Divergent ring-opening coupling between cyclopropanols and alkynes under cobalt catalysis

Article abstract of DOI:10.1039/c8sc02074d

Cobalt-diphosphine catalysts promote ring-opening coupling reactions between cyclopropanols and unactivated internal alkynes, affording either β-alkenyl ketones or multisubstituted cyclopentenol derivatives in good yields with good to excellent regioselectivities. The chemoselectivity between these β-alkenylation and [3 + 2] annulation reactions, which likely share a cobalt homoenolate as a key catalytic intermediate, is exquisitely controlled by the reaction conditions, with the solvent being a major controlling factor. The reactions are proposed to involve ring opening of cobalt cyclopropoxide into homoenolate, migratory insertion of the alkyne into the Co-C bond, and protodemetalation or intramolecular carbonyl addition of the resulting alkenylcobalt species. The feasibility of these reaction steps was supported by DFT calculations.

Full text of DOI:10.1039/c8sc02074d

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DOI: 10.1039/C8SC02074D
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ARTICLE
Divergent ring-opening coupling between cyclopropanols and
alkynes under cobalt catalysis
Received 00th January 20xx,
Accepted 00th January 20xx
Junfeng Yang, Yixiao Shen, Yang Jie Lim, and Naohiko Yoshikai*
DOI: 10.1039/x0xx00000x
Cobalt–diphosphine catalysts promote ring-opening coupling reactions between cyclopropanols and unactivated internal
alkynes, affording either β-alkenyl ketones or multisubstituted cyclopentenol derivatives in good yields with good to
excellent regioselectivities. The chemoselectivity between these β-alkenylation and [3 + 2] annulation reactions, which
likely share a cobalt homoenolate as a key catalytic intermediate, is exquisitely controlled by the reaction conditions, with
the solvent being a major controlling factor. The reactions are proposed to involve ring opening of cobalt cyclopropoxide
into homoenolate, migratory insertion of alkyne into the Co–C bond, and protodemetalation or intramolecular carbonyl
addition of the resulting alkenylcobalt species. The feasibility of these reaction steps was supported by DFT calculations.
www.rsc.org/
6
homoenolates, and amination via copper homoenolates,
,7
8
9
Introduction
among others. Besides the homoenolate-based approach,
recent years have also witnessed other mechanistically distinct
types of ring-opening transformations of cyclopropanols,
The strain-driven C–C bond cleavage of small ring compounds
offers unique entry for the synthesis of linear or larger-ring
1
compounds. Among strained carbocycles, cyclopropanols and
1
0
which employ coupling partners such as (fluoroalkyl) halides,
1
1
12
4
alkynylbenziodoxoles, diazo compounds, and so on to
access the corresponding β-functionalized ketones. Despite all
the progress in the stoichiometric and catalytic cross-couplings
via metal homoenolates, viable coupling partners have thus far
been limited to polar organic electrophiles, and interception of
a homoenolate with a nonpolar unsaturated hydrocarbon as a
reaction partner has been elusive.
related compounds have received considerable attention as
readily accessible starting materials that can undergo ring
opening with the aid of various reagents such as bases, acids,
2
and metal complexes. In this context, the chemistry of metal
homoenolates (or β-metallocarbonyl compounds) generated
from siloxycyclopropanes represents a significant milestone
3
Scheme 1a). Exposure of siloxycyclopropanes to Lewis acidic
(
metal salts such as ZnCl2 and TiCl4 causes ring-opening to
generate the corresponding homoenolates, which are
amenable to trapping with typical organic electrophiles such as
aldehydes, enones, and organic halides in the presence of
appropriate catalysts or additives, affording β-functionalized
carbonyl compounds. A major drawback of this chemistry is,
however, that it often involves a preformed homoenolate and
thus inevitable consumption of a stoichiometric metal salt.
Recently, significant progress has been made in generation
of homoenolates from unmasked cyclopropanols via metal
cyclopropoxide and their use as catalytic intermediates for
4
cross-coupling with electrophiles (Scheme 1b). This strategy
allows for direct, and often fully catalytic conversion of
cyclopropanols into a variety of β-functionalized ketones.
