Synthesis and Functionalization of Allenes by Direct Pd-Catalyzed Organolithium Cross-Coupling

Article abstract of DOI:10.1002/anie.201913132

A palladium-catalyzed cross-coupling between in situ generated allenyl/propargyl-lithium species and aryl bromides to yield highly functionalized allenes is reported. The direct and selective formation of allenic products preventing the corresponding isomeric propargylic product is accomplished by the choice of SPhos or XPhos based Pd catalysts. The methodology avoids the prior transmetalation to other transition metals or reverse approaches that required prefunctionalization of substrates with leaving groups, resulting in a fast and efficient approach for the synthesis of tri- and tetrasubstituted allenes. Experimental and theoretical studies on the mechanism show catalyst control of selectivity in this allene formation.

Full text of DOI:10.1002/anie.201913132

A Journal of the Gesellschaft Deutscher Chemiker
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Accepted Article
Title: Synthesis and Functionalization of Allenes by Direct Pd-
Catalyzed Organolithium Cross-Coupling
Authors: Jaime Mateos-Gil, Mondal Anirban, Marta Castiñeira Reis,
and Ben Lucas Feringa
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To be cited as: Angew. Chem. Int. Ed. 10.1002/anie.201913132
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10.1002/anie.201913132
Angewandte Chemie International Edition
RESEARCH ARTICLE
Synthesis and Functionalization of Allenes by Direct Pd-
Catalyzed Organolithium Cross-Coupling
Jaime Mateos-Gil,+ Anirban Mondal,+ Marta Castiñeira Reis and Ben L. Feringa*
Abstract: A palladium-catalyzed cross-coupling between in situ
generated allenyl/propargyl-lithium species and aryl bromides to yield
highly functionalized allenes is reported. The direct and selective
formation of allenic products preventing the corresponding isomeric
propargylic product is accomplished by the choice of SPhos or XPhos
based Pd catalysts. The methodology avoids the prior transmetalation
to other transition metals or reverse approaches that required
prefunctionalization of substrates with leaving groups, resulting in a
fast and efficient approach for the synthesis of tri- and tetrasubstituted
allenes. Experimental and theoretical studies on the mechanism show
catalyst control of selectivity in this allene formation.
their use as nucleophiles in cross-coupling transformations,
avoiding prior substrate derivatization, have seen limited
explorations (Scheme 1). Since the initial work of Vermeer,[12a] the
use of propargyl metal species in cross-coupling has been nearly
restricted to the use of indium by Lee et al.[13a,c] and the seminal
works on propargyl/allenylzinc derivatives by Ma et al.[14a,b,d,e]
Albeit less explored, the use of allenylstannanes[12b] and the
elegant work on the use of allenylboranes by Fürstner[12e], are to
the best of our knowledge, the few cases in the direct application
of both allenyl and propargylmetal species in cross-coupling
reactions.
Recent advances in the use of organolithium compounds[15]
have revealed that these cheap and widely available reagents
allow for fast and selective protocols in cross-coupling
methodologies. In our efforts to exploit and extend the simplicity
and versatility of organolithium reagents in cross-coupling
transformations,[16] we studied the feasibility of carrying out the
direct lithiation and consecutive cross-coupling reaction of allenes
and propargylic species with ArBr. In particular, we envisioned the
direct synthesis of tri- and tetrasubstituted allenes in a single step,
using substrates without any other prefunctionalization or
avoiding the commonly required transmetalation step to other
transition metals (Scheme 1c).
Introduction
Allenes[1] represent a highly versatile functionality exhibiting
two consecutive orthogonal double bonds with a central sp
hybridized carbon atom. These structural features allow allenes
to display axial chirality, arousing a growing interest in a variety of
applications including chiroptical materials,[2] chiral ligands[3] and
pharmaceutically active compounds.[4] Furthermore, allenes
exhibit fascinating reactivity in cyclization and cycloaddition
reactions[5] and act as
a surrogate in allylic substitution
transformations[6] yielding complex chemical structures.
Such outstanding properties have encouraged chemists to
develop more efficient methodologies that allow for convenient
synthesis and functionalization of allenes.[1,7] Traditional methods
based on 1,2-elimination of functionalized alkenes[8] or prototropic
rearrangement of alkynes,[9] that require specifically activated
structures, have largely been displaced by the more
straightforward metal catalyzed SN2’ reactions of electrophilic
propargyl derivatives (R-Cl, R-Br, R-OCO2R’, R-OPO(OR’)2, R-
OSO2R, etc.) with organometallic reagents.[7b] Moreover, some
examples based on Heck type couplings[10] and other prominent
enantiospecific and enantioselective approaches based on metal
catalyzed transformations of alkynyl derivatives and enynes[4b,11]
have been recently reported.
