Formal Allylation and Enantioselective Cyclopropanation of Donor/Acceptor Rhodium(II) Azavinyl Carbenes

Article abstract of DOI:10.1021/acs.orglett.0c04251

A highly efficient formal allylation of dihydronaphthotriazoles with alkenes under rhodium(II) catalysis is reported. Various allyl dihydronaphthalene derivatives were furnished via rhodium(II) azavinyl carbenes with moderate to good yields and excellent chemoselectivity. When monosubstituted alkenes are used, cyclopropanation occurs and good to excellent enantioselectivities have been achieved. Particularly noteworthy is the allylic C(sp2)-H activation instead of traditional C(sp3)-H activation in the formal allylation process.

Full text of DOI:10.1021/acs.orglett.0c04251

pubs.acs.org/OrgLett
Letter
Formal Allylation and Enantioselective Cyclopropanation of Donor/
Acceptor Rhodium(II) Azavinyl Carbenes
Zhili Liu, Lianfen Chen, Dong Zhu, and Shifa Zhu*
Cite This: Org. Lett. 2021, 23, 1275−1279
Read Online
sı
*
Metrics & More
Article Recommendations
Supporting Information
ACCESS
ABSTRACT: A highly efficient formal allylation of dihydronaphthotriazoles
with alkenes under rhodium(II) catalysis is reported. Various allyl
dihydronaphthalene derivatives were furnished via rhodium(II) azavinyl
carbenes with moderate to good yields and excellent chemoselectivity. When
monosubstituted alkenes are used, cyclopropanation occurs and good to
excellent enantioselectivities have been achieved. Particularly noteworthy is the
allylic C(sp2)−H activation instead of traditional C(sp3)−H activation in the formal allylation process.
Scheme 1. Rh(II)-Catalyzed Reaction of Terminal Alkenes
with 1,2,3-Triazoles
onor/acceptor carbenes have emerged as significant
D
reactive intermediates in related transformations,1 such
as C−H functionalization, cyclopropanation, etc. When the
donor group attenuates the reactivity, donor/acceptor carbenes
are more stable and often exhibit higher selectivity.1g,h
However, the chemistry of donor/acceptor carbenes is limited
by the potential safety issue of diazo compounds. Thus,
developing alternative and stable carbene precursors is highly
desired.
Recently, N-sulfonyl-1,2,3-triazole has become a hot topic in
chemistry due to their role as a source of donor/acceptor
carbene intermediates and versatile reactivity in the synthesis
of diverse nitrogen-containing heterocycles.2 Generally,
triazole in a reversible ring−chain tautomerization equilibrium
could give rhodium azavinyl carbene (Rh-AVC) in the
presence of rhodium(II) catalyst.3 Rh-AVC was equipped
with highly electrophilic carbenoid carbon and highly
nucleophilic α-imino nitrogen, thus particularly effective in
transannulation with unsaturated compounds.2c−i
In 2009, Fokin and co-workers reported the first Rh(II)-
catalyzed asymmetric cyclopropanation of stable and readily
available N-sulfonyl-1,2,3-triazoles with monosubstituted al-
kenes (Scheme 1a).4a Later, they found triazole generated in
situ reacted with an electron rich olefin, leading to the [2 + 3]
transannulation product (Scheme 1b).4b A similar trans-
formation was achieved by Anbarasan’s group with ether-
tethered ethylene utilized in 2014 (Scheme 1b).4c In
continuation of our interest in the development of metal
carbenoids,5 herein we report a novel Rh-catalyzed function-
alization of triazoles with alkenes, which enable the rapid
access of diverse allyl dihydronaphthalene via formal allylation
(Scheme 1c).
surprise, there was no cyclopropanation product detected.
Reducing the ratio of 2a/1a or changing the temperature
would diminish the yield of 3a (entries 6−8). In addition,
exploration of several other solvents resulted in decreased
yields (entries 9−11).
