Development of the "diverted Heck" Reaction for the Synthesis of Five-Membered Rings

Article abstract of DOI:10.1021/acs.organomet.1c00025

The "diverted Heck"reaction has been shown to be a potent method to synthesize cyclopropanes from electron-rich olefins and iodomethyl trifluoroborate. Nevertheless, it is not mechanistically limited to the three-membered rings. The synthesis of five-memb

Full text of DOI:10.1021/acs.organomet.1c00025

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Development of the “Diverted Heck” Reaction for the Synthesis of
Five-Membered Rings
Kevin Breitwieser and Peter Chen*
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ABSTRACT: The “diverted Heck” reaction has been shown to be a potent
method to synthesize cyclopropanes from electron-rich olefins and iodomethyl
trifluoroborate. Nevertheless, it is not mechanistically limited to the three-
membered rings. The synthesis of five-membered rings using bifunctional
substrates with a halide moiety and an organometallic group is described.
Furthermore, the reactions of the respective boron and tin-based substrates are
further investigated and optimized.
he “diverted Heck” reaction was developed as an
alternative cyclopropanation reaction to the established
insertion reactions, the “diverted Heck” reaction is not strictly
limited to the formation of cyclopropanes and should be
applicable to all possible ring sizes in principle. In fact, the
nickel-catalyzed synthesis of indanes and indenes from o-
bromobenzyl zinc bromide and alkenes or alkynes has been
reported before (Scheme 1, eq 3).8 The authors propose
several possible mechanisms for this reaction, with one of them
being strikingly similar to the proposed mechanism for the
“diverted Heck” reaction.
However, their method has considerable disadvantages: 3.5
equiv of the zinc reagent is needed for the reaction. In
addition, due to the nature of zinc organyls, functional group
tolerance is limited compared to reactions with the boron
analogues.
T
use of diazomethane,1 the Simmons−Smith reaction,2 and the
transfer of methylene groups from sulfur ylides (Corey−
Chaykovsky reaction).3 While these reactions are applicable in
many cases, they have notable disadvantages. While diazo-
methane and its precursors are well known for their high
toxicity and explosiveness,4 the Simmons−Smith reaction
produces stoichiometric amounts of zinc waste, and depending
on the procedure, cationic polymerization can become a major
side reaction or the reaction mixture can explode.5 These
methods are furthermore mostly limited to electron-poor and
polar olefins.
While the palladium-catalyzed cyclopropanation of olefins
using iodomethylstannanes had been reported before (Scheme
1, eq 1), a large excess of the norbornene derivatives was used.6
However, as this was intended as a trapping experiment and
not for synthetic applications, the conditions were not
optimized. We subsequently reported the “diverted Heck”
reaction, involving the palladium-catalyzed addition of the
methylene unit from an iodomethylboron species to an olefin
to form a cyclopropane ring (Scheme 1, eq 2).7 It was shown
that this reaction was able to cyclopropanate a wide range of
electron-rich olefins and allylic alcohols in good yields up to
98% with a close to 1:1 ratio of the reagent and substrate. The
mechanism of this reaction was found to follow the mechanism
for the Heck reaction. However, instead of the final β-hydride
elimination, an intramolecular transmetalation intervenes. This
leads to a palladacyclobutane, which can undergo reductive
elimination to form the cyclopropane. The generalized
mechanism of the “diverted Heck” reaction is shown in
Scheme 2. In the reported case, the organometallic moiety [M]
is a trifluoroborate group and the (pseudo)halide X is iodine.
They are connected by a methylene group.
This work reports the development of a cyclopentenation
reaction based on the “diverted Heck” reaction using
bifunctional substrates bearing one halogen moiety as well as
an organometallic group based on boron or tin.
