Iridium-catalyzed annulation of salicylimines with 1,3-dienes

Article abstract of DOI:10.1021/ja504990a

Iridium-catalyzed annulation of salicylimines with 1,3-dienes gave high yields of the corresponding 4-aminochromanes with high stereoselectivity. The use of a chiral diene ligand enabled the asymmetric reaction to give 4-aminochromanes with high enantioselectivity.

Full text of DOI:10.1021/ja504990a

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Iridium-Catalyzed Annulation of Salicylimines with 1,3-Dienes
Yusuke Ebe, and Takahiro Nishimura
J. Am. Chem. Soc., Just Accepted Manuscript • Publication Date (Web): 16 Jun 2014
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Iridium-Catalyzed Annulation of Salicylimines with 1,3-Dienes
Yusuke Ebe and Takahiro Nishimura*
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Department of Chemistry, Graduate School of Science, Kyoto University, Sakyo, Kyoto 606-8502, Japan
Supporting Information Placeholder
Table 1. Iridium-Catalyzed Annulation of Salicylimines 1
with 2aa
ABSTRACT: Iridium-catalyzed annulation of sali-
cylimines with 1,3-dienes gave high yields of the corre-
sponding 4-aminochromanes with high stereoselectivity.
The use of a chiral diene ligand enabled the asymmetric
reaction to give 4-aminochromanes with high enantiose-
lectivity.
Transition metal-catalyzed intermolecular cycloaddi-
entry Ir catalyst
base
yield of 3 (%)b
tion is one of the most powerful methods for the synthe-
sis of carbo- and heterocyclic compounds,1 and in par-
ticular, the development of highly atom-efficient cy-
cloaddition reactions without formation of wastes2 is a
significant objective to realize ideal molecular transfor-
mations of carbon resources in synthetic organic chemis-
try.3 In this regard, we recently reported the iridium-
catalyzed [3 + 2] annulation of cyclic N-sulfonyl
ketimines with 1,3-dienes giving spiroaminoindane de-
rivatives, where the reaction proceeds via aryliridium(I)
species I generated by the chelation-assisted ortho C–H
activation of the aromatic ring (Scheme 1a).4 The ar-
yliridium(I) species I undergoes the oxidative cycliza-
tion5–7 with the 1,3-diene forming π-allyliridium(III)
species II and the subsequent reductive elimination
gives the aminoindane derivative，and thus, two C–C
bond formations occur to create the indane skeleton. We
focused on the oxidative cyclization/reductive elimina-
Scheme 1. Iridium-Catalyzed Annulation Using 1,3-
Dienes
1
[IrCl(cod)]2
[IrCl(cod)]2
[IrCl(cod)]2
[IrCl(cod)]2
[IrCl(cod)]2
[IrCl(cod)]2
[IrCl(cod)]2
[IrCl(coe)2]2
[IrCl(coe)2]2
KOAc
KHCO3
K2CO3
K3PO4
KOt-Bu
NaOAc
3aa
3aa
3aa
3aa
3aa
3aa
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13
3
2
3
4
0
5
0
6
45
6
7
LiOAc·2H2O 3aa
8
NaOAc
NaOAc
3aa
3aa
3aa
3ba
3ca
3ca
3da
92
98d
30
80
58
76d
74d
9c
10
11
12
13e
14e
[RhCl(coe)2]2 NaOAc
[IrCl(coe)2]2
[IrCl(coe)2]2
[IrCl(coe)2]2
[IrCl(coe)2]2
NaOAc
NaOAc
NaOAc
NaOAc
aReaction conditions: salicylimine 1 (0.10 mmol), 2a
(0.15 mmol), [Ir] (5 mol % of Ir), base (50 mol %) in tolu-
ene (0.4 mL) at 80 ºC for 6 h. bDetermined by H NMR
1
analysis using 1,4-dimethoxybenzene as an internal stand-
ard. cSalicylimine 1a (0.20 mmol), 2a (0.30 mmol),
[IrCl(coe)2]2 (2 mol % of Ir), NaOAc (50 mol %) in tolu-
d
ene (0.8 mL) at 80 ºC for 12 h. Isolated yield. eFor 36 h.
tion sequence for the synthesis of oxygen-containing
heterocycles as shown in Scheme 1b, where the reaction
involves phenoxoiridium(I) species III. Here we report
an iridium-catalyzed formal [4 + 2] annulation of sali-
cylimines with 1,3-dienes to give 4-aminochromane de-
rivatives. The asymmetric variant of the reaction by use
of a chiral diene ligand8 is also described.
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Table 2. Scope of 1,3-Dienes 2a
Page 2 of 6
4-Aminochromanes are structurally important core
1
unit found in many biologically active compounds and
natural products,9 and their synthesis has attracted con-
siderable attention. Salicylimines have been used as
good starting materials for the synthesis of 4-
aminochromanes in the acid or base-catalyzed reactions
with electron-rich alkenes,10 azalactones,11 allenic es-
ters,12 and electron-deficient alkenes and alkynes.13 Our
approach is focused on the use of the N-
tosylsalicylimines 1 for the formation of the phenox-
oiridium(I) species III intramolecularly coordinated
with the imine nitrogen (Scheme 1b and Table 1).
