Direct Intramolecular Aminoboration of Allenes

Article abstract of DOI:10.1021/acs.orglett.0c01685

Direct intramolecular aminoboration of sulfonamidoallenes was realized using BCl3 as a boron source. The reactions benefited from the interaction between BCl3 and sulfonamides and provided a variety of borylvinyl heterocycles in good isolated yields. When chiral substrates were involved in the reactions, high stereoselectivity was observed, as can be ascertained by single-crystal X-ray diffraction experiments. Derivatization of the thus-obtained borylvinyl compounds proceeded readily, and different functionalities could be obtained via oxidation, halogenation, and Suzuki coupling reactions.

Full text of DOI:10.1021/acs.orglett.0c01685

pubs.acs.org/OrgLett
Letter
Direct Intramolecular Aminoboration of Allenes
Chun-Hua Yang, Meng Han, Wenyan Li, Ningning Zhu, Zhenzhen Sun, Junjie Wang, Zhantao Yang,*
and Yue-Ming Li*
Cite This: https://dx.doi.org/10.1021/acs.orglett.0c01685
Read Online
ACCESS
Metrics & More
Article Recommendations
*
sı Supporting Information
ABSTRACT: Direct intramolecular aminoboration of sulfonamidoallenes was
realized using BCl3 as a boron source. The reactions benefited from the
interaction between BCl and sulfonamides and provided a variety of borylvinyl
3
heterocycles in good isolated yields. When chiral substrates were involved in the
reactions, high stereoselectivity was observed, as can be ascertained by single-
crystal X-ray diffraction experiments. Derivatization of the thus-obtained
borylvinyl compounds proceeded readily, and different functionalities could be obtained via oxidation, halogenation, and Suzuki
coupling reactions.
rganoboron compounds have drawn considerable
borylative cyclization of Ts-protected o-alkynylanilines with
4
O
attention, because of the easy transformation of boryl
B Pin provided indole boronic esters in good yields. With the
2
2
1
participation of B(C F ) , cyclizations of N,N-dimethyl o-
groups to a variety of functionalities, as well as the widespread
6 5 3
allylaniline, o-homoallylaniline, or o-alkynylanilines were
application of boronic acids in different C−C coupling
2
realized, yielding the desired cyclization products in good
reactions. To this end, significant efforts have been made
5
yields.
toward the preparation of boron compounds, and hydro-
boration of C−C multiple bonds could be regarded as the
most efficient method for the functionalization of alkenes or
Miura et al. reported Cu(I)-catalyzed stereospecific amino-
boration of alkenes, leading to the desired 1,2-aminoboryl
6
products in good yields. Different O-benzoyl-N,N-dialkylhy-
3
alkynes.
droxyamines were tested, and good results were obtained when
O-benzoyl-N,N-dibenzylhydroxyamine was involved.
Recently, a closely related reaction, namely, aminoboration
of C−C multiple bonds (Scheme 1), emerged as a promising
method for the functionalization of different substrates and
allowed the introduction of N atoms and boryl groups to C−C
multiple bonds in a single step. For example, Pd(II)-catalyzed
(
Borylmethyl)cyclopropylamines could be constructed
through intermolecular aminoboration of methylenecyclopro-
panes. The reactions could be controlled by ligands, and
7
regiodivergent aminoboration of different unactivated alkenes
8
could be realized in the presence of different catalysts. The
Scheme 1. Aminoboration of Different C−C Multiple Bonds
reactions tolerated a variety of functional groups, and
enantioselective aminoboration could be realized in the
9
presence of chiral catalysts.
Blum et al. showed that aminoboration products could be
observed when treating o-alkynlamines with catecholborane at
elevated temperature. Further study showed that, in the
presence of a base such as triethylamine, formation of B−N
bond could be observed when treating commercially available
B-chlorocatecholborane with 2-alkynylaniline. The in-situ-
formed B−N intermediate could be transformed to the
corresponding aminoboration products in a short time. In
the presence of an appropriate catalyst, the reaction could be
10
realized under mild conditions.