Notable examples in this respect include allylation via copper
5
catalysis of zinc homoenolates, arylation via palladium
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Pursuing our continuing interest in cobalt-catalyzed C–C bond
1
7-19
formation and transformation of unactivated alkynes,
the
present study commenced with exploration of the coupling
between 1-phenylcyclopropanol (1a) and 5-decyne (2a) (Table
1
). Through extensive experimentation, the feasibility of the β-
alkenylation was revealed first. A catalytic system comprised
of CoBr (10 mol%), 1,2-bis(diphenylphosphino)ethane (dppe,
mol%), Zn dust (50 mol%), and 1,4-
2
1
0
diazabicyclo[2.2.2]octane (DABCO, 150 mol%) promoted the
reaction in dimethylsulfoxide (DMSO) at 80 °C, affording β-
alkenyl ketone 3aa in 97% yield with exclusive syn-selectivity
(entry 1). While 1,3-bis(diphenylphosphino)propane (dppp)
was equally effective as dppe (entry 2), later, dppe proved to
show better performance than other diphosphines for 1-
benzylcyclopropanol (Table S1). The reaction became sluggish
under ligand-free conditions (entry 3). Zn would play an
2
0
important role as a reductant, as its replacement by Mn or its
removal resulted in a sharp drop in the yield (entries 4 and 5).
The beneficial effect of DABCO was apparent from control
experiments performed with a lower loading or in its absence
(entries 6 and 7).
Interestingly, the solvent was found to have a dramatic
impact on the reaction outcome. While dimethylformamide
DMF) gave rise to a small amount of cyclopentenol 4a (entry
(
8
8
), the reaction in MeCN afforded 4a as the major product in
0% yield along with a small amount of 3a (entry 9). The
annulation/alkenylation selectivity was further enhanced to >
0:1 by using CoI as the precatalyst (entry 10). Note that
2
2
neither the β-alkenylation nor the [3 + 2] annulation took place
in the absence of the cobalt catalyst.
Scheme 1 Ring-opening transformations of cyclopropanol derivatives via homoenolate.
Herein, we report that a cobalt catalyst promotes ring-
a
opening coupling between a cyclopropanol and a nonpolar Table 1 Effect of reaction conditions.
internal alkyne to afford a β-alkenyl ketone or a cyclopentenol
derivative, with the solvent being a major selectivity-
controlling factor (Scheme 1c). These divergent β-alkenylation
and [3 + 2] annulation reactions likely involve a cobalt
homoenolate as a common catalytic intermediate, and mark a
sharp contrast with previously reported ring-opening
alkenylation and [3 + 2] annulation of siloxycyclopropanes with
activated, ester-substituted alkynes via stoichiometric
b
Entry
Deviation from std. conditions
Yield (%)
1
3
homoenolates. While intramolecular reactions between
cyclopropanol and alkyne moieties of 1-alkynylcyclopropanols
have been explored using Co, Au, or Ru catalysts to achieve
ring-opening rearrangement into cyclopentenones or
3
a
4a
0
1
2
3
4
5
6
7
8
9
None
97
98
29
30
19
62
11
70
8
dppp instead of dppe
dppe omitted
0
0
1
4
methylenecyclobutanes, the present reactions represent the
first example of intermolecular coupling between
cyclopropanol and unfunctionalized alkyne. Featuring broad
scope and high stereo- and regioselectivity with respect to
alkynes, the present reactions offer unique approaches to γ,δ-
unsaturated ketones and cyclopentenols, which would
complement existing approaches including reductive
Mn instead of Zn
Zn omitted
0
0
DABCO (50 mol%)
DABCO omitted
4
0
DMF instead of DMSO
MeCN instead of DMSO
10
80
88
1
0
CoI
2
and MeCN instead of CoBr
2
and DMSO
3
1
5,16
a
The reaction was performed on using 0.15 mmol of 1a and 0.1 mmol of 2a (0.3
coupling/cycloaddition between enones and alkynes.
M). dppe = 1,2-bis(diphenylphosphino)ethane; dppp = 1,3-
b
bis(diphenylphosphino)propane. Determined by GC using mesitylene as an
internal standard.
