doi:10.1246/cl.2012.

1554
1554 Published on the web November 24, 2012

Highlight Review

Cu­Rh Redox Relay Catalysts for Synthesis

of Azaheterocycles via C­H Functionalization
Shunsuke Chiba

(Received September 18, 2012; CL-120963)

Abstract Ph
H N
III
Rh Cl
This Highlight Review describes a Cu­Rh bimetallic redox H
relay catalytic system that enables efficient synthesis of highly Cl Cl M-OAc
substituted isoquinolines and their derivatives from readily RhIII
available aryl ketoximes or ¡-arylvinyl azides with internal Cl Rh III AcO OAc
alkynes via C­H bond functionalization. A preliminary
mechanistic investigation revealed that both the Cu and Rh
catalysts are prerequisites to achieve the present process, and
play their particular roles with synergistic cooperation during the –OAc – OAc
multistep sequence. O III
Rh
Me
Me Ph III Ph
H N O Rh N
O HO
H H

 Introduction Concerted metallation/deprotonation

via a redox-neutral manner
Transition-metal-catalyzed molecular transformation via
C­H bond functionalization is a powerful tool in synthetic Scheme 1. [Cp*RhCl2]2 for ortho-C­H bond rhodation with
organic chemistry.1 In the process of the C­H bond fission, acetate (¹OAc) sources.
suitable heteroatoms are commonly utilized to direct a metal
center to the target proximal C­H bond. Among such directing Ph
groups, an sp2 nitrogen atom of the imines has played a vital role NH [Cp*RhCl2]2 (1 mol %) Ph
N
in numerous examples of the C­H bond cleavage, while these Cu(OAc)2 H2O (2 equiv)
Ph + Ph Ph
nitrogen atoms have rarely been involved in the new bond DMF, 80 °C
Ph
constructed in the reaction.2 From the stand point of construction
of azaheterocyclic frameworks which are the most essential [RhIII] [RhI]
components in natural alkaloids, potent pharmaceutical drugs, 2CuI 2CuII
and various functional materials, it would be attractive to
Ph [RhIII]
develop the sequential processes of sp2 nitrogen atom-directed [RhIII] N
C­C bond formation on the C­H bond and the C­N bond Ph Ph Ph N
Ph
formation. Ph
It was revealed by Davies that the [Cp*Rh(OAc)n] (Cp*:
C5Me5) species generated from the reaction of [Cp*RhCl2]2 and
NaOAc causes fission of the sp2 C­H bond of aryl imines Scheme 2. Isoquinoline synthesis by Miura and Satoh.
via a redox-neutral concerted rhodation­deprotonation manner
assisted by the imino group, affording rhodacycle complexes
(Scheme 1).3 This process has been deeply investigated in terms use of Cu(OAc)2 as an external oxidant to regenerate the active
of the reaction mechanism of the cyclometallation as well as the Rh(III) catalyst from the resulting Rh(I) species.
reactivity of the rhodacycles by Jones.4 Thus, this method has Recently, the strategy using the N­O bond in the directing
been successfully applied to heterocycle syntheses with the group as an internal oxidant has emerged for ortho sp2 C­H
insertion of alkynes as well as alkenes.1a,1c For example, Miura­ activation and C­N bond formation, in which the stoichiometric
Satoh and Fagnou have independently reported Rh(III)-catalyzed use of external oxidants such as Cu(OAc)2 is not required.7 For
oxidative isoquinoline synthesis using benzophenone imines5 example, Guimond and Fagnou disclosed Rh(III)-catalyzed
and N-tert-butylarylaldimines,6 respectively as a nitrogen source redox-neutral synthesis of isoquinolones from benzohydroxamic
via ortho-aryl C­H vinylation followed by C­N reductive acid derivatives and alkynes (Scheme 3).8 Our group, Li, and
elimination along with the formation of the Rh(I) species Rovis also reported formation of isoquinoline or pyridine
(Scheme 2). These processes, however, require stoichiometric derivatives utilizing aryl ketone or ¡,¢-unsaturated ketone

