Metal-Free Intermolecular Coupling of Arenes with Secondary Amides: Chemoselective Synthesis of Aromatic Ketimines and Ketones, and N-Deacylation of Secondary Amides

Article abstract of DOI:10.1021/acs.joc.6b01647

The direct transformation of common secondary amides into aromatic ketimines and aromatic ketones with C-C bond formation is described. The reaction can also be used for N-deacylation of secondary amides to release amines. This method consists of in situ amide activation with triflic anhydride and intermolecular capture of the resulting highly electrophilic nitrilium intermediate with an arene. The reaction is applicable to various kinds of secondary amides (electrophiles), but only electron-rich and moderately electron-rich arenes can be used as nucleophiles. Thanks to the use of bench stable arenes instead of reactive and basic organometallics as nucleophiles, the reaction proceeded with high chemoselectivity at the secondary amido group in the presence of a series of sensitive functional groups such as aldehyde, ketone, ester, cyano, nitro, and tertiary amido groups. The reaction can be viewed as a Friedel-Crafts-type reaction using secondary amides as acylating agents or as an intermolecular version of the Bischler-Napieralski reaction.

Full text of DOI:10.1021/acs.joc.6b01647

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Article
Metal-free Intermolecular Coupling of Arenes with Secondary
Amides: Chemoselective Synthesis of Aromatic Ketimines
and Ketones, and N-Deacylation of Secondary Amides
Pei-Qiang Huang, Ying-Hong Huang, and Kai-Jiong Xiao
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.6b01647 • Publication Date (Web): 07 Sep 2016
Downloaded from http://pubs.acs.org on September 8, 2016
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Metal-free Intermolecular Coupling of Arenes with Secondary Amides:
Chemoselective Synthesis of Aromatic Ketimines and Ketones, and
N-Deacylation of Secondary Amides
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Pei-Qiang Huang,* Ying-Hong Huang, and Kai-Jiong Xiao
a Department of Chemistry and Fujian Provincial Key Laboratory of Chemical
Biology, Collaborative Innovation Centre of Chemistry for Energy Materials (iChEM),
College of Chemistry and Chemical Engineering, Xiamen University, Xiamen, Fujian
361005, P. R. China
b State Key Laboratory of Elemento-Organic Chemistry, Nankai University, Tianjin
300071, P. R. China
Email: pqhuang@xmu.edu.cn.
O
one-pot
1) Tf2O (1.1 equiv)
2-F-Pyr. (1.2 equiv)
(Ar1)
O
NR1
Ar
R
Ar
R1
(Ar1)
or
1
R
N
(Ar1)
R
H
+
2) ArH (1.5 equiv)
3) aq. HCl (for 2)
or work-up (for 3)
2
R1NH2
3
4
ABSTRACT: The direct transformation of common secondary amides into aromatic
ketimines and aromatic ketones with C−C bond formation is described. The reaction
can also be used for N-deacylation of secondary amides to release amines. This
method consists of in situ amide activation with triflic anhydride and intermolecular
capture of the resulting highly electrophilic nitrilium intermediate with an arene. The
reaction is applicable to various kinds of secondary amides (electrophiles), but only
electron-rich and moderate electron-rich arenes can be used as nucleophiles. Thanks
to the use of bench stable arenes instead of reactive and basic organometallics as
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nucleophiles, the reaction proceeded with high chemoselectivity at secondary amido
group in the presence of a series of sensitive functional groups such as aldehyde,
ketone, ester, cyano, nitro and tertiary amido groups. The reaction can be viewed as a
Friedel–Crafts type reaction using secondary amides as acylating agents or as an
intermolecular version of the Bischler–Napieralski reaction.
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Introduction
With the urgent need for a “greener” and sustainable chemistry,1 development of
chemoselective synthetic methods employing bench stable and readily available
starting materials has attracted considerable attention over the last decades. Those
efforts have resulted in many powerful methodologies utilizing arenes, alkenes and
alkynes as Csp2 and Csp nucleophiles as exampled by the Heck reaction2 and
A3-coupling.3 On the other hand, the intermolecular Friedel–Crafts reaction4 (eq. 1 in
Scheme
1)
and
the
intramolecular
Bischler–Napieralski
reaction
(Bischler–Napieralski cyclization)5 (eq. 2 in Scheme 1) are two classical reactions
utilizing arenes as nucleophiles. In particular, for the Bischler–Napieralski reaction,
highly stable aryl and secondary amide groups serve as nucleophilic and electrophilic
partners, respectively. However, in the Friedel–Crafts reaction, reactive acyl chlorides
are employed as electrophiles, while the Bischler–Napieralski reaction is restricted to
intramolecular reaction. Because of the wide use of Friedel–Crafts reaction in
pharmaceutical industry for the production of aromatic ketones, it is highly
demanding to substitute acyl chlorides by unactivated substrates.6 In this regard,
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although the Friedel–Crafts reactions using carboxylic acids,7 esters,8 and tertiary
amides9 as acylating agents have been documented, very few examples employing
secondary amides as substrates have been reported. Early studies by Hurd and Webb
involved only one example.10 The method for the synthesis of 7-indolylimines report
by Black and coworkers is limited to only one special and highly electron-rich arene
(4,6-dimethoxy-2,3-diphenylindole).11 Using phosphoryl chloride as the coupling
reagent (referred as Vilsmeier conditions),11 those reactions required harsh conditions
and used a large excess of reagents, and are of low functional group tolerance. More
recently, two novel methods using specially designed secondary amides have been
reported. The first one was developed by Tepe and Anderson, which involves the use
of inherently activated (by ring strain) -lactams as substrates.12 The second one was
reported by Klumpp and co-workers, which is based on some specific amides capable
of generating dication intermediates by action of superacid.13 It is not surprised that
both methods are restricted to some specific amides. In view of multiple roles played
by secondary amides in organic synthesis and medicinal chemistry,14 including as
intermediates for resolution15 and as directing groups in C−H functionalization,16 the
development of a general method for the chemoselective intermolecular coupling of
arenes with common secondary amides is highly desirable. Such a reaction could also
serve as an N-deacylation17 method for secondary amides. However, this task is
challenging because, on one hand, amides are the most stable class of carbonyl
compounds,18,19 and on the other hand, a secondary amide contains an acidic proton,
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which renders the nucleophilic addition of an organometallic reagent more
difficult.20,21
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Scheme 1.
As a continuation of our endeavor on the development of C−C bond forming
methods19b,20b,c,e,21 based on the amide activation with triflic anhydride (Tf2O),22 we
report herein a mild and versatile Tf2O-mediated intermolecular coupling of arenes
with secondary amides. This method allows the direct and chemoselective
transformation of common secondary amides into aromatic ketimines and ketones,
and N-deacylation of secondary amides to give amines (eq. 3 in Scheme 1).
