NiICatalyzes the Regioselective Cross-Coupling of Alkylzinc Halides and Propargyl Bromides to Allenes

Article abstract of DOI:10.1002/chem.201603758

We describe the unprecedented formation of allenes by Ni-catalyzed cross-coupling of propargyl bromides with alkylzinc halides. The reaction regioselectivity is complementary to the previously reported formation of propargyl-coupled compounds. Experiments

Full text of DOI:10.1002/chem.201603758

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Accepted Article
Title: Ni(I) Catalyzes the Regioselective Cross-Coupling of Alkylzinc
Halides and Propargyl Bromides to Allenes
Authors: Diego J. Cardenas, Rita Soler-Yanes, Iván Arribas-Álvarez,
Manuel Guisán-Ceinos, and Elena Buñuel
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Ni(I) Catalyzes the Regioselective Cross-Coupling of Alkylzinc
Halides and Propargyl Bromides to Allenes
Rita Soler-Yanes, Iván Arribas-Álvarez, Manuel Guisán-Ceinos, Elena Buñuel, and Diego J.
Cárdenas*[a]
Abstract: We describe the unprecedented formation of allenes by
Ni-catalyzed cross-coupling of propargyl bromides with alkylzinc
halides. The reaction regioselectivity is complementary with the
previously reported formation of propargyl coupled compounds.
Experiments support the formation of Ni(I) complexes as the active
species, as well as the participation of radical intermediates. Kinetic
studies provided the following information: the reaction is first order
in the electrophile, zero-order in the nucleophile (fast
transmetalation), and one-half order relative to the metal catalyst.
cascade reactions involving the formation of two C-C bonds
within the same synthetic operation. Interestingly, in some cases,
the use of first row transition metal catalysts allow the use of
Grignard reagents as nucleophiles even in the presence of
formerly incompatible functional groups, due to the high
reactivity of certain catalytic systems.[10] Nevertheless, the use of
organozinc compounds is more convenient due to the lower
reactivity and higher compatibility of these nucleophiles with a
wide variety of functionalities. Fu has developed the Ni-
catalyzed cross coupling of propargyl halides with R2Zn or RZnX
reagents which afford the corresponding propargyl coupled
compounds.[11]
In this work, we report a detailed study on the Ni-catalyzed
cross-coupling reaction of propargyl halides with alkylzinc
reagents for the formation of allenes. This constitutes the first Ni-
catalyzed reaction for the formation of cumulenes from propargyl
electrophiles involving this metal. In addition to the study of the
reaction scope, which has resulted to be very broad,
mechanistic studies both experimental and computational, have
been performed in order to get insight into the mechanism of this
reaction. This process is complementary of the above mentioned
Fu’s reaction for the alkyl-propargyl cross-coupling, that affords
alkynes instead.[11,12]
Mechanistic studies support
a bimetallic Ni(I)-based pathway
involving fast homolytic cleavage of the C-Br bond by an alkyl-Ni(I)
complex followed by radical coordination to Ni(I) which determines
the observed regioselectivity.
Introduction
Preparation of allenes by metal-catalyzed reactions involving
propargyl derivatives containing
a
good leaving-group
constitutes one of the most convenient methods, since it
involves the concomitant formation of the allene and a new
Ni[6]
carbon-carbon bond.[1] Pd,[2] Cu,[3]
Rh,[4] Fe,[5]
and
derivatives have been used as catalysts in these reactions for
the activation of propargyl halides, esters, carbonates and
phosphonates. For cross-coupling reactions, nucleophiles can
be derived from a wide variety of main group elements (Mg, Zn,
In, B, Ti, Cu), and allow to install different kinds of fragments
(alkyl, aryl, alkenyl, etc). Preparation of chiral allenes has been
achieved by both transfer of stereochemical information from
optically pure propargyl derivatives, or by using chiral ligands.[7]
We are especially interested in the development of novel cross-
coupling reactions involving first-row transition metals for
economic and environmental reasons, and especially for the
different activation mechanisms that are being discovered during
the last years, involving radical intermediates and different
oxidation states. In this respect, we have recently reported alkyl-
alkyl,[8] and alkyl-aryl[9] Ni-catalyzed cross-coupling reactions
using alkylmagnesium reagents and highly compatible alkylzinc
halides. Intermediacy of radicals has made possible to develop
Scheme 1. Ni-catalyzed coupling reactions from propargyl bromides and
alkylzinc halides.