Results and Discussion
2
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We explored the generality of both the β-alkenylation and
3 + 2] annulation reactions. Scheme 2 shows the scope of the
[
β-alkenylation with respect to cyclopropanols. A variety of 1-
aryl- and 1-alkylcyclopropanols smoothly participated in the
reaction with 2a to afford the corresponding adducts 3a–3m in
moderate to high yields. A partial dechlorination was observed
in the reaction of 1-(4-chlorophenyl)cyclopropanol,
presumably due to the oxidative addition of the C–Cl bond to
the cobalt catalyst (see 3e). Tetrahydronaphthalene-fused
cyclopropanol 1n underwent exclusive cleavage of the less
substituted C–C bond to give the adduct 3n in 90% yield. While
monocyclic 1,2-disubstituted cyclopropanol 1o reacted
sluggishly under the standard conditions, the reaction under
modified conditions using 1,4-bis(diphenylphosphino)butane
(
dppb) and MeCN afforded β-alkenyl ketone 3o in 54% yield,
again via cleavage of the less substituted C–C bond. In contrast
to these 1-aryl-2-alkylcyclopropanols, 1,2-
diphenylcyclopropanol and 1-methyl-1-phenylcyclopropanol
failed to undergo β-alkenylation reaction with 2a but
decomposed into 1,3-diphenylpropan-1-one and 4-
phenylbutan-2-one, respectively, as a result of cleavage of the
more substituted C–C bond. This observation may be
rationalized by the formation of cobalt homoenolate with
more stable benzylic C–Co bond. In addition, the reaction a
secondary cyclopropanol, 2-methyl-2-phenylcyclopropanol,
with 2a failed to afford either β-alkenylation product or [3 + 2]
annulation product but resulted in decomposition into
intractable products. Note that the reaction of 1a could be
performed on a 3 mmol scale, affording 3a in 75% yield.
a
Scheme 2 Scope of β-alkenylation with respect to cyclopropanols. Obtained as a
mixture with dechlorinated product (8%).
The β-alkenylation of 1a with 1-phenyl-1-butyne (2b) under
the above conditions took place smoothly but with a moderate
regioselectivity (4.4:1), with preferential C–C bond formation
at the proximity of the ethyl group. Upon reexamination of
diphosphine
ligands
(Table
S2),
1,6-
bis(diphenylphosphino)hexane (dpphex) was found to exhibit
higher regioselectivity (9:1) without compromising the yield
(
Scheme 3, 3p). The modified catalytic system was applicable
to a variety of aryl(alkyl)alkynes, displaying moderate to high
regioselectivities (3:1 to ≥20:1) and tolerance to ester (3t
ab), chloro (3v), trifluoromethyl (3w), bulky aryl (3z), and
,
3
thienyl (3ad) groups. The reaction of an enyne substrate also
took place smoothly, affording γ,δ,ε,ζ-unsaturated ketone 3ae
in good yield and regioselectivity. Diphenylacetylene also took
part in the reaction with 1a to give the adduct 3af with good
stereoselectivity. Terminal alkynes such as phenylacetylene
failed to afford none of possible addition products.
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yields of the accompanying β-alkenylation products were
rather low (3p, 6%; 3r, 3%).
Scheme 3 Scope of β-alkenylation with respect to alkynes.
The scope of the [3 + 2] annulation was explored next
(Scheme 4). A series of 1-arylcyclopropanols reacted with 2a to
give the desired products 4a–4g in good yields except for the
one bearing a para-methoxy group (4c). The low yield of 4c
was the result of its facile decomposition on silica gel during
purification, which could be attributed to the instability of the
electron-rich tertiary alcohol moiety. 1-Alkylcyclopropanols
were also amenable to the [3 + 2] annulation (see 4h and 4i).
Note that the 1,2-disubstituted cyclopropanols 1n and 1o
failed to undergo the annulation reaction, and also did not give
any β-alkenylation products. As a substantial amount of the
cyclopropanol remained unreacted, we speculate that both
the homoenolate formation and the alkyne insertion steps
were problematic for these cases. Upon a slight modification
of the reaction conditions (Table S3), the annulation of 1a and
Scheme 4 Scope of [3 + 2] annulation. The reactions for 4i–4w were performed using
a
1
0 mol% of dppp (instead of dppe) and 50 mol% of DABCO at 0.1 M. The yield was
1
determined by H NMR.