Results and discussion
Our plan was to merge the key features of both the Friedel–Crafts reaction and the
Bischler–Napieralski reaction, and develop a general and chemoselective
intermolecular coupling of arenes with secondary amides. Very recently, we have
developed a versatile and direct method for the intermolecular coupling of alkenes
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with secondary amides to give enimines or enones.21a In that method, nitrilium ion
intermediate D (Scheme 2) was proven to be the pivotal reactive species. In the light
of those results, we envisioned that arenes could be used as nucleophiles to react with
nitrilium ion intermediates D to yield the corresponding aromatic ketimines 3 or
aromatic ketones 1 and amines 4 after acidic hydrolysis (Scheme 2). Thus, for the
current investigation, the conditions established therein21a was adopted.
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Scheme 2.
In the event, secondary N-cyclohexylbenzamide (2a) was successively treated with
1.2 equiv of 2-fluoropyridine (2-F-Pyr.),23 l.1 equiv of triflic anhydride (Tf2O) in
CH2Cl2 at 78 C, and 3.0 equiv of toluene, and the mixture was stirred at room
temperature for 2 h. Unfortunately, the desired coupling product was not observed
even after heating at 40 C for 2 h (Table 1, entry 1). Same disappointing results were
obtained when subjecting acetamide 2b to react with either anisole or
1,2-dimethoxybenzene (Table 1, entries 2 and 3). To our delight, the reaction of 1.5
equiv of electron-rich N,N-dimethylaniline with benzamide 2a proceeded smoothly (rt,
1 h) to give regioselectively diaryl ketimine 3a in 88% yield as a 92: 8 E/Z geometric
mixture (Table 1, entry 4). It is worth mentioning that a simplified purification
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protocol could be used to isolate the product, which consists of direct concentrating
reaction mixture without work-up and subjecting the residue to flash chromatographic
purification. Encouraged by this result, reaction of other arenes and functional group
tolerance of the method were investigated. Reaction of amide 2c with N-methylindole
produced ketimine 3b in 91% yield as a 75: 25 E/Z geometric mixture (Table 1, entry
5). Interestingly, the reaction of diamide 2d (entry 6) showed a preference for
secondary amido over tertiary amido group, which afforded amido imine 3c in 75%
yield with excellent geometric selectivity (ratio of E/Z isomers >20: 1). Significantly,
reaction of amido ester 2e with N-methylindole took place chemoselectively at the
amido group to yield imino ester 3d in excellent yield and stereoselectivity (entry 7,
86% yield, dr (E/Z) = 87: 13). More importantly, the reaction of keto amide 2f and
amido aldehyde 2g with N,N-dimethylaniline occurred chemoselectively at the least
reactive amido group to give the corresponding imino ketone 3e and imino aldehyde
3f in 76% and 86% yield, respectively (entries 8 and 9). As we have mentioned earlier,
because secondary amides constitutes a class of valuable directing group in both
modern catalytic16a-d and classical stoichiometric16e C−H functionalization,
transformation of the resulting C−H functionalization products is imperative. To
demonstrate the value of the current method in this regard, transformation of the
amide 2h, a C−H functionalization products prepared by Daugulis’ method16d was
envisaged. For this purpose, amide 2h was subjected to react with N-methylindole.
Pleasantly, the desired ketimine 3g was isolated in 82% yield (entry 10).
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Table 1. Intermolecular cross-coupling of arenes with secondary amides to give ketimines 3.
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Entry
1.
Substrate
ArH
Product (% yield)a,b
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O
N
H
2a recovered
2a
2b
2.
3.
2b recovered
2b recovered
2b
O
N
H
4.
2a
2c
3a (88, E/Zc = 92: 8)
5.
6.
7.
3b (91, E/Z = 75: 25)
3c (75, E/Z >20: 1)
2d
O
N
H
O
OMe
2e
3d (86, E/Z = 87: 13)
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8.
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2f
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3e (76, E/Z = 88:12)
3f (86, E/Z = 60: 40)
3g (82, E/Z >20:1)
9.
2g
CO2Me
O
10.
N
H
Me
2h
aIsolated yield. Reaction conditions: 1) Amide (1.0 mmol), 2-fluoropyridine (1.2 mmol), CH2Cl2
b
c
(4 mL), 78 C, Tf2O (1.1 mmol), then 0 C, 10 min; 2) Arene (1.5 mmol), rt, 1 h. E/Z ratio of
imine determined by 1H NMR, E/Z-stereochemistry not determined.
After establishing an efficient method for the direct transformation of secondary
amides into aromatic ketimines, we turned our attention to extend this methodology to
synthesize aromatic ketones. This should be readily realizable by in situ acidic
hydrolysis of aromatic ketimines. Indeed, after activation-coupling of N-c-hexyl
acetamide 2b with N,N-dimethylaniline (0 C, 10 min), the resulting mixture was
treated with a solution of 3M HCl at 40 C for 2 h, which yielded N,N-dimethyl
p-acetylaniline 1a in 90% yield (Table 2, entry 1). Similarly, propionylation of
N,N-dimethylaniline with propionamide 2i (entry 2), acetylation of pyrrole with
acetamide 2b (entry 3), benzoylations of furan and benzofuran with N-c-hexyl
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benzamide 2a (entry 4) and N-methyl benzamide 2j (entry 5) afforded respectively
and regioselectively, 1-(4-(dimethylamino)phenyl)propan-1-one (1b) (yield: 92%),
2-acetylpyrrole 1c (yield: 84%), 2-benzoylfuran 1d (yield: 80%), and
2-benzoylbenzofuran 1e (yield: 81%) in good yields. Electron-rich heteroarene
N-butylthiophene-2-carboxamide 2k reacted smoothly with benzofuran to give
benzofuran-2-yl(thiophen-2-yl)methanone 1f in 77% yield (Table 2, entry 6). It is
worth mentioning that 1b has served as an intermediate in the synthesis of trichostatin
A,24 a histone deacetylase inhibitor (HDACi).
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Although less electron-rich arenes such as anisole and 1,2-dimethoxybenzene failed to
undergo cross-coupling reaction with secondary amides (cf. Table 1, entries 1 - 3), to
extend the scope of the method, further efforts have been paid. To this end, we first
examined the alkoylation of 1,3-dimethoxybenzene. To our surprise, reaction of
1,3-dimethoxybenzene with acetamide 2b proceeded smoothly to give
regioselectively the desired acetylated product 1g in 74% yield (Table 2, entry 7). As
exampled by N-methylpentanamide (2l) and 4-methyl-N-phenylbenzamide (2m),
extension of this method to other alkoyl and N-aryl amides proved to be successful
(Table 2, entries 8 and 9), which afforded 1-(2,4-dimethoxyphenyl)pentan-1-one (1h)
in 79% yield and (2,4-dimethoxyphenyl)(p-tolyl)methanone (1i) in 88% yield,
respectively. The significant difference in reactivity between 1,2-dimethoxybenzene
(Table 1, entry 3) and 1,3-dimethoxybenzene (Table 2, entries 7-9) may be attributed
to the matched directing effect of the two methoxyl groups in 1,3-dimethoxybenzene,
which renders the latter more nucleophilic.