EXPERIMENTAL SECTION
■
General Remarks. Unless otherwise stated, all reactions were
carried out under an argon or nitrogen atmosphere using standard
Schlenk or glovebox techniques with anhydrous solvents. Solvents and
reagents were obtained from abcr, Acros Organics, AlfaAesar, Apollo
Scientific, Chemie Brunschwig, Combiblocks, Fluka, Fluorochem,
Sigma-Aldrich, TCI, and VWR. Solvents were dried by distillation
under nitrogen from sodium (toluene), sodium/benzophenone
[diethyl ether, tetrahydrofuran (THF)], sodium/benzophenone/
tetraethylene glycol dimethyl ether (TEGDME) (hexane), or
magnesium (methanol) before use and were stored under dry
Received: January 13, 2021
Published: March 11, 2021
In organic synthesis, the formation of carbocycles can be
challenging, especially if they are not six-membered rings. As is
apparent from the proposed mechanism, unlike carbene
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Scheme 1. Previously Reported Transition-Metal-Catalyzed Cyclization Reactions Using Reagents Containing a Halogen
Moiety and an Organometallic Group
chromatography-flame ionization detection (GC-FID) measurements
were conducted using a Finnigan Focus GC or a Shimadzu GC-2025
with a Thermo Scientific TR-5MS 30 m × 0.25 mm column with a
0.25 μm film. GC-FID quantifications were carried out using
calibration curves and undecane as an internal standard.
Scheme 2. Proposed Catalytic Cycle for the “Diverted
Heck” Cyclization Reaction
Representative Cyclopentenation Procedure in N,N-Dime-
thylacetamide/Ethylene Glycol. Inside a nitrogen-filled glovebox,
a 9 mL screw-cap vial with an oven-dried magnetic stir bar was
charged with K2CO3 (80.9 mg, 5.0 equiv) and 0.1 mL of anhydrous
ethylene glycol (EG). The mixture was stirred for 10 min. A solution
of [(o-tolyl)3P]2PdCl2 (4.6 mg, 5 mol %), o-bromobenzylboronic acid
pinacol ester (41.6 mg, 1.2 equiv), and norbornene (11.0 mg, 1 equiv)
in 0.6 mL of N,N-dimethylacetamide (DMA) was added. Additional
DMA (2 × 0.5 mL) was used to rinse the vials used for transfer and
weighing substrates and the catalyst and added to the reaction
mixture. The vial was sealed, removed from the glovebox, and heated
to 75 °C for 22 h. The mixture was cooled to 0 °C for 10 min, and 5
μL of undecane was added (internal reference). The contents of the
vial were extracted with Et2O (2 × 4 mL) and water (5 mL), and the
organic phase was washed with water (5 mL) and brine (5 mL), dried
(MgSO4), filtered through celite, and analyzed by GC−MS and GC-
FID.
Representative Cyclopentenation Procedure for Solvent
Screening. Inside a nitrogen-filled glovebox, to a 9 mL screw-cap vial
with an oven-dried magnetic stir bar was added a solution of [(o-
tolyl)3P]2PdCl2 (4.6 mg, 5 mol %), o-bromobenzyltributylstannane
(64.4 mg, 1.2 equiv), and norbornene (11.0 mg, 1 equiv) in 0.6 mL of
DMA. Additional DMA (2 × 0.5 mL) was used to rinse the vials used
for transfer and weighing substrates and the catalyst and added to the
reaction mixture. The vial was sealed, removed from the glovebox, and
heated to 75 °C for 22 h. The mixture was cooled to 0 °C for 10 min,
and 5 μL of undecane was added (internal reference). The contents of
the vial were extracted with Et2O (2 × 4 mL) and water (5 mL), and
the organic phase was washed with water (5 mL) and brine (5 mL),
dried (MgSO4), filtered through celite, and analyzed by GC−MS and
GC-FID.