Reverse approaches that involve the direct metalation of
allenes[12] or propargylic substrates[13],[14]are highly attractive but
[*]
Dr. J. Mateos-Gil,[+] A. Mondal,[+] Dr. Marta Castiñeira Reis and
Prof. Dr. B. L. Feringa
Stratingh Institute for Chemistry
University of Groningen
Nijenborgh4, 9747AG Groningen (The Netherlands)
E-mail:b.l.feringa@rug.nl
Scheme 1. State of the art in the arylation of allenyl/propargylmetal species.
[+]
These authors contributed equally to this work
Results and Discussion
Supporting information for this article is given via a link at the end of
the document.
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First, we addressed the direct arylation of allene 1a, which
is not prone to isomerization, using tBuLi as lithiation agent while
screening different palladium catalysts for the subsequent cross-
coupling with p-bromoanisole 2a (Table 1). In toluene at 40°C
(1h), the use of Pd(dba)2 and various bulky biarylphosphine
ligands (Table 1, entries 3-7) was shown to be more efficient in
the formation of tetrasubstituted allene 3a than Pd(PtBu3)2 or Pd-
PEPPSI-iPent (Table 1, entry 1 and 2), in sharp contrast with the
excellent performance demonstrated in other organolithium
cross-coupling reactions.[16a] The choice of SPhos as ligand
(Table 1, entry 4) allowed the isolation of 3a in 85% yield.
p-OTBDMS were tolerated, furnishing the corresponding
tetrasubstituted allenes 3h-3m with good to high yields.
Substrates substituted at the ortho and meta positions afforded
the corresponding products 3n and 3g in moderate yields. Finally,
the optimized conditions could also be extended to the use of
alkenyl bromides, successfully obtaining product 3l from the
reaction with 1-bromocyclohexene in excellent yield (90%).
Table 1. Screening of conditions for the direct arylation of allenyllithium species.
Entry
[Pd] cat. (mol %)
Conv(%)[a]
3a (%)[a]
1
2
3
4
5
6
7
Pd(PtBu3)2
n.c.
n.c.
93
-
Pd-PEPPSI iPent
-
Pd(dba)2 (5)-SPhos (10)
Pd(dba)2 (5)-JohnPhos (10)
Pd(dba)2 (5)-XPhos (10)
Pd(dba)2 (5)-CPhos (10)
Pd(dba)2 (5)-DavePhos (10)
85[b]
15
69
71
55
25
69
Scheme 2. Scope of the arylation of trisubstituted allenes with different aryl
bromides. Reaction conditions: 1 (0.65 mmol) and tBuLi (0.8 mmol), reacted in
THF at -78 °C and then diluted at r.t. with toluene to a final concentration of 0.35
M. Slow addition of this solution for 1h to a solution of Pd(dba)2 (5 mol%), SPhos
(10 mol%) and 2 (0.5 mmol) in toluene (0.75 mL). [a]Reaction performed at 60
oC.
71
55
Reaction conditions: 1a (0.39 mmol) and tBuLi (0.59 mmol), reacted in THF
at -78 °C and then diluted at r.t. with toluene to a final concentration of 0.35 M.
Slow addition of this solution for 1h to a solution of Pd catalyst (5 mol %) and 2a
(0.3 mmol) in toluene (0.5 mL). [a] Determined by 1H-NMR using 1,1’,2,2’-
tetrachloroethane as internal standard. [b] Isolated yield.