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A closer inspection of the results outlined in entries 7-9 allowed us to assume that
N-phenyl amides resulted in a higher yield as compare to N-alkyl amides. To confirm
this assumption, we surveyed the benzoylation reaction of anisole with three
benzamides bearing different N-substituents 2a, 2n and 2o. Attempted benzoylation of
anisole with N-cyclohexylbenzamide 2a failed to yield the desired product, instead the
starting amide was recovered after work-up (Table 2, entry 10). This result is
consistent with that outlined in Table 1, entry 2. To our delight, the reaction of anisole
with N-phenyl benzamide 2n produced the desired benzoylated product 1j in excellent
yield (89%) as a mixture of p- and o-regioisomers (ratio = 8.5: 1) (Table 2, entry 11).
An even higher yield (94%, p- and o-regioisomers ratio = 4.6: 1) was obtained by
reacting anisole with N-(2,6-dimethylphenyl)benzamide (2o), an amide that we have
previously used for the coupling of amides with alkenes21a (Table 2, entry 12).
Furthermore, the reaction of 1,2-dimethoxybenzene with amide 2o afforded the
benzoylated product 1k in 97% yield as a single regioisomer (Table 2, entry 13).
Encouraged by these results, we next attempted the benzolylation of toluene.
However, instead of the desired benzolylation product, reaction of toluene (3.0 equiv)
with N-(2,6-dimethylphenyl)benzamide (2o) at 40 C for 2 h resulted in the formation
of amidine derivative 5 in 87% yield as a single geometric isomer (Table 2, entry 14).
It is worthwhile noting that such amidine derivatives have previously been
synthesized by Wang.25 The fact that amidine derivative 5 was resulted from the
addition of amide 2o to the 2o-derived nitrilium intermediate D-2o (cf. Scheme 2) (a
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self-condensation) implies that in competition with amide substrate, toluene is too
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weak as a nucleophile to react with the nitrilium intermediate D-2o.
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The results outlined in entries 15-19 (Table 2) show that, akin to the formation of
ketimines (cf. Table 1, entries 6-10), the intermolecular coupling reactions of arenes
with secondary amides to yield aromatic ketones 1 also displayed good functional
group tolerance and good chemoselectivity at the amido group. That comparing the
result outlined in entry 5 (Table 1) with those in entries 15-19 (Table 2) shows that
not only electron-rich amides such as 2c, benzamides bearing electron deficient
groups such as nitro, cyano and ester at para position also served well as the
aroylation agents in reacting with arenes.
Finally, in view of the importance of N-deacylation reaction in organic synthesis and
medicinal chemistry,17 and the mildness of the current method, it is expectable that
this method could be applicable for mild N-deacylation of amides as well. Thus, a
simple acid-base extraction procedure was established which was used for the
isolation of amines 4a (yield: 83%) (Table 2, entry 9), 4b (yield: 87%) (entry 12), and
4c (yield: 87%) (entry 19).
Table 2 Intermolecular coupling of arenes with secondary amides to give aromatic ketones 2.
one-pot
1) Tf2O (1.1 equiv)
R1 2-F-Pyr. (1.2 equiv), CH2Cl2
O
O
R1NH2
+
R
N
(Ar')
R
Ar
(Ar')
H
2) ArH (1.5 equiv)
3) aq. HCl
4
2
1
Entry
Substrate
ArH
Product (% yield)a,b
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1.
2b
8
9
1a (90)
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2.
3.
4.
2i
1b (92)
1c (84)
2b
O
N
H
2a
1d (80)c
5.
6.
2j
1e (81)c
1f (77)c
2k
7.
2b
2l
1g (74)c
1h (79)c
8.
9.
2m
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1i (88),d 4a (83)
2a recovered
10.
11.
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2a
2n
1j (89, p:o = 8.5:1)d
12.
13.
1j (94, p:o = 4.6:1),d
4b (87)
2o
2o
1k (97),d 4b (90)
14.
2o
5 (87)c
1l (91)
15.
16.
17.
2p
2p
2q
1m (75)d
1n (75)
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N
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OMe
2e
2r
1o (65)
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1a (87), 4c (85)
aIsolated yield. Reaction conditions: 1) Amide (1.0 mmol), 2-fluoropyridine (1.2 mmol), CH2Cl2
(4 mL), 78 C, Tf2O (1.1 mmol), then 0 C, 10 min; 2) Arene (1.5 mmol), rt, 1 h; 3) aq. HCl (3
M, 5 mL), reflux, 2 h; cThe reaction run at 40 C. dHydrolytic conditions: aq. HCl (3 M, 5 mL) in
EtOH, reflux, 2-12 h.
b
Conclusion
In summary, a method for the intermolecular coupling of common secondary amides
with arenes has been developed, which affords a flexible access to aromatic ketimines
and aromatic ketones. Moreover, the reaction can be used as a mild and high-yielding
method for N-deacylation of amides. Both aliphatic and aromatic amides bearing
either electron-withdrawing or electron-donating groups can be used. The
N-substituent can be a primary, a secondary alkyl group or an aromatic group.
Electron-rich arenes and heteroarenes such as 1,3-dimethoxybenzene,
N,N-dimethylaniline, pyrrole, N-methylpyrrole, N-methylindole, furan, and
benzofuran, can react with all kinds of secondary amides. Moderate electron-rich
arenes such as anisole and 1,2-dimethoxybenzene reacted only with N-aryl secondary
amides to give the corresponding aromatic ketones in 94-97% yields. The method is
unsuitable for non-electron rich arenes such as toluene which yielded the
self-condensation product (an amidine derivative). The method displayed excellent
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functional group tolerance and chemoselectivity, which allows the reaction to take
place at secondary amido group in the presence of a series of sensitive functional
groups including aldehyde, ketone, ester, tertiary amide, nitro, cyano, and OTBDPS.
Except anisole which reacted to give a mixture of p- and o-benzoylated product in a
ratio of 8.5: 1 and 4.6:1, the reactions of all other arenes examined produced only one
regioisomer in each case. The method was used to transform a C−H functionalization
product prepared by the method of Daugulis to the corresponding aromatic ketimine.
In view of the fact that many aromatic ketimines26 and aromatic ketones27 are either
bioactive compounds or serve as pivotal building blocks in the synthesis natural
products and medicinal agents,24,26,27 the present method would find applications in
this regard.
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Experimental Section
For general experimental methods, see: ref. 21c.