Prof. Shunsuke Chiba

Division of Chemistry and Biological Chemistry, School of Physical and Mathematical Sciences, Nanyang
Technological University, Singapore 637371, Singapore
E-mail: shunsuke@ntu.edu.sg

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 1555

O OAc Ph
OPiv [Cp*RhCl2]2 (0.25 mol %) O Ph
N N N
H CsOAc (2 equiv) NH Me Me
+ MeOH, rt, 16 h Ph Me [Cp*RhCl2]2 (2.5 mol %)
Me 3aa 54%
Ph Ph Ph 1a NaOAc (30 mol %)
96% (syn:anti = 1:1) +
+ MeOH, 60 °C HO
N
Ph Ph
Scheme 3. Rh(III)-Catalyzed redox-neutral synthesis of iso- 2a (1.2 equiv)
Me
quinolones from benzohydroxamic acids.
Me syn -4a 36%
(determined by 1H NMR)
OAc
reaction courses of syn - and anti -oximes1a
N Ph
[Cp*RhCl2]2 (2.5 mol %) Ph AcO–[RhIII]
Me N H N
OAc [RhIII] N OAc
NaOAc (30 mol %)
Me [RhIII]–OAc Me Me 2a
+ anti -1a 3aa
MeOH, 60 °C –AcOH
Me Me
Ph Ph
82%
AcO [RhIII]–OAc
OH H N
N [RhIII]–OAc Me
[Cp*RhCl2]2 (2.5 mol %) Ph syn -1a syn -4a
Ph Me Me
CsOPiv (30 mol %) Ph
N
+
Ph Ph
MeOH, 60 °C Ph Me Scheme 5. The reaction of isobutyrophenone O-acetyloxime
under Air
86% (1a) under [Cp*RhCl2]2­NaOAc system.

Scheme 4. Rh(III)-Catalyzed redox-neutral synthesis of iso- OAc Ph

cat. [Mn] (reductant)
quinolones and pyridines from oximes. N
cat. [RhIII]
Ph
N
R + Ph Ph
R
2a
anti-O-acetyloximes with internal alkynes under the catalytic 1 3
[Cp*RhCl2]2­NaOAc (or CsOPiv) system (Scheme 4).9 [Mn]
In the process of oximes, stereochemical requirements of 2a
oximes 1 (i.e., the N­O bond of oximes should be anti to the aryl [Mn+x] [RhIII]
moiety) were a crucial hurdle of the process especially in the N [RhIII] H N [RhIII] N
case of the oximes bearing a bulky alkyl substituent such as –[Mn+x]
R R R
isobutyrophenone O-acetyloxime 1a, that is obtained as a syn/ syn
anti-mixture (1:1).10 Actually, the reaction of oxime 1a and
diphenylacetylene (2a) with 2.5 mol % of [Cp*RhCl2]2 and [Mn+x] [RhIII]
30 mol % of NaOAc in MeOH at 60 °C provided the desired N [RhIII] N
isoquinoline 3aa in a modest 54% yield with recovery of pure –[Mn+x]
R R
syn-isobutyrophenone oxime 4a in 36% yield just through anti
deacetylation (Scheme 5). This drawback is obviously attributed
to the mechanism of C­H rhodation, where the Rh center should Scheme 6. A working hypothesis.
be directed to the ortho C­H bond of oximes 1 by the lone pair
of the oxime sp2 nitrogen for the C­H rhodation prior to the N­O isomerize between anti- and syn-isomers, both of the oxime
bond cleavage and C­N bond formation.11 isomers could be utilized in this transformation.14
Based on this working hypothesis, our studies com-
 Rh–Cu Redox Relay Catalysts for the menced with the reaction of isobutyrophenone O-acetyloxime
(syn:anti = 1:1) (1a) and diphenylacetylene (2a) (1.2 equiv)
Reactions of Oximes
by the use of [Cp*RhCl2]2 combined with Pd(0) and Cu(I)
To develop more general and efficient process that enables complexes as a reductant of oximes. Although the reactions
use of both the syn- and anti-isomers of oximes in the Rh(III)- with Pd(0) complexes by combined use of NaOAc resulted in
catalyzed reactions with internal alkynes, we planned to initiate formation of a complex mixture including only a small amount
the process by reduction of the oxime N­O bond using lower of isoquinoline 3aa, the reaction in the presence of 10 mol % of
valent transition metals [Mn] such as Pd(0)12 and Cu(I)13 species, CuIOAc in DMF under a nitrogen atmosphere proceeded
which could generate the corresponding iminyl metal species smoothly to give isoquinoline 3aa in quantitative yield within
(Scheme 6). If such a metal reductant of oximes and the Rh(III) 45 min, where both syn- and anti-isomers of 1a were converted
complex could work independently in the reaction system, the into 3aa (Scheme 7). It was noteworthy that utilization of
resulting iminyl metals might then undergo transmetallation with CuII(OAc)2 instead of CuIOAc provided 3aa in comparable
Rh(III) to give iminyl rhodium(III) intermediates, which could yield, while a longer reaction time (4 h) was required. No
successively achieve ortho-C­H rhodation and annulation with isoquinoline 3aa was formed in the reaction with CuII(OAc)2 in
alkynes. As the generataed iminyl metal species might be free to the absence of [Cp*RhCl2]2, which indicated that synergistic