Treatment of N-tosylsalicylimine 1a with isoprene (2a)
in the presence of [IrCl(cod)]2 (5 mol % of Ir, cod = 1,5-
cyclooctadiene), KOAc (50 mol %) in toluene at 80 °C
for 6 h gave the annulation product 3aa in 26% yield
(Table 1, entry 1), where a very high regio- and stereose-
lectivity of the annulation was observed: a more substi-
tuted alkene moiety of isoprene participates in the reac-
tion to give 3aa with the 2,4-cis relative stereochemistry.
The reactions with other bases, such as KHCO3 and
K2CO3, gave much lower yields of 3aa than that with
KOAc (entries 2 and 3), and the use of K3PO4 and KOt-
Bu resulted in no formation of the annulation product
(entries 4 and 5). The use of NaOAc gave a higher yield
of 3aa than that obtained with KOAc or LiOAc (entry 6
vs entries 1 and 7). The catalytic activity was dramati-
cally increased by use of [IrCl(coe)2]2 (5 mol % of Ir,
coe = cyclooctene) instead of [IrCl(cod)]2 as a catalyst
precursor, giving a 92% yield of 3aa (entry 8). This
result indicates that the iridium species coordinated with
the 1,3-diene as a ligand formed by a exchange of two
cyclooctenes on [IrCl(coe)2] displays high catalytic ac-
tivity. The reaction with a reduced amount of the iridi-
um catalyst (2 mol % of Ir) also proceeded well, giving a
98% yield of the annulation product (entry 9). A Rh
catalyst [RhCl(coe)2]2 can also catalyze the present reac-
tion, although its catalytic activity was much lower than
that of the Ir catalyst (entry 10). The reactions of N-
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aReaction conditions: salicylimine 1a (0.20 mmol), 2
(0.30 mmol), [IrCl(coe)2]2 (2 mol % of Ir), NaOAc (50
mol %) in toluene (0.8 mL) at 80 ºC for 12 h. bIsolated
benzenesulfonylimine
1b
and
N-
c
nitrobenzenesulfonylimines 1c and 1d proceeded to give
the corresponding annulation products 3ba, 3ca, and
3da, respectively (entries 11–14), where the relatively
electron-deficient substituents on the imine nitrogen
lowered the reactivity.
yields. Performed with [IrCl(coe)2]2 (5 mol % of Ir).
(3ae/4ae = 97:3, entry 5). 2,3-Disubstituted butadienes
are also good substrates for the present annulation (en-
tries 6–8). The reaction of 2,3-dimethyl-1,3-butadiene
(2f) gave 3af in 85% yield (entry 6). On the other hand,
it should be noted that the reactions of unsymmetrically
2,3-disubstituted butadienes 2g and 2h also displayed
high regioselectivity to give annulation products 3ag and
3ah as the major products, respectively (entries 7 and 8),
where less bulky alkene parts preferentially participated
in the reaction. Diene 2i based on a dihydropyrrole
group gave benzobicyclic compound 3ai in 53% yield
(entry 9).
The results obtained for the iridium-catalyzed annula-
tion of salicylimine 1a with various types of 1,3-dienes
are summarized in Table 2. In a similar vein as isoprene
(2a), myrcene (2b) and 2-phenylbutadiene (2c) under-
went the annulation of 1a to give the corresponding an-
nulation products 3ab and 3ac in yields of 86 and 83%,
respectively (entries 1–3).
The reaction of 2-
siloxybutadiene 2d gave 3ad in 86% yield with very
high regio- and stereoselectivity (entry 4). In the reac-
tion of 2-siloxymethylbutadiene 2e, a more substituted
alkene moiety participated in the reaction to give 3ae
accompanied with a small amount of its regioisomer 4ae
Table 3 summarizes the results obtained for the reac-
tion of several salicylimines 1 with 1,3-diene 2a. The
reactions of salicylimines substituted at the 5-position
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Scheme 2. Proposed Catalytic Cycle
Table 3. Scope of Salicylimines 1a
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Table 4. Asymmetric Annulation of 1 with 2a
aReaction conditions: salicylimine 1 (0.20 mmol), 2a
(0.30 mmol), [IrCl(coe)2]2 (2 mol % of Ir), NaOAc (50
mol %) in toluene (0.8 mL) at 80 ºC for 12 h. bPerformed
with [IrCl(coe)2]2 (5 mol % of Ir). For 24 h. The isolated
product includes a 3% of the isomer. eIsomers were also
formed (ca. 3%). fKOAc (50 mol %) was used instead of
NaOAc.
c
d
with electron-donating groups, Me (1e) and MeO (1f),
and electron-withdrawing groups, F (1g), Cl (1h), and
Br (1i) are all good substrates to give high yields of the
annulation products 3ea–3ia (entries 1–5). The reac-
tions of salicylimines 1j and 1k, which are substituted
with a methyl group at meta and ortho to the hydroxy
group, gave the annulation products 3ja and 3ka, respec-
tively, in good yields (entries 6 and 7). Salicylimines 1l
and 1m substituted at the 6-position are also applicable
to the present annulation to give high yields of the corre-
sponding 4-aminochromanes (entries 8 and 9). The an-
nulation of naphthol derivative 1n gave 3na in 80%
yield (entry 10).