General procedure for the direct coupling of arenes with secondary amides 2 to
yield aromatic ketimines 3, aromatic ketones 1 and amines 4.
Into a dry 10-mL round-bottom flask equipped with a magnetic stirring bar were
added successively a secondary amide (1.0 mmol), 4 mL of anhydrous CH2Cl2, and
2-fluoropyridine (103 uL, 1.2 mmol) under an argon atmosphere. After being cooled
to 78 C, trifluoromethanesulfonic anhydride (Tf2O) (185 uL, 1.1 mmol) was added
dropwise via a syringe and the reaction was stirred for 10 min at 0 °C. To the
resulting mixture, an arene (1.5 mmol) was added dropwise at 0 °C. The mixture was
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allowed to warm-up to room temperature and stirred for 2 h. The reaction mixture was
concentrated under reduced pressure, and the residue was purified by flash column
chromatography (FC) on silica gel (pre-neutralized with 2% Et3N in n-hexane) to
afford the desired aromatic ketimine 3.
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Alternately, after concentration, to the residue were added 5 mL of EtOH and 5 mL of
an aqueous solution of HCl (3.0 M). The resulting mixture was heated to reflux until
completion of the reaction as monitored by TLC analysis. After being cooled to room
temperature, 10 mL of CH2Cl2 was added, and the mixture extracted with CH2Cl2 (3 
10 mL). The combined organic layers were washed with brine, dried over anhydrous
Na2SO4, filtered, and concentrated under reduced pressure. The residue was purified
by flash column chromatography on silica gel to afford the desired aromatic ketone 1.
To isolate the corresponding amine, the aqueous layer was basified with an aqueous
solution of 15% NaOH (6 mL), and extracted with dichloromethane (3  10 mL). The
combined organic layers were dried over anhydrous Na2SO4, filtered, and
concentrated under reduced pressure. The residue was purified by flash column
chromatography on silica gel to afford the desired amine 4.
4-[(Cyclohexylimino)(phenyl)methyl]-N,N-dimethylaniline (3a)
Following the general procedure, the reaction of amide 2a (203 mg, 1.0 mmol) with
N,N-dimethylaniline gave, after flash column chromatography on silica gel (eluent:
EtOAc/ n-hexane = 1/ 5), aromatic ketimine 3a (270 mg, yield: 88%) as a 92: 8
inseparable mixture of E/Z isomers. For the major isomer: Yellow oil. IR (film) max
:
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3063, 2933, 2860, 1580, 1546, 1349, 1289, 1243, 1153, 1030, 638 cm-1; H NMR
(400 MHz, CDCl3)  0.97-1.60 (m, 4H), 1.74-1.86 (m, 4H), 1.96-2.09 (m, 2H), 3.14 (s,
6H), 3.36 (tt, J = 11.4, 4.0 Hz, 1H), 6.69 (d, J = 8.6 Hz, 2H), 7.32 (d, J = 8.6 Hz, 2H),
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7.57-7.72 (m, 5H). C NMR (100 MHz, CDCl3)  24.1, 24.6 (2C), 31.6 (2C), 40.1
(2C), 59.5, 111.7 (2C), 116.5, 127.9 (2C), 129.1 (2C), 131.0, 131.7 (2C), 134.6, 155.6,
174.0. MS (ESI) m/z: 307 (M+H+, 100%); HRMS (ESI-TOF) m/z: Calcd for C21H27N2
[M+H]+: 307.2169; found: 307.2163.
N-[(1-Methyl-1H-indol-2-yl)(p-tolyl)methylene]cyclohexanamine (3b)
Following the general procedure, the reaction of amide 2c (217 mg, 1.0 mmol) with
N-methylindole gave, after flash column chromatography on silica gel (eluent:
EtOAc/ n-hexane = 1/ 1), the aromatic ketimine 3b (300 mg, yield: 91%) as a 75:25
inseparable mixture of E/Z isomers. For the major isomer: white solid. Mp: 106−108
C; IR (film) max: 3046, 2922, 2851, 1659, 1598, 1467, 1384, 802, 744 cm-1; H
1
NMR (400 MHz, CDCl3)  1.13-1.37 (m, 3H), 1.52-1.69 (m, 5H), 1.72-1.82 (m, 2H),
3.42 (s, 3H), 3.21-3.30 (m, 1H), 3.63 (s, 3H), 6.69 (s, 1H), 7.12-7.25 (m, 7H), 8.46 (d,
J = 7.7 Hz, 1H). 13C NMR (100 MHz, CDCl3)  21.3, 24.4 (2C), 25.9, 32.8, 34.6 (2C),
60.0, 108.9, 118.1, 120.9, 122.4, 123.3, 126.5, 127.6 (2C), 128.7 (2C), 133.0, 135.6,
137.3, 137.8, 161.8. MS (ESI) m/z: 331 (M+H+, 100%); HRMS (ESI-TOF) m/z: Calcd
for C23H27N2 [M+H]+: 331.2169; found: 331.2177.
(Z)-2-[(n-Butylimino)(1-methyl-1H-pyrrol-2-yl)methyl]-N,N-diethylbenzamide
(3c)
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Following the general procedure, the reaction of amide 2d (276 mg, 1.0 mmol) with
N-methylpyrrole gave, after flash column chromatography on silica gel (eluent:
EtOAc/ n-hexane = 1/ 3), the aromatic ketimine 3c (254 mg, yield: 75%, E/Z > 20:1).
Yellow oil. IR (film) max: 2967, 2934, 2855, 1628, 1399, 1375, 1088, 1051, 923, 748
cm-1; 1H NMR (400 MHz, CDCl3)  0.82 (t, J = 7.0 Hz, 3H), 0.89 (t, J = 7.3 Hz, 3H),
0.98 (t, J = 7.0 Hz, 3H), 1.34-1.46 (m, 2H), 1.58-1.71 (m, 2H), 2.63-2.76 (m, 1H),
2.93-3.14 (m, 2H), 3.20-3.39 (m, 2H), 3.52-3.64 (m, 1H), 3.93 (s, 3H), 5.71 (dd, J =
3.7, 1.7 Hz, 1H), 5.89-5.93 (m, 1H), 6.60-6.64 (m, 1H), 7.23-7.31 (m, 2H), 7.34-7.45
(m, 2H). 13C NMR (100 MHz, CDCl3)  11.8, 13.7, 14.0, 20.7, 33.6, 37.1, 38.0, 42.7,
53.5, 106.4, 115.3, 125.7, 127.0, 127.6, 128.2, 128.5, 132.1, 135.8, 136.1, 158.9,
169.1. HRMS (ESI-TOF) m/z: Calcd for C21H29N3ONa [M+Na]+: 362.2203; found:
362.2216.