nitrogen. Deuterated chloroform was obtained from Cambridge
Isotope Laboratories. Copper(I) iodide and lithium chloride were
dried for several hours in high vacuum and stored under dry argon
before use. Norbornene was distilled under argon and stored in a
nitrogen-filled glovebox before use. Potassium iodomethyltrifluor-
oborate (>98.0%) was washed with diethyl ether, dried, and stored in
a nitrogen-filled glovebox before use. NMR spectra were recorded
with a Bruker Avance III 400 MHz, Bruker Neo 400 MHz, or Bruker
Neo 500 MHz spectrometer using CDCl3 as a solvent. 500 MHz
Representative Cyclopentenation Procedure with Addi-
tives. Inside a nitrogen-filled glovebox, a 9 mL screw-cap vial with an
oven-dried magnetic stir bar was charged with CsF (21.3 mg, 1.2
equiv). A solution of [(o-tolyl)3P]2PdCl2 (4.6 mg, 5 mol %), o-
bromobenzyltributylstannane (64.4 mg, 1.2 equiv), and norbornene
spectra were recorded by the NMR Service of ETH Zurich. Chemical
̈
shifts (δ) are reported in parts per million (ppm) relative to the
residual solvent signal for chloroform (7.26 and 77.16 ppm) as an
1
internal reference. 13C, 19F, and 31P spectra were recorded with H-
t
t
(11.0 mg, 1 equiv) in 0.6 mL of BuOH was added. BuOH (2 × 0.5
mL) was used to rinse the vials used for transfer and weighing
substrates and the catalyst and added to the reaction mixture. The vial
was sealed, removed from the glovebox, and heated to 75 °C for 22 h.
The mixture was cooled to 0 °C for 10 min, and 5 μL of undecane
was added (internal reference). The contents of the vial were
extracted with Et2O (2 × 4 mL) and water (5 mL), and the organic
decoupling. High-resolution mass spectra were recorded by the
Molecular and Biomolecular Analysis Service (MoBiAS) of ETH
̈
Zurich using a Bruker maXis ESI-Qq-TOF-MS or Thermo Scientific
Q Exactive GC Orbitrap with a direct probe (EI) for mass spectra.
Gas chromatography−mass spectrometry (GC−MS) measurements
were carried out using a ThermoFinnigan Trace GC + Trace MS and
a Supelco Equity-5 30 m × 0.25 mm column with a 0.25 μm film. Gas
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Scheme 3. Proposed Mechanism for the Formation of the Four Major Products Observed for the Attempted “Diverted Heck”
Reaction of Norbornene and o-Bromobenzylboronic Acid Pinacol Ester
phase was washed with water (5 mL) and brine (5 mL), dried
(MgSO4), filtered through celite, and analyzed by GC−MS and GC-
FID.
reactions with alcoholic solvents (e.g., EG) and because aryl
halides undergo faster oxidative addition. Preliminary tests
with 3-iodo-2-phenylpropylboronic acid pinacol ester lead to
the 1,3-elimination product phenylcyclopropane as the only
product visible in GC. This elimination reaction is known to
occur under basic conditions.9 Norbornene was chosen as the
model olefin as it shows very high reactivity.10 Moreover, after
migratory insertion, β-hydride elimination (following the
“normal” Heck path) is disfavored as it would violate Bredt’s
rule.11 The expected “diverted Heck” product is 2,3,4,4a,9,9a-
hexahydro-1H-1,4-methanofluorene (C14H16, m/z = 184).
Following the representative cyclopentenation procedure in
DMA/EG, GC−MS does detect four major products, these
being o-bromotoluene, toluene, and hydrocarbons with the
formulas C14H18 and C14H16, the latter matching the target
molecule. The molecules C14H16 and C14H18 are formed
through a mechanism described by Catellani and Ferioli,12 and
C14H16 can be identified as a benzocyclobutene instead of the
desired benzocyclopentenes. While this competing mechanism
can be suppressed by replacing the Brønsted base used as an
activator for transmetalation with CsF,13 two other side
reactions are observed, these being protodeboronation14 and
transfer hydrogenation. The proposed mechanism for the
formation of the observed side products is shown in Scheme 3.
The transfer hydrogenation does not proceed in the absence
of a reducing alcohol (e.g., EG and isopropanol),15 making
suppression possible, but the protodeboronation cannot be
reduced to a reasonable degree. Even with CsF as an activator
and pure DMA as a solvent, next to 9% of the target molecule,
49% o-bromotoluene is formed.