Chem. Lett. 2012, 41, 1554­1559 © 2012 The Chemical Society of Japan www.csj.jp/journals/chem-lett/
1556

OAc [Cp*RhCl2]2 Ph (i) generation of Cu(I) species by reduction of CuII (OAc)2 with DMF
Ph (2.5 mol%) Ph
N additive N CuII(OAc)2 + DMF [CuI]
Me + Me
(ii) reductive formation of iminyl-Cu intermediate
DMF, 60 °C
Me Ph Me [CuII]
under N2
1a 3aa OAc
2a N
(syn:anti = 1:1) [CuI] N
additive time/h yield/% 1a i -Pr
i -Pr ––OAc
CuOAc (10 mol%) 0.8 99 –[CuII]
A B
Cu(OAc)2 (10 mol%) 4 95
[CuII]

Scheme 7. N
[CuI]
i -Pr
(a)
iminyl-Cu(II) C
(iii) ortho C-H rhodation, alkyne insertion,
and C-N reductive elimination
[RhIII]
H N [RhIII] N
[RhIII]
C i -Pr i -Pr
–[CuII] –H+
D E
Ph
Ph [RhIII]
2a N
Ph
Ph i -Pr 3aa
–[RhI]
(b) F
(iv) redox generation of Rh(III) and Cu(I) species

[Rh I] + 2 [CuII] [RhIII] + 2 [CuI]

[Rh] = Cp*Rh(OAc)n

Scheme 8. The proposed reaction pathway.