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Methyl 4-[(cyclohexylimino)(1-methyl-1H-indol-3-yl)methyl]benzoate (3d)
Following the general procedure, the reaction of amide 2e (261 mg, 1.0 mmol) with
N-methylindole gave, after flash column chromatography on silica gel (eluent:
EtOAc/ n-hexane = 1/ 1), the aromatic ketimine 3d (284 mg, yield: 86%) as a 87:13
inseparable mixture of E/Z isomers. For the major isomer: White solid. Mp: 127−128
C; IR (film) max: 3050, 2922, 2847, 1724, 1598, 1536, 1467, 1385, 1276, 1230, 744
cm-1; 1H NMR (400 MHz, CDCl3)  1.06-1.40 (m, 4H), 1.50-1.83 (m, 6H), 3.08-3.18
(m, 1H), 3.65 (s, 3H), 3.95 (s, 3H), 6.61 (s, 1H), 7.17-7.30 (m, 3H), 7.34 (d, J = 7.8
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Hz, 2H), 8.12 (d, J = 7.8 Hz, 2H), 8.48 (d, J = 7.5 Hz, 1H). C NMR (100 MHz,
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CDCl3)  24.3 (2C), 25.8, 32.9, 34.5 (2C), 52.1, 60.3, 109.0, 117.3, 121.1, 122.7,
123.3, 126.3, 127.7 (2C), 129.4 (2C), 129.6, 132.9, 137.8, 143.3, 160.6, 166.8. MS
(ESI) m/z: 375 (M+H+, 100%); HRMS (ESI-TOF) m/z: Calcd for C24H27N2O2 [M+H]+:
375.2067; found: 375.2071.
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1-{4-[(Cyclohexylimino)[4-(dimethylamino)phenyl]methyl]}phenyl}ethanone (3e)
Following the general procedure, the reaction of amide 2f (245 mg, 1.0 mmol) with
N,N-dimethylaniline gave, after flash column chromatography on silica gel (eluent:
EtOAc/ n-hexane = 1/ 10), the aromatic ketimine 3e (264 mg, yield: 76%) as a 88:12
inseparable mixture of E/Z isomers. For the major isomer: Yellow oil. IR (film) max
:
3078, 3029, 2927, 2857, 1687, 1595, 1521, 1364, 1268, 826 cm-1; 1H NMR (500 MHz,
CDCl3)  1.05-1.30 (m, 3H), 1.51-1.80 (m, 7H), 2.66 (s, 3H), 2.96 (s, 6H), 3.00-3.08
(m, 1H), 6.58-6.62 (m, 2H), 7.23-7.78 (m, 2H), 7.39-7.44 (m, 2H), 8.00-8.04 (m, 2H).
13C NMR (125 MHz, CDCl3)  24.4, 25.6, 26.6, 34.1, 40.2, 61.2, 111.2 (2C), 127.6,
128.0 (2C), 128.2 (2C), 129.4 (2C), 136.3, 143.3, 151.5, 164.1, 197.7. HRMS
(ESI-TOF) m/z: Calcd for C23H29N2O [M+H]+: 349.2274; found: 349.2271.
4-{[4-(Dimethylamino)phenyl][(2,6-dimethylphenyl)imino]methyl}benzaldehyde
(3f)
Following the general procedure, the reaction of amide 2g (253 mg, 1.0 mmol) with
N,N-dimethylaniline gave, after flash column chromatography on silica gel (eluent:
EtOAc/ n-hexane = 1/ 10), the aromatic ketimine 3f (306 mg, yield: 86%) as a 60:40
inseparable mixture of E/Z isomers. For the mixture of two isomers: Yellow solid. Mp:
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142−143 C; IR (film) max: 3049, 2921, 2844, 1700, 1598, 1582, 1361, 1201, 1137
cm-1; 1H NMR (500 MHz, CDCl3)  2.03 (s, 2.4H), 2.05 (s, 3.6H), 2.93 (s, 2.4H), 3.04
(s, 3.6H), 6.44-6.48 (m, 0.8H), 6.67-6.97 (m, 5H), 7.27-7.31 (m, 1.2H), 7.65-7.69 (m,
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1.2H), 7.71-7.75 (m, 1.2H), 7.90-7.95 (m, 1.6H), 9.94 (s, 0.6H), 10.10 (s, 0.4H). C
NMR (125 MHz, CDCl3)  18.3, 18.6, 39.9, 40.2, 110.6, 111.1, 122.5, 123.0, 125.6,
126.0, 126.1, 127.6, 127.8, 128.8, 128.9, 129.3, 130.1, 130.5, 135.8, 137.0, 143.7,
146.8, 148.9, 149.2, 150.7, 152.2, 165.3, 166.0, 191.7, 192.1. HRMS (ESI-TOF) m/z:
Calcd for C24H25N2O [M+H]+: 357.1961; found: 357.1959.
(Z)-Methyl 2'-[(cyclohexylimino)(1-methyl-1H-pyrrol-2-yl)methyl]-5'-methyl-
[1,1'-biphenyl]-4-carboxylate (3g)
Following the general procedure, the reaction of amide 2h (351 mg, 1.0 mmol) with
N-methylpyrrole gave, after flash column chromatography on silica gel (eluent:
EtOAc/ n-hexane = 1/ 5), the aromatic ketimine 3g (339 mg, yield: 82%, E/Z > 20:1).
Pale yellow solid. Mp: 151−152 C; IR (film) max: 2913, 2851, 1727, 1603, 1420,
1279, 1093, 1014, 715 cm-1; H NMR (400 MHz, CDCl3)  0.65-0.74 (m, 1H),
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0.94-1.20 (m, 4H), 1.24-1.65 (m, 5H), 2.44 (s, 3H), 2.84-2.92 (m, 1H), 3.81 (s, 3H),
3.89 (s, 3H), 5.91 (dd, J = 3.8, 1.8 Hz, 1H), 5.98 (dd, J = 3.8, 2.6 Hz, 1H), 6.62 (t, J =
2.1 Hz, 1H), 7.11-7.16 (m, 1H), 7.18-7.23 (m, 2H), 7.28-7.33 (m, 2H), 7.89-7.94 (m,
2H). 13C NMR (100 MHz, CDCl3)  21.3, 24.1, 24.3, 25.8, 33.4, 34.0, 37.7, 52.0, 60.7,
106.7, 116.1, 127.3, 128.1, 128.5, 128.6 (2C), 128.8, 129.2 (2C), 129.9, 133.2, 133.4,
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138.1, 139.3, 145.9, 157.7, 167.0. MS (ESI) m/z: 374 (M+H+, 100%); HRMS
(ESI-TOF) m/z: Calcd for C27H31N2O2 [M+H]+: 415.2380; found: 415.2384.