With the optimal reaction conditions in hand, we then
examined the scope and functional group tolerance of this
allylation reaction. As shown in Scheme 2, the reaction was
applicable to various substituted α-methylstyrenes. For
example, alkenes containing alkyl, halogen, ether, aryl, and
even sulfoxide groups on benzene ring were competent in this
reaction, producing formal allylation products 3a−o in 53−
90% yields. It is obvious that styrenes bearing donating groups
(3b−c, 3j−k, 3n−o, 75−90%) generally performed better than
Received: December 24, 2020
Published: February 3, 2021
We initiated our investigation by conducting the reaction of
dihydronaphthotriazole 1a and α-methylstyrene 2a under a
commonly used catalyst system (Table 1, entries 1−5), among
which Rh2(OPiv)4 exhibited superior reactivity by affording
the desired product 3a in 89% yield (entry 5, in bold). To our
https://dx.doi.org/10.1021/acs.orglett.0c04251
© 2021 American Chemical Society
Org. Lett. 2021, 23, 1275−1279
1275

Organic Letters
pubs.acs.org/OrgLett
Letter
a
Table 1. Optimization of the Reaction Conditions
Scheme 2. Substrate Scope of Triazoles and gem-
a
Disubstituted Alkenes
b
entry
cat (1 mol %)
2a (eq)
sol
temp (°C) 3a (%)
1
2
3
4
5
6
7
8
IPrAuCl
Pd(PhCN)2Cl2
CuI
2.0
2.0
2.0
2.0
2.0
1.0
2.0
2.0
2.0
2.0
2.0
DCE
DCE
DCE
DCE
DCE
DCE
DCE
60
60
60
60
60
60
40
80
60
60
60
NR
NR
NR
NR
89
42
37
51
NR
31
AgNTf2
Rh2(OPiv)4
Rh2(OPiv)4
Rh2(OPiv)4
Rh2(OPiv)4
Rh2(OPiv)4
Rh2(OPiv)4
Rh2(OPiv)4
DCE
9
10
11
CH3CN
toluene
DCM
59
a
The reaction was performed under N2 for 12 h; 1a (0.1 mmol), 60
b
mg of 4 Å M.S. (molecular sieve) in 1 mL of solvent. The yield of 3a
was determined by 1H NMR spectroscopy with dimethyl tereph-
thalate as the internal standard.
those bearing electron-withdrawing groups (3d−i, 65−77%).
In addition, the position (3f and 3i) and the number of
substituents (3n and 3o) had slight influence on the reaction
yield. Phenyl and sulfoxide groups on the α-methylstyrene only
gave the desired products 3l and 3m in moderate yields (67%
and 53%) probably due to poor solubility. Notably, the
reaction of tert-butyl-substituted alkene required higher
temperature (3c). Besides, the reaction could be carried out
at the 2 mmol scale and provided 3j without a noticeable
decrease of the yield (72%).
Other substituents on alkenes were also examined. Sterically
hindered, naphthyl-substituted alkenes afforded the products
3p and 3q in 74% and 61% yields, respectively. Alkenes
containing fluorenyl, acetal, and heteroaryl (such as
benzothiophenyl and benzofuranyl) groups also worked well
and furnished the corresponding allyl dihydronaphthalene
(3r−u) in good yields (78−85%). Surprisingly, the reaction of
alkene bearing bulky alkyl substituent at the β-position
succeeded in providing the expected product 3v in excellent
yield of 88%. However, another alkylalkene 2-ethylbutene
resulted in a messy situation and produced 3w in only 37%
yield, presumably due to the presence of β-C(sp3)−H. It is
worth mentioning that alkylalkene 3x, similar to 3w, was
synthesized in good yield (85%) under neat condition, of
which the structure was confirmed by X-ray diffraction analysis.
