Synthesis of Penta-2,4-dien-1-imines and 1,2-Dihydropyridines by Rhodium-Catalyzed Reaction of N-Sulfonyl-1,2,3-triazoles with 2-(Siloxy)furans

Article abstract of DOI:10.1021/acs.orglett.6b03143

A rhodium(II)-catalyzed reaction of N-sulfonyl-1,2,3-triazoles with 2-(siloxy)furans is reported. Either open-chain penta-2,4-dien-1-imines or cyclic 1,2-dihydropyridines are selectively obtained depending on the ligand on rhodium(II).

Full text of DOI:10.1021/acs.orglett.6b03143

Letter
pubs.acs.org/OrgLett
Synthesis of Penta-2,4-dien-1-imines and 1,2-Dihydropyridines by
Rhodium-Catalyzed Reaction of N‑Sulfonyl-1,2,3-triazoles with
2‑(Siloxy)furans
Yuuta Funakoshi, Tomoya Miura,* and Masahiro Murakami*
Department of Synthetic Chemistry and Biological Chemistry, Kyoto University, Katsura, Kyoto 615-8510, Japan
S
* Supporting Information
ABSTRACT: A rhodium(II)-catalyzed reaction of N-sulfonyl-1,2,3-
triazoles with 2-(siloxy)furans is reported. Either open-chain penta-
2,4-dien-1-imines or cyclic 1,2-dihydropyridines are selectively
obtained depending on the ligand on rhodium(II).
N-Sulfonyl-1,2,3-triazoles have emerged as the latent precursors
of α-imino carbenoid species.1 The electron-withdrawing
sulfonyl group on the ring nitrogen induces the ring−chain
tautomerization to generate transient α-imino diazo com-
pounds.2 They promptly react with present transition metal
complexes, rhodium(II) carboxylate dimers in most cases, to
form metal carbene complexes with extrusion of molecular
nitrogen. A number of synthetically useful transformations
involving these metal carbene complexes as the key
intermediate have been developed during the past decade.3 In
2013, Davies and co-workers disclosed a fascinating trans-
annulation reaction of N-sulfonyl-1,2,3-triazoles with electron-
rich 2,5-dialkylfurans to afford substituted pyrroles (Figure
1a).4 During the subsequent year, three groups reported the
1,2,3-triazoles with 2-(siloxy)furans. The products would be
valuable intermediates for the synthesis of polysubstituted
piperidines,9 such as aza sugars.10
Initially, 4-phenyl-1-tosyl-1,2,3-triazole (1a) was prepared
from phenylacetylene and tosyl azide according to Fokin’s
procedure11 using copper(I) thiophene-2-carboxylate (CuTC).
Then the isolated triazole 1a (0.2 mmol) was treated with 2-
(triisopropylsiloxy)furan (2a) (1.5 equiv) in chloroform at 70
°C in the presence of 1.0 mol % Rh2(esp)2 (esp = α,α,α′,α′-
tetramethyl-1,3-benzenedipropionate)12 and 4 Å molecular
sieves (MS) (Table 1, entry 1). After 2 h, the formation of a
34:66 mixture of penta-2,4-dien-1-imine 3aa and 1,2-
1
dihydropyridine 4aa was observed by H NMR analysis of
the crude reaction mixture. The product selectivity notably
varied depending on the ligand on rhodium(II). In the case of
the pivalate ligand, the product ratio slightly shifted to 3aa
(3aa:4aa = 57:43) (entry 2). On the other hand, 3aa became
predominant (3aa:4aa = 78:22) when the sterically bulkier N-
naphthoyl-tert-leucinate (NTTL) ligand13 was employed (entry
3). The reaction with N-mesyl-1,2,3-triazole 1b in place of 1a
proceeded even at room temperature with the exclusive
formation of 3ba (3ba:4ba ≥ 95:5), which was isolated in
76% yield after modified silica gel chromatography (entry 4).14
1
None of the 1,2-dihydropyridine 4ba was detected in the H
NMR spectrum of the reaction mixture in this case.
Figure 1. Rh(II)-catalyzed reaction of triazoles with (a) 2,5-
dialkylfurans and (b) silyl or alkyl enol ethers.
The formation of products 3 and 4 is reasonably explained by
assuming the dichotomous pathways depicted in Scheme 1.
