Room-temperature synthesis of trisubstituted allenylsilanes via regioselective c-h functionalization

Article abstract of DOI:10.1021/ja409861s

A Rh(III)-catalyzed o-C-H bond functionalization-based allenylation reaction of allenylsilanes 2 with N-methoxybenzamides 1 affords poly-substituted allenylsilanes with a wide range of attractive functional groups in moderate to excellent yields under very mild conditions (20 C, compatible with ambient air and moisture). Those products may be transformed to different products with attractive structural features. Careful mechanistic studies suggest the reaction proceeds via o-rhodation, regioselective insertion, and β-H elimination.

Full text of DOI:10.1021/ja409861s

Communication
pubs.acs.org/JACS
Room-Temperature Synthesis of Trisubstituted Allenylsilanes via
Regioselective C−H Functionalization
Rong Zeng, Shangze Wu, Chunling Fu, and Shengming Ma*
Laboratory of Molecular Recognition and Synthesis, Department of Chemistry, Zhejiang University, Hangzhou 310027, Zhejiang,
P. R. China
S
* Supporting Information
afford allenylation products (Scheme 1, b). Herein, we report the
ABSTRACT: A Rh(III)-catalyzed o-C−H bond function-
alization-based allenylation reaction of allenylsilanes 2 with
N-methoxybenzamides 1 affords poly-substituted allenyl-
silanes with a wide range of attractive functional groups in
moderate to excellent yields under very mild conditions
(20 °C, compatible with ambient air and moisture). Those
products may be transformed to different products with
attractive structural features. Careful mechanistic studies
suggest the reaction proceeds via o-rhodation, regioselec-
tive insertion, and β-H elimination.
first example of such a C−H functionalization-based room-
temperature (rt) allenylation reaction of allenylsilanes with
arenes affording the desired extra-substituted allenes (Scheme 1,
b) by applying the versatile silyl functionality as the directing
group, observing the β-H elimination of Rh−C−C−H at rt, or
even at −20 °C.
First, although the regioselectivity of the carbometalation of
allenes forming intermediate M2 was confirmed by the reaction
of arene 1a with 1,1-dialkyl-substituted allene 2a in the presence
of 2 mol% of [Cp*RhCl2]2 and 30 mol% of CsOAc in MeOH/
H2O at −20 °C, as expected, protonolysis occurred exclusively,
affording 82% of allylation product 4aa (entry 1, Table 1).6
Interestingly, it was observed that 1,1-disubstituted allene 2b,
with a slightly bulkier phenyl substituent compared to 2a, in the
presence of 2 mol% of [Cp*RhCl2]2 and 30 mol% of CsOAc in
MeOH/H2O at −20 °C, afforded 62% of the normal insertion-
protonolysis product 4ab, together with a new allene compound
3ab, albeit in 3% yield as judged by NMR analysis of the crude
product (entry 2, Table 1), confirming the steric effect of the
phenyl group as shown in Scheme 1. Furthermore, it is noted that
this β-H elimination for allene synthesis may occur at −20 °C;
such a reaction for alkene synthesis may generally require a high
temperature.3 Moreover, when the tert-butyl-substituted sub-
strate 2c was applied, the more-substituted allenylation product
t is well established that Ar−Rh species may be formed readily
1,2 Such intermediates may react with
Ivia C−H bond cleavage.