When 1a was treated with internal alkenes, unfortunately, none
of them gave the desired products (see details in Supporting
Information).
a
Reaction conditions: N2, 1 mol % Rh2(OPiv)4, 1 (0.2 mmol), 2 (0.4
b
c
mmol), 4 Å M.S. (120 mg), DCE (2 mL); isolated yield. 80 °C. 2
mmol of 1a, 0.5 mol % Rh2(OPiv)4. Neat reaction, 4 mL of
isobutylene solution (2.0 mol/L in DCM). N-Ms-protected triazole
was used instead.
d
e
Scheme 3. Substrate Scope of Alkenes with
Diazonaphthoquinone
a
To further investigate the scope applicability of this reaction,
triazoles with different substituents were next studied.
Significantly, triazoles featuring electron-withdrawing groups
(3aa) gave higher yields than those with electron-donating
groups (3y−z), but slightly lower yields than that with an
electron-neutral group (3a). The sulfonyl group of triazole
could also be Ms and gave the desired product 3ab in 39%
yield.
a
Reaction conditions: N2, 1 mol % of Rh2(OPiv)4, 4 (0.2 mmol), 2
(0.4 mmol), 4 Å M.S. (120 mg), DCE (2 mL), 12 h, isolated yield.
With the above encouraging results in hand, we moved on to
explore the feasibility of this methodology in the systems
involving diazo compounds (Scheme 3). Diazonaphthoqui-
none 4 was subjected to the reaction with α-methylstyrene
derivatives 2. To our delight, the reaction afforded formal
allylation products as expected, rather than the traditional
1276
https://dx.doi.org/10.1021/acs.orglett.0c04251
Org. Lett. 2021, 23, 1275−1279

Organic Letters
pubs.acs.org/OrgLett
Letter
cyclopropanation products.6 Various alkenes bearing electron-
donating, electron-withdrawing, as well as heteroaryl groups
were then tested under the standard conditions, giving
products 5a−f in moderate yields (53−67%). The relatively
low yields are probably caused by the oxygen atom that
exhibits a lower nucleophilic character than the nitrogen atom
of the azavinyl carbene.7 Other carbene precursors such as
benzotriazole and diazoindene were also tested; however, they
were not compatible with this allylation reaction (see details in
Supporting Information).
a
Scheme 5. Further Transformation of 3x
In addition to α-methylstyrene derivatives, we also
investigated the transannulation of naphthotriazole 1a with
styrene derivatives 6 in the presence of 1 mol % Rh2(S-
TFPTTL)4 (Scheme 4). Traditional cyclopropanation took
Scheme 4. Transannulation of Naphthotriazoles with
a
Monosubstituted Terminal Alkenes
a
b
c
Selectfluor, DCM, 60 °C. NBS, toluene/DCM, 70 °C. BF3·Et2O,
d
e
DCM, 0 °C, rt. m-CPBA, DCM, rt. 4-tBuC6H4SH, NFSI, CuCl,
B2Pin2, CH3CN, 45 °C; Ar = 4-tert-butylphenyl.
10.9 In addition, C−O and C−S bonds can also be constructed
according to Li’s10 and Zhu’s11 work, giving the desired
product 11 and 12 in 84% and 72% yield, respectively.
To clarify the mechanism, several control experiments were
carried out. First, the reaction of 1a with equivalent styrene
and α-methylstyrene afforded an isomeric mixture of 3a and 7a
in 97% total yield with a 1:2.7 ratio (Scheme 6a), clearly
a
Scheme 6. Control Experiments
a
Reaction conditions: N2, 1a (0.1 mmol), 6 (0.4 mmol), 1 mol %
Rh2(S−TFPTTL)4, 4 Å M.S. (100 mg), 1 mL of distilled DCM, 24 h;
isolated yield. 60 °C. 2 days.
b
c
place in the reaction of alkyl- and aryl-substituted alkenes,
giving cyclopropanes (7a−f) in moderate to high yields (46−
93%) and good enantioselectivities (85−97% ee). When it
came to ethyl vinyl ether as substrate, the introduction of an
ether functionality caused the formation of dihydropyrrole 7g′
in moderate yield, which was similar to phenomenon found by
Anbarasan and co-workers.4c Similarly, 1,1-diphenylethylene
6h, unlike styrene 6a, underwent further isomerization into
dihydropyrrole 7h′ in 45% yield. These results indicated the
selectivity of naphthotriazoles transformation could be easily
tuned by substituents of terminal alkenes. The absolute
configuration of cyclopropanes was confirmed by X-ray
diffraction analysis.