Results and Discussion
We initially explored the reaction between propargyl substrate
1a and (1,3-dioxolan-2-yl)ethylzinc bromide (2) in the presence
of Ni(Py)4Cl2 as precatalyst.[9b] Two possible cross-coupling
products can be obtained: allene 3a and the product exerting
from the alkylation of the carbon containing the bromide (4a).
The model reaction was performed using 3 equiv of nucleophile,
10 mol% of precatalyst, and 10 mol% of a variety of NHC,
phosphine and nitrogen-based ligands, which afforded different
yields and regioselectivities (see Supporting Information). The
best results were obtained with bipyridine and phenanthroline
derivatives. Thus, bipyridine (L1) and phenanthroline (L2)
[a]
Dr. R. Soler-Yanes, I. Arribas-Álvarez, Dr. M. Guisán-Ceinos, Dr. E.
Buñuel, Prof. D. J. Cárdenas
Departamento de Química Orgánica, Facultad de Ciencias
Universidad Autónoma de Madrid
Av. Francisco Tomás y Valiente 7, Cantoblanco,28049-Madrid,
Spain
E-mail:diego.cardenas@uam.es:
Supporting information for this article is given via a link at the end of
the document.((Please delete this text if not appropriate))
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provided exclusively the allene (Table 1, entries 1-2) while the
reaction was not fully regioselective for 2,2’-biquinoline (L3,
entry 3). The best result in terms of both yield and
regioselectivity was observed for bathophenanthroline (L4).
Substitution next to the N atoms gave reasonable yields, lower
regioselectivity, and even favored the formation of the propargyl
coupling product as the major isomer. This is the case for 6,6’-
dimethylbipyridine (L5), bathocuproine (L6), and neocuproine
(L7). Diketone L8 was totally ineffective. The use of just 5 mol%
of Ni(acac)2 provided similar yields, cleaner reactions and more
reproducible results. On the other hand, the use of 2:1 ligand to
metal ratio did not improve the results, and was also the case
when increasing the reaction temperature to 23 °C.
Table 1. Reaction outcome for bipy- and phen-type ligands.
Scheme 2. Reaction scope for different substituted aryl electrophiles.
We initially studied how the substitution of the aromatic ring of
the electrophile could affect the reaction outcome (Scheme 2).
The reaction works in the presence of
a whole variety
substituents, in moderate to excellent yields to afford allene
compounds 3a’-3i. Formation of alkyne is not observed in any
case. Especially relevant are the cross-coupling of the nitro
derivative (3e) which is not usually compatible in Ni-catalyzed
coupling reactions involving radical species, and the
compatibility of the arylchloride (3i). Alkyl-substituted alkynes
also gave the allene as the major products (Scheme 3) in
contrast to that observed in the previously reported
conditions.[10a]
Entry
Ligand
L1
3a:4a[a]
99:1
Yield (%)[b]
1
2
3
4
5
6
7
8
65
43
50
82
78
63
67
0
L2
99:1
L3
87:13
99:1
L4
L5
40:60
29:71
42:58
-
L6
L7
L8
[a] Calculated by 1H-NMR. [b] Combined isolated yields.