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1-[4-(Dimethylamino]phenylethanone (1a)
Following the general procedure, the deamination reaction of amide 2b (141 mg, 1.0
mmol) with N,N-dimethylaniline gave, after flash column chromatography on silica
gel (eluent: EtOAc/ n-hexane = 1/ 10), the known aromatic ketone 1a28c (146 mg,
yield: 90%). White solid. Mp: 104−105 C; IR (film) max: 2902, 2823, 1658, 1612,
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1358, 1230, 820 cm-1; H NMR (400 MHz, CDCl3)  2.50 (s, 3H), 3.05 (s, 6H), 6.65
13
(d, J = 9.1 Hz, 2H), 7.87 (d, J = 9.1 Hz, 2H). C NMR (100 MHz, CDCl3)  25.9,
40.0 (2C), 110.5 (2C), 125.3, 130.5 (2C), 153.3, 196.3. MS (ESI) m/z: 186 (M+Na+,
100%).
1-[4-(Dimethylamino)phenyl] propan-1-one (1b)
Following the general procedure, the deamination reaction of amide 2i (155 mg, 1.0
mmol) with N,N-dimethylaniline gave, after flash column chromatography on silica
gel (eluent: EtOAc/ n-hexane = 1/ 10), the known aromatic ketone 1b24 (163 mg, yield:
92%). White solid. Mp: 94−95 C; IR (film) max: 2959, 2917, 2847, 1658, 1611,
1191, 1079, 800 cm-1; 1H NMR (500 MHz, CDCl3)  1.21 (t, J = 7.3 Hz, 3H), 2.91 (q,
J = 7.3 Hz, 2H), 3.05 (s, 6H), 6.66 (d, J = 9.0 Hz, 2H), 7.89 (d, J = 9.0 Hz, 2H). 13C
NMR (125 MHz, CDCl3)  8.8, 31.0, 40.0, 110.6 (2C), 125.0, 130.1 (2C), 153.2,
199.2. MS (ESI) m/z: 200 (M+Na+, 100%).
2-Acetylpyrrole (1c)
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Following the general procedure, the deamination reaction of amide 2b (141 mg, 1.0
mmol) with pyrrole gave, after flash column chromatography on silica gel (eluent:
EtOAc/ n-hexane = 1/ 10), the known aromatic ketone 1c28i (92 mg, yield: 84%).
White solid. mp: 88−89 C; IR (film) max: 3276, 3114, 1646, 1447, 1428, 1402, 1129,
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772, 751 cm-1; H NMR (400 MHz, CDCl3)  2.44 (s, 3H), 6.26-6.29 (m, 1H),
6.91-6.94 (m, 1H), 7.03-7.07 (m, 1H), 9.90 (br s, 1H). 13C NMR (100 MHz, CDCl3) 
25.4, 110.6, 116.9, 124.8, 132.2, 188.1. MS (ESI) m/z: 132 (M+Na+, 100%).
Furan-2-yl-phenylmethanone (1d)
Following the general procedure, the deamination reaction of amide 2a (203 mg, 1.0
mmol) with furan gave, after flash column chromatography on silica gel (eluent:
EtOAc/ n-hexane = 1/ 10), the known aromatic ketone 1d28d (138 mg, yield: 80%).
Colorless oil. IR (film) max: 3134, 3058, 1648, 1465, 1390, 1298, 956, 870, 727, 696
cm-1; 1H NMR (400 MHz, CDCl3)  6.59 (dd, J = 3.7, 1.7 Hz, 1H), 7.23 (dd, J = 3.7,
0.7 Hz, 1H), 7.46-7.61 (m, 3H), 7.70 (dd, J = 1.7, 0.7 Hz, 1H), 7.94-7.99 (m, 2H). 13C
NMR (100 MHz, CDCl3)  112.1, 120.5, 128.3 (2C), 129.2 (2C), 132.5, 137.1, 147.2,
152.2, 182.4. MS (ESI) m/z: 195 (M+Na+, 100%).
Benzofuran-2-yl(phenyl)methanone (1e)
Following the general procedure, the deamination reaction of amide 2j (135 mg, 1.0
mmol) with 2,3-benzofuran gave, after flash column chromatography on silica gel
(eluent: EtOAc/ n-hexane = 1/ 10), the known aromatic ketone 1e28b (180 mg, yield:
81%). White solid. Mp: 90−91 C; IR (film) max: 3059, 2959, 2851, 1651, 1613,
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1545, 1444, 1329, 1278, 1184, 971, 753, 696 cm-1; H NMR (400 MHz, CDCl3) 
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1H ). C NMR (100 MHz, CDCl3)  112.5, 116.5, 123.3, 123.9, 126.9, 128.3, 128.5
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(2C), 129.4 (2C), 132.8, 137.2, 152.2, 155.9, 184.3. MS (ESI) m/z: 245 (M+Na+,
100%).
(1H-Inden-2-yl)-phenylmethanone (1f)
Following the general procedure, the deamination reaction of amide 2k (183 mg, 1.0
mmol) with 1,3-dimethoxybenzene gave, after flash column chromatography on silica
gel (eluent: EtOAc/ n-hexane = 1/ 10), the known aryl ketone 1f28a (175 mg, yield:
77%). White solid. Mp: 65−66 C; IR (film) max: 3034, 2959, 2926, 2851, 1622,
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1552, 1411, 1356, 1239, 1180, 953, 773, 738 cm-1; H NMR (400 MHz, CDCl3) 
7.23-7.27 (m, 1H), 7.31-7.37 (m, 1H), 7.47-7.54 (m, 1H), 7.62-7.66 (m, 1H),
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7.71-7.78 (m, 3H), 8.31-8.35 (m, 1H). C NMR (100 MHz, CDCl3)  112.4, 114.5,
123.2, 124.0, 127.0, 128.1, 128.3, 134.4, 134.6, 142.3, 152.5, 155.8, 175.0. MS (ESI)
m/z: 251 (M+Na+, 100%).
1-(2,4-Dimethoxyphenyl)ethanone (1g)
Following the general procedure, the deamination reaction of amide 2b (141 mg, 1.0
mmol) with 1,3-dimethoxybenzene gave, after flash column chromatography on silica
gel (eluent: EtOAc/ n-hexane = 1/ 10), the known aromatic ketone 1g28e (133 mg,
yield: 74%). Colorless oil. IR (film) max: 3003, 2965, 2943, 2840, 1664, 1599, 1466,
1358, 1268, 1163, 1029, 834 cm-1; 1H NMR (400 MHz, CDCl3)  2.57 (s, 3H), 3.85 (s,
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8.7 Hz, 1H).; C NMR (100 MHz, CDCl3)  31.8, 55.4, 55.4, 98.2, 105.0, 121.0,
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132.6, 161.0, 164.5, 197.7. MS (ESI) m/z: 203 (M+Na+, 100%).
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1-(2,4-Dimethoxyphenyl)pentan-1-one (1h)
Following the general procedure, the deamination reaction of amide 2l (115 mg, 1.0
mmol) with 1,3-dimethoxybenzene gave, after flash column chromatography on silica
gel (eluent: EtOAc/ n-hexane = 1/ 5), the aromatic ketone 1h (175 mg, yield: 79%).