Further transformation of the allyl dihydronaphthalene
product 3x was then investigated to demonstrate the potential
synthetic utility of this reaction (Scheme 5). We treated 3x
with a variety of oxidants for aromatization, including TBHP,
DDQ, MnO2, and selectfluor. It turned out that only
selectfluor succeeded in the oxidation of 3x, furnishing
naphthalene 8 in 67% yield. Naphthalene 8 can undergo a
variety of 5-exocyclizations, delivering the corresponding
functionalized indolines 9−12 in moderate to excellent yields.
For example, bromoamination of 8 with N-bromosuccinimide
(NBS) afforded 2-(bromomethyl)pyrroline 9 in 58% yield.8
Treating 8 with boron trifluoride−diethyl ether gave rise to
almost quantitative yield of cyclization product dihydropyrrole
a
b
Reaction condition: N2, alkene (2 equiv), isolated yield. Ar1 = 4-
c
vinylphenyl, Ar2 = 4-isopropenylphenyl. Ar3 = 4-tert-butylphenyl.
indicating that cyclopropanation proceeded faster than
allylation and suggesting the former course possesses higher
reactivity. This result is also supported by another intra-
molecular competition reaction with the mixture products of
14 and 15 (1:3.3) in 66% total yield (Scheme 6b). When
methylstyrene d-2c (90% D) with deuterated methylene was
employed as substrate, the deuterium was introduced onto the
methylene carbon atom of the product d-3c without
1277
https://dx.doi.org/10.1021/acs.orglett.0c04251
Org. Lett. 2021, 23, 1275−1279

Organic Letters
pubs.acs.org/OrgLett
Letter
measurable scrambling of the isotope label (Scheme 6c). In
addition, the reaction of acyclic triazole 1f with α-
methylstyrene was also performed but the substrate decom-
posed into TsNH212 and no formal allylation product could be
detected (Scheme 6d), which implied the importance of the
cyclic effect of the triazole substrate (see details in the
Supporting Information for more control experiments).
Based on the above control experiments, a plausible reaction
mechanism of 1a with 2a is presented in Scheme 7. The
AUTHOR INFORMATION
Corresponding Author
■
Shifa Zhu − Key Laboratory of Functional Molecular
Engineering of Guangdong Province, School of Chemistry and
Chemical Engineering, South China University of Technology,
Guangzhou 510640, P. R. China; State Key Laboratory of
Elemento-Organic Chemistry, Nankai University, Tianjin
300071, P. R. China; orcid.org/0000-0001-5172-7152;
Email: zhusf@scut.edu.cn
Scheme 7. Proposed Mechanism of the Formal Allylation
Authors
Zhili Liu − Key Laboratory of Functional Molecular
Engineering of Guangdong Province, School of Chemistry and
Chemical Engineering, South China University of Technology,
Guangzhou 510640, P. R. China
Lianfen Chen − Key Laboratory of Functional Molecular
Engineering of Guangdong Province, School of Chemistry and
Chemical Engineering, South China University of Technology,
Guangzhou 510640, P. R. China
Dong Zhu − Key Laboratory of Functional Molecular
Engineering of Guangdong Province, School of Chemistry and
Chemical Engineering, South China University of Technology,
Guangzhou 510640, P. R. China
Complete contact information is available at:
https://pubs.acs.org/10.1021/acs.orglett.0c04251
Notes
reaction is initiated by electrophilic attack of Rh(II) into the
nucleophilic diazo compound 1a′, which exists in a closed/
opened form equilibrium with the triazole 1a.13 Subsequently,
nitrogen eliminates from 1a′ and rhodium carbenoid
intermediate A is generated. After nucleophilic attack of α-
methylstyrene 2a onto the electrophilic rhodium carbenoid
carbon of A, the formed charged transition state B undergoes
an intramolecular proton transfer to furnish the desired
product 3a and regenerates the dirhodium catalyst. The cis-
oriented CN geometry and the basic nitrogen atom might
facilitate the proton elimination of the C(sp3)H.