As indicated earlier, the use of propargyl derivatives (i.e. R-Br, R-
Cl, R-OCO2Me, -RPO(OR)2, etc.) with organometallic reagents
has been established as a general tool for the synthesis of
allenes, in contrast to the few examples based on the reaction of
alkynylmetal species with organic halides or pseudohalides. This
latter approach, as proposed in Scheme 1c, may represent a
more straightforward and atom efficient pathway since it implies
the direct use of unfunctionalized allenes and propargylic starting
materials. However, the control of reactivity and selectivity of this
metalated species remains very challenging. The groups of Ma
and Vermeer[12a,14a,b,d,e] reported that it was not possible to directly
react propargyllithium species with aryl bromides or iodides in the
presence of Pd catalysts, requiring a transmetalation step to other
transition metals to yield the corresponding allenes. These
difficulties may be due to the interesting but complex chemistry of
propargyllithium species: the presence of mono- and bislithiated
Having established the optimal conditions, we evaluated the
scope of the reaction with different trisubstituted allenes and aryl
bromides (Scheme 2). The switch of the cyclic motif of allene 1a
to other aliphatic substituents (R1 and R2) did not affect the
reactivity and selectivity, yielding products 3b and 3c in 91% and
74% respectively. Furthermore, different substituents were
evaluated in the aromatic moiety at R3 demonstrating also a
remarkable performance under the reaction conditions even in the
case of highly hindered allenes (3d), as well as bearing electron-
donating (3e) or electron-withdrawing groups (3f). A series of aryl
bromides were also tested with allenes 1a and 1b. Functionalities
including heteroaryl, extended aromatic systems, p-Cl, m-NMe2 or
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species and coexistence of up to four different isomeric forms
derived from the equilibrium and 1,3-H,Li rearrangement of
propargyl/allenylmetal species (Figure 1).[17] These features make
extremely difficult to control and predict the reactivity and
selectivity of these organometallic species, being highly
dependent on the lithiation conditions,[14b,d] temperature, nature of
the solvent, presence of additives, nature of the electrophile[18] or
catalyst choice.[19],[20] In a similar manner Knochel et al. reported
the necessity of the use of mixed Li/Zn bases in order to control
the selective formation of allenic product in silylated alkynes.[13b]
advances in the direct and fast coupling of organolithium reagents
with novel Pd complexes,[16a-c,16e-j] we attempted the direct
coupling of propargyllithium species to yield trisubstituted allenes.
Among the different lithiation conditions tested on 1-phenyl-1-
butyne 4a (Table 2), we found the use of tBuLi or nBuLi at -78 °C
to be the most efficient and reproducible.[21] A mixture of 4a-
Li/4a’-Li in a 65/35 ratio was obtained[22] and subsequently
reacted with 2a in the presence of different Pd catalysts. Similar
to the reaction of the formation of tetrasubstituted allenes (Table
1), biarylphosphines SPhos and XPhos exhibited a better
performance (Table 2, entries 3 and 5), yielding the corresponding
allenyl and propargyl products 5a and 6a in a similar ratio to the
starting organolithium reagent mixture (2:1). Other ligands as
CPhos and DavePhos furnished a complex mixture of byproducts
derived from 4a as well as dehalogenation of 2a (entries 6 and 7).
Much to our surprise, the moderate selectivity achieved by using
Pd(dba)2/XPhos as catalyst (62:38) was improved when XPhos-
Pd-G2 precatalyst was used, affording product 5a (Table 2, entry
8) with excellent conversion (95%) and selectivity (>95:5). No
isomers derived from the 1,3-H,Li rearrangement (Figure 1) were
observed.[14b]
Figure 1. Possible mono- and bislithiated species that can be identified in the
equilibrium of propargyl- and allenyllithium species.
Table 2.Screening of conditions for the direct synthesis of arylated allenes from
alkynes.
entry
[Pd] cat. (mol %)
Conv (%)[a]
n.c.
5a:6a (%)[a]
1
2
3
4
5
6
7
8
Pd(PtBu3)2
-
Pd-PEPPSI iPent
n.c.
-
Pd(dba)2(5)-SPhos (10)
Pd(dba)2(5)-JohnPhos (10)
Pd(dba)2(5)-XPhos (10)
Pd(dba)2(5)-CPhos (10)
Pd(dba)2(5)-DavePhos (10)
XPhos-Pd-G2
50
32:18
n.c.
-
95
62:38
n.c.
-
n.c.
-
Scheme 3. Reaction conditions: 4 (0.65 mmol) and tBuLi (0.8 mmol), reacted in
THF at -78 °C and then diluted at r.t. with toluene to a final concentration of 0.25
M. Slow addition of this solution for 1.5h to a solution of XPhos-Pd-G2 (5
mol%)and 2 (0.5 mmol) in toluene (0.75 mL). [a]Reaction performed at 60 oC.
[b]Combined yield for 5:6 mixture.
>95
>95:5
Reaction conditions: 1a (0.39 mmol) and tBuLi (0.59 mmol), reacted in THF at -
78 °C and then diluted at r.t. with toluene to a final concentration of 0.25 M. Slow
addition of this solution for 1.5 h to a solution of Pd catalyst (5 mol %) and 2a
(0.3 mmol) in toluene (0.5 mL). [a] Determined by NMR using 1,1’,2,2’-
tetrachloroethane as internal standard.