Representative Procedure for the Isolation of Cyclo-
pentenes. Inside a nitrogen-filled glovebox, an oven-dried 250 mL
two-neck flask with an oven-dried magnetic stir bar was charged with
CsF (495.2 mg, 1.2 equiv). A solution of [(o-tolyl)3P]2PdCl2 (109.7
mg, 5 mol %), o-bromobenzyltributylstannane (1499.9 mg, 1.2 equiv),
and norbornene (256.5 mg, 1 equiv) in 37.5 mL of tBuOH was added.
The flask was fitted with a glass stopper and glass tap, removed from
the glovebox and attached to an argon-filled Schlenk line. The mixture
was heated to 75 °C for 22 h. The mixture was cooled to 0 °C and
diluted with 75 mL of Et2O. It was washed with water (2 × 40 mL)
and brine (40 mL), dried (MgSO4), and filtered through a pad of
silica, washing with additional pentane. The solution was concen-
trated, and the residue was purified by column chromatography
(hexane) twice. The product exo-2,3,4,4a,9,9a-hexahydro-1H-1,4-
methanofluorene was obtained as 58.8 mg (12%) of a colorless oil.
1H NMR (400 MHz, CDCl3): δ 7.23−7.09 (m, 4H), 3.27 (dd, J =
17.1, 10.2 Hz, 1H), 3.15 (d, J = 7.9 Hz, 1H), 2.62 (dd, J = 17.1, 3.4
Hz, 1H), 2.45−2.36 (m, 1H), 2.29 (s, 1H), 2.11 (s, 1H), 1.69−1.50
(m, 2H), 1.48−1.37 (m, 1H), 1.34−1.22 (m, 1H), 1.19−1.08 (m,
1H), 1.06−0.95 (m, 1H). 13C NMR (101 MHz, CDCl3): δ 146.51,
144.95, 126.36, 126.32, 124.62, 124.15, 55.60, 45.02, 43.87, 43.56,
39.47, 32.55, 29.13, 28.96. HRMS (EI) calcd for C14H16 [M]+,
184.1247; found, 184.1244.
RESULTS
■
Investigation of Cyclopentenation with Organo-
boron Reagents. As the previously described “diverted
Heck” cyclopropanation7 was based on organoboron reagents,
it was chosen to use o-bromobenzylboronic acid pinacol ester
as a model reagent. An aryl halide was chosen as, compared to
alkyl halides, it does not undergo nucleophilic substitution
To avoid protodemetalation, a system based on the more
stable stannanes was investigated.
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Investigation of Cyclopentenation with Organotin
Reagents. After only a few test reactions, it was clear that the
reagent o-bromobenzyltributylstannane is superior to the
corresponding boronic acid ester for the reaction. In no case
did we see notable formation of o-bromotoluene, which was
the main issue with the boron reagent. In addition, no activator
is necessary for transmetalation. Based on these first successes,
optimization of the reaction was carried out. The first
parameter optimized was the solvent (Table 1).
Table 2. Additive Screening for the “Diverted Heck”
Cyclopentenation of Norbornene with o-
a
Bromobenzyltributylstannane (2a)
b
b
no.
additive
none
yield (%)
conv. 2a (%)
Table 1. Solvent Screening for the “Diverted Heck”
Cyclopentenation of Norbornene with o-
1
2
3
4
5
6
7
19.2
10.8
6.8
2.7
1.4
47.3
>99
95.9
3.9
35.4
>99
>99
LiCl (1.2 equiv)
CuI (0.1 equiv)
CuI (0.2 equiv)
CuI (1.2 equiv)
CsF (1.2 equiv)
CsF (2.4 equiv)
CsF (1.2 equiv)
CuI (0.1 equiv)
CsF (1.2 equiv)
CuI (0.2 equiv)
CsF (2.4 equiv)
CuI (0.1 equiv)
CsF (2.4 equiv)
CuI (0.2 equiv)
CsF (1.2 equiv)
a
Bromobenzyltributylstannane (2a)
64.0
32.3
8
7.0
3.6
3.6
21.6
39.6
44.8
b
b
no.