reduction of O-acetyloximes by Cu(I) species could form anion

Figure 1. (a) UV­vis absorption of Cu(OAc)2 (4 mM) in DMF
at 25 and 90 °C. line A: Cu(OAc)2, 4 mM in DMF at 25 °C
(absorption at 700 nm); line B: Cu(OAc)2, 4 mM in DMF, after
heating at 90 °C for 30 min, recorded at 90 °C (no absorption at
700 nm); line C: The above mixture was recorded again after
cooling down to 25 °C (no absorption at 700 nm). (b) Kinetic
study by recording the absorption of Cu(OAc)2 (4 mM in DMF,
at 90 °C) at 700 nm at 0.5 min interval.
Cu­Rh cooperation should be indispensable for the present
isoquinoline formation from a syn,anti-mixture of O-acetylox-
ime 1a.
In the case of the reaction with CuII(OAc)2, Cu(I) species
might be generated in situ via reduction of CuII(OAc)2 by DMF
via the single-electron-transfer process, which is also supported
by reports of Chang and others.15 Moreover, further evidence
was obtained from the UV­vis spectra in the treatment of
CuII(OAc)2 in DMF at 90 °C, showing disappearance of the
visible band of CuII(OAc)2 at 700 nm within 30 min (Figures 1a
and 1b). These results implied that DMF reduces CuII(OAc)2 to
form Cu(I) species. On the other hand, the UV­vis spectra for
the treatment of [Cp*RhIIICl2]2 in DMF at 90 °C showed no
change of the visible band of [Cp*RhCl2]2 at 410 nm (not
shown).
Based on these findings, a proposed mechanism for
Cu(OAc)2­[Cp*RhCl2]2 bimetallic catalytic system is outlined
in Scheme 8. After the formation of Cu(I) species by the
reduction of CuII(OAc)2 by DMF (step i), one electron
radical A. The homolytic N­O bond cleavage of A might afford
putative iminyl radical B, which could be further reduced by
another Cu(I) species to give iminyl copper(II) C.16 Formation
of rhodacycle E from iminyl copper species C with Rh(III) via
iminyl rhodium D, subsequent insertion of alkyne 2a, and C­N
reductive elimination from F provided isoquinoline 3aa with
generation of Rh(I) species (step iii). Finally, redox reactions
between Rh(I) and Cu(II) species would lead to regeneration of
Rh(III) and Cu(I) (step iv).
By using the optimized Cu(OAc)2­[Cp*RhCl2]2 catalytic
system,17 the generality was next examined (Table 1). The
investigation of the scope of alkynes revealed that both
methoxy- and bromo-substituted diarylacetylenes 2b and 2c
as well as dialkylacetylenes 2d and 2e reacted smoothly with
oxime 1a to afford the corresponding isoquinolines 3 in good
yields (Entries 1­4). Insertion of unsymmetrical alkynes
occurred with high regioselectivity (Entries 5­7). The reaction
of tert-butyl ketone O-acetyloxime (1b), which is a pure syn-
isomer, afforded the corresponding isoquinoline 3ba in excellent
yield (Entry 8). In addition, pyrrolyl, furanyl, and thienyl
ketoximes could be coupled with 4-octyne (2d), forming the
corresponding azaheterocycles in good yields (Entries 9­11).
It is noteworthy that this Cu­Rh bimetallic catalytic system
could be applied for a twofold coupling reaction of 1,4-
naphthoquinone bis(O-acetyloxime) (1f) with internal alkynes to
give novel 1,8-diazapyrenes, which showed efficient two-photon
excited deep blue emission (Scheme 9).18

Chem. Lett. 2012, 41, 1554­1559 © 2012 The Chemical Society of Japan www.csj.jp/journals/chem-lett/
 1557

Table 1. Substrate scopea N2

N N
Oxime 1 Product 3, N
Entry Alkyne 2 R R
(syn :anti ) Yieldb/% –N2 R R'
R' R'
OAc R2 vinyl azides vinyl nitrenes 2H -azirines
N R1
N
Me Me Scheme 10. Thermal decomposition of vinyl azides to 2H-
Me R1 R2 azirines.
Me

