Rh-catalyzed intramolecular cyclization of 1-sulfonyl-1,2,3-triazole and sulfinate. Concise preparation of sulfonylated unsaturated piperidines

Article abstract of DOI:10.1016/j.tetlet.2019.01.012

When 4-[3-(methanesulfinyloxy)propyl]-1-(arenesulfonyl)-1,2,3-triazoles were treated with rhodium catalysts of the type Rh₂(RCO₂)₄, a new intramolecular cyclization took place to afford 2,3-didehydro-1-(arenesulfonyl)-3-(m

Full text of DOI:10.1016/j.tetlet.2019.01.012

Accepted Manuscript
Rh-catalyzed Intramolecular Cyclization of 1-Sulfonyl-1,2,3-triazole and Sul-
finate. Concise Preparation of Sulfonylated Unsaturated Piperidines
Ayana Furukawa, Takeshi Hata, Masayuki Shigeta, Hirokazu Urabe
PII:
S0040-4039(19)30013-9
https://doi.org/10.1016/j.tetlet.2019.01.012
TETL 50545
DOI:
Reference:
To appear in:
Tetrahedron Letters
Received Date:
Revised Date:
Accepted Date:
21 November 2018
4 January 2019
8 January 2019
Please cite this article as: Furukawa, A., Hata, T., Shigeta, M., Urabe, H., Rh-catalyzed Intramolecular Cyclization
of 1-Sulfonyl-1,2,3-triazole and Sulfinate. Concise Preparation of Sulfonylated Unsaturated Piperidines,
Tetrahedron Letters (2019), doi: https://doi.org/10.1016/j.tetlet.2019.01.012
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Rh-catalyzed Intramolecular Cyclization of
-Sulfonyl-1,2,3-triazole and Sulfinate.
Leave this area blank for abstract info.
1
Concise Preparation of Sulfonylated
Unsaturated Piperidines
Ayana Furukawa, Takeshi Hata, Masayuki Shigeta, and Hirokazu Urabe

1
Tetrahedron Letters
Rh-catalyzed Intramolecular Cyclization of 1-Sulfonyl-1,2,3-triazole and Sulfinate.
Concise Preparation of Sulfonylated Unsaturated Piperidines
a
a,b
a
a,
Ayana Furukawa, Takeshi Hata, Masayuki Shigeta, and Hirokazu Urabe 
a
School of Life Science and Technology, Tokyo Institute of Technology, 4259-B-59 Nagatsuta-cho, Midori-ku, Yokohama, Kanagawa 226-8501, Japan
JST, PRESTO, 4-1-8 Honcho, Kawaguchi-shi, Saitama 332-0012, Japan
b
ARTICLE INFO
ABSTRACT
Article history:
Received
When 4-[3-(methanesulfinyloxy)propyl]-1-(arenesulfonyl)-1,2,3-triazoles were treated with
rhodium catalysts of the type Rh (RCO , a new intramolecular cyclization took place to afford
2
2 4
)
Received in revised form
Accepted
Available online
2,3-didehydro-1-(arenesulfonyl)-3-(methanesulfonyl)piperidines in good yields. This reaction
most likely proceeds via a new reorganization of bonds in the same molecule, consisting of the
addition of the sulfur atom of sulfinate ester to the -(sulfonylimino)carbene moiety generated
from the sulfonyltriazole, followed by the counter attack of the sulfonylimino nitrogen to the
carbon bearing the oxygen terminus of sulfinate ester.
Keywords:
Rhodium
Triazole
2
009 Elsevier Ltd. All rights reserved.
Cyclization
Sulfinate
Piperidine
The rhodium-catalyzed decomposition of 1-sulfonyl-1,2,3-
moderate yield, we decided to investigate this reaction in more
depth.
triazoles,
generating
versatile
equivalents
of
-
(
sulfonylimino)carbene or a zwitterionic C-C-N bond linkage,
has found widespread use in organic synthesis [1-3]. Its
application to intramolecular reactions has provided useful
methods for the preparation of various cyclic compounds.
Scheme
1 illustrates such a transformation, where the
aforementioned reactive intermediate 2 and hence 3-4 generated
from 1 insert the X-Y bond at the suitable position to give cyclic
product 5 [2] or 6 [3]. While numerous important reactions of
these types have been reported, a new cyclization of 1 giving 7,
provided that X is a heteroatom group and Y is not present, was
recently reported [4]. A more general case where both X and Y
are imparted, for example, 1  8 in Scheme 1 should be an
advanced observation, which is disclosed in this report.
During the course of our study on the rhodium-catalyzed
intramolecular cyclization via C-H bond activation [5,6], we
were interested in cleaving other heteroatom bonds. When
sulfinate ester 9 [7] was treated with the Rh catalyst under the
same reaction conditions as those of the previous C-H bond
activation (Scheme 2) [6], the expected O-S bond scission was
observed as evidenced by the formation of dihydrofuran 11,
obviously produced by the syn-elimination of primarily formed
sulfoxide 10 [8], albeit in a very low yield. Besides this product
corresponding to 5 in Scheme 1 [X-Y = O-S(O)Me], unexpected
product 12, the structure of which was assigned as depicted by
spectroscopic means and later confirmed by derivatization to a
known compound, was also isolated. As the product 12 is of a
unique structure like 8 in Scheme 1 and was obtained still in a
Scheme 1. Reaction Patterns of Rh-catalyzed Decomposition of
Sulfonyltriazole 1.
—
——

