic triad. Synthesized from cyclohexenone by the
13
condensation−complexation sequence, alcohol 55 (77.5%)
5
2.4%), but a careful examination of their thermal stabilities
5
,11
was converted to cyclic cation 57 under acidic conditions
with subsequent reduction with a 3-fold excess of cobalto-
established that the heating of the isomeric mixture at 70 °C for
3
21
h allows isolation of γ,ε-dimer 65 in pure form (61.1%).
1
1,12
cene
at low temperatures (−78 to −30 °C). Radical 56
Decomplexation with ceric ammonium nitrate afforded organic
γ,ε dimer 69 (77.8%), rich in unsaturation and unique in
topology (Scheme 9). Its carbon framework contains
contiguous 3°−4° carbon atoms, a common structural motif
followed two independent reaction pathways: i.e., dimerization
in the γ position that involves secondary γ-radicals as transient
species and hydrogen atom abstraction at both ends of the
allylic triad. The former afforded γ,γ dimer 58 (59.5%) as an
inseparable diastereomeric mixture (54:46), while the latter
yielded α-HAA 59 and γ-HAA 60 in a 74:26 ratio (10.3%). For
the purposes of characterization, γ-HAA 60 was also
independently synthesized from alcohol 55 by treatment with
17,22
in natural product chemistry,
and also represents multiple
classes of unsaturated compounds (1,3-/1,4-/1,5-/1,7-diene;
1,3-/1,6-/1,7-/1,9-enyne; 1,11-diyne; 1,3-dien-5-yne) ripe for
23
transition-metal-induced cyclizations.
The steric and electronic reasons for the regioselective
formation of γ,ε-dimer 65 as a major product are not entirely
clear at this stage. According to computational studies, among
the organic products the most stable isomer is in fact the γ,ε
dimer 69 (E = 51.2 kcal/mol), with the ε,ε dimer being the
second most stable isomer (E = 52.9 kcal/mol), followed by the
least stable γ,γ dimer (E = 55.2 kcal/mol). In our previous
studies on cobalt-complexed propargyl radicals, formation of
the cross-coupling products varied from nearly statistical to
minor amounts depending upon the charge distribution in the
18
CF COOH−NaBH (56.0%). Overall, the product distribu-
3
4
tion favored a radical coupling reaction (γ,γ-58:α-HAA 59:γ-
HAA 60 72:21:7), providing access to 3,3′-diethynyl-1,1′-
dicyclohex-2,2′-ene derivatives as a result of the regioselective
dimerization of cyclohexenyl radicals of dual α-persistent−γ-
transient nature. Alternative approaches to the carbon frame-
1
9
work at issue are severely limited: i.e., 3,3′-dialkynyl
derivatives have never been reported in the literature, with
only a 3,3′-dimethyl analogue being synthesized by the
11b
reduction of the respective allylic alcohol with ZnI −
requisite propargyl cations. In unsymmetrical allylic systems,
2
1
9a
NaCNBH3
and by the Ti/Pd-mediated coupling of the
formation of the new carbon−carbon bond predominantly
19b
24
respective ethyl carbonate (α,α′:α,γ′ 1:1; syn:anti 1:1).
occurs at the less-substituted terminus of the allylic triad. In
Exploiting Persistency III: Projection α to ε in Acyclic
Systems. Having successfully blocked the dimerization
reaction α to the metal core in cyclic and acyclic systems
3,3-dimethylallyl radical, the ratio 16:30:54 of head to head
(3°−3°), head to tail (3°−1°), and tail to tail (1°−1°) products
was reported that apparently correlates with a decrease in the
25a
(Schemes 7 and 8), we turned our attention to more complex
aggregate steric hindrance. In isoprenoid series with barium
as a reducing agent, cross-coupling products (α,γ′; 1°−3°) were
reported to form in quantities (23−49%) comparable to that of
molecules containing two conjugated double bonds as an α
substituent (D, Figure 1). Among the three alternative methods
for making propargyl radicals persistent (Schemes 4−6), that
employing a higher degree of substitution (3° vs 2°) at the α
carbon atom was chosen as a tool for controlling the
regioselectivity of the process (Scheme 6). Alcohol 61 was
25b
the major homocoupling products (α,α′; 1°−1°).
Overall,
the formation of γ,ε dimer 65, as a major product, represents a
proof of concept that the dimerization reaction can be fully
impeded at the α position with the reaction center being
projected over three (α to γ), or even five (α to ε) atoms away
from the site of the cation generation.
13
synthesized in two steps from commercially available dienone
5
,11
6
2, which was treated with HBF4
to generate the requisite
1
1,20
cation 63 (Scheme 9). The standard protocols
applying a
CONCLUSION
4
−10-fold excess of strong acid failed to work at any
■
temperature regimen, given the cation’s strong susceptibility
An intrinsic transiency of propargyl radicals can be altered by
exploiting, and fine-tuning, the main determinants involved: i.e.,
(1) bulkiness around the radical center, (2) degree of
substitution of the radical center (2°, 3°), (3) degree of
to polymerization. An empirically optimized procedure
included a stepwise addition of 2 equiv of HBF at −40 °C
4
with prolonged stirring after each addition step (1.5 h). The
H
DOI: 10.1021/acs.organomet.6b00435
Organometallics XXXX, XXX, XXX−XXX

Organometallics
Article
substitution of the carbon atom directly attached to the radical
center (2°, 3°, 4°), (4) hybridization state of the carbon atom
attached to the propargylic position, and (5) size of the metal
core. A bulky, removable, and π-bonded Co (CO) cluster
analyses (one plate unless indicated otherwise) were conducted on
silica gel 60 F254 (EM Science; aluminum sheets) and silica gel 60
PF254 (EM Science; w/gypsum; 20 × 20 cm), respectively.
Visualization was carried out with potassium permanganate aqueous
solution unless indicated otherwise. 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 (LIFDI, GCT Premier, Micromass; TOF Agilent 6210 LC-TOF
instrument with a Multimode source). Computational work was
carried out with Spartan’10, version 1.0.1 (Wave function Inc., Irvine,
CA). Full characterization for compounds 53 and 54 is given in ref
11g.
2
6
provided for stabilization of the requisite propargyl cations,
exclusion of the acetylene−allene rearrangement, and site-
selective generation of radicals by a single-electron transfer and
also created the molecular template for attenuating the
bulkiness by altering the volume of an axial substituent. In
contrast to organic radicals dimerizing mostly stereorandomly
in an all-carbon environment, for cobalt-complexed propargyl
radicals a “window of opportunities” was identified wherein
good to excellent stereoselectivities in radical coupling reactions
can be achieved (d,l 62−100%) without surpassing the newly
Radical Dimerizations of Cobalt-Complexed Propargyl
Alcohols with Zinc as a Reducing Agent (General Protocol I).