Our preliminary screening demonstrated the feasibility of
an enantioselective [3 + 2] annulation using a chiral cobalt
catalyst (Scheme 5; see also Table S4). Thus, asymmetric
induction in the reaction of 1a and 2a was observed using a
host of chiral diphosphine ligands having different backbones,
among which (R,R)-QuinoxP* displayed the highest ee of 93%
albeit in a low yield. While further screening of ligands,
additives, and other reaction conditions is currently underway
to improve the yield and enantioselectivity, these results
would serve as a testament to the reaction mechanism
involving an alkenylcobalt species (vide infra).
1-phenyl-1-butyne using dppp (10 mol%) and DABCO (50
mol%) afforded cyclopentenol 4j in 85% yield with exclusive
regioselectivity (> 20:1) and good product selectivity (8:1).
Likewise, a variety of aryl(alkyl)alkynes could be annulated
with 1a to afford cyclopentenols 4k–4u in moderate to high
yields. The enyne and diphenylacetylene also proved to be
excellent substrates for the present annulation (see 4v and
4w). Note that most of the [3 + 2] annulation reactions were
accompanied by the competing β-alkenylation, while the
degree of competition was generally low as judged from TLC
analysis of the crude mixture. For the case of 4j and 4l, the
4
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Zn were present, while dppe and DABCO were not
indispensable for the ring opening. In addition, ZnBr , which
should be generated upon reduction of CoBr with Zn, only
2
2
sluggishly promoted the ring opening in the presence or
absence of DABCO. Thus, a cobalt(I) species generated from
20
the cobalt(II) precatalyst and Zn appears to play a major role
in the ring opening, and formation of a zinc homoenolate from
9
c
cyclopropanol and zinc(II) is less likely to operate under the
present conditions. The reaction of deuterium-labeled
cyclopropanol 1a-d (68% D at the hydroxyl group) with 2a
resulted in the adduct with partial deuterium incorporation
into the vinylic and the carbonyl α-positions (Scheme 7b). A
greater degree of deuterium incorporation was observed for
Scheme 5 Enantioselective [3 + 2] annulation.
the reaction of 1a with 2a in the presence of CD
and the degree of deuterium incorporation was further
enhanced with an increased amount (10 equiv) of CD OD
Scheme 7c). These observations suggest that not only the
3
OD (1.5 equiv),
The β-alkenyl ketone products would be amenable to a
number of follow-up synthetic transformations. To
demonstrate simultaneous utilization of the ketone and olefin
moieties, we derivatized some of the β-alkenyl ketones into
the corresponding O-pivaloyl oximes, and subjected them to
3
(
alcoholic protons but also the carbonyl α-protons are
responsible as the proton source for the vinylic position. We
also confirmed that radical scavengers such as 2,2,6,6-
2
1
the copper-catalyzed aza-Heck type reaction to obtain 3,4-
dihydro-2H-pyrrole derivatives 6a 6c in good yields. (Scheme
a). As a demonstration of the utility of the [3 + 2] adducts, the
cyclopentenol 4w was readily converted to 1,2,3-trisubstituted
cyclopentadiene and the corresponding cyclopentadienyl
(Scheme 6b). Thus, the present [3 + 2]
tetramethylpiperidine
1-oxyl
(TEMPO)
and
1,1-
–
diphenylethylene did not interfere with either β-alkenylation
or [3 + 2] annulation.
6
7
X
III
(Cp )–Rh complex 8
annulation would allow for convenient access to structurally
X
diverse Cp –M complexes, which would find many applications
2
2
in catalysis.
Scheme 6 Product transformations.