This remarkable selectivity led us to extend the conditions to
different alkynes and aryl bromides in the synthesis of
trisubstituted allenes from propargyllithium reagents. As depicted
in Scheme 3, alkynes bearing different aliphatic chains or
Despite the major challenge associated with the use of these
particular organolithium species, but encouraged by our recent
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aromatic substituents were tolerated, preserving the selective
formation of the allene derivative, providing products 5a-5i in good
to high yields.[23] Importantly, aryl bromides functionalized with
electron-withdrawing, electron-donating groups or extended
aromatic systems did not influence significantly the conversion or
selectivity of the reaction (5a, 5d-5f). Protected alcohol and
aldehyde functionalities were also tolerated under the optimized
conditions with no observable cleavage of the protecting groups
(5h and 5i). Curious about the softer nucleophilic character of 4-
Li/4’-Li we wondered if pinacol boronic ester (Bpin), that is prone
to react with organolithium reagents,[24] may remain unaltered
during the reaction. We were rewarded with an excellent reactivity
and chemoselectivity towards organolithium cross-coupling,
without formation of any side product derived from Suzuki type
coupling or reaction of the organolithium with the boronic ester.
Moreover, the presence of Bpin induced a notably electronic
effect, shifting the formation of products 5l:6l to a 1:2.5 ratio.
When the more hindered o-bromoanisole was examined at 40°C,
it was found to be unreactive, requiring 60°C to reach full
conversion. At this temperature, the product ratio 5j:6j drops to
1:1, revealing a significant influence of the enhanced steric
hindrance of the ArBr 2 towards the selectivity of the reaction.[25]
In the search for evidences indicating if the equilibrium between
4-Li and 4’-Li may affect the outcome of the reaction we
evaluated the reactivity of the TMS-protected prop-2-yn-1-
ylbenzene, the lithiation of which was reported to not provide
formation of allenyllithium species.[13b] Under the standard
reaction conditions a remarkable 2:1 ratio of products 5k:6k was
found, revealing the primordial role of the catalyst in governing the
selectivity, with room for further improvement by careful selection
of ligand.
equilibrium, undergo the corresponding reductive elimination to
yield products 5 or 6. According to this catalytic cycle, different
hypothesis about the fundamental aspects that drive the
selectivity of the reaction may be proposed. Our initial studies on
the lithiation of substrate 4a revealed the formation of allenic 4-Li
°
°
as major species at low temperature (-78 C to -20 C) and the
equilibrium shifted at r.t. to a ratio (65:35) of 4-Li/4’-Li (Scheme
5). In view of the experimental results in the cross-coupling, that
reveal a high selectivity in the formation of 5, an initial hypothesis
considering that both species transmetalate to II, followed by a
faster reductive elimination that yields products 5 or 6, with no
effect of the Pd catalyst in the selectivity, might be discarded. In
the same line, the possibility of an exclusive transmetalation of
allenyllithium species 4-Li that push the equilibrium 4-Li/4’-Li
seems also to be not feasible (vide infra) (Table 2, entry 5 and 8).
To ensure that the initial ratio of the allenyl/propargyllithium
reagent is not ruling the selectivity in this transformation and that
the catalyst is mainly responsible for the selectivity, an experiment
under stoichiometric conditions was performed, making the
equilibrium mixture of 4-Li and 4’Li (65:35) to react with a slight
excess of ArPd(XPhos)Br II (Scheme 5). Under these conditions,
that allow both lithiated species 4-Li and 4’-Li to be immediately
transmetalated and yield 5 or 6 after reductive elimination, only
formation of the allenic product 5 was observed.
Scheme 5.Reaction of organolithium species with an excess of the oxidative
additioncomplex.
To exclude that the fast equilibrium 4-Li/4’-Li is not responsible
for this result, via exclusive transmetallation of the allenic species,
the analogous reaction using organozinc reagents, which exhibit
a fixed 4-Zn/4’-Zn ratio, was performed (Scheme 6). A mixture of
4-Zn/4’-Zn (in a 45:55 ratio) was reacted with 2a providing the
formation of 5 and 6 in 82:18 (with Pd(dba)2-XPhos) and >95:5
(with XPhos-G2-Pd) ratios, respectively. These experiments
accompanied by the results using silylated alkyne (Scheme 3, 5k)
highlights the key role of the catalyst, excluding the initial nature
of the lithiated nucleophile as the determining factor governing the
selectivity towards allene 5 or propargyl product 6.