Under an atmosphere of nitrogen, HBF ·Me O (1.50 mmol) was
4
2
added dropwise (10 min) to a solution of propargyl alcohol (0.25
mmol) in dry ether (20 mL) at −20 °C. The reaction mixture was
stirred for 5 min at −20 °C and then 1 h at 0 °C. The precipitate was
allowed to settle at −20 °C, and the ethereal layer was removed. Dry
ether (20 mL) was added along the inner wall of the flask, stirring was
resumed for 15 min, the propargyl cation was allowed to settle, and the
ethereal layer was removed. The washing was repeated twice (2 × 20
mL), the residual amount of ether was removed under reduced
pressure, and the propargyl cation was dissolved in dry CH Cl (5 mL)
3
defined persistency thresholds (3° radicals, 278.2 Å ; 2°
3
radicals, 306.5 or 576.0 Å ). Secondary propargyl radicals
3
were made persistent by introducing quaternary, sp -hybridized
carbon atoms at the propargylic position or by replacing an
axial carbon monoxide with bulkier phosphine ligands in the
cobalt−alkyne complexes. Tertiary propargyl radicals, even with
relatively small substituents such as methyl groups connected to
the radical center, can be made persistent by complexation with
a dicobalt hexacarbonyl core. Double bonds were used in
persistent propargyl radicals for “escaping” highly congested
areas and for projecting reaction sites toward the periphery of
the carbon frameworks. The phenomena of dichotomy in allylic
radicals (α-persistent−γ-transient) and trichotomy in pentadienyl
radicals (α-persistent−γ-transient−ε-transient) were observed
with radical coupling reactions, providing access to molecular
assemblies with contiguous tertiary and quaternary carbon
atoms. New methods for assembling highly congested
molecular units (4°−4°, 4°−3°, 3°−3°) can be used as key
steps in targeted syntheses of organic compounds of relevance
to medicinal chemistry, materials science, and natural product
syntheses. Novel methodologies for creating persistency in π-
bonded organic radicals can be expanded toward new types of
π-bonded unsaturated units (dienes, arenes, diynes, enynes)
and transition metals other than cobalt (Fe, Cr, Mo, W, Mn)
and could also allow for ESR detection of intermediate radicals,
shedding light upon intimate structural details and a mode of
the interaction of an unpaired electron with a π-bonded metal
core.
2
2
at −20 °C. The reaction mixture was then treated with zinc (2.50
mmol) and stirred for 5 min at −20 °C and then for 4 h at 20 °C
(TLC control). Zinc was filtered off on a short bed of Florisil (1 in.),
and the crude mixture was analyzed by NMR to determine the
diastereometic composition (d,l:meso). Individual diastereomers were
isolated by means of preparative TLC (silica gel) or column
chromatography (silica gel or Florisil) in good to high yields.
Radical Dimerizations of Cobalt-Complexed Propargyl
Alcohols with Cobaltocene as a Reducing Agent (General
Protocol II). Under an atmosphere of nitrogen, HBF ·Me O (1.50
4
2
mmol) was added dropwise (10 min) to a solution of propargyl
alcohol (0.25 mmol) in dry ether (20 mL) at −20 °C. The reaction
mixture was stirred for 5 min at −20 °C and then 1 h at 0 °C. The
precipitate was allowed to settle at −20 °C, and the ethereal layer was
removed. Dry ether (20 mL) was added along the inner wall of the
flask, stirring was resumed for 15 min, the propargyl cation was
allowed to settle, and the ethereal layer was removed. The washing was
repeated twice (2 × 20 mL), the residual amount of ether was
removed under reduced pressure, and the propargyl cation was
dissolved in dry CH Cl (3 mL) at −20 °C. At−78 °C, a solution of
2
2
Cp Co (0.50 mmol/2 mL of dry CH Cl ) was added dropwise (5
2
2
2
min), and the reaction mixture was stirred 15 min (TLC control). The
crude mixture was filtered through a short bed of Florisil (1 in.) and
analyzed by NMR to determine the diastereometic composition
(d,l:meso). Individual diastereomers were isolated by means of
preparative TLC (silica gel) or column chromatography (silica gel
or Florisil) in good to high yields.
EXPERIMENTAL SECTION
■
General Considerations. 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). Methylene chloride was stored over CaCl2
Radical Dimerizations of Cobalt-Complexed Methyl Prop-
argyl Ethers with Tf O as a Mediator and Cp Co as a Reducing
2
2
Agent (General Protocol III). Under an atmosphere of nitrogen,
and distilled under dry nitrogen from CaH ; ether was stored over
Tf O (0.26 mmol) was added dropwise to a solution of methyl
2
2
sodium and filtered through an alumina−silica gel column. All reagents
and solvents (pentane, THF, acetone, benzene, methanol) were
purchased from Acros, TCI, Alfa Aesar, and Sigma-Aldrich and used as
received. Zinc was acquired from Aldrich (dust, 10 mm). Co (CO) ,
propargyl ether (0.25 mmol) in dry CH Cl (4 mL) at −50 °C. The
2
2
reaction mixture was brought to −10 °C in 30 min (NMR control),
and then a solution of Cp Co (0.26 mmol) in dry CH Cl (1 mL) was
2
2
2
2
8
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 (Na SO ). The diastereometic composition (d,l:meso)
Cp Co, and Ce(NH ) (NO ) were purchased from Strem. NMR
2
4
2
3 4
1
solvents were supplied by Cambridge Isotope Laboratories. H and
C NMR spectra were recorded on a Bruker Avance III-400 ( H, 400
1
3
1
2
4
MHz) spectrometer. Chemical shifts were referenced to internal
solvent resonances and are reported relative to tetramethylsilane.
Spin−spin coupling constants (JHH) 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 EZ-Melt (Stanford
Research Systems). Silica gel S735-1 (60−100 mesh; Fisher) was used
for flash column chromatography. Analytical and preparative TLC
was determined by NMR, organic solvents were evaporated under
reduced pressure, and individual diastereomers were isolated by means
of preparative TLC (silica gel) or column chromatography (silica gel
or Florisil) in good to high yields.