Therefore, we fixed 5 mol% of Ni(acac)2, 5 mol% of L4
(bathophenanthroline), and 0 °C as the optimized conditions to
study the reaction scope.[13] All reactions were monitored by TLC
and most of them get completed within 40 to 240 min.[14]
Scheme 3. Reaction outcome for alkyl-substituted alkynes. [a] Product ratio
determined by GC.[b] Product ratio determined by 1H-NMR.
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Interestingly, t-butyl substituted alkyne afforded some
propargylic coupling derivative as a minor product (3l:4l; 7.7:1)
in contrast to that observed for octyl or cyclohexyl compounds.
In addition, homocoupling of the electrophile took place leading
to a significantly lower overall yield (21%).[15] On the other hand,
primary propargyl bromide shows very low selectivity, giving rise
to a 1.3:1 mixture of 3n and 4n. It can be concluded that allene
is strongly preferred unless the electrophile is
a primary
Scheme 5. Reaction of enantio-enriched electrophile 1d.
propargyl bromide or it bears a t-butyl substituted alkyne. Finally,
some other alkylzinc bromides could be coupled with a variety of
alkyl- and aryl-substituted propargyl bromides in moderate to
excellent yields (3o-3s, Scheme 4). Interestingly, n-butylzinc
bromide and s-butylzinc bromide afforded the corresponding
derivatives 3r and 3s, respectively, without isomerisation of the
butyl moiety, in contrast to that observed in our previous work on
Ni-catalyzed cyclization-coupling reactions with Grignard
reagents.[8a] Such isomerisation requires a relatively fast –
elimination of hydrogen that does not take place in the current
process, according to the reaction outcome.
In addition, the product exerting from the coupling of the
nucleophile to TEMPO (6, 19% yield) was also observed for the
reaction of 1d. It may result from the reaction of an alkyl-Ni(I)
complex with TEMPO followed by reductive elimination.[8b]
Scheme 6. Coupling reaction in the presence of TEMPO
Experiments were conducted with the aim of determining the
oxidation state of the active species. Reaction of Ni(II)
precatalysts with alkylzinc halides leads to an overall reduction
of the metal along with the formation of formally oxidized organic
derivatives, such as alkyl homocoupling and/or the alkene
resulting from -elimination. Homocoupling compound 7 (Figure
1) was the only organic product observed when the reaction was
performed at 0 °C. No –elimination or alkane formation took
place.
Scheme 4. Reaction scope with different nucleophiles ([a]: two
diastereoisomers obtained as a 1:1 mixture, as shown by 1 H NMR, could not
be separated).
Mechanistic studies
Several reports on cross-couplings support the formation of
alkyl-Ni(I) derivatives that are able to activate primary and
secondary alkyl halides by homolytic C-X cleavage leading to
radicals and alkyl-Ni(II)-X species. Formation of Ni(I) seems to
proceed through comproportionation of Ni(II) precursors and
Ni(0) complexes formed upon reduction of the precatalyst by the
organometallic nucleophile.[8,16] In order to probe the possible
existence of intermediate radicals, enantiomerically enriched 1d
(er = 98:2) was submitted to cross-coupling with 2’. The
expected allene 3d was obtained as a racemic mixture, with a
complete loss of stereochemical information, suggesting the
intermediacy of a propargyl radical (Scheme 5). Recovery of 1d
when running the reaction at 75% conversion showed no
racemization of the starting halide.
0,035
0,03
0,025
0,02
0,015
0,01
0,005
0
-5
5
15
25
35
45
Organozinc 2' (equiv )
On the other hand, when the reactions of 1d and 1e were
performed in the presence of TEMPO, the main products were
those resulting from the coupling of propargyl radicals to
TEMPO (5d and 5e, respectively, Scheme 6).
Figure 1. Determination of the oxidation state of Ni in the catalytic system by
GC monitoring.
