Rhodium(III)-catalyzed transannulation of cyclopropenes with n-phenoxyacetamides through C-H activation

Article abstract of DOI:10.1002/anie.201408555

An efficient rhodium(III)-catalyzed synthesis of 2H-chromene from N-phenoxyacetamides and cyclopropenes has been developed. The reaction represents the first example of using cyclopropenes as a three-carbon unit in rhodium(III)- catalyzed C(sp²)-H activations.

Full text of DOI:10.1002/anie.201408555

Angewandte
Chemie
DOI: 10.1002/anie.201408555
Carbenes
Rhodium(III)-Catalyzed Transannulation of Cyclopropenes with
À
N-Phenoxyacetamides through C H Activation**
Hang Zhang, Kang Wang, Bo Wang, Heng Yi, Fangdong Hu, Changkun Li, Yan Zhang, and
Jianbo Wang*
Abstract: An efficient rhodium(III)-catalyzed synthesis of 2H-
chromene from N-phenoxyacetamides and cyclopropenes has
been developed. The reaction represents the first example of
using cyclopropenes as a three-carbon unit in rhodium(III)-
2
À
catalyzed C(sp ) H activations.
À
T
ransition-metal-catalyzed activation of C H bonds has
attracted considerable attention and significant progress has
been achieved.[1] Among the various directing-group-assisted
À
C H bond-activation systems developed recently, the
rhodium(III)-catalyzed reactions have been demonstrated
as effective transformations with remarkable diversity.[1b,g,i,2]
As summarized in Scheme 1, these transformations start from
À
the directing-group-assisted C H activation, thus generating
the rhodium(III) intermediate A, from which the reactions
may be categorized into three different types according to the
number of carbon units in the coupling partners participating
in the reaction. In the one-carbon insertion (Scheme 1a),
either isonitriles[3] or diazo compounds[4] are employed as the
2
À
Scheme 1. Rhodium(III)-catalyzed C(sp ) H activation.
À
substrates. The insertion of a one-carbon unit into the Rh C
bond generates the benzyl rhodium(III) species B. In the case
of two-carbon unit insertion, which forms the rhodium(III)
intermediate C (Scheme 1b), a wide range of unsaturated
components, including alkynes,[5] alkenes,[l,6] allenes,[7]
imines,[8] and isocyanates,[9] have been explored as the
substrates.
Although significant progress has been made in rhodium-
À
(III)-catalyzed C H activation, it is still highly desirable to
further expand this type of reaction. It is known that
cyclopropenes can also be used as vinyl metal carbene
precursors.[12] These highly strained unsaturated compounds
are excellent three-carbon units for organic synthesis. The
metal carbene species generated through ring opening
undergo typical carbene transformations, such as cyclopropa-
For the three-carbon insertion, to the best of our knowl-
edge there have been only two examples documented in the
literature. Cui and co-workers used vinyldiazo compounds as
the three-carbon components, thus generating the benzyl allyl
rhodium(III) intermediate D through rhodium(III) carbene
migratory insertion (Scheme 1c).[10] More recently, Yu and Li
[14]
nation,[13] C H insertion,
olefin metathesis,[15] and other
À
related rearrangement reactions.[16] Rovis and co-workers
have recently reported a rhodium(III)-catalyzed synthesis of
isoquinolones from amides and activated cyclopropenes
[17]
À
have used cyclopropenones as coupling partners in rhodium-
through C H activation. Although to our knowledge this
[11]
À
(III)-catalyzed C H activation.
is the first example using cyclopropenes as a coupling partner
À
in transition-metal-catalyzed C H activation, it is categorized
as the type shown in Scheme 1b where the cyclopropene
serves as an alkene, and the sp3-carbon atom of the cyclo-
propene does not participate in the newly formed ring
structure.
[*] H. Zhang, K. Wang, B. Wang, H. Yi, F. Hu, Dr. C. Li, Dr. Y. Zhang,
Prof. Dr. J. Wang
Beijing National Laboratory of Molecular Sciences (BNLMS) and
Key Laboratory of Bioorganic Chemistry and Molecular Engineering
of Ministry of Education, College of Chemistry
Peking University, Beijing 100871 (China)
In connection to our interest in both catalytic carbene
À
transformations and C H bond activation, we herein report
E-mail: wangjb@pku.edu.cn
À
a rhodium(III)-catalyzed C H bond activation of N-phenox-
Prof. Dr. J. Wang
The State Key Laboratory of Organometallic Chemistry
Chinese Academy of Sciences, Shanghai 200032 (China)
yacetamide with cyclopropenes, which are utilized as three-
carbon component to form the intermediate E (Scheme 1d).
This reaction employs an oxidizing directing group, which
[**] The project is supported by National Basic Research Program of
China (973 Program, No. 2015CB856600), Natural Science Foun-
dation of China (Grant No. 21272010 and 21332002).