2
(μ-η -4,4-Dimethylpent-1-yn-3-ol)dicobalt Hexacarbonyl
(22). Under an atmosphere of nitrogen, ethynylmagnesium chloride
(1.25 g, 14.74 mmol; 24.6 mL, 0.6 M in THF) was added dropwise
(15 min) to a solution of pivaloyl aldehyde (1.15 g, 13.40 mmol) in
I
DOI: 10.1021/acs.organomet.6b00435
Organometallics XXXX, XXX, XXX−XXX

Organometallics
Article
dry THF (30 mL) at −20 °C. Upon addition, the reaction mixture was
stirred for 20 min at −20 °C, brought to 20 °C, and stirred for 10 min
(8 mL; dropwise, 10 min; N atmosphere). The reaction mixture was
2
stirred for 1 h at −78 °C, brought to −30 °C, stirred an additional 1 h,
and warmed to −15 °C over 1 h. Saturated brine (15 mL) was added
at −10 °C, and stirring was continued for another 15 min. An aqueous
layer was extracted with ether (3 × 10 mL), the combined ethereal
layers were filtered over a short bed of MgSO4 (2 in.), and
concentrated under reduced pressure (200 mbar). Under an
atmosphere of nitrogen, the residue (36 + 37) was dissolved in
ether (5 mL) and added dropwise (10 min) to a solution of Co (CO)
(
TLC control). The crude mixture was quenched with saturated
NH Cl(aq) (10 mL) at 0 °C, stirred for 15 min, diluted with water (50
4
mL), and extracted with ether (25 mL). An aqueous layer was
separated, combined ethereal layers were washed with water (3 × 20
mL) and dried (Na SO ), and solvents were evaporated under reduced
2
4
pressure. Under an atmosphere of nitrogen, the crude alcohol (1.128 g,
0.07 mmol) was dissolved in dry ether (10 mL) and added dropwise
10 min) to a solution of dicobalt octacarbonyl (3.44 g, 10.07 mmol)
in dry ether (20 mL) at 20 °C. The reaction mixture was stirred for 3 h
TLC control), concentrated under reduced pressure, and fractionated
1
(
2
8
(85.5 mg, 0.25 mmol) in ether (30 mL) at 20 °C. The reaction
mixture was stirred for 3 h at 20 °C, concentrated under reduced
pressure (250 mbar), and fractionated by preparative TLC (pentane,
two runs) to afford 38 (3 mg, 3.0%, d,l-38:meso-38 86:14) and HAA
39 (2 mg, 2.0%).
(
on silica gel (200 g, anaerobic conditions, dry ice jacket; PE:E, 10:1) to
afford 22 (904 mg, 17.0% over two steps) as a dark red oil. TLC
1
2
(
PE:E, 5:1): R 0.47. H NMR (400 MHz, δ, CDCl ): 1.05 (s, 9H,
(μ-η -3-Methylbut-1-yne)dicobalt Hexacarbonyl (47) and (μ-
f
3
2
3
CH ), 1.83 (d, J = 5.2, 1H, OH), 4.47 (d, 1H, CH, J = 5.6), 6.06 (s,
η -3-methoxy-3-methylbut-1-yne)dicobalt Hexacarbonyl (48).
3
13
1
H, HC). C NMR (100 MHz, δ, CDCl ): 26.4 (3CH ), 36.9
Under an atmosphere of nitrogen, HBF ·Et O (243 mg, 1.50 mmol)
4 2
3
3
was added dropwise (5 min) to a solution of alcohol 44 (92.5 mg, 0.25
mmol) in dry pentane (20 mL) and ether (2 mL) at −20 °C. The
reaction mixture was stirred for 20 min at −20 °C until the solution
became colorless. The cation 45 was washed with dry pentane (2 × 20
mL; 30 min stirring for each cycle) at −20 °C, and residual organic
solvents were evaporated under reduced pressure (−20 °C, 30 min).
The cation 45 was dissolved in dry CH Cl (5 mL), and a solution of
(
C4), 72.7, 81.0 (C3, HCC), 96.4 (HCC), 199.9 (CO). MS TOF
+
FD+: m/z M 398. MS HR TOF FD+: m/z calcd for C H O Co
13
12
7
2
+
M 397.9242, found 397.9260. Anal. Found: C, 38.62; H, 3.02. Calcd
for C H O Co : C, 39.22; H, 3.04.
1
3
12
7
2
2
(
μ-η -4,4-Dimethylpent-1-yne)dicobalt Hexacarbonyl (26)
2
and (μ-η -3-methoxy-4,4-dimethylpent-1-yne)dicobalt Hexa-
carbonyl (27). Cp Co-mediated dimerization reaction: under an
2
2
2
atmosphere of nitrogen, HBF ·Et O (243 mg, 1.50 mmol) was added
dropwise (5 min) to a solution of alcohol 22 (99.5 mg, 0.25 mmol) in
dry pentane (20 mL) at −20 °C. The reaction mixture was stirred for
Cp Co (94.5 mg, 0.50 mmol) in dry CH Cl (2 mL) was added
4
2
2
2
2
dropwise (10 min) at −78 °C. The reaction mixture was stirred for 1 h
at −78 °C, an additional 1 equiv of Cp Co (47.3 mg, 0.25 mmol; dry
2
2
0 min at −20 °C until the solution became colorless. The precipitate
CH Cl , 1 mL) was added dropwise (10 min) at −78 °C, and stirring
2
2
was washed with pentane (2 × 20 mL) at −20 °C, and residual organic
solvent was evaporated under reduced pressure (−20 °C). The cation
2
was continued for an additional 1 h. The solution was brought to −30
°C, stirred for 2 h, treated with methanol (0.5 mL) at −20 °C, and
stirred for another 20 min at the same temperature. The crude mixture
was washed with water (2 × 10 mL), extracted with pentane (3 × 10
mL), and dried (Na SO ). The reaction mixture (NMR: HAA 47:Me
3 was dissolved in dry CH Cl (4 mL), and a solution of Cp Co
2
2
2
(
94.5 mg, 0.50 mmol) in dry CH Cl (2 mL) was added dropwise (10
2 2
min) at −30 °C. The solution was stirred for 8 h at −30 °C and
treated with MeOH (1 mL), and stirring was continued for an
additional 1 h at −30 °C. The reaction mixture was diluted with ether
2
4
ether 48 69:31) was concentrated under reduced pressure (350 mbar),
and the residue was fractionated by preparative TLC (pentane) to
afford HAA 47 (46 mg, 52.0%; 4 h, 350 mbar) and Me ether 48
(
30 mL), washed with water (20 mL), extracted with ether (3 × 10
mL), and dried (Na SO ). The crude mixture (NMR: HAA 26:Me
(repurified by preparative TLC, P:E, 5:1, 11 mg, 11.5%; 4 h, 400
2
4
1
ether 27 17:83) was concentrated under reduced pressure (350 mbar),
and the residue was fractionated by preparative TLC (pentane, −16
mbar). HAA 47: Dark red oil. TLC (PE): R 0.57. H NMR (400
f
MHz, δ, CDCl ): 1.28 (6H, d, 2CH , J = 6.4), 3.05 (1H, septet of
3
3
1
3
°
C) to afford HAA 26 (10 mg, 10.5%; 350 mbar, 6 h) and Me ether 27
doublets, H-3, J = 6.7, J = 1.0), 6.04 (1H, d, HC, J = 1.2). C NMR
(
54 mg, 52.4%; 350 mbar, 4 h). HAA 26: dark red oil. TLC (PE): Rf
(100 MHz, δ, CDCl ): 25.3 (3-Me, C4), 32.7 (C3), 72.8 (HCC),
3
1
+
0
.68. H NMR (400 MHz, δ, CDCl ): 1.04 (9H, s, 3CH ), 3.02 (2H, s,
106.5 (HCC), 200.3 (CO). MS TOF FD+: m/z M 354. MS HR
3
3
+
+
CH ), 6.08 (1H, s, HC). MS TOF FD+: m/z M 382. MS HR TOF
TOF FD+: m/z calcd for C H O Co M 353.8979, found 353.8970.
