Organic Letters
Letter
intermediate, and CuOAc might couple to this triplet nitrene
intermediate leading to the reduction of the formation of
11a.19 When TEMPO was added to the P(O)−N coupling
reaction of 1a and 2a (eq 4), compound 3a was not observed
but the product 12a containing two TEMPO units and the
product 13a with one TEMPO unit were detected. In addition,
the EPR experiment shows the phosphine center radical29 was
formed under catalytic conditions (see the details in Scheme
S2 in SI). Including the outcomes from the radical capture
reactions of 1a or 2a respectively (eqs 5−6), the results
suggested that the reaction system may involve the triplet
nitrene intermediate18i and a Ph2PO· radical.29 When primary
Cu(I)-catalytic cycle. It is mechanistically different from
known methods and may have great potential in the synthesis
of drug molecules and natural products.
ASSOCIATED CONTENT
* Supporting Information
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sı
The Supporting Information is available free of charge at
Experimental details including product characterization
and NMR experiments (PDF)
i
amine BuNH2 or (p-Tol)NH2 was added (Scheme 5C),
AUTHOR INFORMATION
Corresponding Author
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product 3a was observed but no coupling product of 2a and
primary amine was obtained, suggesting that no primary amine
intermediate was formed. Competitive reactions of 2a with
show that p-chlorophenyl azide (26%) is preferred over 4-
methyl phenyl azide (14%). Steric hindrance has little effect on
the reaction (2-iodophenyl azide (22%) vs 4-methylphenyl
azide (35%)) and 4-methylphenyl azide (57%) is much more
reactive than tetradecanyl azide (0%).
A plausible mechanism with three catalytic cycles is
proposed (Scheme 5D). Visible light induces [Ir(ppy)3]3+ to
produce [Ir(ppy)3]3+* which participates in two catalytic
cycles: an SET process with 2 to obtain [Ir(ppy)3]2+ and
formation of a phosphoryl radical A accompanied by proton
dissociation, and an EnT process involving 1, resulting in the
loss of N2 and the formation of the triplet nitrene B.30 B is
captured by Cu(I) to generate a Cu(III) nitrene intermediate
C.19 After undergoing the SET process and protonation,31 C is
converted to a Cu (II) complex D which is then coupled with
A to give Cu(III) complex E.32 Reductive elimination of E
forms 3 and regenerates the Cu(I) catalyst.33 Cu(II) species
might be reduced to Cu(I) species by an excess amount of
P(O)−H compound 2 under the reaction conditions,34 which
is the reason why Cu(OAc)2 could also promote the reaction
(entry 6, Table 1). As a minor reaction pathway, B can convert
to nitrogen radical F directly via the SET process and
protonation. Radical coupling of A and F leads to the
formation of product 3 in the absence of CuOAc (entry 1,
Table 1).
In summary, we have demonstrated a practical synthetic
strategy for the redox-neutral construction of P(O)−N bond.
The reaction merges the photoredox catalysis with copper
catalysis and enables the coupling reactions of P(O)−H
compounds and organic azides, providing verstile phosphina-
mides, phosphonamides, and phosphoramides with environ-
ment friendly N2 as the sole byproduct. The use of versatile
P(O)−H compounds including diphenyl-, dialkyl-, alkylphen-
yl-, alkoxylphenyl-, dialkoxyl-, diphenoxyl-phosphine oxides,
and organic azides including aryl and alkyl azides, reveals the
universal nature of the method. In contrast to classical nitrogen
nucleophilic substitution reactions8−11 and oxidative P(O)−N
coupling reactions,14 this reaction exhibited remarkable
chemoselectivity and tolerates many nucleophilic functional
groups such as phenol, benzoic acid, alkyl carboxylic acid,
amide, aniline, and alkylamines. Late-stage functionalization of
azido-bearing synthetic intermediates of bioactive compounds,
potential applications in asymmetric versions, and flow
chemistry through use of a microchannel device are also
demonstrated. Mechanistic studies reveal that the reaction may
go through visible-light-induced EnT and SET processes and a
Hongjian Lu − Institute of Chemistry and BioMedical Sciences,
Jiangsu Key Laboratory of Advanced Organic Materials, School
of Chemistry and Chemical Engineering, Nanjing University,
Authors
Yanan Wu − Institute of Chemistry and BioMedical Sciences,
Jiangsu Key Laboratory of Advanced Organic Materials, School
of Chemistry and Chemical Engineering, Nanjing University,
Nanjing 210093, China
Ken Chen − Institute of Chemistry and BioMedical Sciences,
Jiangsu Key Laboratory of Advanced Organic Materials, School
of Chemistry and Chemical Engineering, Nanjing University,
Nanjing 210093, China
Xia Ge − Institute of Chemistry and BioMedical Sciences, Jiangsu
Key Laboratory of Advanced Organic Materials, School of
Chemistry and Chemical Engineering, Nanjing University,
Nanjing 210093, China
Panpan Ma − Institute of Chemistry and BioMedical Sciences,
Jiangsu Key Laboratory of Advanced Organic Materials, School
of Chemistry and Chemical Engineering, Nanjing University,
Nanjing 210093, China
Zhiyuan Xu − Institute of Chemistry and BioMedical Sciences,
Jiangsu Key Laboratory of Advanced Organic Materials, School
of Chemistry and Chemical Engineering, Nanjing University,
Nanjing 210093, China
Guigen Li − Institute of Chemistry and BioMedical Sciences,
Jiangsu Key Laboratory of Advanced Organic Materials, School
of Chemistry and Chemical Engineering, Nanjing University,
Nanjing 210093, China; Department of Chemistry and
Biochemistry, Texas Tech University, Lubbock, Texas 79409-
Complete contact information is available at:
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
We are grateful for financial support by National Natural
Science Foundation of China (21871131).
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REFERENCES
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(1) (a) Denmark, S. E.; Stavenger, R. A.; Wong, K. T.; Su, X. P.
J. Am. Chem. Soc. 1999, 121, 4982−4991. (b) Nakashima, D.;
D
Org. Lett. XXXX, XXX, XXX−XXX