White wax. IR (film) max: 3083, 2963, 2930, 2872, 1665, 1575, 1466, 1262, 1163,
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1029, 836, 798 cm-1; H NMR (400 MHz, CDCl3)  0.93 (t, J = 7.4 Hz, 3H),
1.31-1.42 (m, 2H), 1.61-1.70 (m, 2H), 2.93 (t, J = 7.4 Hz, 2H), 3.85 (s, 3H), 3.88 (s,
3H), 6.45 (d, J = 2.2 Hz, 1H), 6.52 (dd, J = 8.7, 2.2 Hz, 1H), 7.77 (d, J = 8.7 Hz, 1H).
13C NMR (100 MHz, CDCl3)  14.0, 22.6, 26.7, 43.3, 55.4, 55.5, 98.4, 105.0, 121.5,
132.5, 160.5, 164.1, 201.0. HRMS (ESI-TOF) m/z: Calcd for C13H18O3Na [M+Na]+:
245.1148; found: 245.1149.
(2,4-Dimethoxyphenyl)(p-tolyl)methanone (1i)
Following the general procedure, the deamination reaction of amide 2m (211 mg, 1.0
mmol) with 1,3-dimethoxybenzene gave, after flash column chromatography on silica
gel (eluent: EtOAc/ n-hexane = 1/ 5), the known aromatic ketone 1i (225 mg, yield:
88%) and aniline hydrochloride 4a (107 mg, yield: 83%). 1i: Colorless oil. IR (film)
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max: 3007, 2937, 2847, 1655, 1604, 1575, 1284, 1217, 1159 cm-1; H NMR (500
MHz, CDCl3)  2.40 (s, 3H), 3.71 (s, 3H), 3.86 (s, 3H), 6.50-6.56 (m, 2H), 7.21 (d, J
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= 8.0 Hz, 2H), 7.36 (d, J = 8.4 Hz, 1H), 7.69 (d, J = 8.0 Hz, 2H). 13C NMR (125 MHz,
CDCl3)  21.6, 56.5, 56.5, 98.8, 104.4, 121.8, 128.7 (2C), 129.9 (2C), 131.9, 136.0,
143.1, 159.4, 163.0, 195.3. MS (ESI) m/z: 279 (M+Na+, 100%);
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(4-Methoxyphenyl)(phenyl)methanone + (2-Methoxyphenyl)(phenyl)methanone
(1j)
Following the general procedure, the deamination reaction of amide 2n (197 mg, 1.0
mmol) or 2o (225 mg, 1.0 mmol) amide with anisole gave, after flash column
chromatography on silica gel (eluent: EtOAc/ n-hexane = 1/ 10), the known aromatic
ketone 1j28d (189 mg, yield: 89%, p:o = 8.5:1 from 2n, or 199 mg, yield: 94%, p:o =
4.6:1 from 2o) as an inseparable mixture of two regioisomer and 2, 6-dimethylaniline
4b (105 mg, yield: 87% from 2o). 1j for the mixture of two regioisomers: Colorless
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oil. IR (film) max: 3062, 2959, 2921, 2831, 1656, 1601, 1258, 695 cm-1; H NMR
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(500 MHz, CDCl3)  3.72 (s, 0.55H), 3.88 (s, 2.45H), 6.61-7.85 (m, 9H). C NMR
(125 MHz, CDCl3)  55.5, 55.6, 111.4, 113.5, 117.9, 120.4, 121.6, 128.1 (2C), 128.2,
128.8, 129.5, 129.7 (2C), 129.8, 130.1, 131.9, 132.5, 132.9, 137.8, 138.2, 157.3, 163.2,
195.5, 196.4. MS (ESI) m/z: 235 (M+Na+, 100%);
(3,4-Dimethoxyphenyl)(phenyl)methanone (1k)
Following the general procedure, the deamination reaction of amide 2o (225 mg, 1.0
mmol) with 1,2-dimethoxybenzene gave, after flash column chromatography on silica
gel (eluent: EtOAc/ n-hexane = 1/ 5), the known aromatic ketone 1k28f (235 mg, yield:
97%) and 2,6-dimethylaniline 4b (109 mg, yield: 90%). 1k: Colorless oil. IR (film)
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max: 3068, 3007, 2965, 2933, 1646, 1591, 1511, 1268, 1130, 1027, 723 cm-1; H
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NMR (500 MHz, CDCl3)  3.94 (s, 3H), 3.96 (s, 3H), 6.89 (d, J = 8.3 Hz, 1H), 7.38
(dd, J = 8.3, 1.6 Hz, 1H), 7.45-7.51 (m, 3H), 7.54-7.59 (m, 1H), 7.74-7.78 (m, 2H).
13C NMR (125 MHz, CDCl3)  56.0, 56.0, 109.6, 112.0, 125.4, 128.1 (2C), 129.6
(2C), 130.1, 131.8, 138.2, 148.9, 152.9, 195.5. MS (ESI) m/z: 265 (M+Na+, 100%);
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(1-Methyl-1H-pyrrol-2-yl)(4-nitrophenyl)methanone (1l)
Following the general procedure, the deamination reaction of amide 2p (248 mg, 1.0
mmol) with N-methylpyrrole gave, after flash column chromatography on silica gel
(eluent: EtOAc/ n-hexane = 1/ 5), the known aromatic ketone 1l28h (210 mg, yield:
91%). Yellow solid. Mp: 151−152 C; IR (film) max: 3092, 2955, 2839, 1627, 1596,
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1515, 1409, 1349, 1251, 848, 744 cm-1; H NMR (400 MHz, CDCl3)  4.06 (s, 3H),
6.20 (dd, J = 4.0, 2.4 Hz, 1H), 6.69 (dd, J = 4.0, 1.5 Hz, 1H), 6.98-7.02 (m, 1H), 7.92
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(d, J = 8.7 Hz, 2H), 8.30 (d, J = 8.7 Hz, 2H). C NMR (100 MHz, CDCl3)  37.5,
108.8, 123.3 (2C), 123.6, 129.8 (2C), 132.7, 145.3, 149.2, 183.6. MS (ESI) m/z: 253
(M+Na+, 100%).
(1-Methyl-1H-indol-2-yl)(4-nitrophenyl)methanone (1m)
Following the general procedure, the deamination reaction of amide 2p (248 mg, 1.0
mmol) with N-methylindole gave, after flash column chromatography on silica gel
(eluent: EtOAc/ n-hexane = 1/ 5), the known aryl ketone 1m28g (210 mg, yield: 75%).