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
This work was supported by the Ministry of Science and
Technology of the People’s Republic of China
(2016YFA0602900), the NSFC (22071062, 21871096,
21672071), Guangdong Science and Technology Department
(2018B030308007, 2018A030310359).
REFERENCES
■
In summary, we have developed a formal allylation of
alkenes with rhodium azavinyl carbenes generated in situ from
dihydronaphthotriazoles. This unique process also can be
compatible with the diazo compounds. An intramolecular
proton transfer was proposed to account for the unusual
allylation reaction. When monosubstituted alkenes are used,
cyclopropanation is dominated and good enantioselectivities
have been achieved.
(1) For selected reviews: (a) Davies, H. M. L.; Antoulinakis, E. G.
Organic Reactions. 2001, 1−326. (b) Lebel, H.; Marcoux, J. F.;
Molinaro, C.; Charette, A. B. Chem. Rev. 2003, 103, 977−1050.
(c) Davies, H. M. L.; Beckwith, R. E. J. Chem. Rev. 2003, 103, 2861−
2904. (d) Davies, H. M. L.; Loe, Ø. Synthesis 2004, 2004, 2595−2608.
(e) Davies, H. M. L.; Hedley, S. J. Chem. Soc. Rev. 2007, 36, 1109−
1119. (f) Davies, H. M. L.; Manning, J. R. Nature 2008, 451, 417−
424. (g) Davies, H. M. L.; Denton, J. R. Chem. Soc. Rev. 2009, 38,
3061. (h) Davies, H. M. L.; Morton, D. Chem. Soc. Rev. 2011, 40,
1857−1869. (i) Zhu, S. F.; Zhou, Q. L. Acc. Chem. Res. 2012, 45,
1365−1377. (j) Davies, H. M. L. J. Org. Chem. 2019, 84, 12722−
12745.
ASSOCIATED CONTENT
■
sı
* Supporting Information
(2) (a) Gulevich, A. V.; Gevorgyan, V. Angew. Chem., Int. Ed. 2013,
52, 1371−1373. (b) Xia, Y.; Qiu, D.; Wang, J. Chem. Rev. 2017, 117,
13810−13889. For reviews on transannulation of triazoles, see:
(c) Chattopadhyay, B.; Gevorgyan, V. Angew. Chem., Int. Ed. 2012, 51,
862−872. (d) Davies, H. M. L.; Alford, J. S. Chem. Soc. Rev. 2014, 43,
5151−5162. (e) Anbarasan, P.; Yadagiri, D.; Rajasekar, S. Synthesis
2014, 46, 3004−3023. (f) Wang, Y.; Lei, X.; Tang, Y. Synlett 2015, 26,
2051−2059. (g) Jia, M.; Ma, S. Angew. Chem., Int. Ed. 2016, 55,
9134−9166. (h) Jiang, Y.; Sun, R.; Tang, X. Y.; Shi, M. Chem. - Eur. J.
2016, 22, 17910−17924. (i) Li, Y.; Yang, H.; Zhai, H. Chem. - Eur. J.
2018, 24, 12757−12766.
The Supporting Information is available free of charge at
https://pubs.acs.org/doi/10.1021/acs.orglett.0c04251.