alkenes to afford the Heck-type substituted olefins via β-H
elimination at high temperatures (60−140 °C).3 However, upon
reacting with allenes, there is an issue of regioselectivity4 in
forming cyclization products5 via π-allyl metal intermediates M1
or protonolysis products6 via alkenyl metal intermediates M2
because a C−Rh bond favors protonolysis over β-H elimination.7
Such Rh-catalyzed reactions of allenes, forming Heck-type more-
substituted allene products, have never been realized since β-H
elimination forming allenes is usually believed to be thermally
unfavorable due to a much higher energy level of this class of
compounds as compared to M2 (Scheme 1, b). We propose that
the steric effect of the R1/R2 groups of geminal-disubstituted
allenes may direct the R group in R−M to the 1-position of
allenes, affording alkenyl metal intermediates M2 (Scheme 1,
lower). Moreover, the bulkier R1/R2 groups may further push the
transition metal M in M2 for a greater agostic interaction with the
Ha atom at the 1-position, promoting facile β-H elimination to
Table 1. The Substituent Effect
Scheme 1. Carbometalation of Allenes with R−M Species
NMR yield, %
entry
R
M
temp, °C 3 (X = H) 1 (X = OMe)
4
1
2
3
4
5
6
7
8
Bu
Cs
Cs
Cs
Cs
Na
Na
Na
Na
−20
−20
−20
−20
−20
−15
−10
20
− (3aa)
3 (3ab)
− (1aa)
− (1ab)
8 (1ac)
− (1ad)
− (1ad)
− (1ad)
− (1ad)
− (1ad)
82 (4aa)
62 (4ab)
4 (4ac)
Ph
tBu
70 (3ac)
41 (3ad)
51 (3ad)
64 (3ad)
80 (3ad)
91 (3ad)
TMS
TMS
TMS
TMS
TMS
− (4ad)
− (4ad)
− (4ad)
− (4ad)
− (4ad)
Received: September 26, 2013
Published: November 12, 2013
© 2013 American Chemical Society
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Journal of the American Chemical Society
Communication
3ac was formed in 70% yield as the major product together with
only 4% of insertion-protonolysis product 4ac, detected in the
reaction by NMR analysis of the crude product (entry 3, Table
1). For the major product 3ac, there is no methoxy group in the
final product, indicating that it may act as an intramolecular
oxidant.2 Based on such results, we considered that this tert-butyl
may be replaced with a synthetically more attractive trialkylsilyl
group: in the presence of 2 mol% of [Cp*RhCl2]2 and 30 mol%
of CsOAc in MeOH/H2O at −20 °C, the reaction of allenylsilane
2d with 1.0 equiv of 1a exclusively afforded “more-substituted”
allenylation product 3ad in 42% yield, and no insertion-
protonolysis product 4ad was detected. When CsOAc was
replaced with NaOAc, the yield of 3ad was improved to 51%
(entry 4, Table 1). The yield was further improved by elevating
the temperature (entries 5−8, Table 1), and finally we found that,
when the reaction was conducted at 20 °C, 3ad was formed in
91% yield (entry 8, Table 1), so this was defined as the standard
conditions for further investigation.
With this set of optimized reaction conditions, the scope of C−
H allenylation of allenes via C−H functionalization of arenes is
demonstrated with a variety of differently substituted N-
methoxybenzamides (1a−1g) and allenes (2d−2j). Gratifyingly,
good to excellent yields for the allenylation of arenes were
generally obtained for most of the substrates at rt (Table 2). The
reaction provided the allenylation products 3 regardless of the
substrates 1 with either electron-donating substituents, such as 4-
OMe (1b) and 4-But (1c), or synthetically attractive electron-
withdrawing groups, such as 4-Br (1d), 4-Cl (1e), 4-COOMe
(1f), and 3-CF3 (1g); when N-methoxy-3-trifluoromethylbenz-
amide 1g was applied, the reaction occurred highly selectively at
the o-C−H with less steric hindrance, affording the correspond-
ing allenylation product 3gd in 91% yield (entry 7, Table 2);
carbon−halogen bonds (1d,1e) and ester group (1f) were
tolerated, affording the corresponding C−H allenylation
products 3dd−3fd in good yields (entries 4−6, Table 2). The
R1 substituent of silyl allenes 2 could be alkyl (2d−2g) or phenyl
(2h); the c-Pr group with a highly strained ring was also tolerated
(2g). Intriguingly, when terminal allenes 2i,2j with different
functionalities were treated with arene 1a, the corresponding
allenylation products 3ai,3aj were afforded in moderate yields,
and all these functionalities, such as the ester group of 2i (entry
12, Table 2) and the silyl ether group of 2j (entry 13, Table 2),
remained untouched. Gratifyingly, large-scale reactions of 1a,1e
with 2d also afforded 3ad,3ed in 85% and 80% yield, respectively
(entries 14 and 5, Table 2).
