Organic Letters
Letter
chemical agents,17 in one step with 64% and 85% yields,
respectively (Figure 5a). 2-Chloropyrimidines 7 and 9 were
accessible via a Vilsmeier−Haack strategy18 from cyanoimine
3m and 3n, respectively. Replacement of the chlorine atom
through nucleophilic aromatic substitution reaction enabled
the installation of a variety of nucleophiles into 2-
chloropyrimidine. For instance, treatment of 2-chloropyrimi-
dine 7 with 3-aminobenzenesulfonamide afforded anticancer
reagent19 2-aminopyrimidine 8 in 70% yield (Figure 5b).
Nucleophilic substitution of 2-chloropyrimidine 9 with
carbazole 10 delivered pyrimidinylcarbazole 11 in 96% yield.
Suzuki cross coupling of pyrimidinylcarbazole 11 with
arylboronic acid 12 resulted in a potential organic electro-
luminescent material 1320 in 98% yield (Figure 5c).
To determine the reaction mechanism, several control
experiments were carried out. It was found that no desired
cyanoimine was detected in the absence of photocatalyst or
visible-light irradiation (Figure 6a). When copper and ligand
Figure 7. Proposed mechanism.
IrIV.11e,12,23 The resultant IrIV species oxidizes LCuICN
complex to afford oxidized LCuII(CN)2 complex in the
presence of TMSCN and the carboxylic anion with concurrent
regeneration of the IrIII species.11e,f,12,24 The CuII complex
could capture iminyl radical I to furnish the high-valent CuIII
complex II. Finally, reductive elimination affords the
cyanoimine 3 with concurrent regeneration of the catalytic
CuI species to close the copper catalytic cycle.25
In summary, we have described an efficient strategy for the
synthesis of cyanoimines as well as cyanamides. This strategy is
enabled by dual photoredox/copper-catalyzed cyanation of O-
acyl oximes or O-acyl hydroxamides. This state of the art
protocol for cyanoimines and cyanamides features readily
available starting materials, mild reaction conditions, good
functional group tolerance, and operational simplicity. The
resultant cyanoimines are synthetically valuable, which can be
demonstrated by several transformations of the cyanoimines to
structurally diverse and functionally important N-containing
heterocycles.
Figure 6. Mechanistic studies.
ASSOCIATED CONTENT
* Supporting Information
■
sı
were removed from the reaction mixture, no cyanoimine was
observed, and benzophenone 14 (16% yield) and 1,2-
bis(diphenylmethylene)hydrazine 15 (11% yield) were iso-
lated. This result clearly showed that iminyl radical could be
generated under photoredox catalytic conditions and the
copper catalytic system was crucial to cyanation of the iminyl
radical. Moreover, the formation of the desired cyanoimine 3a
was effectively inhibited upon the addition of radical inhibitor
TEMPO (Figure 6b). These consequences suggested the
radical nature of this reaction and involvement of iminyl radical
16. Furthermore, the redox potential of 1a was determined to
be −1.22 V vs Fc/Fc+ in MeCN via cyclic voltammogram
studies (Figure S1), which suggests that a SET event between
1a and excited photocatalyst IrIII* (E1/2IV/III* = −1.90 V vs Fc/
Fc+)21 could occur in this reaction. The Stern−Volmer plot
results also demonstrate that the excited photocatalyst IrIII*
could be quenched by the O-acyl oxime 1a effectively (Figure
The Supporting Information is available free of charge at
Reaction condition optimization details, general proce-
dures, analytical data, and copies of NMR spectra (PDF)
AUTHOR INFORMATION
Corresponding Authors
■
Ai Hua Zhang − Institute of Marine Biology, College of
Oceanography, Hohai University, Nanjing 210098, China;
Shouyun Yu − State Key Laboratory of Analytical Chemistry for
Life Science, Jiangsu Key Laboratory of Advanced Organic
Materials, Chemistry and Biomedicine Innovation Center
(ChemBIC), School of Chemistry and Chemical Engineering,
On the basis of the aforementioned experimental observa-
tion and related literature,11,12,22 a dual photoredox/copper
catalytic pathway is proposed to account for the formation of
cyanoimines. As depicted in Figure 7, this reaction is initiated
by reduction of O-acyl oxime 1 by the excited IrIII* species via
single-electron transfer. Fragmentation of reduced 1 generates
Authors
Hao Zhang − State Key Laboratory of Analytical Chemistry for
Life Science, Jiangsu Key Laboratory of Advanced Organic
Materials, Chemistry and Biomedicine Innovation Center
(ChemBIC), School of Chemistry and Chemical Engineering,
Nanjing 210023, China
−
iminyl radical I, together with carboxylic anion (ArCO2 ) and
D
Org. Lett. XXXX, XXX, XXX−XXX