These annulation reactions presumably go through a
catalytic cycle illustrated in Scheme 2. The reaction of
salicylimine 1a with a chloroiridium complex, which is
coordinated with a 1,3-diene, in the presence of NaOAc
forms phenoxoiridium(I) species A intramolecularly
coordinated with the imine nitrogen. The species A un-
dergoes oxidative cyclization with the 1,3-diene via 18-
electron species B forming π-allyliridium(III) species C.
aReaction conditions: salicylimine 1 (0.24 mmol), 2
(0.20 mmol), [IrCl((S,S)-Fc-tfb*)]2 (5 mol % of Ir), NaB-
ArF4 (50 mol %), DABCO (10 mol %) in CH2Cl2 (0.8 mL)
b
at 20 ºC for 48 h. For 72 h.
The intermediate C undergoes reductive elimination
forming a carbon–oxygen bond to give species D, and
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Page 4 of 6
T.S. thanks the JSPS for a research Fellowship for Young
Scientists.
subsequent protonolysis gives 3aa and regenerates the
phenoxoiridium A.
1
2
Because iridium/diene complexes can catalyze the
present reaction,14 the use of chiral diene ligands is
promising for the development of the asymmetric vari-
ant. On the other hand, the high catalytic activity of the
iridium complex coordinated with the substrate 1,3-
diene observed above indicates a requirement of the use
of a chiral diene ligand that has a stronger coordination
ability than the substrate diene to avoid the non-
enantioselective background reaction. After screening
of the reaction conditions using recently developed chi-
ral diene ligands based on a tetrafluorobenzobarrelene
framework in our group,15 it was found that an enanti-
oselective annulation of salicylimines 1 with isoprene
(2a) or myrcene (2b) proceeds in the presence of a chiral
Ir/diene catalyst. Thus, treatment of salicylimine 1a (1.2
equiv) with 2a in the presence of [IrCl((S,S)-Fc-tfb*)]2
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4
diazabicyclo[2.2.2]octane (DABCO) (10 mol%) in di-
chloromethane at 20 °C for 48 h gave the annulation
product 3aa in 89% yield with 99% ee (Table 1, entry
1).16 The very high enantioselectivity was also observed
in the reactions of salicylimines 1e and 1g–1i substituted
at the 5-position (entries 2–5). The reactions of sali-
cylimines 1j and 1k having a methyl group at the 4- and
3-position were slow to give the corresponding products
3ja and 3ka in yields of 78 and 54%, respectively, for
72 h (entries 6 and 7). Myrcene (2b) can also be applied
to the annulation of 1a to give 3ab in 65% yield with
99% ee (entry 8). The relative and absolute configura-
tion of 3ha obtained with (S,S)-Fc-tfb* were determined
to be (2R,4R) by X-ray crystallographic analysis.
(6)
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Oka, M.; Kurosawa, H. J. Am. Chem. Soc. 2006, 128, 7077.
In summary, we have developed a new type of annula-
tion reaction of salicylimines with 1,3-dienes using an Ir
catalyst that gives 4-aminochromane derivatives with
high regio- and stereoselectivity. The asymmetric annu-
lation with high regio- and enantioselectivity has also
been realized by use of an Ir/chiral diene catalyst.
(7)
For selected examples of iridium-catalyzed reductive cou-
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Soc. 2007, 129, 12644.
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Supporting Information. Experimental procedures and
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free of charge via the Internet at http://pubs.acs.org.
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AUTHOR INFORMATION
Corresponding Author
tnishi@kuchem.kyoto-u.ac.jp.
Funding Sources
No competing financial interests have been declared.
ACKNOWLEDGMENT
This work has been supported by a Grant-in-Aid for Scien-
tific Research on Innovative Areas "Molecular Activation
Directed toward Straightforward Synthesis", MEXT, Japan.
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(16) The use of NaOAc slightly decreased the ee: The reaction
of 1a with 2a in the presence of NaOAc instead of NaBArF and
4
DABCO at 20 °C for 48 h gave 3aa in 93% yield with 95% ee.
(14) The use of binap as a ligand gave no annulation product in
the reaction of 1a with 2a.
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R1
R2
Ts
H
R1
R2
cat. [IrCl(coe)2]2
NaOAc
OH
N
R3
O
+
toluene, 80 ºC
NHTs
X
H
R3
O
X
Ir
Ts
N
via
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H
X
Ir = Ir(1,3-diene)
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