Scheme 4. Proposed catalytic cycle for the Pd-catalyzed cross-coupling
reaction of allenyl-/propargyllithium species with aryl bromides.
In the proposed catalytic cycle depicted in Scheme 4 the lithiated
species 4a-Li and 4a’-Li, which are in equilibrium, transmetalate
to ArPdLBr II, forming the corresponding allenyl-PdL-Ar IIIA and
propargyl-PdL-Ar IIIB. These intermediates III, being also in
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Scheme 6. Comparison of the effect of catalyst in the reactivity and selectivity
of the reaction of different propargylmetal (M: Li, Zn) species.
Intrigued by the remarkable influence of the use of the precatalyst
XPhos-Pd-G2 instead of Pd(dba)2/XPhos system on the
selectivity for 5:6 (Table 2, entry 5 and 8), a model reaction was
performed under the optimized conditions using a 10 mol% of
(dba) as additive in order to find out its influence in the reaction
outcome (See SI, S19). A significant effect was found in the
presence of dba, observing a major decrease in the reactivity
(from 95% to 45% conversion) and the selectivity (from 95:5 to
65:35).[26] As indicated above, a similar effect in the selectivity was
also found when using the corresponding 4-Zn/4’-Zn as
nucleophile under the presence of dba. This result highlights
again the importance of the Pd catalyst and the non-spectator role
of dba. The effect of dba and other related ligands in Pd catalyzed
transformations is well established, acting as a  ligand that
diminishes the rate of oxidative addition to Pd complexes and may
accelerate the reductive elimination.[27] Our findings disclose not
only an effect on the reactivity but also on the selectivity of the
reaction, suggesting the presence of Pd(XPhos)(dba) or related
species that may favor the formation of the propargylic product 6
by accelerating the reductive elimination in the formation of the
Csp2-Csp3 and/or modifying the equilibrium IIIA-IIIB.[28] More
comprehensive studies (beyond the scope of this work) to unveil
the actual role of dba and species that can be formed in this
specific reaction are warranted.
Figure 2. Energy profiles for the evolution of species IIIA and IIIB. The energies
reported are relative Gibbs free energies, they have been obtained at the
M06L/def2svp[29] computational level, at 298 K and 1atm.
The described novel protocols offer a unique way for the synthesis
of tri- and tetrasubstituted allenes without prior derivatization or
transmetalation of starting materials, by means of the simple
lithiation of unfunctionalized alkynes and allenes and consecutive
Pd catalysed cross-coupling reaction with aryl bromides. To show
the versatility of these new coupling methods, the two optimized
reactions were performed sequentially even on a larger scale (4.0
mmol), allowing the synthesis of the tetrasubstituted allenes 7a-d
endorsed with three different aryl moieties directly from simple
alkynes 4a and 4b (Scheme 7a). In order to minimize risks, the
n
sequential protocol was performed by using BuLi, avoiding the
t
use of large amounts BuLi. In addition diversification of the
synthesized allenes was also carried out. Tetrasubstituted allenes
3b and 3e were converted into iodoindenes 8a-b in high yields
(Scheme 7b),[30] providing in this way an appealing scaffold
present in intermediates and structures with potential biological
activity.[31] We also exploited the versatility of Cu catalyzed
hydroboration of unsaturated bonds on trisubstituted allene 5b.
While the hydroboration of mono and disubstituted allenes is well
established,[32] tri- and tetrasubstituted allenes are still
unexplored, mainly because of selectivity issues due to the
possible formation of vinylboronate and allylboronate products
and their corresponding regio- and stereoisomers. By suitable
choice of ligand, we were delighted to establish the regio- and
stereoselective formation of the vinylboronate 9 in the presence
of CuCl/PPh3 as catalyst, representing a novel regio- and
stereoselective hydroborylation of trisubstituted allenes. Finally, 9
was reacted with thienyllithium to furnish product 10 in high yields
through an organoborate migratory insertion,[33,34] providing an
easy strategy for the synthesis of functionalized 1,1-
diarylmethanes.
To corroborate these experimental findings and provide insight
how the Pd catalyst determines the selectivity of the reaction,
computational studies were performed. Calculations revealed
close values for the corresponding energies of IIIA and IIIB, being
IIIA slightly more stable than IIIB. The energy penalties for the
evolution of these two intermediates through a reductive
elimination is, as expected, significantly different. Thus, the
formation of the allenic species 5 involves a barrier of only 8.22
kcal/mol whereas for the formation of 6 involves an energy penalty
of more than 16 kcal/mol needs to be overcome (Figure 2). The
energy profile found for the evolution of these two species (IIIA
and IIIB) is in agreement with the experimental evidence
previously described (for further details on the mechanistic
exploration, see SI).
