Catalytic Synthesis of 8-Membered Ring Compounds via Cobalt(III)-Carbene Radicals

Article abstract of DOI:10.1002/anie.202002674

The metalloradical activation of o-aryl aldehydes with tosylhydrazide and a cobalt(II) porphyrin catalyst produces cobalt(III)-carbene radical intermediates, providing a new and powerful strategy for the synthesis of medium-sized ring structures. Herein we make use of the intrinsic radical-type reactivity of cobalt(III)-carbene radical intermediates in the [Co^II(TPP)]-catalyzed (TPP=tetraphenylporphyrin) synthesis of two types of 8-membered ring compounds; novel dibenzocyclooctenes and unprecedented monobenzocyclooctadienes. The method was successfully applied to afford a variety of 8-membered ring compounds in good yields and with excellent substituent tolerance. Density functional theory (DFT) calculations and experimental results suggest that the reactions proceed via hydrogen atom transfer from the bis-allylic/benzallylic C?H bond to the carbene radical, followed by two divergent processes for ring-closure to the two different types of 8-membered ring products. While the dibenzocyclooctenes are most likely formed by dissociation of o-quinodimethanes (o-QDMs) which undergo a non-catalyzed 8π-cyclization, DFT calculations suggest that ring-closure to the monobenzocyclooctadienes involves a radical-rebound step in the coordination sphere of cobalt. The latter mechanism implies that unprecedented enantioselective ring-closure reactions to chiral monobenzocyclooctadienes should be possible, as was confirmed for reactions mediated by a chiral cobalt-porphyrin catalyst.

Full text of DOI:10.1002/anie.202002674

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Accepted Article
Title: Catalytic Synthesis of 8-Membered Ring Compounds via
Cobalt(III)-Carbene Radicals
Authors: Minghui Zhou, Marianne Lankelma, Jarl Ivar van der Vlugt,
and Bas de Bruin
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10.1002/anie.202002674
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RESEARCH ARTICLE
Catalytic Synthesis of 8-Membered Ring Compounds via
Cobalt(III)-Carbene Radicals
Minghui Zhou, Marianne Lankelma, Jarl Ivar van der Vlugt,and Bas de Bruin*[a]
[a]
M. Zhou, M. Lankelma, Dr. Ir. J. I. van der Vlugt, Prof. dr. B. de Bruin
Homogeneous, Supramolecular and Bio-Inspired Catalysis group (HomKat)
Van ’t Hoff Institute for Molecular Sciences (HIMS)
University of Amsterdam (UvA)
Science Park 904, 1098 XH Amsterdam, The Netherlands
E-mail: B.deBruin@uva.nl
Supporting information (ESI) for this article is given via a link at the end of the document.
Abstract: The metalloradical activation of o-aryl aldehydes with
tosylhydrazide and a cobalt(II) porphyrin catalyst produces cobalt(III)-
carbene radical intermediates, providing a new and powerful strategy
for the synthesis of medium-sized ring structures. Herein we make
use of the intrinsic radical-type reactivity of cobalt(III)-carbene radical
ring-opening reactions.[11] However, the harsh reaction conditions,
poor functional group tolerance, inevitable by-product formation
or the necessity of noble metal catalysts can put limitations on the
general applicability of the existing methods in both academic and
industrial settings. Therefore, developing efficient and broadly
applicable strategies to synthesize 8-membered ring systems,
especially those employing inexpensive metal catalysts, remains
an important challenge in the field of synthetic organic chemistry.
intermediates
in
the
[CoII(TPP)]-catalyzed
(TPP
=
tetraphenylporphyrin) synthesis of two types of 8-membered ring
compounds; novel dibenzocyclooctenes and unprecedented
monobenzocyclooctadienes. The method was successfully applied to
afford a variety of 8-membered ring compounds in good yields and
with excellent substituent tolerance. Density functional theory (DFT)
calculations and experimental results suggest that the reactions
proceed via hydrogen atom transfer from the bis-allylic/benzallylic
CH bond to the carbene radical, followed by two divergent processes
for ring-closure to the two different types of 8-membered ring products.
While the dibenzocyclooctenes are formed by dissociation of
o-quinodimethanes (o-QDMs) which undergo a non-catalyzed 8-
cyclization, DFT calculations suggest that ring-closure to the
monobenzocyclooctadienes involves a radical-rebound step in the
coordination sphere of cobalt. The latter mechanism implies that
unprecedented enantioselective ring-closure reactions to chiral
monobenzocyclooctadienes should be possible, as was confirmed for
reactions mediated by a chiral cobalt-porphyrin catalyst.