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Thus, different vials containing the same amount on Ni(acac)2
and bipy (L1) were treated with increasing amounts of 2’, in the
presence of 1j to mimic the actual reaction conditions. After
completion of the reactions, mixtures were analysed by GC. As it
can be seen in Figure 1, the amount of homocoupling product 7
increases upon addition of increasing amounts of organozinc
compound 2’, and stabilizes at half of the starting amount of Ni,
even after adding 40 equiv of nucleophile. These data indicate
that one-half of the starting Ni(II) gets reduced to Ni(0), which
implies formal to reduction to Ni(I). Double transmetalation from
2’ to Ni(acac)2, followed by reductive elimination to give Ni(0)
and 7, and subsequent fast comproportionation of Ni(0) with
remaining Ni(II) species would explain the formation of Ni(I)
(Scheme 7).[16c] This mechanism accounts for the formation of
sole organic oxidized compound formed in this reaction.
order reaction is dependent on the Ni concentration, and taking
into account the rate equation:
the reaction order with respect to the metal can be derived from
equation 2 by measuring the apparent rate constant at different
Ni concentrations (Figure 2). A value of a= 0.5 is obtained for the
reaction order with respect to Ni. This suggests that a dimeric
complex could be involved in the rate-limiting step. The reaction
orders contrast with those previously reported for Ni-catalyzed
alkyl-aryl couplings of aryl Grignard reagents and alkyl halides,
which show for which second order in both the nucleophile and
the catalyst, and zero order in the nucleophile.[18]
Scheme 7. Plausible pathway for Ni(I) complex generation involving
comproportionation
Surprisingly, in contrast to that observed in our previous studies
on Fe catalysis,[17] the catalytically active Ni(I) solution was EPR
silent, suggesting that no paramagnetic species were actually
present. Kinetic and computational studies provided an
explanation (see below). We performed a kinetic study on
model reaction involving 2-bromo-3-dodecine (1j) and
ethoxycarbonylethylzinc bromide (8) (Scheme 8).
Figure 2. Reaction kinetics for different Ni concentrations.
In order to get additional information we calculated the reaction
and activation steps for putative reaction steps at DFT level.
Computational studies
The results of the reduction experiments of the Ni precatalysts
with alkylzinc halide strongly supported the formation of Ni(I)
active complexes. On the other hand, Ni(I)-alkyl complexes have
been appointed as the competent species for Negishi, Kumada,
and Suzuki cross-couplings involving alkyl electrophiles.[9,17] We
chose (phen)Ni-Me (I) as a model for the active catalyst.
Interestingly, we found that I may dimerize to a diamagnetic
complex Idim exothermically (-1.4 kcal mol-1, Figure 3).[19]
Scheme 8. Conversion vs t for this model coupling reaction shows an overall
first order kinetics.
The integral method was employed, by fitting the variation of the
concentration along the whole reaction period. Overall first order
kinetics was observed (See Supporting Information). In
subsequent experiments, variation of the concentration of 1j
while keeping constant the concentration of nucleophile 8 and
catalyst, allowed determining a first order reaction with respect
to the electrophile.
On the other hand, performing the reaction under different
concentrations of the organozinc halide, the reaction coherently
showed zero order with respect to the concentration of the
nucleophile. Interestingly, the overall constant rate for the first
Figure 3. Calculated structure for Ni(I) dimer Idim.
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This complex shows a Ni-Ni bond distance of 2.29 Å, indicating
a metal-metal interaction (Van der Waals radium of Ni is 1.63 Å).