When N-methoxy-2-naphthamide 1h was used in the reaction,
the 3-position C−H bond with less steric hindrance was
selectively functionalized to afford the corresponding product
3hd in 76% yield (Scheme 2, a), with no reaction at the 1-
position C−H bond of the naphthyl skeleton. Interestingly,
treatment of N-methoxybenzo[d][1,3]dioxole-5-carboxamide 1i
with 2d provided the 4-position allenylation product 3id in 84%
yield; the reaction occurred at the C−H bond with more steric
hindrance, with no 6-position C−H allenylation product
(Scheme 2, b), which may be explained by a coordination effect
between the oxygen atom at the 3-position and the transition
metal.8
Scheme 2. Selective Heck Allenylation of 1h,1i with 2d
Table 2. Rh(III)-Catalyzed Heck Allenylation Reactions of N-
a
Methoxybenzamides 1 with Silyl Allenes
To further probe the reaction mechanism, firstly, the intra- and
intermolecular kinetic isotope effects (KIEs, kH/kD) of C−H
bond cleavage were determined to be ∼5.1:1, respectively, by
reacting 1a-D and 1a-D5 with 2d (Scheme 3, a,b). The KIE of
the β-H elimination process had been determined to be 1.6:1 by
using 2d-D as the substrate.
entry
R
R1
time, h yield of 3, %
1
2
3
4
H (1a)
Bu (2d)
Bu (2d)
Bu (2d)
Bu (2d)
Bu (2d)
Bu (2d)
Bu (2d)
11
11
12
11
16
14
36
14
72
16
59
36
16
13
91 (3ad)
86 (3bd)
85 (3cd)
85 (3dd)
80 (3ed)
86 (3fd)
91 (3gd)
84 (3ae)
86 (3af)
84 (3ag)
59 (3ah)
63 (3ai)
82 (3aj)
85 (3ad)
4-OMe (1b)
4-tBu (1c)
4-Br (1d)
4-Cl (1e)
4-CO2Me (1f)
3-CF3 (1g)
H (1a)
Furthermore, to capture the Rh intermediate before β-
elimination, 3-(dimethylphenyl)silyl-1,2-butadiene 2k was pre-
pared as the probe substrate: besides 70% of allenylation product
3ak, the reaction at −20 °C afforded 7% of insertion-protonolysis
product 4ak; in comparison, the reaction at 20 °C afforded the
corresponding allenylation product 3ak in 78% yield, exclusively
(Scheme 4, a). These facts indicate that the reaction should
proceed through the Rh(III) intermediate Int 2, which
undergoes a β-H elimination to afford 3ak exclusively at rt or
partial protonolysis, producing 4ak, at −20 °C (Scheme 4, b).
This conclusion was further confirmed by running the reaction in
CD3OD/D2O, yielding the product 4ak-D in 5% yield with 31%
of deuterium incorporation at the olefinic position. Moreover,
when the protonolysis product 4ak was subjected to the standard
conditions, no allenylation product was observed, and 86% of
4ak was recovered, even after stirring for 24 h. Even when the
b
5
6
c
7
8
nC5H11 (2e)
9
H (1a)
Bn (2f)
c
10
H (1a)
Pr (2g)
d
11
H (1a)
Ph (2h)
12
13
H (1a)
CH2CO2Et (2i)
(CH2)2OTBS (2j)
Bu (2d)
H (1a)
b
14
H (1a)
a
Reaction was conducted with 1 (1.0 mmol), 2 (1.0 mmol),
[Cp*RhCl2]2 (0.02 mmol), NaOAc (0.3 mmol), MeOH (6 mL),
and H2O (0.3 mL), and monitored by TLC. Reaction was conducted
on 10 mmol scale. Reaction occurred at the C−H bond with less
steric hindrance. 3.0 equiv of 1a and 4 mol% of [Cp*RhCl2]2.
b
c
d
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Journal of the American Chemical Society
Communication
generated HOAc affords the intermediate Int 3. This is followed
by a very fast β-H elimination, yielding the intermediate Int 4,
with which the Rh(I) species coordinates with the amide
functionality. Reductive elimination forming HOAc, oxidative
addition of Rh(I) with C(O)−OMe bond, and protonolysis with
HOAc would remove the methoxy group from the amide
functionality and regenerate the catalytically active Rh(III)
species. Thus, the N-methoxy group leaves the product as an
efficient intramolecular oxidant2 to finish the catalytic cycle.