Received: May 18, 2020
©
XXXX American Chemical Society
https://dx.doi.org/10.1021/acs.orglett.0c01685
A
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
pubs.acs.org/OrgLett
Letter
Replacing amide substrates with hydrazones provided the
desired borylated pyrazoles in good yields. Using o-
Scheme 4. Scope of Intramolecular Aminoboration of
Allenes
1
1
a
alkynylthioanisoles as the substrates, thioboration could also
12
be realized under mild conditions. In the presence of Cu(I)-
catalyst, oxyboration reaction of unactivated alkenes gave the
desired oxyborane products in good yields and regioselectiv-
1
3
ity. Borylated isocoumarins and 2-pyrones could be obtained
14
from esters via catalyst-free electrophilic oxyborations, and a
densiy functional theory (DFT) study provided the possible
15
mechanism of the reaction.
We have developed a direct intramolecular aminoboration
16
17
and thioboration of unfunctionalized alkenes. Shi et al.
18
described the aminoboration of alkynes using BCl3. Ingleson
et al. reported BCl -induced annulative oxoborations and
3
19
thioborations of alkynes. It is highly desirable to develop a
general method for the regioselective and stereoselective
aminoboration of allenes, and to provide a general method
for the preparation of borylvinyl heterocycles that could be
used as viable substrates in subsequent coupling reactions.
Herein, we wish to present intramolecular aminoboration of
allenes using BCl as a boron source.
3
We have shown that, in the presence of stoichiometric
a
Reaction conditions: (1) 1 (0.1 mmol), BCl3 (0.12 mmol).
Reactions were performed in 1 mL of 1,2-dichloroethane under
amount of BCl , 4-penten-1-tosylamides could be cyclized at
3
room temperature, leading to the desired aminoboration
16
argon atmosphere; (2) pinacol (0.5 mmol) and Et N (1.5 mmol).
3
products in good yields. Shi et al. reported aminoboration
of alkynes for the synthesis of 3-borylated indoles using BCl as
the boron source. Encouraged by these results, we decided to
study the reaction between allenes and BCl3 to further
3
18
aminoboration of N-(hexa-4,5-dien-1-yl)sulfonamides. The
reactions proceeded smoothly for sulfonamides such as
tosylamides, benzenesulfonamides, or nosylamides. For exam-
ple, aminoboration of substrate 1d proceeded readily and the
desired borylvinyl piperidine 2d could be obtained in good
yield.
understand the BCl -involved direct aminoboration reactions
3
on one hand, and to expand the scope of the reaction on the
other (see Scheme 2). To the best of our knowledge, such
After the successful aminoboration of simple N-(hexa-4,5-
dien-1-yl)sulfonamide substrates, our attention turned to the
construction of piperazine skeletons, which could also be
important subunits in organic synthesis and drug synthesis. At
first, the corresponding substrates such as (S)-N-tethered
allenylsulfonamide 1e was prepared via derivatization of L-
valine. When substrate 1e was subjected to the aminoboration
reaction conditions, the desired product 2e was obtained under
the optimal conditions. NMR spectrum of the crude product
mixture showed the presence of a single diastereomer and the
minor diastereomer was not detected in NMR analysis. Single-
crystal X-ray diffraction (XRD) experiments suggested a
Scheme 2. Proposed Intramolecular Aminoboration of
Allenes
reactions have not been reported so far, and successful
aminoboration of allenes would provide different 2-borylvinyl
piperidines or pyrrolidines, which could be further converted
to different structures via conventional functional group
transformations such as Suzuki coupling reactions.
To test this assumption, sulfonamidoallene 1a was chosen as
the model substrate to study the intramolecular aminoboration
of allenes (Scheme 3). Thin-layer chromatography (TLC)
(
2S,5S)-configuration of the product 2e (see Figure 1). The
diastereoselectivity is rationalized by a chairlike transition state
where the vicinal tosyl and alkyl substituents adopt pseudo-
17,20
axial positions.
Similarly, substrates 1f−1h provided the
Scheme 3. Intramolecular Aminoboration of 1a
analysis indicated that, under previously optimized condi-
1
6
tions, a new compound was formed when 1a was allowed to
mix with 1.2 equiv of BCl . After the reaction mixture was
3
treated with pinacol/Et N, the boronate 2a was isolated as the
3
final product in 80% yield (see Scheme 3).