Formation of Idim explains the absence of signal when
conducting the EPR experiments on the solution of the reduced
precatalyst. Facile dissociation affords the active complex I,
which has the unpaired electron localized on Ni (spin density
calculations), in contrast to the related complexes containing tpy
or pybox previously described,[9b,17c] for which this electron
resides on the -orbitals of the ligand (see Supporting
Information). Complex I is able to readily react with the propargyl
states for the coordination of the radical to Ni(II) in III to give
diorgano-Ni(III) complexes. Interestingly, structures leading to
allenyl-Ni derivatives, and not their propargyl analogues, were
located.[20] Activation energy for coordination to Ni(II) complex III
through TSIII-IV is 17.9 kcal mol-1 (Ga = 17.0 kcal mol-1) and
leads to allene complex IV in an exothermic process (-3.6 kcal
mol-1) entropically disfavoured (G = +5.4 kcal mol-1). Alternative
coordination to Ni(I) derivative I through triplet TSI-V is far more
favorable both kinetic and thermodynamically. Thus, calculated
activation energy is 2.9 kcal mol-1 (Ga = 13.7 kcal mol-1) and the
process is highly exothermic (-58.0 kcal mol-1, (G = -11.6 kcal
mol-1). In conclusion, alkyl-Ni(I) derivative is more reactive
towards propargyl radical, and therefore formation of Ni(II)
complex V constitutes the preferred pathway. In addition,
according to kinetic data, we propose reaction of alkyl-Ni
complex I with propargyl radical as the rate limiting step.
Equilibrium between I and Idim explains the 0.5 order with
respect to Ni. No transition state could be located for the
formation of a propargyl-Ni(II) derivative instead of the allenyl-Ni
isomer. It is important to note that coordination of the radical is
slower compared to previous C-Br activation, and fixes the
regioselectivity of the reaction. Formation of relatively long-lived
propargyl radicals explains products 5 observed when running
the reaction in the presence of TEMPO (Scheme 6). Finally,
relatively fast reductive elimination would lead to the final
product.
bromide to afford a square-planar Ni(II) derivative and
a
propargyl radical in an exothermic process (-22.5 kcal mol-1,
Figure 4).
Figure 4. Calculated oxidative addition process. ZPE-corrected relative
energies (kcal mol-1) are calculated in THF (PCM) at B3LYP/6-311G(2df,2p)
(C,H,N) cc-pVTZ (Ni,Br)//B3LYP/6-31G(d) (C,H,N) LANL2DZ (Ni, Br) level.
Calculated G in gas–phase are shown in brackets.
Scheme 9. Proposed reaction pathway.
Scanning of the potential energy surface demonstrates that this
halogen abstraction takes place with no activation barrier.
Alternative activation of propargyl bromide II by halide complex
(phen)NiBr has been calculated to be endothermic (0.6 kcal mol-
1) and cannot compete with activation by I, in contrast to that
proposed for the Ni-catalyzed coupling of propargyl bromides
and bis(aryl)Zn reagents in the presence of pybox ligands.[12]
Once the electrophile has been activated, the resulting radical
may react with either the alkyl-Ni(II) complex formed in the same
reaction (III) or, alternatively, it may react with alkyl-Ni(I) species.
The latter process has been proposed for Ni-catalyzed alkyl-
alkyl cross-couplings on the basis of experimental evidence and
computational support.[18b] We initially searched for transition
Seminal studies by Kochi revealed that reductive elimination
from (alkyl)(aryl)Ni(II) complexes is difficult and may require prior
oxidation to Ni(III).[21] Alternatively, coordination of electron
deficient olefins has been also proposed to induce this
process.[22] At this stage we cannot propose
a detailed
mechanism, but fast reductive elimination is compatible with the
experimental evidence. Complex III may be involved in the
formation of Ni(I) promoting, participating or even after reductive
elimination. Regeneration of the active species I takes place by
fast transmetalation with the alkylzinc halide, in accord with the
zero-order found for the organozinc. In addition, our previous
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[2]
Pd catalyzed reactions: a) A review: S. Ma, Eur. J. Org. Chem. 2004,
1175-1183. b) T. Mandai, Handbook of Organopalladium Chemistry for
Organic Synthesis 2002, 2, 1827-1832. c) Y. Yang, K. J. Szabó, J. Org.
Chem. 2016, 81, 250-255. d) Q.-H. Li, J.-Y. Jeng, H.-M. Gau, Eur. J.