Figure 1. Natural products, fragrances and ligands containing 8-membered
rings.
Introduction
The importance of medium-sized cyclic compounds, especially
eight-membered rings, is exemplified by their prevalence in a
broad variety of bio-active natural products,[1] fuels,[2] fragrances[3]
and catalysts[4] (Figure 1). Although many synthetic approaches
exist to generate 5- and 6-membered ring structures, ring-closure
reactions to form medium-sized ring structures are still rather
challenging in general.[5] Due to entropic factors and transannular
interactions, the flexible, linear precursor molecules typically
employed in these procedures tend to react in an intermolecular
way, leading to unwanted dimerization or polymerization instead
of intramolecular cyclization. These side reactions are particularly
problematic in the synthesis of 7- and 8-membered ring
compounds. Over the past years, several methods to form
8-membered rings have been developed, including ring-closing
metathesis,[6] metal complex assisted alkynyl/dienyl or carbene-
carbene cyclizations,[7] metal-catalyzed [4+4],[8] [4+2+2],[9] and
[6+2][10] cyclo-additions, as well as oxabicyclic metal-promoted
Recently, we demonstrated that metalloradical catalysis
based on the intrinsic radical-type reactivity of cobalt(III)-carbene
radicals provides access to a particular class of 8-membered ring
compounds: dibenzocyclooctenes (Scheme 1A).[12] In these
reactions, cobalt(II) complexes react with carbene precursors,
such as N-tosylhydrazones or diazo compounds, to produce
cobalt(III)-carbene radical intermediates that enable unusual
catalytic radical-type pathways.[13] This metalloradical strategy
has so far been employed in the synthesis of cyclopropanes,[14]
chromenes,[15] furans,[16] indenes,[17] indolines,[18] ketenes,[19]
butadienes,[20]
dihydronaphthalenes,[20]
piperidines,[21]
pyrrolidines[22] and some dibenzocyclooctenes.[12] Furthermore,
for many reactions, the Co(II) system tolerates in situ generation
of the carbene precursor from a readily available aldehyde via a
in situ generation of the N-tosylhydrazone intermediate using
p-toluenesulfonyl hydrazide. Follow-up conversion to the diazo
compound upon deprotonation and subsequent trapping by the
1
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RESEARCH ARTICLE
catalyst (Figure 2)[23] significantly simplifies the synthetic Results and Discussion
methodology and makes the overall metalloradical strategy more
widely applicable.[21, 24]
In an attempt to expand the scope of 8-membered ring synthesis
via metalloradical catalysis, we first decided to examine the
influence of changing the (hetero)aromatic benzyl moiety on the
ring closure efficacy. We were particularly interested to explore
the possibility of using substrates with naphthyl and pyridyl
moieties (Table 1). These substrates proved to be surprisingly
suitable for the synthesis of new dibenzocyclooctenes, as for
substrates 1-3 the eight-membered ring products were generated
in good yields (Table 1, entry 1-3). The reaction with substrate 4
also worked well, but afforded structural isomers 4a and 4b in a
1:1 ratio (Table 1, entry 4). Each isomer could be isolated by
column chromatography. The assigned structures of
dibenzocyclooctenes 1-4, as determined by NMR spectroscopy
(see SI), are in accordance with previous work, with the C=C
double bond in the product migrating from the 4- to the 5-position,
Figure 2. In situ generation of cobalt(III)-carbene radical intermediate from
aldehyde in a one-pot sequence
Table 1. Substrate scope of dibenzocyclooctene synthesis, varying the
(hetero)aromatic benzylic moiety of the substrate.[a]
Entry
Substrate
Product
Yield[b]
Scheme 1. Metalloradical strategy for the synthesis of
a variety of
dibenzocyclooctenes and monobenzocyclooctadienes.
Herein, we report our efforts to advance the reactivity of
cobalt(III)-carbene radicals for the generation of 8-membered
rings. The method enables the synthesis of two types of ring
systems: novel dibenzocyclooctenes and unprecedented
monobenzocyclooctadienes. We first investigated the synthesis
of novel dibenzocyclooctenes from substrates containing other
aromatic carbocycles and heterocycles than previously
reported,[12] such as pyridyl and naphthyl moieties (Scheme 1B).