Several control experiments were performed to gain
mechanistic insight into the β-alkenylation reaction. To probe
the role of each component of the catalytic system on the ring- Scheme 7 Control experiments.
opening of cyclopropanol, conversion of 1-
benzylcyclopropanol 1j into 1-phenylbutan-2-one was
examined under different conditions in the absence of alkyne alkenylation and [3 + 2] annulation reactions. We consider that
Scheme 7a; see also Table S5). As a result, the ring opening these reactions share a cobalt homoenolate
, which would be
(generated from the
(
)
Scheme 8 illustrates proposed catalytic cycles for the β-
(
C
2
was found to take place most smoothly when both CoBr and formed from a cobalt(I) species
A
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2
1, and base acetonitrile to obtain free energy profiles. While CP1t was
9
cobalt(II) precatalyst and Zn), cyclopropanol
(
DABCO) via a cobalt cyclopropoxide
intermediate. Insertion of alkyne into
which would then undergo identified on both the singlet and triplet surfaces. On the
protodemetalation to furnish β-alkenyl ketone or singlet surface, CP1s undergoes very facile and exergonic ring
B
, as a common found to be more stable than CP1s by 11.2 kcal/mol, viable
2
C would give an reaction pathways for the [3 + 2] annulation could be
2
3
29
alkenylcobalt species
D,
3
18c
‡
intramolecular carbonyl addition and protodemetalation to opening (TS1s, ΔG = 0.7 kcal/mol) to give cobalt homoenolate
afford cyclopentenol . The proton source in the former CP2s with a square-planar geometry. This is followed by
4
protodemetalation step would be the alcoholic proton of complexation of the alkyne (CP3s) and slightly endergonic syn-
‡
cyclopropanol (or externally added alcohol) or the carbonyl α- migratory insertion into the Co–C bond (TS2s; ΔG = 22.2
proton of the β-alkenyl ketone
3, as suggested from the kcal/mol) to afford non-chelated alkenylcobalt species CP4s
.
deuterium labeling experiments (Scheme 7b,c). DABCO is Cyclization of CP4s requires very low activation energy (TS3s
;
‡
assumed to serve as a proton shuttle, which would facilitate ΔG = 0.7 kcal/mol) to afford cyclized product complex CP5s
the formation of and the catalytic turnover ( to or to The triplet complex CP1t also undergoes facile and exergonic
while being engaged in the exchange of the alcoholic protons ring opening (TS1t, ΔG = 8.4 kcal/mol) to give homoenolate
of and the carbonyl α-protons of . We are tempted to CP2t with a distorted tetrahedral geometry. Complexation of
interpret the solvent-controlled product divergence in terms of the alkyne to CP2t is endergonic (CP3t), and subsequent
.
B
D
A
E
A)
‡
1
3
2
4
‡
the solvent-dependent acidity. Thus, the proton source (e.g., alkyne insertion (TS2t; ΔG from CP2t = 28.3 kcal/mol) occurs
base•HX, cyclopropanol) would exhibit higher acidity in more with large exergonicity to give alkenylcobalt species CP4t
polar solvents, and hence direct protodemetalation of the which is chelated by the C=O group through π-coordination.
alkenylcobalt intermediate would be favored in DMSO (ε = Intramolecular cyclization of CP4t takes place through TS3t
6.8) rather than in MeCN (ε = 35.7). In addition, coordination with modest activation energy (9.9 kcal/mol) to afford cyclized
,
D
4
of the carbonyl oxygen to the cobalt center in
D
might be product complex CP5t
.
stronger in less Lewis basic MeCN, thus assisting
intramolecular carbonyl addition in MeCN. The possibility of a
radical mechanism for the cyclopropanol opening and a β-keto
radical intermediate may be excluded on the basis of the
cleavage of the less substituted C–C bond of 1n and 1o
(Scheme 2), the exclusive syn-selectivity of the alkenylation,
and the lack of inhibitory effects of radical scavengers.
Scheme 8 Proposed reaction pathways.
To probe feasibility of the key steps in the proposed
mechanism, we performed density functional theory (DFT)
calculations on a model reaction using 1-methylcyclopropanol
and 2-butyne as the reactants and a (dppe)cobalt(I)–
cyclopropoxide (CP1s, singlet or CP1t, triplet) as the starting
complex (Scheme 9). Geometry optimization was performed in
2
5
the gas phase with the M06L functional
using the
2
6
Stuttgart/Dresden effective core potential (SDD) for cobalt
and the 6-31G(d) basis set for all other atoms. For the
optimized structures, single-point energy calculations were
performed with the M06L function and the def2-TZVP basis
2
7
28
set for all atoms using the SMD solvation model for
6
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Figure 1 Energy diagrams for (dppe)Co(I)-mediated [3 + 2] annulation of 1-
methylcyclopropanol and 2-butyne (blue, S = 0; red, S = 1).