Org. Chem. 2014, 7916-7923. e) Y. Wang, W. Zhang, S. Ma, J. Am.
Chem. Soc. 2013, 135, 11517-11520. f) From bromodienes: Z. Wu, F.
Berhal, M. Zhao, Z. Zhang, T. Ayad, V. Ratovelomanana-Vidal, ACS
Catal. 2014, 4, 44-48. g) D. Girard, S. Broussous, O. Provot, J. D. Brion,
M. Alami, Tetrahedron Lett. 2007, 48, 6022–6026. h) G. A. Molander, E.
M. Sommers, S. R. Baker, J. Org. Chem. 2006, 71, 1563-1568. i) M.
Yoshida, T. Okada, K. Shishido, Tetrahedron 2007, 63, 6996-6998. j) M.
Yoshida, T. Gotou, M. Ihara, Tetrahedron Lett. 2004, 45, 5573-5576.
Cu-catalyzed reactions: a) H. Li, D. Grassi, L. Guénée, T. Bürgi, A.
Alexakis, Chem. Eur. J. 2014, 20, 16694-16706. b) H. Li, D. Müller, L.
Guénée, A. Alexakis, Org. Lett. 2012, 14, 5880-5883. c) M. R. Uehling,
S. T. Marionni, G. Lalic, Org. Lett. 2012, 14, 362-365. d) H. Ohmiya, U.
Yokobori, Y. Makida, M. Sawamura, Org. Lett., 2011, 13, 6312-6315 e)
C. K. Hazra, M. Oestreich, Org. Lett. 2012, 14, 4010-4013. f) U.
Yokobori, H. Ohmiya, M. Sawamura, Organometallics 2012, 31, 7909-
7913. g) Coupling involving C-Si bond formation: D. J. Vyas, C. K.
Hazra, M. Oestreich, Org. Lett., 2011, 13, 4462-4465. h) J. Li, W. Kong,
C. Fu, S. Ma, J. Org. Chem. 2009, 74, 5104-5106. i) H. Ito, Y. Sasaki,
M. Sawamura, J. Am. Chem. Soc. 2008, 130, 15774-15775.
Substitution reactions involving stoichiometric amounts of cuprates can
be found in ref. [1].
work on a related system afforded a calculated low activation
energy.[10]
To sum up, stereochemical, titration and kinetic experiments,
along with computational data lead us to propose the reaction
pathway shown in Scheme 9. Precatalyst is reduced to the
active alkyl-Ni(I) species by the nucleophile, which dimerizes to
a diamagnetic complex. The subsequent extremely fast bromide
abstraction is followed by rate-determining radical coordination
to dimeric Ni(I) species, which constitutes the catalyst resting
state. This process also fixes the observed regioselectivity. Fast
reductive elimination affords the coupling product, with the
tentative participation of previously formed (alkyl)Ni(II)Br
intermediate. Two different Ni(I) complexes are formed: the
active alkyl-Ni(I) and Ni(I)Br, which is converted into the active
species by transmetalation, and restarts the cycle.
[3]
Conclusions
In conclusion, we have developed an unprecedented Ni-
catalyzed cross-coupling reaction of propargyl halides leading to
allenes using alkylzinc reagents as nucleophiles. The reaction
shows broad scope and functional group compatibility, and it is
complementary with previously reported work. The reaction
mechanism has been studied by means of experimental and
computational tools. The reaction shows first order in the
electrophile, zero order in the nucleophile, and half order with
respect to the catalyst. It seems to be catalyzed by Ni(I)
complexes and to involve propargyl radicals whose coordination
to Ni(I) determines the regiochemical outcome of the reaction. In
contrast to other related reactions, nucleophile concentration is
[4]
Rh-catalyzed reactions: a) J. Ruchti, E. M. Carreira, Org. Lett. 2016, 18,
2174-2176. b) H. Ohmiya, H. Ito, M. Sawamura, Org. Lett. 2009,11,
5618-5620. c) S. Wu, X. Huang, W. Wu, P. Li, C. Fu, S. Ma, Nat.