Corresponding author. Tel.: +81-045-924-5849; fax: +81-045-924-5849; e-mail: hurabe@bio.titech.ac.jp

2
Tetrahedron
As the formation of 12 was not expected at the outset, its
structural confirmation was undertaken by derivatization as
shown in Scheme 3. When the known desulfonylation of vinyl
sulfones with Na S O [9] was applied to 12, it was slowly
2
2
4
converted to known unsaturated piperidine 17 [10], yet the
completion of the reaction was not attempted. Alternatively,
standard Pd-catalyzed hydrogenation of 12 gave unsymmetrically
disulfonylated piperidine 18, consistent with the original
structure of 12.
a
Scheme 2. Rh-catalyzed Reaction of Sulfonyltriazole 9.
a
Rh (oct) refers to Rh (C H CO ) .
2
4
2
7
15
2 4
Table 1 shows optimization of the yield of 12. First, three
substrates 9, 13, and 15 having different sulfinyl groups were
allowed to react with Rh (oct) (entries 1-3). Among these,
2
4
Scheme 3. Structural Confirmation of 12.
methanesulfinate 9 proved the most suitable starting material
entry 1), and other aromatic and sterically more demanding
(
Table 2 summarizes other products obtained by this method.
A variety of 1-sulfonyl-1,2,3-triazoles 9 and 19-23 gave the
desired products 12 and 30-34 in good yields (entries 1-6).
Starting materials 24-27 having substituent  to triazole (or
sulfinate ester) also participated in this transformation to afford
aliphatic sulfinates (13 and 15) were found far less useful.
Although solvents did not give rise to much difference on the
product yields (entries 1 and 4-6), dichloroethane was selected
for this reaction (entry 1), because of the highest yield and the
least formation of side products. As far as the Rh catalysts and
their loads are concerned (entries 1 and 7-12), Rh (OAd) (2
5
-substituted-2,3-didehydropiperidines 35-38 (entries 7-10).
2
4
However, 28 with a substituent at the -position to triazole
furnished 39 in somewhat lower yield due to the concomitant
formation of a small amount of dihydrofuran 41 resulting from
the O-S bond insertion (entry 11 and its footnote). In addition to
these piperidines, an aromatic substrate 29 can be utilized as well
to give dihydroisoquinoline 40 (entry 12). The formation of
these substituted piperidine and isoquinoline derivatives shows
synthetic flexibility of this method [11].
mol%) was found the catalyst of choice (entry 10) among the
several Rh complexes with less or more sterically hindered
ligands.
Table 1. Optimization of Substrates, Catalysts, and Conditions.
Mechanism of this reaction is proposed as in Scheme 4. The
sulfur atom of sulfinate 9 first interacts with the intermediate
carbene species like 42a, forming zwitterion 43a or 43b [4],
which then collapses to 12 via the intramolecular alkylation of
the nitrogen with the sulfinate (path a). Alternatively, alkylation
of the sulfonimide with sulfinate takes place first (42b  44),
followed by the addition of the released sulfinate anion to the
carbenionic site in 45 to reach 12 (path b).
To get an insight into the above mechanism, a couple of
additional experiments were performed. First, the reaction of 9
(entry 1, Table 2) was attempted in the presence of externally
added EtSO Na as shown in eq 1. Expected products 12 and 46
2
coming from the uptake of ethanesulfonyl group were not
detected, while the starting material was consumed. Thus, the
presence of the sulfinate anion is not beneficial to the reaction
itself, so that the adoption of path b is discouraged. Secondly,
sec-alkyl sulfinate 47 was submitted to the reaction (eq 2), giving
only an intractable mixture of products including neither desired
a
oct = C H CO -, Ac = CH CO-, Piv = t-BuCO-, OAd =
7
15
2
3
4
8 nor simple insertion product 49.
This suggests that
adamantanecarboxylate, tpa
C H (CH CMe CO -) .
Determined by H NMR analysis with internal standard.
Isolated yields in parentheses.
=
Ph CCO -, esp
=
m-
3
2
intermediate 43b of more S 1-like character than 43a in path a
N
6
4
2
2
2
2
less contributes to the reaction course [4]. As a whole, the high
nucleophilicity of sulfur (42a), the formation of by-products 11
and 41 showing that the reaction could take place near the sulfur,
and the highly regioselective reaction owing to the totally
intramolecular process (43) should support that path a is more
likely than path b.
b
1
c
d
e
f
Another product 11 was detected as shown in Scheme 2.
Product 11 was also detected in 26% yield.
Impure product with some unknown by-products.
Not determined.