solvent
hexane
toluene
fluorobenzene
THF
yield (%)
conv. 2a (%)
9
1
2
3
4
2.1
4.2
5.1
8.8
16.8
28.9
9.6
10
0.7
11
6.7
53.5
87.8
5
6
7
8
ethyl acetate
acetone
DMA
4.2
1.5
9.1
16.4
7.3
c
12
83.1
a
52.6
62.4
47.3
89.2
16.7
30.9
58.0
62.2
23.3
Standard conditions: norbornene (11.0 mg, 1.0 equiv), stannane 2a
(64.4 mg, 1.2 equiv), [(o-tolyl)3P]2PdCl2 (4.6 mg, 5 mol %), 1.6 mL
DMF
13.2
19.2
10.2
3.2
13.7
18.2
10.3
10.7
b
t
tBuOH
DMSO
acetonitrile
iPrOH
of BuOH, 75 °C, 22 h. Yields and conversions were evaluated by
9
c
i
t
GC-FID. Reaction run in PrOH instead of BuOH.
10
11
12
13
14
15
MeOH
EG
without an additive, it is superior in combination with CsF,
leading to a yield of more than 80% based on the limiting
reagent norbornene.
c
water
a
Standard conditions: norbornene (11.0 mg, 1.0 equiv), stannane 2
With an optimized solvent and additive in hand, the next
component to optimize is the stannane itself. There are two
functional groups to be modified, these being the stannyl group
and the halide (Table 3). Using the corresponding aryl
chloride (entry 2) or aryl triflate (entry 4), barely any reaction
is noticed, while the reaction proceeds, when the correspond-
ing aryl iodide (entry 3) is used, although the yield is notably
lower. The same is true for the benzyl iodide, although in this
case, contrary to the aryl halides, the reagent is completely
consumed. The trimethylstannane (entry 5) leads to a similar
yield as the tributylstannane.
The last component to optimize is the catalyst itself.
Accordingly, the same reaction was conducted using several
different palladium catalysts with different ligands (Table 4).
As is immediately apparent, the reaction strongly favors
phosphine complexes. The tested NHC (entry 9) and
isocyanide (entry 10) complexes do not lead to any product
formation. The same is true for palladium acetate (entry 11)
without any added ligand. In the case of tris(o-tolyl)phosphine-
based ligands, increasing the electron density (entry 2) does
not notably change the performance, while the electron-poorer
complex (entry 3) leads to a yield increase of 10%. Switching
from phosphine to arsine ligands (entry 4) is also detrimental.
Comparing the tetrakis(triphenylphosphine) complexes of
palladium (entry 5) and nickel (entry 6) also shows that a
nickel-catalyzed system, while being slightly less active, could
be developed.
(64.4 mg, 1.2 equiv), [(o-tolyl)3P]2PdCl2 (4.6 mg, 5 mol %), 1.6 mL
b
of the solvent, 75 °C, 22 h. Yields and conversions were evaluated by
c
GC-FID. All components except for the solvent were put into a 9 mL
screw-cap vial with a septum cap. The degassed water was added
outside of the glovebox through the septum.
Evidently, the reaction works best in polar protic solvents,
such as methanol (entry 13) or tert-butanol (entry 9), with
yields reaching almost 20% in the set of exploratory reactions.
Water (entry 15) or EG (entry 14) lead to a much poorer
yield, most likely due to phase separation. Polar aprotic and
apolar solvents gave worse yields, with only dimethylforma-
mide (DMF) (entry 8) and dimethyl sulfoxide (DMSO)
(entry 10) getting higher than 10%. Other solvents, such as
acetonitrile (entry 11), acetone (entry 6), THF (entry 4), or
toluene (entry 2), lead to yields well below 5%.
Having found a suitable solvent in tert-butanol, the
application of additive salts was investigated (Table 2).
While Brønsted bases were ruled out as they would enable
the undesirable C−H activation described before, LiCl, CuI,16
and CsF13 are known additives for palladium-catalyzed
reactions. Notably, LiCl and CuI addition to the reaction is
highly detrimental. 1.2 equiv of LiCl cut the yield of the
reaction in half, while even 0.1 equiv of CuI cut the yield by 2/
3, with higher loadings being even worse. However, CsF
addition is highly beneficial, with 1.2 equiv doubling the yield.