2
11
8
6
2
+
FD+: m/z calcd for C H O Co M 381.9292, found 381.9291. Me
Anal. Found: C, 37.43; H, 2.33. Calcd for C H O Co : C, 37.32; H,
13
12
6
2
11 8 6 2
1
1
ether 27: dark red oil. TLC (PE:E, 5:1): R 0.68. H NMR (400 MHz,
2.28. Me ether 48: brick red oil. TLC (PE:E, 5:1): R 0.53. H NMR
f
f
δ, CDCl ): 1.03 (9H, s, Me C), 3.61 (3H, s, OCH ), 3.95 (1H, d, CH,
(400 MHz, δ, C
6
D
6
): 1.32 (6H, s, 2CH
3
), 2.98 (3H, s, OCH
3
), 5.48
3
3
3
13
13
J = 0.4), 6.03 (1H, d, HC). C NMR (100 MHz, δ, CDCl ): 26.8
(1H, s, HC). C NMR (100 MHz, δ, CDCl
3
): 29.5 (3-Me, C4),
3
(
Me C), 38.1 (C-4), 61.0 (OMe), 73.1 (HCC), 91.5 (C-3), 93.0
50.4 (OMe), 73.2 (HCC), 77.2 (C3), 101.0 (HCC), 200.0 (CO).
3
+
+
(
HCC). MS TOF FD+: m/z M 412. MS HR TOF FD+: m/z calcd
MS TOF FD+: m/z M 384. MS HR TOF ESI/APCI: calcd for
+
+
for C H O Co M 411.9398, found 411.9412. Anal. Found: C,
C
12
H
10
O
7
Co
2
M 383.9085, found 383.9095. Anal. Found: C, 37.52;
14
14
7
2
4
0.87; H, 3.43. Calcd for C H O Co : C, 40.80; H, 3.42.
H, 2.64. Calcd for C12H O Co : C, 37.53; H, 2.62.
10 7 2
14
14
7
2
2
2
2
(
μ-η -d,l-3,4-Diphenyl-1,5-hexadiyne)- and (μ-η -meso-3,4-
{μ-η -1-[(Trimethylsilyl)ethynyl]cyclohex-2-en-1-ol}dicobalt
Hexacarbonyl (55). Under an atmosphere of nitrogen, n-butyllithium
(352 mg, 5.50 mmol; 3.44 mL, 1.6 M in hexane) was added dropwise
(5 min) to a solution of (trimethylsilyl)acetylene (539 mg, 5.50 mmol)
in dry THF (20 mL) at −10 °C. Upon addition, the reaction mixture
was stirred for 5 h at −10 °C, a solution of cyclohex-2-en-1-one (480
mg, 5.00 mmol) in dry THF (5 mL) was added dropwise (8 min) at
−10 °C, and the reaction mixture was stirred for 2 h at 20 °C (TLC
control). The crude mixture was quenched with saturated NaCl(aq)
(50 mL) at −10 °C and diluted with ether (40 mL), and an aqueous
layer was separated and extracted with ether (3 × 20 mL). The
combined ethereal layers were dried (Na SO ), and organic solvents
Diphenyl-1,5-hexadiyne)bis(dicobalt hexacarbonyl) (38) and
2
(μ-η -3-phenyl-1-propyne)dicobalt Hexacarbonyl (39). Under
an atmosphere of nitrogen, HBF ·Et O (243 mg, 1.50 mmol) was
4
2
added dropwise to a solution of alcohol 30 (163 mg, 0.25 mmol) in
degassed pentane (20 mL) and ether (20 mL) at −20 °C. The reaction
mixture was stirred at −20 °C (15 min), and the precipitant was
allowed to settle. The cation 32 was washed with degassed pentane (2
×
20 mL) at −20 °C, and residual solvent was evaporated under
reduced pressure (30 min, −20 °C). The residue was dissolved in dry
CH Cl (5 mL) and stirred for 5 min at −20 °C. Degassed zinc (163
2
2
mg, 2.50 mmol) was added in one portion at −20 °C, and the reaction
mixture was stirred for 5 min, warmed to 20 °C, and stirred for an
additional 2 h (TLC control). At −10 °C, quenching was performed
with MeOH (1 mL) and the temperature was raised to 20 °C over 20
min. Zinc was filtered off on a short bed of Florisil (1 in.), and the
crude mixture (34 + 35) was concentrated under reduced pressure,
dissolved in degassed acetone (5 mL), and treated at −78 °C with a
solution of Ce(NH ) (NO ) (1.10 g, 2.00 mmol) in degassed acetone
2
4
were evaporated under reduced pressure. Under an atmosphere of
nitrogen, the crude alcohol (970 mg, 5.00 mmol, assuming 100%
yield) was redissolved in dry ether (20 mL) and added dropwise (22
min) to a solution of dicobalt octacarbonyl (1.80 g, 5.25 mmol) in dry
ether (20 mL) at 20 °C. The reaction mixture was stirred for 3 h at 20
°C (TLC control), concentrated under reduced pressure, and
fractionated on silica gel (250 g, anaerobic conditions, dry ice jacket;
4
2
3 6
J
DOI: 10.1021/acs.organomet.6b00435
Organometallics XXXX, XXX, XXX−XXX

Organometallics
Article
PE:E, 10:1) to afford 55 (1.86 g, 77.5% over two steps) as dark red
crystals. Tdecomp = 56.3−110.5 °C (by TLC, partial decomposition;
56.0%; γ-HAA 60:α-HAA 59 98:2) as a dark red solid. TLC (P): Rf
1
0.60. H NMR (400 MHz, δ, C D ): 0.31 (9H, s, Me Si), 1.36 (2H, m,
6
6
3
sealed capillary, dried by coevaporation with benzene, 3 × 1 mL). TLC
CH ), 1.52 (2H, m, CH ), 1.85 (2H, m, CH ), 2.33 (2H, m, CH ),
2 2 2 2
1
13
(
PE:E, 5:1): R 0.42. H NMR (400 MHz, δ, CDCl ): 0.31 (9H, s,
6.31 (1H, m, 2-H). C NMR (100 MHz, δ, CDCl ): 1.0 (Me Si),
3 3
f
3
3
CH ), 1.76−1.88 (3H, m, 3CH), 1.92 (1H, s, OH), 1.99−2.23 (3H,
22.2, 23.3, 26.6, 31.4 (C3−C6), 79.9, 109.9 (CC), 131.0 (C2),
3
+
m, 3CH), 5.67 (1H, spl d, 2-H, J = 9.6), 5.91 (1H, ddd, 3-H, J = 4.8, J
=
134.7 (C1), 200.8 (CO). MS TOF FD+: m/z M 464. MS HR TOF
2.4). 13C NMR (100 MHz, δ, CDCl ): 1.1 (3CH ), 19.7, 25.5 (C5,
+
FD+: m/z calcd for C H O SiCo M 463.9531, found 463.9511.
