Relay Catalysis of Rh (II) and Cobaloxime: Stereoselective Synthesis of Spiroindanones from N-Sulfonyl-1,2,3-triazoles

Article abstract of DOI:10.1021/acs.orglett.8b03275

A novel relay Rh (II)/cobaloxime (III) dual catalysis strategy has been developed for the stereoselective synthesis of indolyl spiroindanones from readily accessible N-sulfonyl-1,2,3-triazoles. This binary-catalyst system enables an aza-vinyl carbene init

Full text of DOI:10.1021/acs.orglett.8b03275

Letter
pubs.acs.org/OrgLett
Cite This: Org. Lett. XXXX, XXX, XXX−XXX
Relay Catalysis of Rh (II) and Cobaloxime: Stereoselective Synthesis
of Spiroindanones from N‑Sulfonyl-1,2,3-triazoles
Zhao Liu, Qiuchen Du, Hongbin Zhai, and Yun Li*
State Key Laboratory of Applied Organic Chemistry, College of Chemistry and Chemical Engineering, Lanzhou University, Lanzhou
730000, China
S
* Supporting Information
ABSTRACT: A novel relay Rh (II)/cobaloxime (III) dual
catalysis strategy has been developed for the stereoselective
synthesis of indolyl spiroindanones from readily accessible N-
sulfonyl-1,2,3-triazoles. This binary-catalyst system enables an
aza-vinyl carbene initiated Pictet-Spengler-type cyclization
and sequential cobaloxime promoted intramolecular Mannich-
type reaction cascade. The easily accessible reagents, high
diastereoselectivity, and operational simplicity make this
reaction a method of choice for the preparation of
functionalized spiroindanones, which are difficult to access by other classic reactions in one step.
piroindanones are privileged substructures owing to the
occurrence of many bioactive natural products1 and the
Scheme 1. Divergent Synthesis of Polycyclic Indole
Derivatives from N-Sulfonyl-1,2,3-triazoles
S
discovery of many medicinally significant compounds.2 The
development of concise methods of synthesizing these
heterocyclic compounds is therefore attractive for synthetic
organic chemists. Different strategies have been reported for the
construction of the indanone framework including intra-
molecular Friedel−Crafts reaction,3 Heck cyclization reactions,4
Nazarov cyclization,5 carbene involved cyclization,6 and other
methods.7 In this regard, while much effort has been devoted to
the synthesis of such scaffold, an alternative or complementary
method with mild reaction conditions and high stereoselectivity,
especially from easy-to-assemble substrates, is still of great
interest. On the other hand, a cascade transformation provides
an ideal platform for the formation of multiple bonds with one
single operation. By avoiding protecting group manipulations
and tedious purification of the intermediates, desirable time- and
cost-saving operations could easily be achieved.
reactivity and lead to the new possibilities for construction of
different cyclic scaffolds. Herein, we now describe a rhodium
and cobaloxime dual catalyzed denitrogenative cyclization
reaction of N-sulfonyl-1,2,3-triazoles for the diastereoselective
construction of the biologically important spiroindanones
(Scheme 1, path 2).
Our research began with evaluation of the N-sulfonyl-1,2,3-
triazole-4-yl-benzamide 4a in the Rh-catalyzed tandem reaction.