Although isopropanol was a worse solvent than tert-butanol
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pentenation reaction. It was found that competing proto-
deboronation, C−H activation, and transfer hydrogenation
lead to a large number of major side products. While the latter
two reactions can be prevented through modification of the
reaction conditions, the protodeboronation product remains
the major product.
Table 3. Reagent Screening for the “Diverted Heck”
Cyclopentenation of Norbornene
a
As a result of these stability issues, a tin-based system was
developed. While this system immediately showed much better
results than the boron-based system, especially only negligible
protodestannylation, this system was further optimized. For
the solvent optimization, it was found that alcoholic solvents
are the best. Tchawou et al.7 did describe the presence of
palladium−alcoholate species during the reaction. It is
reasonable to assume that such species are also formed here
and are important for the reaction. It should also be noted that
unlike for the boron system, reducing alcohols are not
problematic. This can be easily explained as while for the
boronates protodeboronation did already make transmetala-
tion uncompetitive, in the tin system, the intramolecular
transmetalation is possible. In this case, it outcompetes any
hydrogen-transfer reaction.
b
b
no.
reagent
yield (%)
conv. 2a−f (%)
1
2
3
2a
2b
2c
2d
2e
2f
83.1
0.6
36.0
0.0
76.6
24.4
87.8
28.4
38.2
7.5
94.2
>99
c
4
5
6
For additives, it was found that CsF notably increases the
performance of the system, while LiCl or CuI are detrimental.
CsF is believed to facilitate the transmetalation step by either
activating the stannane by coordinating to the tin atom or
replacing other halides on palladium and enabling the
formation of the cyclic transition state as a ligand for tin.
For the choice of the reagent, the aryl bromide proved to be
the most efficient. While the aryl chloride was not expected to
lead to any improvement due to the much slower oxidative
addition,17 the results for the triflate were not necessarily
predictable. It has been shown before that the performance of
aryl triflates for palladium-catalyzed reactions is highly variable.
While in some cases they are superior to the bromides, they
have been reported to be worse than the aryl chlorides in other
cases, especially when bulky and electron-rich ligands like
PtBu3 are employed.18 Apparently, this is also the case in the
system described here. Surprisingly, the aryl iodide forms less
product than the bromide, although it should lead to a faster
oxidative addition. However, if the oxidative addition is not
rate-limiting in the bromide case, no improvement should be
expected from this. For the “diverted Heck” cyclopropanation,
the migratory insertion and not the transmetalation was found
to be rate-limiting.7 On the other hand, aryl iodides have been
found to slow down the transmetalation step of the Stille
reaction as less reactive palladium iodide complexes are
formed.19 In both the bromide and the iodide case, the
catalyst itself decays before the reaction can completely finish
as both starting materials are still present at the end of the
reaction. If the catalyst decomposition is more or less
independent from the halide, this implies that if a slower
transmetalation is rate-determining, less product can be formed
until the catalyst decomposes, lowering the overall yield of the
reaction. While benzyl iodide 2f does form the cyclo-
pentenation product as expected, it is less efficient than the
aryl bromide or iodide. While benzyl halides are expected to
undergo faster oxidative addition than aryl halides,20 unlike
aryl halides, they are susceptible to nucleophilic substitution
reactions. Under the reaction conditions (75 °C, alcoholic
solvent), ethers should be formed. In fact, among the used
reagents, only for the benzyl halide was no trace of it found in
GC-FID at the end of the reaction, implying that side reactions
occur. It is reasonable that the formed ethers, by still
a
Standard conditions: norbornene (11.0 mg, 1.0 equiv), stannane
2a−f (1.2 equiv), CsF (21.3 mg, 1.2 equiv), [(o-tolyl)3P]2PdCl2 (4.6
b
i
mg, 5 mol %), 1.6 mL of PrOH, 75 °C, 22 h. Yields and
c
Conversions were evaluated by GC-FID. Reaction was conducted
with all volumes and masses of solvents and reagents cut in half.