3
3
17 18
6
2
2
C6), 40.9 (C4), 71.6 (C1), 78.4, 121.1 (CC), 130.5, 133.3 (C2,
[μ-η -(E)-3,7-Dimethyl-1-(trimethylsilyl)octa-4,6-dien-1-yn-3-
ol]dicobalt Hexacarbonyl (61). Under an atmosphere of nitrogen,
ethylmagnesium bromide (732 mg, 5.50 mmol; 1.83 mL, 3 M/ether)
was added dropwise (5 min) to a solution of (trimethylsilyl)acetylene
(539 mg, 5.50 mmol) in dry THF (20 mL) at −10 °C. Upon addition,
the reaction mixture was stirred for 5 h at −10 °C, a solution of ketone
62 (620 mg, 5.00 mmol) in dry THF (5 mL) was added dropwise (5
min) at −10 °C, and stirring was continued for additional 2.5 h at 20
+
C3), 200.6 (CO). MS TOF FD+: m/z M 480. MS HR TOF FD+: m/
+
z calcd for C H O SiCo M
Found: C, 42.52; H, 3.63. Calcd for C H O SiCo : C, 42.51; H, 3.78.
479.9480, found 479.9469. Anal.
17
18
7
2
1
7
18
7
2
2
{
μ-η -3,3′-[Bis(trimethylsilyl)ethynyl]-1,1′-dicyclohex-2,2′-
2
ene]}bis(dicobalt hexacarbonyl) (58), {μ-η -3-[(Trimethylsilyl)-
2
ethynyl]cyclohexene}dicobalt Hexacarbonyl (59), and {μ-η -2-
[(Trimethylsilyl)ethynyl]cyclohexene}dicobalt Hexacarbonyl
(60). Under an atmosphere of nitrogen, HBF ·Et O (243 mg, 1.50
4
2
°
C (TLC control). The crude product was treated with saturated
mmol) was added dropwise (1 min) to a solution of alcohol 55 (120
mg, 0.25 mmol) in dry pentane (20 mL) at −20 °C. The reaction
mixture was stirred for 30 min at −20 °C, and the precipitate was
washed with dry pentane (2 × 20 mL; precooled, −20 °C; stirring 20
min per wash) at −20 °C. The cation 57 was dissolved in dry CH Cl
NaCl(aq) (25 mL) at 0 °C and diluted with ether (25 mL), and an
aqueous layer was separated and extracted with ether (3 × 25 mL).
The combined organic layer was dried (Na SO ), and volatile solvents
2
4
were evaporated under reduced pressure. Under an atmosphere of
nitrogen, the crude alcohol (1.11 g, 5.00 mmol, assuming 100% yield)
was dissolved in ether (10 mL) and added dropwise (10 min) to a
solution of dicobalt octacarbonyl (1.71 g, 5.00 mmol) in ether (20
mL) at 20 °C. The reaction mixture was stirred for 3 h at 20 °C (TLC
control), concentrated under reduced pressure, and fractionated on
Florisil (100 g, anaerobic conditions, dry ice jacket, PE:E, 10:1;
repurification 75 g, anaerobic conditions, dry ice jacket, PE:E, 10:1) to
afford 61 (1.46 g, 57.5%; over two steps) as a brick red solid. Mp:
2
2
(
5 mL) at −20 °C, stirred for 5 min, and Cp Co (142 mg, 0.75 mmol;
2
precooled, −50 °C; degassed, 5 min) was added in one portion at −78
°
C. The reaction mixture was stirred for 1 h at −78 °C and then for an
additional 1 h at −30 °C (TLC control). A saturated NaCl(aq)
solution (10 mL) was added dropwise at −20 °C, and stirring was
continued for 5 min. The organic layer was washed with DI water (3 ×
1
5 mL) and dried (Na SO ). The crude mixture (by NMR, (d,l-58 +
2 4
meso-58):α-HAA 59:γ-HAA 60 72:21:7; d,l-58:meso-58, 54:46, relative
configurations unassigned; α-HAA 59:γ-HAA 60, 74:26) was
fractionated by preparative TLC (two plates, P; loading/development
at −13 °C) to isolate inseparable mixtures of d,l-58 + meso-58 (74 mg)
and α-HAA 59 + γ-HAA 60 (30 mg; α-HAA 59:γ-HAA 60 76:24).
Both fractions were repurified by preparative TLC to afford d,l-58 +
meso-58 (69 mg, 59.5%; P; loading/development at −13 °C; d,l-
5
×
2.7−54.0 °C (sealed capillary, dried by coevaporation with benzene, 3
1
1 mL). TLC (PE:E, 5:1): R 0.55. H NMR (400 MHz, δ, CDCl ):
f 3
0
.33 (9H, s, Me Si), 1.66 (3H, s, 3-CH ), 1.789, 1.791 (3H/3H, s/s,
3
3
CH , 7-CH ; baseline separation can be achieved in C D ), 1.85 (1H,
3
3
6
6
s, OH), 5.72 (1H, d, 4-H, J = 15.2), 5.77 (1H, spl d, 6-H, J = 11.0, J
av
av
13
=
0.6), 6.58 (1H, dd, 5-H, J = 10.8). C NMR (100 MHz, δ, CDCl ):
3
1
7
2
.16 (Me Si), 18.59 (CH ), 26.29 (CH ), 32.29 (CH ), 74.90 (C3),
3 3 3 3
5
1
−
8:meso-58, 54:46; purity 98%) and α-HAA 59 + γ-HAA 60 (12 mg,
0.3% by NMR, 99.4% purity; P, two runs; loading/development at
13 °C; α-HAA 59:γ-HAA 60, 56:44; α-HAA 60 partially decomposes
8.03, 121.31 (CC), 123.90, 124.33, 137.17, 137.66 (C4−C7),
+
00.42 (CO). MS TOF FD+: m/z M 508. MS HR TOF FD+: m/z
+
calcd for C H O SiCo M 507.9793, found 507.9769. Anal. Found:
19
22
7
2
on the preparative TLC plate, altering the original ratio of HAA
products). d,l-58 + meso-58: dark red crystals. TLC (P): R 0.52. H
NMR (400 MHz, δ, CDCl ): minor 0.32 (18H, s, 6CH ), major 0.34
C, 44.82; H, 4.27. Calcd for C H O SiCo : C, 44.89; H, 4.36.