Conclusions
In summary, we have disclosed cobalt-catalyzed divergent
coupling reactions between cyclopropanols and internal
alkynes, which afford β-alkenyl ketones or 1,2,3-trisubstituted
cyclopentenols with high syn-selectivity and good to high
regioselectivity. These β-alkenylation and [3 + 2] annulation
reactions likely share the same reaction steps involving ring-
opening formation of a cobalt homoenolate and subsequent
alkyne insertion to form an alkenylcobalt intermediate. The
fate of the alkenylcobalt intermediate, i.e., the
chemoselectivity of the reaction, can be exquisitely controlled
by the reaction conditions, with the solvent being major
controlling factor. The feasibility of the key steps in the
proposed reaction mechanism was supported by DFT
calculations. Overall, by engaging nonpolar alkynes as reaction
partners, the present study has expanded the scope of direct
catalytic transformation of cyclopropanols under transition
metal catalysis. The development of an enantioselective
variant of the [3 + 2] annulation reaction and further
exploration of cobalt-catalyzed cross-couplings between
cyclopropanols and other nonpolar unsaturated hydrocarbons
and their mechanistic underpinnings are ongoing in our
laboratory and will be reported in due course.
Scheme 9 Reaction pathways for (dppe)Co(I)-mediated [3 + 2] annulation of 1-
methylcyclopropanol and 2-butyne starting from cobalt cyclopropoxide species (CP1s
for singlet and CP1t for triplet), obtained by DFT calculations (SMD(MeCN)-M06L/def2-
TZVP//M06L/SDD(Co)-6-31G(d)). Values in the parentheses refer to free energies
relative to CP1t.
The energy diagrams in Figure 1 demonstrate that there is
no critically large energy gap between the singlet and triplet
surfaces, and both the reaction pathways would be feasible on
their own. The crossings of the singlet and the triplet surfaces
suggest that spin crossover may take place multiple times
throughout the reaction, e.g., upon alkyne complexation (CP2
Acknowledgements
This work was funded by the Ministry of Education (Singapore)
and Nanyang Technological University (RG3/15, RG114/15, and
MOE2016-T2-2-043). We thank Dr. Rakesh Ganguly and Dr.
Yongxin Li (Nanyang Technological University) for their
assistance with the X-ray crystallographic analysis. The High-
Performance Computing Centre of NTU is acknowledged for
computer resources.
to CP3; triplet to singlet) and alkyne insertion (TS2 to CP4
;
singlet to triplet). Despite this complexity, it is clear that the
alkyne insertion step requires a distinctly higher activation
barrier than other steps, that is, ring opening and
intramolecular carbonyl addition.
Notes and references
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1
(a) G. Fumagalli, S. Stanton and J. F. Bower, Chem. Rev., 19 For selected reviews on cobalt-catalyzed C–C bond
017, 117, 9404; (b) P.-H. Chen, B. A. Billett, T. Tsukamoto formation, see: (a) M. Moselage, J. Li and L. Ackermann, ACS
and G. Dong, ACS Catal., 2017, , 1340; (c) I. Marek, A. Catal., 2016, , 498; (b) P. Röse and G. Hilt, Synthesis, 2016,
2
7
6
Masarwa, P. O. Delaye and M. Leibeling, Angew. Chem., Int.
Ed., 2015, 54, 414; (d) L. Souillart and N. Cramer, Chem. Rev.,
2015, 115, 9410; (e) M. Murakami and T. Matsuda, Chem.
Commun., 2011, 47, 1100.
48, 463; (c) P. Gandeepan and C.-H. Cheng, Acc. Chem. Res.,
2015, 48, 1194; (d) G. Cahiez and A. Moyeux, Chem. Rev.,
2010, 110, 1435; (e) W. Hess, J. Treutwein and G. Hilt,
Synthesis, 2008, 3537.