1 1a (1:1) 2b (R1, R2 = 4-MeO-C6H4) 3ab, 87 N2 [Cp*RhCl2]2 (2.5 mol%) Ph

2 1a (1:1) 2c (R1, R2 = 4-Br-C6H4) 3ac, 92 N additive (20 mol%) Ph
3 1a (1:1) 2d (R1, R2 = n -Pr) 3ad, 78 AcOH (1 equiv) N
4 1a (1:1) 2e (R1, R2 = CH2OTBS) 3ae, 79 + Ph Ph Me
5 1a (1:1) 2f (R1 = Me, R2 = Ph) 3af, 93 2a DMF, 90 °C
6 1a (1:1) 2g (R1 = CH2OTBS, R2 = Ph) 3ag, 98 (13:1)c 5a (1.2 equiv) 6aa
7 1a (1:1) 2h (R1 = n-hexyl, R2 = 2-thienyl) 3ah, 81 yield/%
additive time/h
Ph
AcO NaOAc or CsOPiv 6 0
N Ph
N CuOAc 0.5 84
Me Ph Ph Me
8 Cu(OAc)2 2 84
Me Me
Me 2a Me
1b (pure syn ) 3ba, 99 Scheme 11.
n-Pr n-Pr
N OAc
N C­H vinylation with alkynes, which might be followed by C­N
X Me
Me
bond formation to construct azaheterocyclic frameworks.
X
9 1d (X = NTs, pure anti ) 2d 3dd, 91
We embarked on our investigation of the reaction of ¡-
10 1e (X = O, syn :anti = 1:20) 2d 3ed, 77
azidostyrene (5a) and diphenylacetylene (2a) using [Cp*RhCl2]2
11 1f (X = S, syn :anti = 1:4) 2d 3fd, 81 as a catalyst to construct the isoquinoline framework
(Scheme 11). Although use of NaOAc or CsOPiv (30 mol %)
a
The reactions were carried out by treatment of a mixture as an carboxylate source did not afford any ortho C­H
of oxime 1 (0.5 mmol) and alkyne 2 (1.2 equiv) with functionalization product, the reaction with CuIOAc (20
[Cp*RhCl2]2 (2.5 mol %) and Cu(OAc)2 (10 mol %) in DMF mol %) in the presence of AcOH at 90 °C in DMF gave
(0.2 M) at 60 °C for 4­10 h under N2 atmosphere. bIsolated 1-methyl-3,4-diphenylisoquinoline (6aa) in 84% yield. When
yield. cIsolated as a mixture of regioisomers. utilizing CuII(OAc)2 instead of CuIOAc, the same yield of 6aa
was obtained, while the reaction rate became slow. It was
OAc X confirmed that the reaction with Cu(OAc)2 in the absence of
N
[Cp*RhCl2]2 did not afford isoquinoline 6aa at all, which
X suggested the presence of the synergistic Cu­Rh cooperation in
N
this catalytic process.
N The proposed mechanistic possibility under the
[Cp*RhCl2]2 (5 mol%)
1f OAc [Cp*RhCl2]2­Cu(OAc)2 catalytic system is outlined in
Cu(OAc)2 (20 mol%)
+ Scheme 12. First, CuII(OAc)2 might be reduced by DMF to
DMF, 60 °C, 18 h N form Cu(I) species (step i). Thermal denitrogenative decom-
X X
X
position of vinyl azide 5a gave 2H-azirines G, which could be
(2equiv) reduced by the Cu(I) species, affording anion radical H (step ii).
2a (X = H)
X
Consecutive C­N bond cleavage of H formed iminyl copper(II)
2d (X = Br)
3fa (X = H); 72%
radical intermediate I, which could be further reduced with Cu(I)
3fd (X = Br); 71% and protonated to deriver iminyl copper species K along with
Cu(II) species. Formation of rhodacycle G from iminyl copper
Scheme 9. Synthesis of 1,8-diazapyrenes. species K with Rh(III) via iminyl rhodium L, subsequent
insertion of alkyne 2a, and C­N reductive elimination from N
 Rh–Cu Redox Relay Catalysts for the provided isoquinoline 6aa with generation of Rh(I) species
(step iii). Finally, a redox reaction between Rh(I) and Cu(II)
Reactions of α-Aryl Vinyl Azides species would lead to regeneration of Rh(III) and Cu(I) (step iv).
Our group has been interested in application of readily By utilizing the [Cp*RhCl2]2­Cu(OAc)2 catalytic system,
available vinyl azides as a nitrogen-containing source for we examined the generality of this catalytic method for the
synthesis of azaheterocycles.19 It is known that vinyl azides synthesis of substituted isoquinolines (Table 2). The present
undergo thermal denitrogenative decomposition to form highly process showed wide substrate tolerance with the use of internal
strained 3-membered cyclic imines, 2H-azirines, which could be alkynes (Entries 1­6). Diarylacetylenes reacted smoothly with
regarded as the equivalent of vinyl nitrenes (Scheme 10).20 We vinyl azide 5a, giving isoquinolines 6 in good yields (Entries 1
were interested in using these nitrogen atoms derived from and 2). The reactions with dialkyl-substituted alkynes also
¡-arylvinyl azides to direct the transition-metal species for ortho proceeded smoothly (Entries 3 and 4). Insertion of unsym-