1
19 22
7
2
f
2
[
μ-η -3,7,7,10-Tetramethyl-8-(2′-methylprop-1′-en-1′-yl)-
3
3
dodeca-3E,5E,9E-triene-1,11-diyne-1,12-bis(trimethylsilyl)]bis-
(
1
18H, s, 6CH ), minor + major 1.24−1.44, 1.59−1.72, 1.75−1.84,
2
3
(dicobalt hexacarbonyl) (65), [μ-η -3,8-Dimethyl-5,6-bis(2′-
.86−1.96 (8H + 8H, m, 5-H, 6-H, 5′-H, 6′-H), 2.19−2.45 (6H + 6H,
methylprop-1′-en-1′-yl)deca-3E,7E-diene-1,9-diyne-1,10-bis-
2
m, 1-H, 4-H, 1′-H, 4′-H), minor 6.03 (2H, s, 2-H, 2′-H), major 6.11
(
1
(trimethylsilyl)]bis(dicobalt hexacarbonyl) (66), and [μ-η -[(2,6-
13
2H, s, 2-H, 2′-H). C NMR (100 MHz, δ, CDCl ): minor + major
dimethylocta-2,4E-dien-7-yn-8-trimethylsilyl)]dicobalt Hexa-
3
carbonyl (68). Under an atmosphere of nitrogen, HBF ·Et O (40.5
.1 (Me Si), 23.1 (C5, C5′), 80.2, 80.4, 109.5 (CCSiMe ), 200.6
4
2
3
3
mg, 0.25 mmol) was added to a solution of alcohol 61 (127 mg, 0.25
mmol) in degassed pentane (20 mL) at −40 °C. The reaction mixture
(
(
(
CO); minor 25.9, 31.9 (C4, C6, C4′, C6′), 42.1 (C1, C1′), 133.8
C2, C2′), 136.5 (C3, C3′); major 24.1, 31.7 (C4, C6, C4′, C6′), 41.7
+
was stirred for 1.5 h at −40 °C, an additional 1 equiv of HBF ·Et O
C1, C1′), 134.3 (C2, C2′), 136.0 (C3, C3′). MS TOF FD+: m/z M
4
2
+
(40.5 mg, 0.25 mmol) was added, and stirring was continued for
9
26. MS HR TOF FD+: m/z calcd for C H O Si Co M 925.8911,
34
34 12
2
4
another 1.5 h at −40 °C. The cation 63 was allowed to precipitate, the
found 925.8937. Anal. Found: C, 42.94; H, 3.83. Calcd for
C H O Si Co : C, 44.08; H, 3.70. α-HAA 59 + γ-HAA 60: red
viscous oil. TLC (P): R 0.60. H NMR (400 MHz, δ, C D ): α-HAA
supernatant solution was added dropwise to methanol (5 mL) at −20
34
34 12
2
4
1
°
C, and this mixture was stirred for 20 min, warmed to 20 °C, diluted
f
6
6
with water (10 mL), and extracted with pentane (30 mL). By NMR,
the solvolysis product (54 mg) contained no unreacted alcohol 61, or
its Me ether, but a myriad of side products. The cation 63 was washed
with precooled, degassed pentane (−40 °C, 2 × 20 mL, 30 min each)
and, upon evaporation of the residual solvent under reduced pressure
5
9 0.27 (9H, s, Me Si), 1.41, 1.58, 1.79, 2.05 (1H, 2H, 2H, 1H, all
3
multiplets, 3CH ), 3.50 (1H, m/10 lines, 3-H, Jav = 2.83), 5.69 (2H,
AB/unsymm splitting pattern, 1-H, 2-H, J
for H NMR spectrum, see the next experiment. MS TOF FD+: m/z
M
2
= 10.4); γ-HAA 60,
H(A)‑H(B)
1
+
+
464. MS HR TOF FD+: m/z calcd for C H O SiCo M
17 18 6 2
4
63.9531, found 463.9546.
(−50 °C, 30 min), was dissolved in dry, precooled CH
mL). A solution of Cp Co (95.0 mg, 0.50 mmol) in dry, precooled
CH Cl (−40 °C, 2 mL) was added dropwise (2 min) at −78 °C, and
2 2
Cl (−40 °C, 5
2
{
μ-η -2-[(Trimethylsilyl)ethynyl]cyclohexene}dicobalt Hexa-
2
carbonyl (60). Under an atmosphere of nitrogen, NaBH (5.7 mg,
4
2
2
0.15 mmol) and CF COOH (74 mg, 0.65 mmol) were consecutively
the reaction mixture was stirred for 20 min (TLC control). The
temperature was raised to −20 °C, and the crude mixture was
quenched with saturated brine (20 mL), warmed to +20 °C over 20
min, and extracted with pentane (30 mL). The organic layer was
washed with water (3 × 30 mL), dried (Na SO ), and concentrated
3
added to a solution of alcohol 55 (48 mg, 0.10 mmol) in dry CH Cl2
2
(7 mL) at 0 °C. The suspension was stirred for 75 min at 0 °C (TLC
control). The crude mixture was quenched with degassed saturated
NaCl(aq) (10 mL) and diluted with water (10 mL). The aqueous layer
was extracted with pentane (3 × 10 mL), and combined organic
fractions were dried (Na SO ) and concentrated under reduced
pressure. The crude product was fractionated and then repurified by
preparative TLC (P, −13 °C; P, −13 °C), affording γ-HAA 60 (26 mg,
2
4
under reduced pressure. The crude mixture (NMR: γ,ε-65:γ,γ-66:α-
HAA 68 69:5:26; regioselectivity γ,ε-65: γ,γ-66 93:7; chemoselectivity
(γ,ε-65 + γ,γ-66):α-HAA 68 74:26) was fractionated by preparative
TLC (two plates, pentane, −16 °C; loading was carried out at −16 °C
2
4
K
DOI: 10.1021/acs.organomet.6b00435
Organometallics XXXX, XXX, XXX−XXX

Organometallics
Article
using a PTLC plate which was precooled at −16 °C for 40 min),
affording the inseparable dimers γ,ε-65 and γ,γ-66 (γ,ε:γ,γ 92:8; 36 mg,
C), 116.6, 117.6, 123.2, 123.3, 132.9, 137.8, 139.3 (CC), 145.2
+
(C6). MS TOF FD+: m/z MH 411. MS HR ESI-APCI+: m/z calcd
+
5
=
2.4% based on the amount of cation dimerized, i.e. 127 mg − 54 mg
73 mg (0.14 mmol)) as a dark brown oil and highly unstable α-HAA
8 (13 mg, 18.9% based on the amount of cation dimerized) as a dark
for C H Si MH 411.2898, found 411.2900.