Experimental details and characterization data of all new
compounds; structures, spectra, crystallographic data,
NMR spectra, and HPLC data (PDF)
Accession Codes
CCDC 1970500 and 2047547 contain the supplementary
crystallographic data for this paper. These data can be obtained
free of charge via www.ccdc.cam.ac.uk/data_request/cif, or by
emailing data_request@ccdc.cam.ac.uk, or by contacting The
Cambridge Crystallographic Data Centre, 12 Union Road,
Cambridge CB2 1EZ, UK; fax: +44 1223 336033.
(3) Horneff, T.; Chuprakov, S.; Chernyak, N.; Gevorgyan, V.; Fokin,
V. V. J. Am. Chem. Soc. 2008, 130, 14972−14974.
(4) (a) Chuprakov, S.; Kwok, S. W.; Zhang, L.; Lercher, L.; Fokin,
V. V. J. Am. Chem. Soc. 2009, 131, 18034−18035. (b) Grimster, N.;
1278
https://dx.doi.org/10.1021/acs.orglett.0c04251
Org. Lett. 2021, 23, 1275−1279

Organic Letters
pubs.acs.org/OrgLett
Letter
Zhang, L.; Fokin, V. V. J. Am. Chem. Soc. 2010, 132, 2510−2511.
(c) Rajasekar, S.; Anbarasan, P. J. Org. Chem. 2014, 79, 8428−8434.
(5) (a) Zhu, D.; Ma, J.; Luo, K.; Fu, H.; Zhang, L.; Zhu, S. Angew.
Chem., Int. Ed. 2016, 55, 8452−8456. (b) Chen, L.; Liu, Z.; Zhu, S.
Org. Biomol. Chem. 2018, 16, 8884−8898. (c) Chen, L.; Chen, K.;
Zhu, S. Chem. 2018, 4, 1208−1262. (d) Zhu, D.; Chen, L.; Zhang, H.;
Ma, Z.; Jiang, H.; Zhu, S. Angew. Chem., Int. Ed. 2018, 57, 12405−
12409. (e) Zhu, D.; Chen, L.; Fan, H.; Yao, Q.; Zhu, S. Chem. Soc.
Rev. 2020, 49, 908−950. (f) Luo, H.; He, C.; Jiang, H.; Zhu, S. Chin.
J. Chem. 2020, 38, 1052−1056. (g) Wu, R.; Chen, K.; Ma, J.; Yu, Z.
X.; Zhu, S. Sci. China: Chem. 2020, 63, 1230−1239.
(6) (a) Bertilsson, S. K.; Andersson, P. G. J. Organomet. Chem. 2000,
603, 13−17. (b) Chen, L.; Bovee, M. O.; Lemma, B. E.; Keithley, K.
S. M.; Pilson, S. L.; Coleman, M. G.; Mack, J. Angew. Chem., Int. Ed.
2015, 54, 11084−11087.
(7) Miura, T.; Tanaka, T.; Hiraga, K.; Stewart, S. G.; Murakami, M.
J. Am. Chem. Soc. 2013, 135, 13652−13655.
(8) Yu, S. N.; Li, Y. L.; Deng, J. Adv. Synth. Catal. 2017, 359, 2499−
2508.
(9) Bondalapati, S.; Indukuri, K.; Ghosh, P.; Saikia, A. K. Eur. J. Org.
Chem. 2013, 2013, 952−956.
(10) Liu, G. Q.; Li, L.; Duan, L.; Li, Y. M. RSC Adv. 2015, 5,
61137−61143.
(11) Li, D.; Mao, T.; Huang, J.; Zhu, Q. Chem. Commun. 2017, 53,
3450−3453.
(12) Zhu, C. Z.; Wei, Y.; Shi, M. Org. Chem. Front. 2019, 6, 2884−
2891.
(13) Kim, S.; Kim, J. E.; Lee, J.; Lee, P. H. Adv. Synth. Catal. 2015,
357, 3707−3717.
1279
https://dx.doi.org/10.1021/acs.orglett.0c04251
Org. Lett. 2021, 23, 1275−1279