In addition, we found that the protocol can be extended to enable
the synthesis of monobenzocyclooctadienes, for which no
synthetic protocols currently exist. In this paper, we show that the
latter products can be synthesized by ring-closure of o-aryl
aldehydes containing bis-allylic CH bonds, and they seem to be
formed via a different mechanism than previously reported for the
dibenzocyclooctenes.[12] While the dibenzocyclooctenes are
formed by dissociation of o-quinodimethanes (o-QDMs) from the
catalyst and a subsequent non-catalyzed 8-cyclization (Scheme
1A), DFT calculations suggest that ring-closure to the
monobenzocyclooctadienes involves a direct radical-rebound
step within the coordination sphere of cobalt (Scheme 1B). The
latter mechanism implies that enantioselective ring-closure
reactions to chiral monobenzocyclooctadienes should be possible,
as was confirmed by use of a chiral cobalt-porphyrin catalyst. The
reactions have a broad substrate scope, are operationally simple
and can be carried out on a (near) gram scale. The details are
disclosed in this paper.
[a] Reaction conditions: 1-4 (0.1 mmol, 1.0 equiv), LiOtBu (0.12 mmol, 1.2 equiv),
p-TsNHNH2 (0.1 mmol, 1.0 equiv), [Co(TPP)] (5 mol%), benzene (1 mL), 60 C,
overnight. [b] Isolated yield, corrected for the E/Z ratios of the substrates.
2
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10.1002/anie.202002674
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thus implying that the products are formed via o-QDM
intermediates, as reported previously.[12] The isolated yields
reported in Table 1 are corrected for the E/Z ratios of the
substrates, because only the E-isomer can undergo ring-closure
in these reactions.[12] It is remarkable that these reactions are so
tolerant to the use of naphthyl- and pyridyl moieties at the benzylic
position, thus enabling the synthesis of interesting new
8-membered ring product classes.
unprecedented 8-membered ring products: monobenzocyclo-
octadienes.
In contrast to the observed migration of the double bond from the
4- to the 5-position during the synthesis of dibenzocyclooctenes,
the position of the acrylic C=C double bond does not shift during
the formation of monobenzocyclooctadienes (Table 2). No
6-membered ring product formation was observed at all, which is
remarkable in view of the fact that 6-membered rings are
generally formed more easily than 8-membered rings.
Table 2. Substrate scope of monobenzocyclooctadiene synthesis, varying the
substituents of the aromatic moiety of the substrate.[a,b]
Table 3. Substrate scope of monobenzocyclooctadiene synthesis, varying the
substituents at the terminal allylic position of the substrate.[a, b]
[a] Reaction conditions: For 18, 19, 21-24: (0.1 mmol, 1.0 equiv), LiOtBu (0.12
mmol, 1.2 equiv), p-TsNHNH2 (0.1 mmol, 1.0 equiv), [Co(TPP)] (5 mol%),
benzene (1 mL), 60C, overnight. For 20: (0.1 mmol, 1.0 equiv), LiOtBu (0.12
mmol, 1.2 equiv), p-TsNHNH2 (0.1 mmol, 1.0 equiv), [Co(TPP)] (10 mol%),
benzene (1 mL), room temperature, 48 h. [b] Isolated yield, corrected for the E/Z
ratios of the substrates.
[a] Reaction conditions: For 5-12: (0.1 mmol, 1.0 equiv), LiOtBu (0.12 mmol, 1.2
equiv), p-TsNHNH2 (0.1 mmol, 1.0 equiv), [Co(TPP)] (5 mol%), benzene (1 mL),
60 C, overnight. For 13-16: (0.1 mmol, 1.0 equiv), LiOtBu (0.12 mmol, 1.2
equiv), p-TsNHNH2 (0.1 mmol, 1.0 equiv), [Co(TPP)] (10 mol%), benzene (1
mL), room temperature, 48 h. [b] Isolated yield, corrected for the E/Z ratios of
the substrates.
We next explored the substrate scope for 8-membered
monobenzocyclooctadiene ring synthesis. We first looked at the
effect of different aromatic ring substituents on the efficacy of the
reaction (Table 2). In general, good yields were obtained, but we
found that substrates containing electron-withdrawing groups (13-
16) are not very stable when heated in presence of base. This
explains the lower yield of the corresponding products obtained
under the standard reaction conditions (60 C, 5 mol% catalyst).