Encouraged by this preliminary result, the scope of the
substrates was studied. The results are summarized in Scheme
Figure 1. ORTEP drawings of 2e and 4g at 30% displacement
ellipsoid probability (the H atoms were omitted for clarity).
4
. A series of pyrrolidines were prepared through the
B
https://dx.doi.org/10.1021/acs.orglett.0c01685
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
pubs.acs.org/OrgLett
Letter
desired aminoboration products in good yields and diaster-
eoselectivity. Reaction of 1i gave the desired (2R,5R)-2i in
provided the desired tetrahydroisoquinoline in 86% isolated
yield. Aminoboration of 3a at 5 mmol scale provided 1.7 g of
the desired product (81% isolated yield), indicating a good
scalability of the reaction.
5
2% yield.
Next, reactions of 2-allenylphenylmethanamines were
performed to further expand the scope of the reaction and
to get important functionalized isoindolines. The results are
summarized in Scheme 5. When 2-allenylphenylmethanamine
To demonstrate the application potential of the current
reaction system, functional group transformations were studied
using 4a as a model (see Scheme 6). Using NaBO as an
3
Scheme 5. Scope of Intramolecular Aminoboration of
Allenes
Scheme 6. Derivatization of Aminoboration Product 4a
a
oxidant, the vinylboronate could be oxidized to hydroxyl
group, and ketone 5 was isolated as the final product. Treating
4
a with CuBr converted the vinylborate functional group to
2
vinyl bromide 6, and Suzuki coupling of 4a with iodobenzene
provided the desired product 7 in high yield (Scheme 6).
The literature results showed that BCl might serve as a
3
carbophilic Lewis acid, resulting in cyclization to zwitter-
1
9,22
ions.
On the basis of literature results, a tentative
mechanism is proposed and is shown in Scheme 7. Taking
Scheme 7. A Tentative Reaction Mechanism
a
Reaction conditions: (1) 3 (0.1 mmol), BCl3 (0.12 mmol).
Reactions were carried out in 1 mL of 1,2-dichloroethane under
argon atmosphere; (2) pinacol (0.5 mmol) and Et N (1.5 mmol).
3
(3a) was subjected to the reaction conditions, the desired
aminoboration product isoindoline (4a) was obtained in good
yield. Moreover, aminoboration reaction can be performed
smoothly, irrespective of whatever substituents were present in
the substrates (3b−3e).
1e as an example, complex I, consisting of substrate and BCl3,
1
When R = methyl or ethyl, the aminoboration products (4f
was formed upon the addition of BCl . Intramolecular
3
23
and 4g) could be obtained in good yield. Again, 1,3-cis
configuration was observed when chiral substrate 3g was
subjected to the reaction conditions, and the stereochemistry
of 4g was also confirmed by single-crystal XRD experiments
cyclization provided zwitterions intermediate II. The cyclized
product would then sit at the zwitterion until the addition of
pinacol/Et N to generate the final boronate (2e).
3
In summary, direct intramolecular aminoboration of
(
recall Figure 1). Reaction of disubstituted allenes 3h−3j
allenylsulfonamides is reported. Using BCl as the boron
3
proceeded readily, and the desired products were isolated in
satisfactory yields. When substrates 3i and 3j were subjected to
the reaction conditions, the aminoboration products 4i and 4j
were obtained with E-configuration. We hypothesized that the
nucleophile sulfonamide would approach from the less-
hindered face, rather than the alkyl-substituted side, and E
isomers were obtained as the single products. Reaction of
trisubstituted allene substrate 3k gave the target product in
6
source and reaction promotor, the aminoboration of a variety
of allenes occurs smoothly at room temperature, affording the
corresponding borylvinyl-substituted N-heterocycles in good
yields with high diastereoselectivity. The thus-obtained
borylvinyl heterocycles can be potentially useful building
blocks in drug design and synthesis. Derivatization of these
borylvinyl products are easy to perform, and complex
structures can be obtained through conventional oxidation,
bromination, and Suzuki coupling reactions.
21
0% yield. Aminoboration of 2-allenylphenylethanamine (3l)
C
https://dx.doi.org/10.1021/acs.orglett.0c01685
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
pubs.acs.org/OrgLett
Letter
ASSOCIATED CONTENT
ACKNOWLEDGMENTS
We acknowledge financial support from the National Natural
Science Foundation of China (Nos. 21801006, 81703353,
1672106), China Postdoctoral Science Foundation (No.