Table 4. Catalyst Screening for the “Diverted Heck”
Cyclopentenation of Norbornene
a
b
b
no.
catalyst
yield (%)
conv. 2a (%)
1
2
3
4
5
6
7
8
[(o-tol3P)2PdCl2] (3a)
64.0
68.4
75.6
22.4
35.7
30.2
50.8
2.0
>99
98.3
91.3
63.7
72.5
49.6
83.7
89.5
<1
[(R1 P)2PdCl2] (3b)
3
[(R2 P)2PdCl2] (3c)
3
[(o-tol3As)2PdCl2] (3d)
[(Ph3P)4Pd] (3e)
[(Ph3P)4Ni] (3f)
[(dppf)PdCl2] (3g)
tBuXPhos Pd G3 (3h)
3i
9
10
11
0.0
0.0
0.0
[(tBuNC)2PdCl2] (3j)
Pd(OAc)2 (3k)
<1
<1
a
Standard conditions: norbornene (11.0 mg, 1.0 equiv), stannane 2a
(64.4 mg, 1.2 equiv), CsF (21.3 mg, 1.2 equiv), catalyst 3a−k (5 mol
b
t
%), 1.6 mL of BuOH, 75 °C, 22 h. Yields were evaluated by GC-
FID.
DISCUSSION
■
Following up on the invention of the “diverted Heck”
cyclopropanation, we report the first “diverted Heck” cyclo-
pentenation. While the cyclopropanation uses a boron-based
reagent, we show that this is problematic for the cyclo-
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Author
Kevin Breitwieser − Laboratorium fu
containing the heavy stannyl group, are not volatile enough to
be detected in GC.
̈
r Organische Chemie,
Eidgenössische Technische Hochschule (ETH) Zu
Zurich CH-8093, Switzerland; orcid.org/0000-0002-
̈
rich,
For the catalyst choice, it was found that phosphine
complexes are vastly preferred. Neither the tested NHC
complex nor the isocyanide complex led to any product
formation, as did the ligand-free variant with palladium acetate.
For the phosphine systems, only 3h did not form any notable
amounts of the product. This is not surprising as an activation
of the precatalyst through a base is necessary,21 which is not
possible here. For tris(o-tolyl)phosphine-based complexes 3a−
c, the difference of performance of the unsubstituted ligand 3a
and the more electron-rich ligand 3b might not be statistically
relevant. Nevertheless, the electron-poor ligand 3c shows some
increased activity. This would match the description for the
cyclopropanation that the migratory insertion is rate-limiting as
a lower electron density on the catalyst should accelerate this
step.22 While a more weakly binding arsine can also be used,
complex 3d is less efficient. This can be explained with the
lower stability of arsine complexes compared to the phosphine
complex, leading to faster catalyst decomposition.
Notably, nickel catalyst 3f is not much less active than the
corresponding palladium catalyst 3e. In fact, it appears to be
more selective. This implies that a nickel-catalyzed variant of
the “diverted Heck” reaction is possible, although a higher
catalyst loading might be needed.
While for the stannane systems no notable side products
were visible in GC, certain systems showed a notable
discrepancy between yield and conversion, implying that the
reagent has to have reacted in a way invisible to GC. The most
obvious side reaction is the formation of non-volatile oligomers
through Stille coupling as a tin analogue to Suzuki
polycondensation.23 This implies that the intermolecular
transmetalation reaction competes with the migratory
insertion. The selectivity for Stille coupling or “diverted
Heck” reaction therefore depends on the relative rates of these
two reactions.
̈
7012-8750
Complete contact information is available at:
https://pubs.acs.org/10.1021/acs.organomet.1c00025
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
We acknowledge financial support from the ETH Zu
the Swiss National Science Foundation. We acknowledge the
help of the high pressure lab under Ján Kovacovic for pressure
reactions.
■
̈
rich and
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Peter Chen − Laboratorium fu
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