2
3
4
5
O. G. Kulinkovich, Chem. Rev., 2003, 103, 2597.
I. Kuwajima and E. Nakamura, Top. Curr. Chem., 1990, 133, 3.
A. Nikolaev and A. Orellana, Synthesis, 2016, 48, 1741.
(a) P. P. Das, K. Belmore and J. K. Cha, Angew. Chem., Int. Ed.,
20 L. Fiebig, J. Kuttner, G. Hilt, M. C. Schwarzer, G. Frenking, H.
G. Schmalz and M. Schafer, J. Org. Chem., 2013, 78, 10485.
21 A. Faulkner, N. J. Race, J. S. Scott and J. F. Bower, Chem. Sci.,
2014, 5, 2416.
2
012, 51, 9517; (b) B. B. Parida, P. P. Das, M. Niocel and J. K. 22 T. Piou, F. Romanov-Michailidis, M. Romanova-Michaelides,
Cha, Org. Lett., 2013, 15, 1780; (c) R. V. N. S. Murali, N. N.
Rao and J. K. Cha, Org. Lett., 2015, 17, 3854.
(a) N. Nithiy, D. Rosa and A. Orellana, Synthesis, 2013, 45,
3199; (b) D. Rosa, A. Nikolaev, N. Nithiy and A. Orellana, 23 (a) P.-S. Lin, M. Jeganmohan and C.-H. Cheng, Chem. Eur. J.,
Synlett, 2015, 26, 441.
(a) D. Rosa and A. Orellana, Org. Lett., 2011, 13, 110; (b) D.
Rosa and A. Orellana, Chem. Commun., 2013, 49, 5420; (c) K.
Cheng and P. J. Walsh, Org. Lett., 2013, 15, 2298; (d) N.
Nithiy and A. Orellana, Org. Lett., 2014, 16, 5854.
K. E. Jackson, N. Semakul, T. D. Taggart, B. S. Newell, C. D.
Rithner, R. S. Paton and T. Rovis, J. Am. Chem. Soc., 2017,
139, 1296.
6
7
2008, 14, 11296; (b) K. Murakami, H. Yorimitsu and K.
Oshima, Org. Lett., 2009, 11, 2373; (c) B.-H. Tan, J. Dong and
N. Yoshikai, Angew. Chem., Int. Ed., 2012, 51, 9610.
24 E. Rossini and E. W. Knapp, J. Comput. Chem., 2016, 37
1082.
,
8
9
(a) Z. Ye and M. Dai, Org. Lett., 2015, 17, 2190; (b) Y. Li, Z. Ye, 25 Y. Zhao and D. G. Truhlar, Theor. Chem. Acc., 2007, 120, 215.
26 M. Dolg, U. Wedig, H. Stoll and H. Preuss, J. Chem. Phys.,
1987, 86, 866.
T. M. Bellman, T. Chi and M. Dai, Org. Lett., 2015, 17, 2186.
(a) D. C. Davis, K. L. Walker, C. Hu, R. N. Zare, R. M.
Waymouth and M. Dai, J. Am. Chem. Soc., 2016, 138, 10693; 27 (a) A. Shafer, C. Huber, R. Ahlrichs, J. Chem. Phys., 1994, 100
,
(
(
b) X. Zhou, S. Yu, L. Kong and X. Li, ACS Catal., 2016,
6
, 647;
c) L. R. Mills, L. M. B. Arbelaez and S. A. L. Rousseaux, J. Am.
5829; (b) F. Weigend and R. Ahlrichs, Phys. Chem. Chem.
Phys., 2005, , 3297.
Chem. Soc., 2017, 139, 11357. (d) P. Wu, M. Jia, W. Lin and S. 28 A. V. Marenich, C. J. Cramer and D. G. Truhlar, J. Phys. Chem.,
7
Ma, Org. Lett., 2018, 20, 554.
0 Z. Ye, K. E. Gettys, X. Shen and M. Dai, Org. Lett., 2015, 17
074.
2009, 113, 6378.
29 See the Supplementary Information for computational
details.