018T110744), Natural Science Foundation of Henan
■
■
*
sı Supporting Information
The Supporting Information is available free of charge at
https://pubs.acs.org/doi/10.1021/acs.orglett.0c01685.
2
2
Province (No. 182300410295), the project of Science and
Technology Department of Henan Province (No.
Experimental procedures, compound characterization,
X-ray diffraction data (PDF)
1
82102210202), and the Industrial Research Project of
Technology Bureau of Anyang.
Accession Codes
CCDC 1984436 and 1984444 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.
REFERENCES
■
(
(
1) (a) Brown, H. C.; Gupta, S. K. J. Am. Chem. Soc. 1971, 93, 1816.
b) Brown, H. C.; Gupta, S. K. J. Am. Chem. Soc. 1972, 94, 4370.
2) (a) Miyaura, N.; Suzuki, A. Chem. Rev. 1995, 95, 2457.
(b) Suzuki, A. Angew. Chem., Int. Ed. 2011, 50, 6722. (c) Jana, R.;
Pathak, T. P.; Sigman, M. S. Chem. Rev. 2011, 111, 1417.
(
(
3) (a) Burgess, K.; Ohlmeyer, M. J. Chem. Rev. 1991, 91, 1179.
(
b) Thomas, S. P.; Aggarwal, V. K. Angew. Chem., Int. Ed. 2009, 48,
AUTHOR INFORMATION
■
1896. (c) Wei, D.; Darcel, C. Chem. Rev. 2019, 119, 2550. (d) Perry,
G. J. P.; Jia, T.; Procter, D. J. ACS Catal. 2020, 10, 1485.
Corresponding Authors
(4) Huang, J.; Macdonald, S. J. F.; Harrity, J. P. A. Chem. Commun.
Zhantao Yang − Henan Key Laboratory of New Optoelectronic
Functional Materials, College of Chemistry and Chemical
Engineering, Anyang Normal University, Anyang 455000,
People’s Republic of China; orcid.org/0000-0003-1575-
2
009, 46, 8770.
(5) (a) Voss, T.; Chen, C.; Kehr, G.; Nauha, E.; Erker, G.; Stephan,
D. W. Chem. - Eur. J. 2010, 16, 3005. (b) Melen, R. L.; Hansmann, M.
M.; Lough, A. J.; Hashmi, A. S. K.; Stephan, D. W. Chem. - Eur. J.
2
013, 19, 11928.
3
665; Email: zhantaoyang@163.com
(6) (a) Matsuda, N.; Hirano, K.; Satoh, T.; Miura, M. J. Am. Chem.
Yue-Ming Li − State Key Laboratory of Medicinal Chemical
Biology, College of Pharmacy and Tianjin Key Laboratory of
Molecular Drug Research, Nankai University, Tianjin 300353,
People’s Republic of China; orcid.org/0000-0003-2632-
Soc. 2013, 135, 4934. (b) Sakae, R.; Hirano, K.; Satoh, T.; Miura, M.
Angew. Chem., Int. Ed. 2014, 54, 613−617.
(7) Sakae, R.; Matsuda, N.; Hirano, K.; Satoh, T.; Miura, M. Org.
Lett. 2014, 16, 1228.
8) (a) Kato, K.; Hirano, K.; Miura, M. J. Org. Chem. 2017, 82,
9
253; Email: ymli@nankai.edu.cn
(
1
1
0418. (b) Sakae, R.; Hirano, K.; Miura, M. J. Am. Chem. Soc. 2015,
37, 6460.
Authors
(
9) (a) Wu, L.; Zatolochnaya, O.; Qu, B.; Wu, L.; Wells, L. A.;
Chun-Hua Yang − Henan Key Laboratory of New
Kozlowski, M. C.; Senanayake, C. H.; Song, J. J.; Zhang, Y. Org. Lett.
Optoelectronic Functional Materials, College of Chemistry and
Chemical Engineering, Anyang Normal University, Anyang
2
2
2
019, 21, 8952. (b) Kato, K.; Hirano, K.; Miura, M. Chem. - Eur. J.