To solve this problem we lowered the reaction temperature while
slightly increasing the catalyst loading to suppress base-mediated
substrate decomposition. With these slightly modified reaction
conditions, monobenzocyclooctadienes 13a-16a could be
obtained in good yields. For the most part, substrates with either
Inspired by the flexibility and functional group tolerance of
this protocol, we wondered if 8-membered ring formation would
still be possible when the benzylic moiety in the substrates is
replaced by an allylic moiety. We therefore continued our
investigations by testing bis-allylic substrate 5 (Table 2, R1 = H) in
the metalloradical ring-closure protocol. While we expected to
observe 6-membered ring formation in this case, to our surprise
this substrate still produced the 8-membered ring in a high yield,
thus opening up the catalytic synthesis of
a range of
3
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10.1002/anie.202002674
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RESEARCH ARTICLE
electron-withdrawing or electron-donating groups on the aromatic
ring afforded the desired products in good yields, but substrates
with electron-donating groups produced the monobenzocyclo-
octadienes in slightly higher yields. The experimental results also
indicate that the substitution pattern on the phenyl ring or the
presence of an extended aromatic system do not have a
pronounced effect on the yield of the reaction. Notably, the
experimental observations also indicated that heating is not a
strict requirement to convert the N-tosylhydrazones to the
required diazo compounds, thus enabling us to expand the
substrate scope to less stable substrates and simplifying the
mode of operation of these reactions.
To further expand the scope, we explored the possibility of
8-membered ring formation from substrates containing different
substituents on the terminal allyl moiety (Table 3). Since the
terminal vinyl group is directly involved in the ring-closing step
(regardless of the mechanism), the introduction of substituents on
this C=C double bond was expected to have a large steric,
electronic and geometric influence on the intermediates and
transition states leading to the desired product, and hence low(er)
yields were anticipated. However, quite unexpectedly, the desired
8-membered structures were still obtained in decent to good
yields (56-86%, depending on the substituents). For substrate 20,
several by-products were generated upon heating the reaction
mixture to 60 ºC, but lowering the reaction temperature and
increasing the catalyst loading allowed us to obtain the
8-membered ring product in good yield (79%). Substrate 24 did
not cyclize to the desired monobenzocyclooctadiene, but this is
not surprising considering the high torsional energy required to
generate the intermediate and in view of the expected instability
of the ring-strained product.
unidentified) products in the catalytic reaction. Notably, double
bond isomerization leading to formation of conjugated dienes also
prevented us from synthesizing various substrates with different
substituents on the internal C=C double bond (see caption of
Table 4, with R2= -Ph, -SO2Me and -C(O)NMe2. See ESI for
details). For 25, the accessibility of unwanted side reactions due
to in situ carbene formation from the ketone might also play a role
(see ESI for details).
Overall, the above observations show that these cobalt-
catalysed reactions are compatible with a wide variety of
substituents and with overall excellent chemoselectivity. In
addition, the reaction can be carried out in (near) gram scale, and
even lowering the catalyst loading to 1 mol% did not have an
obvious influence on the yield (Scheme 2).
The molecular structures of monobenzocyclooctadiene
products 13a and 19a were confirmed by single crystal X-ray
diffraction, as shown in Figure 3 (see ESI for details).
Scheme 2. Catalytic monobenzocyclooctadiene synthesis performed at larger
scale.
Table 4. Substrate scope of monobenzocyclooctadiene synthesis, varying the
substituent on the internal C=C double bond.[a, b]
Figure 3. Molecular structures of 13a (left) and 19a (right), as determined by
single crystal X-ray diffraction. Selected bond distances [Å] for 13a: C1C2
1.530(2); C2C3 1.501(2); C3C4 1.334(2); C4C5 1.478(2); C5C6 1.374(1);
C6C7 1.471(2); C7C8 1.405(2); C8C1 1.506(2). For 19a: C1C2 1.536(2);
C2C3 1.504(2); C3C4 1.328(2); C4C5 1.473(2); C5C6 1.341(2); C6C7
1.469(2); C7C8 1.399(2); C8C1 1.501(2).