Ring−chain tautomerization of 1 generates α-diazo imine 1′,
which promptly reacts with the rhodium(II) complex to afford
α-iminorhodium(II) carbene complex A with extrusion of
molecular nitrogen. The electrophilic character of A is suitably
combined with the highly electron-rich and nucleophilic
character of 2-(triisopropylsiloxy)furan (2a) to allow cyclo-
synthesis of substituted pyrroles by a rhodium(II)-catalyzed [3
+ 2] annulation reaction of triazoles with silyl or alkyl enol
ethers, which were significantly more nucleophilic than 2,5-
dialkylfurans (Figure 1b).5−7 Those results led us to examine
the use of 2-(siloxy)furans as the analogous electron-rich and
nucleophilic partner for the carbenoid species.8 We now report
that either open-chain penta-2,4-dien-1-imines or cyclic 1,2-
dihydropyridines, not pyrrole derivatives, are selectively
obtained by a rhodium(II)-catalyzed reaction of N-sulfonyl-
Received: October 20, 2016
© XXXX American Chemical Society
A
DOI: 10.1021/acs.orglett.6b03143
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
other hand, an analogous stereospecific ring opening of minor
bicyclic intermediate E gives (2Z,4Z)-penta-2,4-dien-1-imine F.
Because of the 2Z configuration, spontaneous 6π-electro-
cyclization follows, leading to the production of 4 [path (b)].
Variation of the N-mesyl triazole was examined for the
selective production of open-chain imines 3 by the reaction
with 2-(siloxy)furan 2a at room temperature using Rh2[(S)-
NTTL]4 as the catalyst (Table 2). Triazoles 1c−g, possessing
Table 1. Rh(II)-Catalyzed Reaction of N-Sulfonyl-1,2,3-
triazoles 1 with 2-(Siloxy)furan 2a
a
Table 2. Synthesis of (2E,4Z)-Penta-2,4-dien-1-imines 3
a
from Various Triazoles and 2-(Siloxy)furan 2a
b
yields (%)
entry
1
R2
Rh2(L)n
Rh2(esp)2
Rh2(OCOtBu)4
Rh2[(S)-NTTL]4
Rh2[(S)-NTTL]4
3
4
1
2
3
1a
1a
1a
1b
Ts
Ts
Ts
Ms
32
50
69
61 (47)
37
b
entry
1
R1
3
yield (%)
19
1
2
3
4
5
6
1c
1d
1e
1f
p-MeOC6H4
p-MeC6H4
p-BrC6H4
3ca
3da
3ea
3fa
98
85
83
87
92
c
4
89 (76)
<3
a
On a 0.20 mmol scale. Ts = p-toluenesulfonyl. Ms = methanesulfonyl.
b
1H NMR yields using CHCl2CHCl2 as an internal standard; isolated
p-CF3C6H4
3-thienyl
c
yields are shown in parentheses. At room temperature for 4 h.
1g
1h
3ga
3ha
c
1-cyclohexenyl
69
a
b
c
Scheme 1. Proposed Mechanism for the Formation of 3 and
4
On a 0.20 mmol scale. Isolated yields. 24 h.
an electronically diverse array of aryl and heteroaryl groups at
the 4-position, selectively afforded the corresponding penta-2,4-
dien-1-imines 3ca−ga in yields ranging from 83% to 98%
(entries 1−5). 1-Cyclohexenyl-substituted triazole 1h was also a
suitable substrate (entry 6). None or little (<5% yield) of the
1
corresponding 1,2-dihydropyridines 4 were detected in the H
NMR spectra of the crude reaction mixtures.
Interestingly, the isolated 3ba gradually isomerized to the
cyclic dihydropyridine 4ba when it was heated at 70 °C in
chloroform in the presence of pyridine (3.0 equiv). After 24 h,
4ba was obtained in 68% yield by chromatography (eq 1). The
propanation of 2a at its remote double bond. There are two
diastereomeric faces for carbenoid A to approach 2a, and the
two transition state models B and C become conceivable
depending on which face the carbenoid A prefers for
approaching 2a.15 The N-sulfonylimino group is more
stereodemanding than the phenyl group, and transition state
B with the bulkier imino group on the convex side is more
stable than the other diastereomeric transition state C. The
sterically bulkier NTTL ligand augments the differentiation
between B and C to favor transition state B: the sterically more
demanding NTTL ligands destabilize the crowded and hence
disfavored transition state C even more, improving the
selectivity. The use of N-mesyl triazole 1b in place of 1a as
the substrate mitigates the steric congestion to promote the
cyclopropanation even at room temperature. Then the major
bicyclic intermediate D undergoes ring opening in a stereo-
specific manner to afford (2E,4Z)-penta-2,4-dien-1-imine 3,
which is readily isolated by chromatography [path (a)]. On the
isolated 3aa also underwent the pyridine-mediated isomer-
ization to 4aa in an analogous manner. We assume that
pyridine mediates the isomerization of 3 from its 2E isomer to
its 2Z isomer, which then undergoes 6π-electrocyclization to
give 4.