Initially, 4a was treated with Rh2(oct)4 (5 mol %) in chloroform
at 100 °C for 12 h; however, only 5% yield of cyclized product 6a
could be isolated as a single isomer (Table 1, entry 1). The full
structural information of 6a was later secured by both NMR
spectroscopic data and comparison to the X-ray crystallographic
analyses of 6e (Scheme 2).13 An extensive condition survey
indicated that the yield of 6a could be improved to 43% when
additional Yb(OTf)3 (5 mol %) was employed as a cocatalyst in
the reaction (entry 2). This interesting observation prompted us
Rh (II)-catalyzed denitrogenative transannulation of N-
sulfonyl-1,2,3-triazoles has evolved as a useful synthetic strategy
for constructing a wide variety of important heterocycles.8 The
α-imino carbenes derived from the N-sulfonyl 1,2,3-triazoles via
a Dimroth-type equilibrium exhibit unique reactivity and have
received much attention in recent years.9 This electrophilic
intermediate could be trapped by various nucleophiles leading to
a highly reactive ylide and could undergo a variety of subsequent
transformations.10 In a program directed toward the develop-
ment of cyclization reactions for quick assembly of a natural
product scaffold from readily available starting materials, we
have recently described the merit of the rhodium-catalyzed
denitrogenative [3 + 2] cyclization reaction for the construction
of aspidospermidine11 (Scheme 1, path 1) and montanine-
type12 scaffolds from N-sulfonyl-1,2,3-triazoles. Hence, it was
envisioned that extension of this concept to the benzoamide
tethered triazole substrate 4 (Scheme 1) might provide new
Received: October 13, 2018
© XXXX American Chemical Society
A
DOI: 10.1021/acs.orglett.8b03275
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
a
Table 1. Dual Metal Relay Catalyzed Cyclization of 4a
Scheme 2. Scope Investigation of Spiroindanones
a b
,
Synthesis
b
entry
Rh catalyst
Co catalyst
solvent
yield (%)
1
2
3
4
5
6
7
8
Rh2(oct)4
Rh2(oct)4
Rh2(oct)4
Rh2(oct)4
Rh2(oct)4
Rh2(oct)4
Rh2(oct)4
Rh2(NTTL)4
Rh2(esp)4
Rh2(oct)4
Rh2(oct)4
none
none
CHCl3
CHCl3
CHCl3
CHCl3
CHCl3
CHCl3
CHCl3
CHCl3
CHCl3
DCE
5
Yb(OTf)3
Fe(NO3)3
CoBr2
Cat 1
Cat 2
Cat 3
Cat 2
Cat 2
Cat 2
Cat 2
34
12
30
65
81(78)
55
0
23
66
0
c
9
10
11
12
toluene
CHCl3
Cat 2
0
a
All reactions were performed with 0.03 mmol of triazole 4a and 5
mol % of the Rh catalyst and 5 mol % cocatlyst in 1 mL solvent at 100
b
°C. 1H NMR yield (1,3,5-trimethoxybenzene as internal standard).
c
Isolated yield.
a
Reactions were performed (in a sealed tube) with 4 (0.5 mmol, 1
to further evaluate more Lewis acids as the cocatalyst in this
reaction. It was found that Fe(NO3)3 and CoBr2 (entry, 3, 4)
gave inferior results compared to Yb(OTf)3. On the basis of our
previous experience in cobaloxime-catalyzed alkyne hydration
reactions,14 cobaloxime (Table 1, Cat 1−Cat 3) that possesses a
unique chemical structure could serve as a strong π-acid in
alkyne hydration reactions. Thus, we wondered that whether
these catalysts could also pay as a strong Lewis acid and promote
this cascade reaction; later experimental results proved our
hypothesis quite successful. When Cat 1 was employed, the yield
of 6a could be greatly improved to 65% (entry 5). More
electronic deficient bromo-complex Cat 2 gave an even better
result (entry 6). The desired product could be isolated in 78%
yield (81% NMR yield) with a single diastereo isomer. Pyridine
coordinated Cat 3 gave lower yield (entry 7). A survey of various
Rh (II) catalysts revealed that Rh2(oct)4 is the optimal catalyst
(entry 8, 9). A solvent variation did not further improve the yield
of 6a (entry 10, 11). Notably, the reaction gave none of the
desired product when cobaloxime alone was employeded as the
catalyst (entry 12), which indicated that both rhodium and
cobalt catalysts play critical roles in this transformation.
equiv), Rh2(oct)4 (5 mol %), cobaloxime (5 mol %) in CHCl3 (5 mL)
at 100 °C for 10 h. Yield of the isolated product. Isolated yield at
1.4 mmol scale.
b
c
(4e−4h) gave relative lower yields compared with electron-
neutral and deficient ones (4i, 4j). Substrates with N-Mesyl-
1,2,3-triazole motif (4k) gave relative higher yield of product
than corresponding tosyl one (4j). In all cases, the antiproducts
(respect to two ortho amino groups) were obtained exclusively
as determined by 1H NMR spectroscopy.