1
1
,
6
1 (a) S. Wang, L.-N. Guo, H. Wang and X.-H. Duan, Org. Lett., 30 We did not examine protonation of the alkenylcobalt
2
015, 17, 4798; (c) C.-Y. Wang, R.-J. Song, Y.-X. Xie and J.-H.
intermediates CP4s and CP4t (i.e., β-alkenylation pathway)
because of the ambiguity of the proton source, which would
make quantitatively meaningful comparison of the two
competing pathways difficult.
Li, Synthesis, 2016, 48, 223; (b) K. Jia, F. Zhang, H. Huang and
Y. Chen, J. Am. Chem. Soc., 2016, 138, 1514.
2 H. Zhang, G. Wu, H. Yi, T. Sun, B. Wang, Y. Zhang, G. Dong
and J. Wang, Angew. Chem., Int. Ed., 2017, 56, 3945.
1
1
3 (a) I. Ryu, K. Matsumoto, Y. Kameyama, M. Ando, N.
Kusumoto, A. Ogawa, N. Kambe, S. Murai and N. Sonoda, J.
Am. Chem. Soc., 1993, 115, 12330; (b) M. T. Crimmins and P.
G. Nantermet, J. Org. Chem., 1990, 55, 4235; (c) M.
T.
Crimmins, P. G. Nantermet, B. W. Trotter, I. M. Vallin, P. S.
Watson, L. A. Mckerlie, T. L. Reinhold, A. W. H. Cheung, K. A.
Stetson, D. Dedopoulou and J. L. Gray, J. Org. Chem., 1993,
58, 1038.
1
4 (a) N. Iwasawa, T. Matsuo, M. Iwamoto and T. Ikeno, J. Am.
Chem. Soc., 1998, 120, 3903; (b) J. P. Markham, S. T. Staben
and F. D. Toste, J. Am. Chem. Soc., 2005, 127, 9708; (c) B. M.
Trost, J. Xie and N. Maulide, J. Am. Chem. Soc., 2008, 130
7258; (d) E. Gyanchander, S. Ydhyam, N. Tumma, K.
Belmore and J. K. Cha, Org. Lett., 2016, 18, 6098.
,
1
1
1
5 (a) A. Herath, B. B. Thompson and J. Montgomery, J. Am.
Chem. Soc., 2007, 129, 8712; (b) W. Li, A. Herath and J.
Montgomery, J. Am. Chem. Soc., 2009, 131, 17024; (c) H.-T.
Chang, T. T. Jayanth, C.-C. Wang and C.-H. Cheng, J. Am.
Chem. Soc., 2007, 129, 12032.
6 (a) A. Herath and J. Montgomery, J. Am. Chem. Soc., 2006,
128, 14030; (b) A. D. Jenkins, A. Herath, M. Song and J.
Montgomery, J. Am. Chem. Soc., 2011, 133, 14460; (c) C.-H.
Wei, S. Mannathan and C.-H. Cheng, Angew. Chem., Int. Ed.,
2
012, 51, 10592.
7 (a) K. Gao and N. Yoshikai, Acc. Chem. Res., 2014, 47, 1208;
b) N. Yoshikai, Bull. Chem. Soc. Jpn., 2014, 87, 843.
8 (a) J. Yang and N. Yoshikai, J. Am. Chem. Soc., 2014, 136
1
1
(
,
1
2
3
6748; (b) J. L. Wu and N. Yoshikai, Angew. Chem., Int. Ed.,
016, 55, 336; (c) J. Yan and N. Yoshikai, ACS Catal., 2016,
738; (d) J. Yang, A. Rerat, Y. J. Lim, C. Gosmini and N.
6,
Yoshikai, Angew. Chem., Int. Ed., 2017, 56, 2449.
8
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DOI: 10.1039/C8SC02074D
Table of contents entry
OH
R OH
O
H
R
cat. Co
DMSO
cat. Co
R2
R2
+
R
R2
MeCN
R1
β-alkenylation
2 examples
R1
R1
[3 + 2] annulation
3
23 examples
Cobalt catalysts promote ring-opening coupling between cyclopropanols and
unactivated alkynes to give β-alkenyl ketones or cyclopentenols with exquisite
chemoselectivity control.