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1558

(i) generation of Cu(I) species by reduction of Cu II(OAc)2 with DMF Table 2. Substrate scopea
CuII(OAc) 2 + DMF [CuI]
Vinyl Isoquinolines 6,
Entry Alkynes 2
(ii) reductive formation of N-H imines azides 5 Yieldb
from vinyl azides and Cu(I) species
N2 R2
N2
[CuII] N R1
N N [CuI] N N
R1 R2
Ph –N2 Ph Ph CH3
5a G H 2
[CuII] [CuII] [CuII] 1 5a 2b (R1, R2
= 4-MeO-C6H4) 6ab, 77
[CuI] H+ 2c 5a 2c (R1, R2
= 4-Br-C6H4) 6ac, 83
N N N 3 5a 1 2
2d (R , R = n -Pr) 6ad, 71
[CuII] 4 5a 2e (R1, R2 = CH2OTBS) 6ae, 54
Ph Ph –[CuII] Ph CH3
I J K 5 5a 2f (R1 = CH3, R2 = Ph) 6af, 82
6 5a 2h (R1 = n -hexyl, R2 = 2-thienyl) 6ah, 52
(iii) ortho C-H rhodation, alkyne insertion, and C-N reductive elimination
Ph
Ph
[RhIII] N2
[CuII] H N [RhIII] N N N
7 N 5b 2a
N [RhIII] Ts
N
CH3 CH3 Ts CH3
Ph CH3 –Cu(II) –H+ 6ba, 82
K L M Ph
Ph
Ph [RhIII] N2
N N
Ph Ph N 8 5c 2a
Ph N N
2a Ts CH3
CH3 6aa Ts
–[RhI] 6ca, 77
N CH3
(iv) Redox regeneration of Rh(III) and Cu(I) species N N N
2
[RhI] + 2 [CuII] [RhIII] + 2 [CuI] 9 5d 2a Ph
[Rh] = Cp*Rh(OAc)n
S S
Ph
6da, 75
Scheme 12. The proposed reaction pathway. N2 Ph
N Ph
N
metrical alkyne, 1-phenyl-1-propyne (2f) occurred regioselec-
10 5e 2a
tively to provide 1,4-dimethyl-3-phenylisoquinoline (6af) as a
CH3 CH3
sole product (Entry 5). Similarly, thienylacetylene 2h afforded
isoquinoline 6ah regioselectively albeit in moderate yield 6ea, 85
(Entry 6). This method allowed for the construction of £- N2
Ph
Ph
carboline and 1H-pyrrolo[2,3-c]pyridine structures (Entries 7 N N
and 8). Similaly, benzothiophen-3-ylvinyl azide 5d could be 11 O 5f 2a O
utilized for this transformation (Entry 9). At the ¢-position of N N
vinyl azides 5, methyl and aminomethyl functionalities could be
introduced leading to the corresponding isoquinolines 6 in good O O
6fa, 85
yields (Entries 10 and 11).
It could be speculated that the reductive formation of imine a
The reactions were carried out by treatment of a mixture of
derivatives from vinyl azides proceeds via protonation of the vinyl azides 1 (1.2 equiv) and alkyne 2 (0.5 mmol) with
Cu(II) aza-enolates such as J (Scheme 12, step ii). We envi- [Cp*RhCl2]2 (5 mol %) and Cu(OAc)2 (20 mol %) in the
sioned trapping such putative aza-enolates for further function- presence of AcOH (1 equiv) in DMF (2.5 mL) at 90 °C under
alization of isoquinoline derivatives. It was found that the N2 atmosphere for 1­2 h. bIsolated yields. c1.5 equiv of vinyl
reaction of vinyl azide 5e with alkyne 2a in the presence of azides 1a was used.
TEMPO (2 equiv) under the [Cp*RhCl2]2­Cu(OAc)2 catalytic
system, isoquinoline­TEMPO adduct 7ea and alcohol 8ea were
isolated in good combined yields (Scheme 13).
N2
[Cp*RhCl2]2 (2.5 mol %)
N
Cu(OAc)2 (20 mol %)
 Conclusion + Ph Ph + N
Me 2a O DMF, 90 °C, 1 h
This review highlighted the Cu­Rh heterobimetallic system 5e (1.5 equiv) (2 equiv)
for redox relay catalytic reactions for azaheterocycle synthesis
developed in our group. The processes perform sequential Ph Ph
Ph Ph
reactions, in which Cu catalyst achieves the initial reductive step N N N
to give an imine intermediate that is relayed to Rh catalyst for O + OH
the next oxidative transformation including C­H functionaliza- Me Me
tion to produce the final product. Multimetallic catalytic systems 7ea 68% 8ea 15%
including their synergistic cooperation can potentially achieve
chemical transformations that are unprecedented in monometal- Scheme 13.