018, 24, 5775. (c) Nishikawa, D.; Hirano, K.; Miura, M. Org. Lett.
016, 18, 4856. (d) Kato, K.; Hirano, K.; Miura, M. Angew. Chem., Int.
4
55000, People’s Republic of China; orcid.org/0000-0002-
3
770-9887
Ed. 2016, 55, 14400. (e) Jiang, H.-C.; Tang, X.-Y.; Shi, M. Chem.
Commun. 2016, 52, 5273.
Meng Han − Henan Key Laboratory of New Optoelectronic
Functional Materials, College of Chemistry and Chemical
Engineering, Anyang Normal University, Anyang 455000,
People’s Republic of China
Wenyan Li − Henan Key Laboratory of New Optoelectronic
Functional Materials, College of Chemistry and Chemical
Engineering, Anyang Normal University, Anyang 455000,
People’s Republic of China
Ningning Zhu − Henan Key Laboratory of New Optoelectronic
Functional Materials, College of Chemistry and Chemical
Engineering, Anyang Normal University, Anyang 455000,
People’s Republic of China
(
10) (a) Chong, E.; Blum, S. A. J. Am. Chem. Soc. 2015, 137, 10144.
(b) Yuan, K.; Wang, S. Org. Lett. 2017, 19, 1462.
(11) Tu, K. N.; Kim, S.; Blum, S. A. Org. Lett. 2019, 21, 1283.
(12) Faizi, D. J.; Davis, A. J.; Meany, F. B.; Blum, S. A. Angew. Chem.,
Int. Ed. 2016, 55, 14286.
(
13) Itoh, T.; Matsueda, T.; Shimizu, Y.; Kanai, M. Chem. - Eur. J.
015, 21, 15955.
14) Faizi, D. J.; Issaian, A.; Davis, A. J.; Blum, S. A. J. Am. Chem.
Soc. 2016, 138, 2126.
2
(
(
(
15) Jiang, J.; Zhang, Z.; Fu, Y. Asian J. Org. Chem. 2017, 6, 282.
16) Yang, C.-H.; Zhang, Y.-S.; Fan, W.-W.; Liu, G.-Q.; Li, Y.-M.
Angew. Chem., Int. Ed. 2015, 54, 12636.
Zhenzhen Sun − Henan Key Laboratory of New Optoelectronic
Functional Materials, College of Chemistry and Chemical
Engineering, Anyang Normal University, Anyang 455000,
People’s Republic of China
Junjie Wang − Henan Key Laboratory of New Optoelectronic
Functional Materials, College of Chemistry and Chemical
Engineering, Anyang Normal University, Anyang 455000,
People’s Republic of China
(17) Yang, Z.; Yang, C.-H.; Chen, S.; Chen, X.; Zhang, L.; Ren, H.
Chem. Commun. 2017, 53, 12092.
(18) Lv, J.; Zhao, B.; Liu, L.; Han, Y.; Yuan, Y.; Shi, Z. Adv. Synth.
Catal. 2018, 360, 4054.
(19) Warner, A. J.; Churn, A.; McGough, J. S.; Ingleson, M. J. Angew.
Chem., Int. Ed. 2017, 56, 354.
(
(
20) Sequeira, F. C.; Chemler, S. R. Org. Lett. 2012, 14, 4482.
21) Kim, J. H.; Park, S. W.; Park, S. R.; Lee, S.; Kang, E. J. Chem. -
Asian J. 2011, 6, 1982.
Complete contact information is available at:
https://pubs.acs.org/10.1021/acs.orglett.0c01685
(22) Bagutski, V.; Del Grosso, A.; Carrillo, J. A.; Cade, I. A.; Helm,
M. D.; Lawson, J. R.; Singleton, P. J.; Solomon, S. A.; Marcelli, T.;
Ingleson, M. J. J. Am. Chem. Soc. 2013, 135, 474.
(
23) Liu, W.; Zeng, R.; Han, Y.; Wang, Y.; Tao, H.; Chen, Y.; Liu,
Notes
F.; Liang, Y. Org. Biomol. Chem. 2019, 17, 2776.
The authors declare no competing financial interest.
D
https://dx.doi.org/10.1021/acs.orglett.0c01685
Org. Lett. XXXX, XXX, XXX−XXX