Scheme 3. Kinetic Isotopic Experiments
Scheme 5. Possible Mechanism
reaction of 1a and 2k was conducted in the presence of 4ak at 20
°C for 18 h, 4ak was recovered in ∼100% NMR yield, with 3ak
still being formed in 80% yield. These facts exclude the possibility
that 3ak originated from the dehydrogenative elimination of 4ak
(Scheme 4, c).
Scheme 4. Mechanistic Studies
Finally, the synthetic potentials of the prepared 2-
(silylallenyl)benzamides were examined (Scheme 6): (a) Alkyne
5a could be afforded in 78% yield by treating the product 3ad
with 2.5 equiv of TiCl4 in dichloromethane at −78 °C for 2 h.9
Scheme 6. Application of the Products
Based on this evidence, a plausible mechanism for this reaction
is proposed as shown in Scheme 5. The first step of the
transformation should be C−H bond rhodation of 1a in the
presence of NaOAc, providing cyclic intermediate Int 1,2−6
followed by insertion of allene to afford the sp2 C−Rh
intermediate Int 2,4 exclusively, as controlled by the steric effect
of both the R and [Si] groups. Protonolysis with the in situ-
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Journal of the American Chemical Society
Communication
2011, 133, 6449. (c) Wang, H.; Grohmann, C.; Nimphius, C.; Glorius,
(b) Product 3ad could serve as alkynylation reagent to react with
acetyl chloride in the presence of AlCl3. Subsequent cyclization
reaction would afford substituted furan product 6a in moderate
yield.9 (c) The isoquinolinone products 7a and 7b could be
obtained by K3PO4-promoted cyclization reaction of 3 in toluene
at 110 °C. (d) The product 7b could be further converted to 7c
by desilylation reaction in the presence of TBAF and Selectfluor
reagent in excellent yields.9 (e) Diarylation product 7d, whose
structure was confirmed by single-crystal X-ray diffraction
study,10 could be formed in a decent yield by Suzuki coupling
reaction of 7b with aryl boronic acid in the presence of Pd(OAc)2
and LB-Phos.11
In conclusion, we have developed the first example of a direct
allenylation reaction of allenes with N-methoxybenzamides via
C−H bond cleavage, allene insertion, and β-H elimination
affording useful 2-(3-silylallenyl)benzamides. These reactions
proceed at 20 °C and are compatible with ambient air and
moisture. Moreover, a wide range of both arenes and
allenylsilanes with many synthetically attractive functionalities
are applicable for this reaction. The products obtained could be
used for the highly stereoselective synthesis of substituted
alkynes, furans, and isoquinolinones. Considering the easy
availability of the starting silylallenes12 and N-methoxybenz-
amides and the broad applications of the products, this protocol
will be of high interest in organic chemistry and related
disciplines. Further studies in this area are being carried out in
our laboratory.
F. J. Am. Chem. Soc. 2012, 134, 19592. (d) Hyster, T. K.; Knorr, L.;
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of olefins: (a) Umeda, N.; Hirano, K.; Satoh, T.; Miura, M. J. Org. Chem.
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Chem. Soc. 2011, 133, 2350. (l) Park, S. H.; Kim, J. Y.; Chang, S. Org.
Lett. 2011, 13, 2372. (m) Wang, C.; Chen, H.; Wang, Z.; Chen, J.;
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F.; Zhao, W.; Du, Z.; Li, X. Angew. Chem., Int. Ed. 2012, 51, 11819.