Chem. Lett. 2012, 41, 1554­1559 © 2012 The Chemical Society of Japan www.csj.jp/journals/chem-lett/

lic catalysts. In spite of recent other significant development of
the multimetallic catalytic reactions in organic synthesis,21 it is
still challenging and highly attractive to achieve rational design
of artificial multimetallic catalytic systems and their application
to highly advanced molecular transformations.
My co-workers whose names appear in the references are
gratefully acknowledged for their intellectual and experimental
contributions. These works were supported by funding from
Nanyang Technological University, Singapore Ministry of
Education (Academic Research Fund Tier 2: MOE2010-T2-1-
009), and Science and Engineering Research Council (A*STAR
grant No. 082 101 0019).
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10 Unsymmetrical oximes have two stereoisomers, i.e., syn- and
anti-isomers. In this manuscript, the syn-isomer is defined as
oximes bearing the N­O bond on the same side of the aryl
group and vice versa for the anti-isomer as shown below.
AcO
N N
OAc
R R
syn anti
Chem. Lett. 2012, 41, 1554­1559 © 2012 The Chemical Society of Japan
1559
11 For the detailed discussion about the reaction mechanism on
the C­N bond forming process, see: ref. 8a and ref. 9d.
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alkenyl O-acyloximes, where both of syn- and anti-oximes
could be employed for cyclization (see refs. 12c and 12d).
Hartwig isolated iminyl Pd(II) species generated via oxidative
addition of the N­O bond of O-pentafluorobenzoyloxime to
a Pd(0) complex, and characterized its structure by X-ray
crystallographic analysis which revealed that the bond angle of
C=N­Pd is about 120° (see ref. 12a). Based on these results,
iminyl Pd(II) species should be free to isomerize between syn-
and anti-isomers. Liebeskind reported synthesis of N-substi-
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with O-acyloximes via putative iminyl copper species (see
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anti-oximes derived from phenyl 2-furyl ketone with 3-
hydroxyphenylboronic acid in the presence of Cu(OAc)2
catalyst resulted in formation of the corresponding N-aryl
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free isomerization between anti- and syn-forms of the iminyl
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17 For the ease of handling, CuII(OAc)2 was mainly utilized as the
catalyst because CuIOAc is very sensitive to air, moisture, and
light.
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