The pyridine-mediated isomerization of 3 into 4 was
successfully integrated into a one-pot sequential procedure
for the selective production of 1,2-dihydropyridines 4 from N-
tosyl triazole 1a using Rh2(esp)2 as the catalyst (Table 3).
Thus, the Rh2(esp)2-catalyzed reaction of 1a with 2a was
immediately followed by the pyridine-mediated isomerization,
and a single isolation procedure afforded cyclized 4aa in 80%
yield (entry 1). Moreover, the reaction was amenable to a
larger-scale experiment using 1.2 g of 1a (4.0 mmol), and 4aa
was isolated in 71% yield. Various 1,2-dihydropyridines 4ia−qa
were produced from N-tosyl triazoles 1i−q and 2a (entries 2−
10). None of the corresponding penta-2,4-dien-1-imines 3 were
detected in the 1H NMR spectra of the crude reaction mixtures.
B
DOI: 10.1021/acs.orglett.6b03143
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
Table 3. One-Pot Synthesis of 1,2-Dihydropyridines 4 from
a
Various Triazoles and 2-(Siloxy)furan 2a
b
entry
1
R1
4
yield (%)
1
2
1a
1i
Ph
4aa
4ia
80
78
70
79
75
63
76
46
84
85
p-MeOC6H4
p-MeC6H4
p-BrC6H4
3
1j
4ja
4
1k
1l
4ka
4la
5
p-EtO2CC6H4
p-CF3C6H4
m-MeC6H4
o-BrC6H4
6
1m
1n
1o
1p
1q
4ma
4na
4oa
4pa
4qa
7
8
9
3-thienyl
10
1-cyclohexenyl
A sequential one-pot procedure starting from phenyl-
acetylene (7) and mesyl azide (8) was performed to save the
time and solvent required for a workup/purification after the
triazole synthesis (eq 6). A mixture of 7, 8, CuTC, and MS was
a
b
On a 0.20 mmol scale. Isolated yields.
In the case of n-propyl-substituted triazole 1r, the product
4ra was produced in 17% NMR yield together with uncyclized
and isomerized 3ra′ (41% NMR yield) (eq 2).
stirred for 13 h to form triazole 1b. Subsequently, 2a and
Rh2[(S)-NTTL]4 were added to the same reaction vessel,
which was further stirred at room temperature for 4 h. Penta-
2,4-dien-1-imine 3ba was thus obtained in 73% overall yield.
In summary, an efficient synthetic route to penta-2,4-dien-1-
imines and 1,2-dihydropyridines from N-sulfonyl-1,2,3-triazoles
and 2-(siloxy)furans has been developed.
2-(Siloxy)furans 2b−d possessing a substituent at the 4-
position were applied to the sequential reaction with 1a. The
corresponding dihydropyridines 4ab−ad were obtained in good
to high yields (eq 3).
ASSOCIATED CONTENT
■
S
* Supporting Information
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.or-
glett.6b03143.
Experimental procedures and spectral data for the new
compounds (PDF)
AUTHOR INFORMATION
Corresponding Authors
■
*E-mail: tmiura@sbchem.kyoto-u.ac.jp.
When 5-methyl-2-(siloxy)furan 2e was subjected to the
Rh2(esp)2-catalyzed reaction with 1a, the dihydropyridine 4ae
was selectively produced in 53% yield without any formation of
the corresponding penta-2,4-dien-1-imine 3ae (eq 4).16 The
transition state C′ would be dominant because, with the other
transition state B′, the repulsive interaction between the imino
group and the methyl group would be significant. On the other
hand, the Rh2(esp)2-catalyzed reaction of 3-methyl-2-
(triisopropylsiloxy)furan with 1a was sluggish, affording the
corresponding product in 17% yield.
The resulting dihydropyridine 4aa acted as the diene in a [4
+ 2] cycloaddition reaction with N-methylmaleimide (5). Only
the endo adduct 6 was obtained in 81% yield (eq 5). The
structure of 6 was determined by NMR studies.
*E-mail: murakami@sbchem.kyoto-u.ac.jp.
ORCID
Tomoya Miura: 0000-0003-2493-0184
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
We thank Dr. Y. Nagata (Kyoto University) for his kind help
with X-ray analysis. This work was supported in part by Grants-
in-Aid for Scientific Research (S) (15H05756) and (C)
(16K05694) from MEXT. Y.F. acknowledges a JSPS Fellowship
for Young Scientists.
C
DOI: 10.1021/acs.orglett.6b03143
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Organic Letters
Letter
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DOI: 10.1021/acs.orglett.6b03143
Org. Lett. XXXX, XXX, XXX−XXX