(o) Zhang, J.; Loh, T.-P. Chem. Commun. 2012, 48, 11232. (p) Zheng,
L.; Wang, J. Chem.Eur. J. 2012, 18, 9699. (q) Schroder, N.; Besset, T.;
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Glorius, F. Adv. Synth. Catal. 2012, 354, 579. (r) Unoh, Y.; Hashimoto,
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Zhu, J. J. Am. Chem. Soc. 2013, 135, 468. In these reported cases, the β-H
elimination involving Rh occurred at 60−140 °C.
(4) For a review on the regioselectivity of carbometallation of allenes,
see: Bai, T.; Ma, S.; Jia, G. Coord. Chem. Rev. 2009, 253, 423.
(5) (a) Tran, D. N.; Cramer, N. Angew. Chem., Int. Ed. 2010, 49, 8181.
(b) Tran, D. N.; Cramer, N. Chimia 2011, 65, 271. (c) Wang, H.;
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ASSOCIATED CONTENT
* Supporting Information
Experimental procedures and spectroscopic characterization
data. This material is available free of charge via the Internet at
http://pubs.acs.org.
■
S
(6) (a) Zeng, R.; Fu, C.; Ma, S. J. Am. Chem. Soc. 2012, 134, 9597.
(b) Ye, B.; Cramer, N. J. Am. Chem. Soc. 2013, 135, 636.
AUTHOR INFORMATION
Corresponding Author
masm@sioc.ac.cn
Notes
■
(7) A theoretical study on conjugate addition vs Heck reaction: Peng,
Q.; Yan, H.; Zhang, X.; Wu, Y. J. Org. Chem. 2012, 77, 7487.
(8) Selected reports on C−H activation occurring at the C−H bond
with more steric hindrance in benzo[d][1,3]dioxole derivatives:
(a) Orito, K.; Horibata, A.; Nakamura, T.; Ushito, H.; Nagasaki, H.;
Yuguchi, M.; Yamashita, S.; Tokuda, M. J. Am. Chem. Soc. 2004, 125,
14342. (b) Padala, K.; Jeganmohan, M. Org. Lett. 2011, 13, 6144.
(c) Karthikeyan, J.; Haridharan, R.; Cheng, C.-H. Angew. Chem., Int. Ed.
2012, 51, 12343. (d) Chinnagolla, R. K.; Jeganmohan, M. Chem.
Commun. 2012, 48, 2030. (e) Padala, K.; Pimparkar, S.; Madasamy, P.;
Jeganmohan, M. Chem. Commun. 2012, 48, 7140. (f) Chan, W.-W.; Lo,
S.-F.; Zhou, Z.; Yu, W.-Y. J. Am. Chem. Soc. 2012, 134, 13565.
(g) Kornhaaß, C.; Li, J.; Ackermann, L. J. Org. Chem. 2012, 77, 9190.
(h) Parthasarathy, K.; Senthilkumar, N.; Jayakumar, J.; Cheng, C.-H.
Org. Lett. 2012, 14, 3478. (i) Padala, K.; Jeganmohan, M. Org. Lett. 2012,
14, 1134.
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
Financial support is acknowledged from National Natural
Science Foundation (Nos. 21232006 and 21172192) and
National Basic Research Program (No. 2011CB808700) of
China. S.M. is a Qiu Shi Adjunct Professor at Zhejiang
University. We thank Ruizhi Lu in this group for reproducing
̈
the results for synthesis of 3ae, 3aj, and 7a.
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(10) 7d: C H NOSi, MW = 377.59, triclinic, space group P1, final R
̅
24 31
indices [I > 2σ(I)], R1 = 0.0934, wR2 = 0.2574; R indices (all data), R1 =
0.1562, wR2 = 0.3161; a = 9.1348(16) Å, b = 10.404(2) Å, c = 13.375(3)
Å, α = 103.609(17)°, β = 94.386(16)°, γ = 108.491(17)°, V = 1155.8(4)
Å3, T = 293(2) K, Z = 2, reflections collected/unique 7410/4212 (Rint
=
0.0505); number of observations [>2σ(I)] 2214; parameters, 249.
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