Commun. 2015, 6, 7946-7954. c) T. Miura, M. Shimada, S.-Y. Ku, T.
Tamai, M. Murakami, Angew. Chem. Int. Ed. 2007, 46, 7101-7103. d) T.
Miura, M. Shimada, P. de Mendoza, C. Deutsch, N. Krause, M.
Murakami, J. Org. Chem. 2009, 74, 6050-6054.
[5]
[6]
[7]
[8]
a) S. N. Kessler, J.-E. Bäckvall, Angew. Chem. Int. Ed. 2016, 55, 3734-
3738. b) A. Fürstner, M. Méndez, Angew. Chem. Int. Ed. 2003, 42,
5355-5357.
a) Q.-H. Li, J.-W. Liao, Y.-L. Huang, R.-T. Chiang, H.-M. Gau, Org.
Biomol. Chem. 2014, 12, 7634-7642. b) Q.-H. Li, H.-M. Gau, Synlett
2012, 23, 747-750.
kinetically irrelevant, pointing to
a
fast irreversible
transmetalation step. Data support the formation of a Ni(I) dimer
as the catalyst resting state. The involvement of radicals opens
the possibility to develop new cascade processes, and the key
coordination the former to Ni suggests that enantioselective
processes may be discovered for this kind of systems.
Stereoselective synthesis of allenes involving organometallic reagents:
A. H. Cherney, N. T. Kadunce, S. E. Reisman, Chem. Rev. 2015, 115,
9587-9652.
a) M. Guisán-Ceinos, R. Soler-Yanes, D. Collado-Sanz, V. B. Phapale,
E. Buñuel, D. J. Cárdenas, Chem. Eur. J. 2013, 19, 8405-8410. b) V. B.
Phapale, E. Buñuel, M. García-Iglesias, D. J. Cárdenas, Angew. Chem.
Int. Ed. 2007, 46, 8790-8795. c) R. Soler-Yanes, M. Guisán-Ceinos, E.
Buñuel, D. J. Cárdenas, Eur. J.Org. Chem. 2014, 6625-6629. d) V. B.
Phapale, D. J. Cárdenas, Chem. Soc. Rev. 2009, 38, 1598-1607.
V. B. Phapale, M. Guisán-Ceinos, E. Buñuel, D. J. Cárdenas, Chem.
Eur. J. 2009, 15, 12681-12688.
Acknowledgements
This work was supported by the MINECO (grant CTQ2013-
42806-R, and a fellowship to R. S.-Y.). We thank the UAM for a
fellowship to M. G.-C. Dr. F. Tato and D. Collado-Sanz are
gratefully acknowledged for helpful suggestions. We thank the
Centro de Computación Científica-UAM for computation time
and Gema Caballero for some experiments.
[9]
[10] a) O. Vechorkin, X. Hu, Angew. Chem. Int. Ed. 2009, 48, 2937-2940. b)
O. Vechorkin, A. Godinat, R. Scopelliti, X. Hu, Angew. Chem. Int. Ed.
2011, 50, 11777-11781. c) P. M. P. Garcia, T. Di Franco, A. Epenoy, R.
Scopelliti, X. Hu, ACS Catal. 2016, 6, 258-261. d) J. Breitenfeld, O.
Vechorkin, C. Corminboeuf, R. Scopelliti, X. Hu, Organometallics 2010,
29, 3686-3689. e) X. Hu, Chem. Sci. 2011, 2, 1867-886.
Keywords: Nickel • Cross-coupling • Allenes • Reaction
mechanisms • Density functional calculations
[11] a) S. W. Smith, G. C. Fu, Angew. Chem. Int. Ed. 2008, 47, 9334-9336.
b) S. W. Smith, G. C. Fu, J. Am. Chem. Soc. 2008, 130, 12645-12647.
c) A. J. Oelke, J. Sun, G. C. Fu, J. Am. Chem. Soc. 2012, 134, 2966-
2969.