26
43
2
6
AUTHOR INFORMATION
Corresponding Author
E-mail for G.G.M.: gagik.melikyan@csun.edu.
1
■
*
red oil. γ,ε-65 + γ,γ-66 (92:8): TLC (P): R 0.70. H NMR (400 MHz,
f
δ, C D ): γ,ε-65 0.34 (9H, s, Me Si), 0.35 (9H, s, Me Si), 1.09 (6H, s,
6
6
3
3
7
-Me, 7-Me), 1.53 (3H, s, HCCMeMe), 1.56 (3H, s, HC
CMeMe), 2.04, 2.13 (3H/3H, s/s, 3-Me/10-Me), 3.14 (1H, t, 8-H, J =
Notes
1
1
0.0), 5.16 (1H, d, HCCMeMe, J = 9.6), 6.09 (1H, d, 6-H, J =
5.2), 6.15 (1H, d, 9-H), 6.43 (1H, dd, 5-H, J = 11.2), 6.89 (1H, d, 4-
The authors declare no competing financial interest.
H, J = 10.8); γ,γ-66 0.33 (18H, s, 2Me Si), 1.63 (6H, s, 2HC
3
ACKNOWLEDGMENTS
2
6
■
CMeMe), 1.67 (6H, s, 2HCCMeMe), 2.08 (6H, s, 3-Me, 8-Me),
This material is based upon work supported by the National
Science Foundation under CHE-1112129. The authors are
greatly indebted to the Office of Graduate Studies, Research
and International Programs, University Corporation, and
College of Science and Mathematics, California State University
Northridge, for their generous support.
3
.56 (2H, m/five lines, 5-H, 6-H, J = 6.4), 5.31 (2H, br d, 2HC
av
CMeMe, J = 8.4), ∼6.17 (4-H, 7-H; partially overlapped with vinylic H
atoms of γ,ε-65). 13C NMR (100 MHz, δ, CDCl ): γ,ε-65 0.87
3
(
Me Si), 1.09 (Me Si), 18.7, 19.2, 19.6 (3-Me, 10-Me, Me Me CC),
3
3
E
Z
2
7
1
1
1
4.9, 25.6, 26.3 (7-Me, 7-Me, Me Me CC), 41.7 (C8), 48.8 (C7),
E Z
9.6, 80.6, 111.1, 112.1 (CC), 123.0, 124.3, 131.2, 132.1, 132.9,
33.3, 134.9 (CC), 144.7 (C6), 200.6 (CO); γ,γ-66 0.93 (Me Si),
3
8.4, 19.5, 23.3, 26.1, 29.9, 42.4, 43.2 (6Me), 77.9, 112.0 (CC),
REFERENCES
26
■
23.6, 124.8, 131.1, 131.8, 133.1, 135.1, 144.9 (CC). MS TOF FD
+
(1) (a) Encyclopedia of Radicals in Chemistry, Biology, and Materials;
Chatgilialoglu, C., Studer, A., Eds.; Wiley: New York, 2012, Vols. 1 and
+
: m/z M 982. MS HR TOF FD+: m/z calcd for C H O Si Co
38
42 12
2
4
+
M 981.9537, found 981.9498. Anal. Found: C, 45.57; H, 4.46. Calcd
2
. (b) Rowlands, G. J. Tetrahedron 2009, 65, 8603−8655. (c) Zard, S.
for C H O Si Co : C, 46.45; H, 4.31. α-HAA 68: TLC (P): R 0.75.
3
8
42 12
2
4
f
1
Z. Radical Reactions in Organic Synthesis; Oxford University Press: New
York, 2003; pp 1−256. (d) Bar, G.; Parsons, A. F. Chem. Soc. Rev.
H NMR (400 MHz, δ, C D ): 0.27 (9H, s, Me Si), 1.32 (3H, d, 6-
6
6
3
Me, J = 6.8), 1.63 (6H, s, 2-Me, CH ), 3.51 (1H, quintet, 6-H, J
=
3
av
2
003, 32, 251−263. (e) Radicals in Organic Synthesis; Renaub, P.; Sibi,
7
1
.1), 5.56 (1H, dd, 5-H, J = 14.8, J = 8.4), 5.88 (1H, spl d, 3-H, J =
+
M. P., Eds.; Wiley: Weinheim, Germany, 2001; Vols. 1 and 2.
(f) Malacria, M. Chem. Rev. 1996, 96, 289−306. (g) Curran, D. P.
Radical Addition Reactions. In Comprehensive Organic Synthesis; Trost,
B. M., Ed.; Pergamon Press: London, 1992; Vol. 5, Chapters 4.1 and
0.8, J = 0.8), 6.34 (1H, dd, 4-H). MS TOF FD+: m/z M 492. MS
+
HR TOF FD+: m/z calcd for C H O SiCo M 491.9844, found
19
22
6
2
4
91.9864.
Isolation of γ,ε-65 in an Individual Form. Under an atmosphere
4
1
.2. (h) Jasperse, C. P.; Curran, D. P.; Fevig, T. L. Chem. Rev. 1991, 91,
of N , an inseparable mixture of γ,ε-65 and γ,γ-66 (36 mg, 0.037
2
237−1286. (i) Giese, B. Radicals in Organic Synthesis: Formation of
mmol; ε,γ:γ,γ 92:8) in benzene (3 mL) was heated at 70 °C for 3 h
and concentrated under reduced pressure. The crude mixture was
fractionated by preparative TLC (pentane, −16 °C; loading was
carried at −16 °C using a PTLC plate which was precooled at −16 °C
for 40 min), affording pure γ,ε-65 (22 mg, 61.1%) as a dark brown oil.
Carbon-Carbon Bonds; Pergamon: Oxford, U.K., 1986; pp 1−282.
(
j) Smith, M. B. March’s Advanced Organic Chemistry: Reactions,
Mechanisms, and Structure, 7th ed.; Wiley: Hoboken, NJ, 2013; pp
34−248. (k) Gibian, M. J.; Corley, R. C. Chem. Rev. 1973, 73, 441−
2
4
1
64.
H NMR (400 MHz, δ, C D ): 0.34 (9H, s, Me Si), 0.35 (9H, s,
6
6
3
(
(
2) Gomberg, M. J. Am. Chem. Soc. 1900, 22, 757−771.