3
Table 2. Preparation of Various Sulfonylated Unsaturated
Piperidines.
Scheme 4. Proposed Reaction Mechanism.
It is worth noting that this reaction at least formally represents
a new version of sulfinate-sulfone rearrangement as shown in
Scheme 5. While the usual sulfinate-sulfone rearrangement is
performed on the allylic system from 50 to 51, providing a
versatile method for the preparation of allyl sulfones 51 [7], the
present reaction incorporates the carbenoid and sulfinate carbons
to the above system to effect the formation of cyclic sulfones 53
from 52 in good yields.
a
By-product 41 (18%, see below), like 11 in Scheme 2, was also
detected.
b
This reaction was performed with 8 mol% of Rh (OAd) .
2
4
Scheme 5. New Variant of Sulfinate-sulfone Rearrangement.
In summary, the treatment of 1-sulfonyl-1,2,3-triazoles having
a side chain of sulfinyl ester with a catalytic amount of
Rh (OAd) afforded a variety of C,N-disulfonylated unsaturated
2
4
piperidines, which should be versatile synthetic intermediates

4
Tetrahedron
(
3
b) Y. Yu, L. Zhu, Y. Liao, Z. Mao, X. Huang, Adv. Synth. Catal.
58 (2016) 1059-1064.
[
12] based on their vinyl sulfone [7] and enamide [13] moieties.
From the mechanistic point of view, the new bond reorganization
between sulfonyltriazole and sulfinate should be quite interesting,
demonstrating a unique collaboration of the modern Rh-catalyzed
reactions and traditional organosulfur chemistry.
In an iodide-promoted version, the mechanism is proposed to be
different from the above benzylic reactions: (c) Z. Man, H. Dai, Y.
Shi, D. Yang, C.-Y. Li, Org. Lett. 18 (2016) 4962-4965.
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1
31 (2009) 3166-3167.
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[
[
Acknowledgments
(
See also reference [2g].
This research was supported partially by JSPS KAKENHI
Grant Numbers JP26810019 and 25288018 and JST PRESTO
Grant Number JPMJPR14KC.
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as shown in Scheme 5. (a) S. Oae, Organic Sulfur Chemistry:
Structure and Mechanism; CRC Press: Boca Raton, 1991;
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5
•
Strictly ordered scission and formation of a few
bonds are attained in one flask
•
Traditional S and new Rh chemistries elegantly
collaborated to yield a new field
•
Sulfur magic between its two exchangeable states
leads an intriguing bond behavior
•
Versatile unsaturated piperidines with N-sulfonyl
protection are readily accessible