À
contains an N O bond, and has recently been developed by
Liu, Lu, and co-workers.[5f,6d] The transformation provides an
efficient method for the synthesis of 2H-chromene[18] with
good yields and broad substrate scope.
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/anie.201408555.
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At the outset, N-phenoxyacetamide (1a)[19] and cyclo-
propene (2a) were used as the substrates to investigate this
reaction. Through extensive optimization of the reaction
conditions, the 2H-chromene product 3a could be obtained in
86% yield under the following reaction conditions: 1a
(0.1 mmol), 2a (0.13 mmol), [{RhCp*Cl2}2] (2.5 mol%),
CsOPiv (0.25 equiv), MeOH (2 mL), 258C, 5 min [Eq. (1);
Cp* = C5Me5, Piv = pivaloyl].[20]
yields (3i, j and 3k, l, respectively). Notably, cyclopropenes
bearing a heteroatom could also participate in the reaction.
Moreover, the reactions with the siloxymethyl-substituted
cyclopropene 2m and benzyloxymethyl-substituted cyclopro-
pene 2n proceeded smoothly, albeit with prolonged reaction
times (3m, n).
Next, the scope with respect to the N-phenoxyacetamides
was studied (Scheme 3). To our delight, various substituents
on the aromatic ring were tolerated and good to excellent
We next proceeded to study the scope of the reaction. A
series of 3,3-disubstituted cyclopropenes (2a–n) were first
examined (Scheme 2). It was found that the reaction was
affected by the steric bulk of the substituents on the sp3-
Scheme 3. Scope with respect to the N-phenoxyacetamides. Reactions
were carried out with 1b–l (0.20 mmol), 2a (0.26 mmol), [{RhCp*Cl2}2]
(2.5 mol%), and CsOPiv (0.25 equiv) in MeOH (4 mL) at 258C for
5 min under air. Yields are those of the products isolated after column
chromatography.
yields of the corresponding 2H-chromene products could be
obtained. Electronic effects do not significantly affect the
outcomes of the reaction. For the substrates substituted with
electron-withdrawing groups, the desired product 3v could be
obtained in 72% yield. It is noteworthy that vinyl, iodo,
bromo, and chloro substituents are tolerated under the
reaction conditions, and is beneficial for further transforma-
tions through coupling reactions (3q–s, 3x). In the case of
a meta-substituted substrate, 3y was detected as the major
Scheme 2. Scope with respect to the cyclopropenes. If not otherwise
noted, the reactions were carried out with 1a (0.20 mmol), 2a–
n (0.26 mmol), [{RhCp*Cl2}2] (2.5 mol%), and CsOPiv (0.25 equiv) in
MeOH (4 mL) at 258C for 5 min under air. Yields are those of the
products isolated after column chromatography. [a] Cyclopropene was
added as a solution in pentane (0.3m). [b] The reactions were carried
out with 1a (0.36 mmol), 2m, n (0.20 mmol) at 258C for 10 min under
air. Ad=adamantyl, TBS=tert-butyldimethylsilyl.
1
product by H NMR spectroscopy, and resulted from activa-
À
tion of the C H bond in the position para to the methyl group,
thus suggesting that the reaction is sensitive to steric effects
and occurs at the less-hindered site.
We propose a plausible mechanism as depicted in
Scheme 4. The reaction commences with anion exchange to
generate an active catalyst, [Cp*Rh(OPiv)2], which coordi-
carbon atom of the cyclopropene. When one of the substitu-
ents is a methyl group, the reaction results in moderate yields
(3a–g). The alkyl-substituted cyclopropene 2h could also give
the corresponding product 3h in decent yield. However,
cyclopropenes substituted with more bulky groups, and spiro-
cyclopropenes afforded the corresponding products in low
À
nates to 1a to form the intermediate F. Subsequent C H bond
cleavage results in the formation of the rhodacyclic inter-
mediate G, from which two possible pathways may be
followed. In path a, the cyclopropene is activated by G to
2
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Scheme 5. Deuterium exchange and KIE experiments.
Scheme 4. Proposed reaction mechanism.
generate the intermediate H, from which ring opening occurs
to form the rhodium(III) carbene I. Rhodium(III) carbene
migratory insertion from I affords the rhodacyclic intermedi-
ate J. Next, the eight-membered rhodacyclic intermediate K is
generated through 1,3-allylic migration, followed by intra-
Scheme 6. Competition experiment.
À
molecular substitution to form the C O bond and break the
[5f]
À
N O bond with the aid of acid. Finally, the product 3 is
formed along with the regeneration of the rhodium(III)
catalyst. Alternately, the reaction may follow path b. The
indicates that the electron-deficient 1h is only slightly more
reactive. The lack of significant electronic preference suggests
À
double bond of cyclopropene first inserts into the Rh C bond
that concerted metalation deprotonation (CMD) may be
[1e]
À
of G. Then, b-carbon elimination from M gives the rhodacy-
clic intermediate K, which undergoes the process as shown
above to afford 3.
responsible for the C H activation.