Yellow solid. Mp: 183−184 C; IR (film) max: 2914, 1620, 1597, 1524, 1463, 1370,
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1345, 1234, 844, 744, 706 cm-1; H NMR (400 MHz, CDCl3)  3.87 (s, 3H),
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8.36-8.42 (m, 1H). C NMR (100 MHz, CDCl3)  33.7, 109.8, 115.3, 122.6, 123.2,
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123.6 (2C), 124.2, 126.8, 129.3 (2C), 137.7, 138.1, 146.3, 149.1, 188.3. MS (ESI) m/z:
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303 (M+Na+, 100%).
4-(2,4-Dimethoxybenzoyl)benzonitrile (1n)
Following the general procedure, the deamination reaction of amide 2q (202 mg, 1.0
mmol) with 1,3-dimethoxybenzene gave, after flash column chromatography on silica
gel (eluent: EtOAc/ n-hexane = 1/ 5), the aromatic ketone 1n (200 mg, yield: 75%).
White solid. Mp: 108−110 C; IR (film) max: 2916, 2847, 2228, 1656, 1600, 1574,
1502, 1462, 1418, 1309, 1275, 939, 854, 835, 766 cm-1; 1H NMR (400 MHz, CDCl3)
 3.65 (s, 3H), 3.89 (s, 3H), 6.49 (d, J = 2.2 Hz, 1H), 6.59 (dd, J = 8.6, 2.2 Hz, 1H),
7.50 (d, J = 8.6 Hz, 1H), 7.71 (d, J = 8.4 Hz, 2H), 7.80 (d, J = 8.4 Hz, 2H). 13C NMR
(100 MHz, CDCl3)  55.4, 55.6, 98.6, 105.3, 115.1, 118.3, 120.2, 129.5 (2C), 131.8
(2C), 132.8, 142.9, 159.9, 164.4, 193.8. MS (ESI) m/z: 290 (M+Na+, 100%); HRMS
(ESI-TOF) m/z: Calcd for C16H13NO3Na [M+Na]+: 290.0788; found: 290.0794.
Methyl 4-(2,4-dimethoxybenzoyl)benzoate (1o)
Following the general procedure, the deamination reaction of amide 2e (261 mg, 1.0
mmol) with 1,3-dimethoxybenzene gave, after flash column chromatography on silica
gel (eluent: EtOAc/ n-hexane = 1/ 5), the aromatic ketone 1o (195 mg, yield: 65%).
White solid. Mp: 99−101 C; IR (film) max: 3005, 2947, 2843, 1724, 1657, 1598,
1436, 1311, 1245, 1106, 821, 753 cm-1; H NMR (400 MHz, CDCl3)  3.66 (s, 3H ),
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3.88 (s, 3H), 3.95 (s, 3H), 6.50 (d, J = 2.2 Hz, 1H), 6.58 (dd, J = 8.5, 2.2 Hz, 1H),
7.48 (d, J = 8.5 Hz, 1H), 7.78 (d, J = 8.5 Hz, 2H), 8.08 (d, J = 8.5 Hz, 2H). 13C NMR
(100 MHz, CDCl3)  52.3, 55.4, 55.5, 98.7, 104.9, 120.9, 129.2 (2C), 129.2 (2C),
132.6, 132.9, 142.8, 159.9, 164.0, 166.5, 194.8. MS (ESI) m/z: 323 (M+Na+, 100%).
HRMS (ESI-TOF) m/z: Calcd for C17H16O5Na [M+Na]+: 323.0890; found: 323.0888.
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(R)-1-[(tert-Butyldiphenylsilyl)oxy]-3-methylbutan-2-amine (4c)
Following the general procedure, the deamination reaction of amide 2r (383 mg, 1.0
mmol) with N,N-dimethylaniline gave, after flash column chromatography on silica
gel (eluent: EtOAc/ n-hexane = 1/ 1), the known aromatic ketone 1a (141 mg, yield:
87%) and amine 4c28j (290 mg, yield: 85%). 4c: Colorless oil. IR (film) max: 3388,
3074, 2962, 2930, 2859, 1425, 1114, 707 cm-1; 1H NMR (400 MHz, CDCl3)  0.83 (d,
J = 6.8 Hz, 3H), 0.87 (d, J = 6.8 Hz, 3H), 1.06 (s, 9H), 1.53 (br s, 2H), 1.58-1.67 (m,
1H), 2.61-2.67 (m, 1H), 3.48 (dd, J = 9.9, 7.8 Hz, 1H), 3.68 (dd, J = 9.9, 4.1 Hz, 1H),
7.35-7.45 (m, 6H), 7.64-7.69 (m, 4H). 13C NMR (100 MHz, CDCl3)  18.2, 19.2, 19.5,
26.9 (2C), 30.4, 58.4, 67.3, 127.7 (4C), 129.6 (2C), 133.6, 133.6, 135.6 (4C). MS
(ESI) m/z: 342 (M+Na+, 100%);
Acknowledgment: The authors are grateful to the National Natural Science
Foundation of China (21332007) and to the Program for Changjiang Scholars and
Innovative Research Team in University of Ministry of Education, China, for
financial support.
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Supporting Information Available: 1H and C NMR spectra of all products. This
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material is available free of charge via the Internet at http://pubs.acs.org.
AUTHOR INFORMATION
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Corresponding Author: *E-mail: pqhuang@xmu.edu.cn.
Notes
The authors declare no competing financial interest.
References
1. (a) Li, C.-J. Green Chem. 2016, 18, 1836−1838. (b) Li, C.-J. Sci. China Chem.
2011, 54, 1815−1830. (c) Li, C.-J.; Trost, B. M. Proc. Natl. Acad. Sci. U. S. A.
2008, 13197−13202.
2. For selected reviews, see: (a) Cabri, W.; Candiani, I. Acc. Chem. Res. 1995, 28,
2–7. (b) Amatore, C.; Jutand, A. Acc. Chem. Res. 2000, 33, 314–321. (c)
Beletskaya, I. P.; Cheprakov, A. V. Chem. Rev. 2000, 100, 3009–3066.
3. For recent reviews on the metal-catalyzed three-component A3-coupling reaction
(Aldehyde-Alkyne-Amine), see: (a) Yoo, W.-J.; Zhao, L.; Li, C.-J. Aldrichim.
Acta 2011, 44, 43−51. (b) Li, C.-J. Acc. Chem. Res. 2010, 43, 581−590. For a
related work, see: (c) Dong, Q.-L.; Liu, G.-S.; Zhou, H.-B.; Chen, L.; Yao, Z.-J.
Tetrahedron Lett. 2008, 49, 1636−1640.
4. (a) Friedel, C.; Crafts, J. M. Compt. Rend. 1877, 84, 1450. For recent reviews,
see: (b) Sartori, G.; Maggi, R. Chem. Rev. 2011, 111, PR181–PR214. (c) Heaney,
H. 3.2 - The Bimolecular Aromatic Friedel–Crafts Reaction, Reference Module
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