Next, the effect of the R2-substituents on the benzene ring of
the benzoamide fragment was explored for the reaction (Scheme
3). The substrates bearing a chloride at the para- or meta-
position (4l−4m) afforded the desired products in reasonable
yields (59−79%), whereas switching to more electron-deficient
fluorine group furnished the corresponding cyclization in quite
lower yield (37%). Both electron donating (4o, 4p) and neutral
groups (4q) at the para- or meta-position led to preparative
yields. It should be mentioned that the electron-rich group (such
as methyl or allyl) on the indolic nitrogen N1 position was
essential for the cyclization (4a−4r), while the carbomethoxy
derivative did not give any of the desired product. When the
tryptamine fragment was changed to 5-methoxyl tryptamine in
the substrate (4s−4w), only negligible influence was observed
for the cyclization. The replacement of indole fragment in the
substrates by benzene and benzofuran failed to deliver the
desired products.15
With the optimal conditions established, we then explored
various substituted indole derivatives to examine the substrate
scope of this reaction (Scheme 2). Generally, this protocol
tolerated a variety of functionalities on the indole moiety and
gave synthetically useful yields. Different substituents on the
indole N1 such as Me, Bn, PMB, and Allyl (4a−4d) have little
influence on the efficiency of the reaction. Substrates with
electron-rich substituent (-OMe) at C5 position of indolyl motif
A mechanistic rationale for the formation of the spiroinda-
none is provided in Scheme 4. Heating the triazole 4 in the
B
DOI: 10.1021/acs.orglett.8b03275
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
a b
,
enolate D, the following stereoselective intramolecular Man-
nich-type cyclization yielded the desired spiroindanone 6.
In conclusion, we have demonstrated that the Rh (II)/
cobaloxime binary-catalyst system enables relay cascade
cyclization with steadily available N-sulfonyl-1,2,3-triazoles as
the precursor. This reaction showed excellent stereoselectivity
and expeditious access to indoly spiroindanones. A wide range of
substrates are tolerated in this transformation, and various
products can be obtained in good yields. The operational
simplicity coupled with the mild reaction conditions of the
present approach has established a new entry to a diverse set of
valuable spiroindanones.
Scheme 3. Continued Scope Investigation
ASSOCIATED CONTENT
* Supporting Information
■
S
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.orglett.8b03275.
Full experimental procedures; characterization data, and
NMR spectra data (PDF)
Accession Codes
CCDC 1866860 contains the supplementary crystallographic
data for this paper. These data can be obtained free of charge via
www.ccdc.cam.ac.uk/data_request/cif, by e-mailing data_
request@ccdc.cam.ac.uk, or by contacting The Cambridge
Crystallographic Data Centre, 12 Union Road, Cambridge
CB2 1EZ, U.K.; fax: +44 1223 336033.
AUTHOR INFORMATION
■
Corresponding Author
*E-mail: liyun@lzu.edu.cn.
ORCID
Hongbin Zhai: 0000-0003-2198-1357
Yun Li: 0000-0003-2236-9880
Notes
a
Reactions were performed (in a sealed tube) with 4 (0.5 mmol, 1
The authors declare no competing financial interest.
equiv), Rh2(oct)4 (5 mol %), cobaloxime (5 mol %) in CHCl3 (5 mL)
at 100 °C for 10 h. Yield of the isolated product.
b
ACKNOWLEDGMENTS
■
We gratefully acknowledge the financial support from the
National Natural Science Foundation of China (21572089), the
Program for Changjiang Scholars and the Innovative Research
Team in University (PCSIRT: IRT_15R28), the FRFCU
(lzujbky-2018-61), and the Gansu Provincial Sci. and Tech.
Department (2016B01017).
Scheme 4. Proposed Reaction Mechanism
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D
DOI: 10.1021/acs.orglett.8b03275
Org. Lett. XXXX, XXX, XXX−XXX