3) (a) Ruchardt, C. Steric Effects in Free Radical Chemistry. In
Me Si), 1.088 (3H, s, 7-Me), 1.090 (3H, s, 7-Me), 1.53 (3H, d, HC
3
CMeMe, J = 1.2), 1.56 (3H, s, HCCMeMe, J = 0.8), 2.04 (3H, d, 3-
Me or 10-Me, J = 1.2), 2.12 (3H, d, 3-Me or 10-Me, J = 1.2), 3.14 (1H,
t, 8-H, J = 10.0), 5.16 (1H, spl d, HCCMeMe, J = 8.4, J = 1.2), 6.09
Topics in Current Chemistry: Organic Chemistry: Syntheses and
Reactivity; Springer-Verlag: Berlin, 1980; Vol. 88, pp 1−32. . For
reviews on persistent radicals see: (b) Griller, D.; Ingold, K. U. Acc.
Chem. Res. 1976, 9, 13−19. (c) Fischer, H. Chem. Rev. 2001, 101,
581−3610. (d) Studer, A. Chem. - Eur. J. 2001, 7, 1159−1164.
(4) (a) Schreiner, K.; Berndt, A. Angew. Chem., Int. Ed. Engl. 1975, 14,
(
1H, d, 6-H, J = 15.2), 6.15 (1H, spl d, 9-H, J = 1.2), 6.43 (1H, dd, 5-
H, Jav = 15.4, Jav = 11.0), 6.90 (1H, d, 4-H, J = 10.8).
,7,7,10-Tetramethyl-8-(2′-methylprop-1′-en-1′-yl)dodeca-
E,5E,9E-triene-1,11-diyne-1,12-bis(trimethylsilyl) (69). Under
an atmosphere of N , a solution of Ce(NH ) (NO ) (48 mg, 0.088
3
3
3
366−367. (b) Mendenhall, G. D.; Griller, D.; Lindsay, D.; Tidwell, T.
T.; Ingold, K. U. J. Am. Chem. Soc. 1974, 96, 2441−2447. (c) Griller,
D.; Icli, S.; Thankachan, C.; Tidwell, T. T. J. Chem. Soc., Chem.
Commun. 1974, 913−914. (d) Hart, D. J.; Seely, F. L. J. Am. Chem. Soc.
1988, 110, 1631−1633. (e) Neumann, W. P.; Hillgartner, H.; Baines,
K. M.; Dicke, R.; Vorspohl, K.; Kobs, U.; Nussbutel, U. Tetrahedron
1989, 45, 951−960.
(5) Melikyan, G. G. Acc. Chem. Res. 2015, 48, 1065−1079.
(6) Melikyan, G. G.; Bright, S.; Monroe, T.; Hardcastle, K. M.;
Ciurash, J. Angew. Chem., Int. Ed. 1998, 37, 161−164.
(7) Persistency in radical dimerization reactions should be distinguished
from the persistency in radical addition reactions, since the volume of
the recipient of the radical attack, such as the compound with an
activated double bond, is much lower than the volume of the bulky
radical itself. In other words, a given radical can be persistent in a
dimerization reaction when it reacts with the counterpart of the same
size and, in contrast, be transient in addition reactions when the
smaller size of the recipient of the radical attack makes the rate
constant of the bimolecular addition reactions much higher than that
in self-coupling reactions.
2
4
2
3 6
mmol) in degassed acetone (3 mL) was added dropwise (5 min) to a
solution of γ,ε-65 (22 mg, 0.022 mmol) in degassed acetone (5 mL) at
−
78 °C and stirred for 2 h. An additional portion of Ce(NH ) (NO )
4 2 3 6
(
(
°
48 mg, 0.088 mmol) in degassed acetone (3 mL) was added dropwise
5 min) at −78 °C, and the reaction mixture was stirred for 2 h at −78
C and for another 2 h at −50 °C (TLC control). The crude mixture
was warmed to −10 °C, treated with saturated NaCl(aq) (11 mL), and
diluted with pentane (30 mL). The aqueous layer was extracted with
pentane (3 × 10 mL), dried (Na SO ), and concentrated under
2
4
reduced pressure. The crude mixture was fractionated by preparative
TLC (pentane, −16 °C; loading was carried out at −16 °C using a
PTLC plate which was precooled at −16 °C for 40 min), affording 69
1
(
(
(
7 mg, 77.8%) as a colorless viscous oil. TLC (P): R 0.29. H NMR
f
400 MHz, δ, C D ): 0.24 (9H, s, Me Si), 0.28 (9H, s, Me Si), 0.92
6
6
3
3
6H, s, 7-Me, 7-Me), 1.45 (3H, d, HCCMeMe, J = 1.2), 1.60 (3H, s,
HCCMeMe, J = 1.2), 1.82 (6H, d, 3-Me/10-Me, J = 1.2), 3.04 (1H,
t, 8-H, J = 10.2), 4.98 (1H, spl d, HCCMeMe, J = 10.0, J = 1.2),
av
5
.68 (1H, d, 6-H, J = 15.6), 6.09 (1H, spl d, 9-H, J = 10.4, J = 1.6),
.22 (1H, dd, 5-H, Jav = 15.4, Jav = 11.0), 6.58 (1H, d, 4-H, J = 11.2).
C NMR (100 MHz, δ, CDCl ): 0.32 (Me Si), 0.34 (Me Si), 17.6,
6
1
3
3
3
3
(8) (a) Eichin, K.; McCullough, K.; Beckhaus, H.; Ruchardt, C.
Angew. Chem., Int. Ed. Engl. 1978, 17, 934−935. (b) Greene, F. D.;
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1
7.9, 18.6 (3-Me, 10-Me, Me Me CC), 25.3, 26.3 (7-Me/7-Me,
E
Z
Me Me CC), 41.2 (C8), 48.2 (C7), 90.3, 92.9, 109.0, 109.5 (C
E Z
L
DOI: 10.1021/acs.organomet.6b00435
Organometallics XXXX, XXX, XXX−XXX

Organometallics
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(
(
(26) Stereochemical assignment (3E,7E) was carried out on the basis
1
1g
(
of NMR analogies with a structurally related γ,γ dimer for which the
geometry was independently verified by means of X-ray crystallog-
2
M
DOI: 10.1021/acs.organomet.6b00435
Organometallics XXXX, XXX, XXX−XXX

Organometallics
Article
raphy. The number of resonances in the 13C NMR spectrum for
methyl groups and vinylic carbon atoms was indicative of the presence
of two diastereomers.
N
DOI: 10.1021/acs.organomet.6b00435
Organometallics XXXX, XXX, XXX−XXX