Synthesis of enaminones by rhodium-catalyzed denitrogenative rearrangement of 1-(N -Sulfonyl-1,2,3-triazol-4-yl)alkanols

Article abstract of DOI:10.1021/ja308285r

Enaminones are synthesized by the rhodium(II)-catalyzed denitrogenative rearrangement reaction of 1-(N-sulfonyl-1,2,3-triazol-4-yl)alkanols, which are readily prepared from propargylic alcohols and N-sulfonyl azides. Intramolecular 1,2-hydride (or -alkyl)

Full text of DOI:10.1021/ja308285r

Communication
pubs.acs.org/JACS
Synthesis of Enaminones by Rhodium-Catalyzed Denitrogenative
Rearrangement of 1‑(N‑Sulfonyl-1,2,3-triazol-4-yl)alkanols
Tomoya Miura,* Yuuta Funakoshi, Masao Morimoto, Tsuneaki Biyajima, and Masahiro Murakami*
Department of Synthetic Chemistry and Biological Chemistry, Kyoto University, Katsura, Kyoto 615-8510, Japan
S
* Supporting Information
-alkyl) migration onto the adjacent electrophilic carbenoid
carbon,10,11 as with the case of the semipinacol rearrangement,
ABSTRACT: Enaminones are synthesized by the
rhodium(II)-catalyzed denitrogenative rearrangement re-
action of 1-(N-sulfonyl-1,2,3-triazol-4-yl)alkanols, which
are readily prepared from propargylic alcohols and N-
sulfonyl azides. Intramolecular 1,2-hydride (or -alkyl)
migration occurs with an intermediary α-imino rhodium-
(II) carbenoid species generated through denitrogenation
of the 1,2,3-triazol-4-yl moiety. The resulting enaminones
is converted into various heterocycles with replacement of
the N-sulfonyl group.
leading to the formation of enaminones.
Thus, we initially prepared 1-(N-tosyl-1,2,3-triazol-4-yl)-
ethanol (1a) from but-3-yn-2-ol and tosyl azide according to
the method reported by Hu (91% yield).5c Then, 1a was
treated with a catalytic amount of Rh2(Oct)4 (0.5 mol %, Oct =
octanoate) in CHCl3 at 140 °C under microwave irradiation
(MW) for 15 min.12 To our delight, (Z)-4-(tosylamino)but-3-
en-2-one (2a) was produced in 94% isolated yield (Table 1,
Table 1. Rh(II)-Catalyzed Denitrogenative Rearrangement
a
of 1-(N-Tosyl-1,2,3-triazol-4-yl)alkanols 1a−h
naminones are important synthetic intermediates for a
Ewide variety of heterocycles contained in natural products
and pharmaceutical compounds,1 and the development of new
methods for their synthesis is highly desired.2−4 We report
herein a rhodium(II)-catalyzed denitrogenative rearrangement
reaction of 1-(N-sulfonyl-1,2,3-triazol-4-yl)alkanols, leading to
the formation of enaminones. The starting 1-triazolylalkohols
are readily prepared from propargylic alcohols and N-sulfonyl
azides.5 Figure 1 depicts how the segments of a propargylic
alcohol and N-sulfonyl azide construct the product structure
through the whole process.
b
b
entry
1
R1
R2
2 (yield/%)
2′ (yield/%)
1
2
3
4
5
6
7
8
1a
1b
1c
1d
1e
1f
Me
n-Pr
i-Pr
t-Bu
Ph
H
2a (94)
2b (91)
2c (87)
2d (79)
2e (58)
2a′ (0)
2b′ (0)
2c′ (0)
2d′ (0)
H
H
H
c
H
2e′ (25)
c
c
Me
i-Pr
Me
Ph
Me
Me
2f (86)
2f′ (5)
c
c
1g
1h
2g (47)
2g′ (19)
c
2h (90)
a
Conditions: Rh2(Oct)4 (1 μmol) and 1 (0.2 mmol) in CHCl3 (4 mL)
were heated at 140 °C under microwave irradiation for 15 min.
Isolated yield (average of 2 runs). E/Z isomeric mixtures; 2e′
Figure 1. Construction of enaminones from propargylic alcohols and
tosyl azide.
b
c
(30:70), 2f (12:88), 2f’ (70:30), 2g (24:76), 2g′ (9:91), 2h (22:78).
Recently, Gevorgyan,6 Fokin,6a,7 and our group8 have
reported denitrogenative annulation reactions of N-sulfonyl-
1,2,3-triazoles with unsaturated organic molecules such as
nitriles, alkynes, and alkenes. α-Diazo imine formed by ring−
chain tautomerization reacts with a rhodium(II) or nickel(0)
complex to generate the corresponding metal carbenoid, which
undergoes cyclization with an unsaturated organic molecule.
We have recently reported the rhodium(II)-catalyzed deni-
trogenative hydration reaction of N-sulfonyl-1,2,3-triazoles.9
The intermediate α-imino rhodium(II) carbenoid is electro-
philic enough to induce nucleophilic addition of water. This
study demonstrated the electron-deficient nature of the
carbenoid carbon, and led us to envisage that, with the α-
imino rhodium(II) carbenoid generated from 1-(N-sulfonyl-
1,2,3-triazol-4-yl)alkanol, an electron pushing effect of the
hydroxyl group might facilitate intramolecular 1,2-hydride (or
entry 1). The selective production of 2a suggested the 1,2-
hydride migration predominated over 1,2-methyl migration.
Substrates 1b−d possessing a variety of alkyl groups afforded
the corresponding products 2b−d in yields ranging from 79%
to 91% (entries 2−4). On the other hand, the reaction of
phenyl-substituted substrate 1e gave a mixture of 2e (58%