It has been noted that in one case a 1,3-diene is observed
as the byproduct (Scheme 2; 3l), thus suggesting the possi-
bility that the 2H-chromene products may be formed through
ring closure of 1,3-dienes. To verify such speculations, we
isolated the the byproduct 1,3-diene 4 in 30% yield when N-
phenoxyacetamide (1a) and spiro-cyclopropene (2l) were
used as the substrates in the reaction (Scheme 7). Subse-
quently, 4 was submitted to the standard reaction conditions.
None of the ring-closure product 3l was identified. This result
is contradictory to the speculation that 1,3-dienes are the
reaction intermediates. The generation of 1,3-diene is likely
associated with the steric bulk of R1 and R2, which would slow
down the conversion of K into L in the catalytic cycle shown
in Scheme 4. The 1,3-diene byproduct is formed through b-
hydride elimination from K.
To gain insight into the reaction mechanism, a series of
experiments were carried out (Schemes 5–8). First, 1a was
treated with [{RhCp*Cl2}2] and CsOPiv in CD3OD (Sche-
me 5a). After stirring for 0.5 minutes, 97% of 1a was
recovered and no deuterium incorporation was observed.
When the reaction was conducted with 1a and 2a in CD3OD
for 0.5 minutes, deuterium incorporation was not observed in
either the recovered 1a or the product 3a (Scheme 5b). These
À
results suggest that under the reaction conditions the C H
bond activation step is largely irreversible. The kinetic isotope
effects (KIE) were determined at 08C because of the high
conversion when carrying out the reaction at 258C. An
evident primary KIE value was observed (4.0 determined by
intermolecular competition and 3.4 determined by parallel
reaction, both at low conversion), thus indicating that the C
H bond-cleavage process is presumably the rate-determining
step (Scheme 5c).
Additional experiments have been carried out to identify
the effect of the substrate structure on the reaction
(Scheme 8). When O-pivaloyl benzhydroxamine (5) was
employed as the coupling partner in the reaction with 2h
under the standard reaction conditions, the cyclopropane
product 6 was isolated in 90% yield (Scheme 8a). The result,
which is consistent with those reported by Hyster and
À
Subsequently, competition experiments of equimolar
amounts of 1h and 1b under the standard reaction conditions
with 2a was carried out (Scheme 6). The ratio of the products
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In summary, we have demonstrated the use of cyclo-
propene as the three-carbon unit in rhodium(III)-catalyzed
À
C H bond activation. An efficient rhodium(III)-catalyzed
synthesis of 2H-chromene from N-phenoxyacetamides and
À
cyclopropenes through C H activation has been developed.
The reaction proceeds under mild reaction conditions at room
temperature and does not need external oxidants. A wide
range of substrates are tolerated in this transformation, and
various products can be obtained in good to excellent yields.
Received: August 26, 2014
Published online: && &&, &&&&
À
Keywords: carbenes · C H activation · heterocycles ·
small ring compounds · rhodium
.
Scheme 7. Rhodium(III)-catalyzed reaction of 1a and 2l.
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Scheme 8. Rhodium(III)-catalyzed reaction with various substrates.
Rovis,[17] suggests that the directing group plays the crucial
role in determining the reaction path.
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either the cyclopropene 7 or 8 was investigated (Scheme 8b).
The reactions gave neither the expected product 9 nor 10. The
results may be interpreted as follows: In path a of the
mechanism, H is destabilized because of the electron-with-
drawing ester substituents, while in the path b, the carbonyl
group of the ester substituent may stabilize the intermediate
M through coordination with rhodium, thus making b-carbon
elimination unfavorable.[21] Lastly, the vinyldiazoester 11 was
subjected to the reaction as a three-carbon component,[10] and
the anticipated product 12 was obtained, albeit in low yield
(Scheme 8c). This result supports path a of the mechanism
shown in Scheme 4. However, further studies are necessary to
unambiguously confirm the proposed reaction mechanisms.
4
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À
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Communications
Carbenes
H. Zhang, K. Wang, B. Wang, H. Yi, F. Hu,
C. Li, Y. Zhang, J. Wang*
&&&& — &&&&
Rhodium(III)-Catalyzed Transannulation
of Cyclopropenes with N-
The three C’s: An efficient rhodium(III)-
catalyzed synthesis of 2H-chromenes
from N-phenoxyacetamides and cyclo-
propenes has been developed. The reac-
tion represents the first example of using
cyclopropenes as a three-carbon unit in
2
À
rhodium(III)-catalyzed C(sp ) H activa-
À
Phenoxyacetamides through C H
Activation
tions. Preliminary mechanistic investiga-
tions are discussed.
6
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