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Experimental Section
Preparation of allenyl lithium solution
In a dry Schlenk flask, under inert atmosphere, allene 1 or alkyne 4 (0.65
mmol) were dissolved in 0.5 mL of dry THF and cooled to -78 °C, followed
by dropwise addition of tBuLi (0.47 mL of a 1.7 M solution in pentane). The
mixture was stirred at this temperature during 30 or 90 min., and
subsequently the temperature was allowed to reach r.t. during another 30
min. The mixture was then diluted with toluene (0.6-0.7 mL) to provide a
0.35 M (for 1-Li) or 0.25 M (for 4-Li) solution of the freshly prepared
organolithium reagent.
Synthesis of tri- and tetrasubstituted allenes
In a dry Schlenk flask, under inert atmosphere, Pd(dba)2 (0.025 mmol, 14.4
mg) and SPhos (0.05 mmol, 20.5 mg) or XPhos-Pd G2 (0.025 mmol, 19.7
mg) were stirred in toluene (0.75 mL) at 40 °C for about 15 min. followed
by the addition of the aryl bromide 2 (0.5 mmol). The solution of the
°
°
prepared organolithium was then slowly added at 40 C or 60 C) during
the indicated time using a syringe pump. After the addition was completed,
a saturated aqueous solution of NH4Cl was added and the mixture was
extracted with AcOEt. The organic phase was collected, dry over Na2SO4
and the solvent evaporated under reduced pressure to yield the crude
product 3 or 5 which were purified by column chromatography.
Acknowledgements
Financial support from The Netherlands Organization for
Scientific Research (NWO-CW, NSF program) is gratefully
aknowdleged. MCR thanks the Centro de Supercomputacion de
Galicia (CESGA) for the free allocation of computational
resources and to the Xunta de Galicia (Galicia, Spain) for the
financial support through the ED481B-Axudas de apoio á etapa
de formación posdoutoral (modalidade A) fellowhip.
Scheme 7. a) Synthesis of tetrasubstituted allenes 7 from unfunctionalized
alkyne 4. b) and c) Synthetic application of tri- and tetra-substituted allenes
prepared through the described Pd catalyzed organolithium cross-coupling.
Conclusion
In summary, a Pd-catalyzed methodology for the synthesis of tri-
and tetrasubstituted allenes by direct lithiation/cross-coupling
reaction is reported. The direct metalation of allenes allows its
arylation with good to high yields with a broad range of aryl
bromides. Lithiation of suitable alkynes at the propargylic position
has also been exploited in order to accomplish the selective
synthesis of trisubstituted allenes in a simple way, with no
necessity of prior formation of transition metal reagents. The
question on the determining factors governing the selectivity of
this transformation with respect to the formation of allenic and
propargylic products has also been addressed. Computational
and experimental studies have been conducted, revealing a
dynamic kinetic resolution process between the intermediates IIIA
and IIIB with the formation of product 5 as the more favored
pathway. In specific cases, when strong steric and electronic
effects are involved, the selectivity is decreased. An interesting
role of dba has been found, demonstrating to not be a spectator
in the reaction, modifying both reactivity and selectivity of the
transformation. The described protocols provide a new and
efficient way of preparing tri- and tetrasubstituted allenes directly
from readily available starting materials under mild conditions,
allowing subsequent diversification to versatile building blocks as
iodoindenes or vinylboronates.
Keywords: allenes•alkynes•organolithium•cross-
coupling•palladium
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Entry for the Table of Contents (Please choose one layout)
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RESEARCH ARTICLE
Jaime Mateos-Gil,+Anirban Mondal+ Marta
Castiñeira Reis and Ben L. Feringa*
Page No. – Page No.
Synthesis and Functionalization of
Allenes by Direct Pd-Catalyzed
Organolithium Cross-Coupling
Selective formation of allenic product is achieved in the direct cross-coupling of allenyl- and propargyllithium species with
aryl bromides. The fundamental role of ligand in the selectivity of the transformation is described, allowing the synthesis of tri- and
tetrasubstituted allenes in good to excellent yields without any previous formation of transition metal species, resulting in a fast and
efficient methodology. The determining factors that drive the selectivity and the critical role of dba in the selectivity have been
discovered.
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