yield) and 2e′ (25% yield), suggesting that 1,2-phenyl
migration could compete with 1,2-hydride migration (entry
5). In the case of disubstituted substrate 1f, the phenyl group
migrated preferentially over the methyl group (entry 6). With
the disubstituted substrate 1g, the methyl group migrated in
preference to the isopropyl group (entry 7). These results
Received: August 21, 2012
Published: October 9, 2012
© 2012 American Chemical Society
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Journal of the American Chemical Society
Communication
implied the migratory aptitude to be hydride > phenyl >
primary alkyl > secondary alkyl. This order was similar to that
observed with analogous rhodium(II) carbenoid intermediate-
s.10a,b,g With the dimethyl-substituted substrate 1h, even the
less labile methyl group migrated to give the product 2h in 90%
yield (entry 8). The enaminones 2a−e took (Z)-configuration,
which allowed intramolecular hydrogen bonding between the
N−H and carbonyl groups. On the other hand, a mixture of (E)
Table 2. Rh(II)-Catalyzed One-carbon Ring-Expansion of 1-
(N-Tosyl-1,2,3-triazol-4-yl)cycloalkanols 3a−i
a
1
and (Z)-isomers was observed by H NMR for α-substituted
enaminones 2e′−h, probably because the planar structure of
(Z)-configuration with intramolecular hydrogen bonding was
disfavored by steric repulsion between R1 and R2 substituents.13
A plausible mechanism for the production of 2 from 1 is
depicted in Scheme 1. Initially, a reversible ring−chain
Scheme 1. Plausible Mechanism for the Formation of 2 from
1
tautomerization of the N-sulfonyl-1,2,3-triazol-4-yl moiety of
1 generates α-diazo imine 1′.14 The subsequent irreversible
reaction of 1′ with rhodium(II) affords α-imino rhodium(II)
carbenoid A with release of molecular nitrogen. The imine
nitrogen acts as a base to deprotonate the hydroxyl group,
which exerts an electron-pushing effect to induce 1,2-migration.
The resulting anionic rhodium of zwitterionic intermediate B
releases an electron pair, which flows into the cationic iminium
moiety to give the product 2 with regeneration of the
rhodium(II) catalyst.
Next, the intramolecular 1,2-alkyl migration reaction was
applied to cyclic 1-triazolylalkanols, aiming at ring expansion
(Table 2).15,16 The migration reaction worked well with
substrates 3a−e of four- to eight-membered ring structures.
The carbocyclic structures were expanded by one carbon,
furnishing the products 4a−e in yields ranging from 74% to
95% (entries 1−5). Substrates 3f−h having heteroatoms within
their cyclic skeletons were reactive as well to afford the
products 4f−h, that were difficult to synthesize via conventional
routes starting from symmetrical ketones and formamide
acetals (entries 6−8).3 Interestingly, the ring-expansion
reaction of fluorenol-substrate 3i furnished phenanthrene
derivative 4i in an enol form (entry 9).
a
Conditions: Rh2(Oct)4 (1 μmol) and 3 (0.2 mmol) in CHCl3 (4 mL)
were heated at 140 °C under microwave irradiation for 15 min.
b
c
Isolated yield (average of 2 runs). E/Z isomeric mixtures; 4a (7:93),
d
4b (6:94). Using Rh2(Oct)4 (2 μmol).
We also investigated the site-selectivity in the migratory step
using a diastereomeric pair of unsymmetrical 1-triazolylcycloal-
kanols. In the case of cis-2-phenyl-1-triazolylcyclohexanol 3j,
the methylene carbon selectively migrated to give the product
4j in 92% yield (eq 1). On the other hand, the trans-isomer 3j
afforded a mixture of products 4j (53% yield) and 4j′ (8%
yield) (eq 2). These results indicated that the migratory
aptitude with cyclic substrates was not so simple, but also
subject to a configurational factor.17
The one-pot synthesis of enaminones starting from
propargylic alcohols was carried out to demonstrate the practical
convenience of the present method (eqs 3−5). The
enaminones 2a, 4c, and 4k were directly obtained in one-pot
from the corresponding propargylic alcohols 5a, 5c, and 5k,
which were all available from commercial sources. Although the
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Communication
AUTHOR INFORMATION
Corresponding Author
tmiura@sbchem.kyoto-u.ac.jp; murakami@sbchem.kyoto-u.ac.
jp
■
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
This work was supported in part by MEXT (Grant-in-Aid for
Scientific Research on Innovative Area Nos. 22105005 and
22106520, Young Scientists (A) No. 23685019), Takeda
Science Foundation, and Asahi Glass Foundation. M.
Morimoto is grateful for the JSPS Research Fellowship for
Young Scientists.
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* Supporting Information
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