To gain a better understanding of the mechanism, the
generation of 5a from substrate 5 was investigated by DFT
calculations (Scheme 3). First, aldehyde substrate 5 is in situ
converted to the corresponding N-tosylhydrazone and diazo
compound 5’ by a non-catalyzed process. Diazo compound 5’ is
trapped and activated by the cobalt(II) catalyst (intermediate B) to
[a] Reaction conditions: 25,26 (0.1 mmol, 1.0 equiv), LiOtBu (0.12 mmol, 1.2
equiv), p-TsNHNH2 (0.1 mmol, 1.0 equiv), [Co(TPP)] (5 mol%), benzene (1 mL),
60 C overnight. [b] Isolated yield, corrected for the E/Z ratios of the substrates.
To further explore the generality of the reaction, substrates
varying in substituents on the internal C=C double bond were
synthesized (Table 4). While both substrates 25 and 26 afforded
the desired monobenzocyclooctadienes, replacing the ester at
this position for an acetyl or cyano group proved to have a
damping effect on the obtained yields. This behavior seems to be
related to the low thermal stability of 26 toward double bond
isomerization, thus resulting in formation of other (yet
produce cobalt(III)-carbene radical intermediate
C through
irreversible, exergonic dinitrogen loss via low barrier (+11.3 kcal
mol-1) transition state TS1. Subsequently, H-atom transfer (HAT)
from the terminal allylic position to the carbene radical carbon
affords delocalized allyl radical intermediate D. This process is
also exergonic with a low barrier (TS2, barrier +8.1 kcal mol-1).
4
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Scheme 3. Proposed mechanism for the [Co(porphyrin)]-catalyzed formation of monobenzocyclooctadienes, based on DFT calculations (BP86, def2-TZVP, m4
grid, disp3). All Gibbs free energies (G333K in kcal mol-1) including those of TS1–TS4, are reported relative to the energy of intermediate A. The ellipse represents
the porphyrin ligand. To reduce computation time, a COOMe group and a simplified porphyrin without phenyl substituents on the meso-positions were used.
The first steps of the mechanism (from A to D) are similar to
those proposed for closely related ring-closure reactions of
carbene precursors, catalyzed by [Co(TPP)].[12, 13, 17-21] For these
reactions, PBN spin trapping experiments confirmed formation of
carbene radical complexes of type C,[12,17] which have also been
detected in relation to cyclopropanation reactions.[13c,d]
process is ring-closure via a radical-rebound step in the
coordination sphere of cobalt, in which the terminal carbon atom
of the allyl radical moiety of D attacks the antibonding orbital of
the cobalt(III)-carbon bond, leading to simultaneous CC bond
formation and homolysis of the weak CoC bond (TS4) to form
product 5a in an exergonic process (ΔG333K = 24.4 kcal mol-1)
with regeneration of the cobalt(II) catalyst. This process has a low
barrier of only +10.5 kcal mol-1 (Scheme 3, blue arrows). An
alternative pathway involves dissociation of o-QDM intermediate
E from intermediate D (and the regenerated cobalt(II) catalyst) by
a homolysis reaction of the weak CoC bond that is decoupled
from the CC bond forming ring-closure step (Scheme 3, red
arrows). The final product 5a is then formed by a non-catalyzed,
exergonic and low-barrier re-aromatizing 8-cyclization step
(Scheme 3, red arrows, TS3).
We also computed the energy barriers for the various
mechanisms leading to formation of the thermodynamically more
stable 6-membered 1,2-dihydronaphthalene ring product from
intermediate D. However, in good agreement with the
experimental results, the energy barriers for those reactions are
all much higher than those leading to the 8-membered ring
product, thus explaining the experimentally observed formation of
monobenzocyclooctadienes as the kinetically favored products
(see ESI for more details). The transition states for 6-membered
ring formation cannot adopt a favorable boat conformation in
these reactions, which probably contributes to the kinetic
preference for formation of 8-membered rings. The reaction is
highly chemoselective and no 6-membered ring product is formed
at all.
To gather more experimental data about the 1,6-HAT
process in TS2 we decided to perform kinetic H,D-isotope
competition
experiments.