[1]
a) R. K. Neff, D. E. Frantz, ACS Catal. 2014, 4, 519-528. b) S. Yu, S.
Ma, Chem. Commun. 2011, 47, 5384-5418. c) J. Ye, S. Ma, Org. Chem.
Front. 2014, 1, 1210-1224. d) A. Hoffmann-Röder, N. Krause, Angew.
Chem. Int. Ed. 2004, 43, 1196-1216. e) K. M. Brummond, J. E.
DeForrest, Synthesis 2007,795-818. f) M. Ogasawara, Tetrahedron:
Asymmetry 2009, 20, 259-271.
[12] N. D. Schley, G. C. Fu, J. Am. Chem. Soc. 2014, 136, 16588-593.
[13] Addition of just 1.5 equiv of organozinc halide 8 in the reaction with 1j
afforded a slightly lower yield compared to the use of the standard 3
equiv (76% and 86%, respectively).
[14] Reactions involving CF3(C6H4)-substituted propargyl bromide took
longer to complete and were performed overnight.
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[15] TMS-substituted propargyl bromide gave homocoupling of the
electrophile (over 80% yield).
[18] a) J. Breitenfeld, M. D. Wodrich, X. Hu, Organometallics 2014, 33,
5708-5715. b) J. Breitenfeld, J. Ruiz, M. D. Wodrich, X. Hu, J. Am.
Chem. Soc. 2013, 135, 12004-12012.
[16] Mechanistic aspects for Ni-catalyzed Suzuki- and Negishi-type alkyl-
alkyl couplings: a) M. S. Cheung, F. K. Sheong, T. D. Marder, Z. Lin, Z.
Chem. Eur. J. 2015, 21, 7480-7488. Suzuki-type: b) Z. Li, Y.-Y. Jiang, Y.
Fu, Chem. Eur. J. 2012, 18, 4345-4357. Nesghisi-type: c) G. D. Jones,
J. L. Martin, C. McFarland, O. R. Allen, R. E. Hall, A. D. Haley, R. J.
Brandon, T. Konovalova, P. J. Desrochers, P. Pulay, D. A. Vicic, J. Am.
Chem. Soc. 2006, 128, 13175-13183; d) X. Lin, D. L. Phillips, J. Org.
Chem. 2008, 73, 3680-3688. e) X. Lin, J. Sun, Y. Xi, D. Lin,
Organometallics 2011, 30, 3284-3292.
[19] Complexes containing N-Ni bonds and redox-active ligands.: a) Y.-Y.
Zhou, D. R. Hartline, T. J. Steiman, P. E. Fanwick, C. Uyeda, Inorg.
Chem. 2014, 53, 11770-11777. B) C. Uyeda, T. J. Steiman, S. Pal,
Synlett 2016, 27, 814-820.
[20] In fact, propargyl-Ni(III) complexes were also located. They may be
formed by isomerisation form allenyl-Ni derivatives by 1,3 Ni shift.
Nevertheless, but they could be disregarded according to the faster
coordination of radicals to Ni(I) derivatives.
[17] M. Guisán-Ceinos, F. Tato, E. Buñuel, P. Calle, D. J. Cárdenas, Chem.
Sci. 2013, 4, 1098-1104.
[21] D. G. Morrell, J. K. Kochi, J. Am. Chem. Soc., 1975, 72, 7262-7270.
[22] R. Giovannini, N. Stüdemnann, A. Devasagayaraj, G. Dussin, P.
Knochel, J. Org. Chem., 1999, 64, 3544-3553.
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Title
Text for Table of Contents: Coupling of alkyl bromides and alkylzinc reagents to
allenes shows excellent complementary regioselectivity, is catalyzed by Ni(I)
complexes, and involves radical intermediates
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