Nickel-catalyzed decarbonylative addition of phthalimides to alkynes

Article abstract of DOI:10.1021/ja7114426

An intermolecular nickel-catalyzed addition reaction has been developed where N-arylphthalimides react with alkynes to afford substituted isoquinolones. A mechanistic rationale is proposed, implying nucleophilic attack of Ni(0) to an amide as the primary step of the catalytic cycle. Copyright

Full text of DOI:10.1021/ja7114426

Published on Web 04/16/2008
Nickel-Catalyzed Decarbonylative Addition of Phthalimides to
Alkynes
Yuichi Kajita, Seijiro Matsubara,* and Takuya Kurahashi*
Department of Material Chemistry, Graduate School of Engineering, Kyoto UniVersity,
Kyoto 615-8510, Japan
Received December 28, 2007; E-mail: matsubar@orgrxn.mbox.media.kyoto-u.ac.jp; tkuraha@orgrxn.mbox.media.kyoto-u.ac.jp
Table 1. Nickel-Catalyzed Decarbonylative Addition of
A direct oxidative addition of a low-valent transition-metal
catalyst into a C-N bond generates the active species (C-M-N),
N-Arylphthalimides to 4-Octynea
which may perform a carboamination with alkyne (Scheme
1).1–6 The reaction will form C-C and C-N bonds simulta-
neously. It should be a useful transformation to prepare a
nitrogen atom containing compound, however, it has not been
studied well because of the difficulty of such oxidative addition.
We postulated that a nickel(0) with electron-donating phosphine
ligands will attack an amide nucleophilically; the addition may
afford the C-M-N species via decarbonylation and might allow
an insertion reaction to alkynes.7 Thus, we attempted the
addition of phthalimide 1 to alkyne 2 using a nickel(0) catalyst
to form isoquinolone 3.8,9
Initially, N-phenylphthalimide (1a) was treated with 4-octyne
(2a), 10 mol % of Ni(cod)2, and 40 mol % of PMe3 in toluene
at 110 °C for 3 h. This led to isoquinolone 3aa in 18% isolated
yield (Table 1, entry 1). Trace or lower amounts of 3aa were
obtained in the case using PBu3, PCy3, and PPh3 in place of
PMe3 (17, 11, and 8% yields, respectively). Under these
conditions, the reaction of 2a with N-phenylphthalimides
possessing an electron-donating or -withdrawing group afford
the correspondingly substituted isoquinolones in 13 and 34%
yield (entries 2 and 3). Since an electron-withdrawing substi-
tutent gave the higher yield, we presumed that electron-deficient
N-arylphthalimides react with alkynes efficiently. Indeed, the
reaction of 2a with N-perfluorophenylphthalimide (1d) success-
fully provided isoquinolone in 84% yield (entry 4). N-Pyridi-
nylphthalimides (1e-1g) also reacted with 2a smoothly to give
the corresponding isoquinolones in good yields (entries 5-7).10
The reactions of 2a with N-diazinephthalimides 1h and 1i
afforded the products in 90 and 85% yields, respectively (entries
8 and 9). Imides such as 1j also reacted with 2a to provide the
corresponding addition products in excellent yields (entry 10).
It is noteworthy that N-phenylquinolimide 1k reacted with
2a to give 3ka as a single isomer along with a trace amount of
N-phenylpicolinamide (Scheme 2). The starting material 1k was
recovered in 25% yield. This regioselectivity can be rationalized
by nucleophilic attack of Ni(0) to more electrophilic carbonyl.
The reaction with a regioisomer 1l, which would not induce
the directing effect for the formation of an intermediate, also
showed regioselectivity. Actually, N-phenylquinolimide (1l) also
a Reactions were carried out using Ni(cod)2 (10 mol %), PMe3 (40
mol %), N-arylphthalimide (0.5 mmol), and 2a (0.75 mmol) in 2 mL of
refluxing toluene (110 °C) for 7 h. b Isolated yields.
reacted with 2a to give 3la as a major product in 65% yield.
Scheme 1. Pathways to C-M-N Species
The additions of 1e to various alkynes were examined (Table
2). The reaction of unsymmetrical dialkyl alkyne 2b with 1e
gave the products consisting of regioisomers in a 1/1 ratio (entry
1), whereas reaction of 4-methyl-2-pentyne (2c) gave adduct
3ec as a major product (entry 2). 1,4-Dimethoxy-2-butyne (2d)
9
6058 J. AM. CHEM. SOC. 2008, 130, 6058–6059
10.1021/ja7114426 CCC: $40.75
2008 American Chemical Society

C O M M U N I C A T I O N S
Scheme 2. Nickel-Catalyzed Decarbonylative Addition of
N-phenylquinolimides to 2a
Education, Culture, Sports, Science, and Technology, Japan.
T.K. also acknowledges the Novartis Foundation (Japan) for
the Promotion of Science, and the Takeda Chemical Industry
Award in Synthetic Organic Chemistry, Japan.
Supporting Information Available: Experimental procedures
including spectroscopic and analytical data of new compounds. This
material is available free of charge via the Internet at http://
pubs.acs.org.
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Scheme 3. Plausible Pathway for Decarbonylative Addition of
N-Arylphthalimides to Alkynes
reacted similarly to give 3ed in excellent yield (entry 3). The
reaction of tolane (2e) was relatively slow to give corresponding
isoquinolone 3ee in moderate yield (entry 4). Terminal alkynes,
such as 1-octyne and phenylacetylene, failed to participate in
the reaction, presumably due to rapid oligomerization of alkynes.
We propose a plausible mechanism involving nucleophilic
attack of Ni(0) having electron-rich phosphine ligands to an
amide, giving the nickelacycle 4 (Scheme 3).11,12 Subsequent
decarbonylation and insertion of 2 to the C-Ni bond leads to
the seven-membered nickelacycle 6, which undergoes reductive
elimination to give 3 and regenerates the starting Ni(0) complex.
In summary, we have developed a new nickel-catalyzed
reaction of alkynes with N-arylphthalimides to provide isoqui-
nolones. It was demonstrated that amide C-N bonds are
susceptible to nucleophilic attack of the Ni(0) complex, which
allows intermolecular addition to alkynes via decarbonylation.
Further studies for explanation of the detailed mechanism are
currently under investigation in our laboratories.
Acknowledgment. This work was supported by Grants-in-
Aid for Young Scientist (B) (19750031) from the Ministry of
JA7114426
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