Unfortunately,
selective
(mono)deuteration of substrate 5 is non-trivial. Therefore we
performed these studies on a related cyclization producing a
6-membered (piperidine) ring.[21] This reaction also proceeds via
an intramolecular radical-type 1,6-HAT step, similar to TS2
connecting C and D in Scheme 3, as could be confirmed by a
combination of intermolecular (kH/kD= 1) and intramolecular
(kH/kD= 8.5) kinetic isotope effect (KIE) measurements (see ESI
for details). Furthermore, the data show that the HAT step in these
ring-closure reactions is not rate-limiting, in good agreement with
the DFT calculations (see also ref [21]). The experimentally
determined intramolecular KIE (kH/kD= 8.5) is a bit larger than the
DFT calculated value (kH/kD= 4.1) based on the harmonic
oscillator approximation in the gas phase (333 K), which is
perhaps caused by solvation effects or a tunneling contribution to
the 1,6-HAT process. Similar inter- and intramolecular KIE values
were measured for the [Co(TMP)]-catalyzed cyclization of
(4-azidobutyl)benzene to the corresponding pyrrolidine product,
which proceeds via a 1,5-HAT process involving a nitrene radical
intermediate.[25]
From D, two competitive pathways for formation of the final
product 5a are conceivable, each with similar barriers. One
5
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RESEARCH ARTICLE
Conclusions
Relative to the energy of species D, the overall barrier of the
8-cyclization (TS3) is computed to be ~4 kcal mol-1 higher than
the barrier of the radical-rebound process (TS4). The DFT data
thus suggest that the reaction might proceed via a metal-
catalyzed ring-closure step in the coordination sphere of cobalt,
involving radical-rebound transition state TS4, which is of
relevance for the development of enantioselective reactions (vide
infra). However, since the TS3 pathway via o-QDM E is
associated with a significant entropy change (which is difficult to
compute), distinguishing between the TS3 and TS4 pathways
solely on the basis of DFT is not reliable (also because the ring-
closing mechanism could very well be dependent on the applied
reaction temperature).
In conclusion, cobalt(II) metalloradical catalysis enables the
synthesis of two types of 8-membered ring compounds. Both
dibenzocyclooctenes and unprecedented monobenzocycloo-
ctadienes are readily obtained. The method described in this
paper has a broad substrate scope, thus allowing the synthesis of
a variety of new 8-membered ring compounds in good yields and
with excellent functional group tolerance. The carbene precursor
in this reaction is prepared by reacting the corresponding
aldehyde with p-toluenesulfonyl hydrazide in one pot, which
greatly simplifies the experimental operation. The reactions
proceed via initial hydrogen atom transfer from the bis-
allylic/benzallylic CH bond to the carbene radical, followed by
two different ring-closure steps leading to the two types of
8-membered ring products. While the dibenzocyclooctenes are
formed by dissociation of o-QDMs that undergo a non-catalyzed
ring-closure via 8-cyclization, DFT calculations suggest that the
monobenzocyclooctadienes are likely formed via a radical-
rebound step in the coordination sphere of cobalt, thus allowing
enantioselective formation of chiral monobenzocyclooctadienes,
as supported by our initial results.
Hence, to get more information about the reaction
mechanism and to explore the prospects for enantioselective
formation of 8-membered rings, we decided to perform the ring-
closure reaction of substrate 18 and 19 using Zhang’s
D2-symmetric chiral catalyst [CoII(3,5-di(tBu)ChenPhyrin)].[26]
Interestingly,
monobenzocyclooctadienes
initial
results
can be
demonstrate
obtained
that
an
in
enantioselective manner and with similar yields as with
[CoII(TPP)] (Table 5). While the obtained enantiomeric excesses
are moderate at present, the results clearly show that catalytic
enantioselective 8-membered ring synthesis via a carbene radical
intermediate is possible. The mechanistic implications of these
results currently remain a bit ambiguous. The data strongly
suggest that ring-closure proceeds via the TS4 pathway. However,
we cannot fully exclude the TS3 pathway based on these results,
because ring-closure of o-QDM intermediate E via TS3 could in
principle also occur in an enantioselective manner via H-bonding
interactions with the catalyst in the second coordination
sphere.[26, 27] We are currently investigating the origin of the
enantioselectivity and are trying to obtain the products in a higher
enantiomeric excess.
Acknowledgements
We thank Ed Zuidinga for HRMS measurements. Financial
support from the Netherlands Organization for Scientific
Research (NWO ARC CBBC), the University of Amsterdam
(Research Priority Area Sustainable Chemistry) and the China
Scholarship Council for a PhD fellowship (CSC 201806050112) is
gratefully acknowledged.
Conflict of interest
Table 5. First attempts towards enantioselective [Co(porphyrin)]-catalyzed
synthesis of monobenzocyclooctadienes.[a]
The authors declare no conflict of interest.
Keywords: carbene radicals • cobalt • dibenzocyclooctenes •
monobenzocyclooctadienes • metalloradicals • radical-rebound •
o-quinodimethanes
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Table of Contents
Back in the ring! An efficient strategy based on metalloradical catalysis for the synthesis of 8-membered ring compounds has been
developed. Both dibenzocyclooctenes and monobenzocyclooctadienes can be obtained in high yields under mild reaction conditions.
DFT calculations indicate different ring-closure pathways for the formation of these two structures. The methodology described in this
paper could be applied to the synthesis of e.g. natural products, fragrances, specialty chemicals and ligands.
8
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