Ruthenium-catalyzed coupling of aldimines with arylboronates: New synthetic method for aromatic ketones

Article abstract of DOI:10.1039/b415810e

Using the chelation strategy, the reaction of aldimines bearing the 3-picolin-2-yl group with various arylboronates in the presence of a ruthenium catalyst furnished the corresponding ketimines in high yields for a short reaction time; the resulting ketimines were readily converted to ketones by hydrolysis. The Royal Society of Chemistry 2005.

Full text of DOI:10.1039/b415810e

View Article Online / Journal Homepage / Table of Contents for this issue
COMMUNICATION
www.rsc.org/chemcomm | ChemComm
Ruthenium-catalyzed coupling of aldimines with arylboronates: new
synthetic method for aromatic ketones{
Young Jun Park, Eun-Ae Jo and Chul-Ho Jun*
Received (in Cambridge, UK) 13th October 2004, Accepted 24th November 2004
First published as an Advance Article on the web 18th January 2005
DOI: 10.1039/b415810e
or 1-cyclohexenone were ineffective in suppressing the formation
of 6a and 7a.
Using the chelation strategy, the reaction of aldimines bearing
the 3-picolin-2-yl group with various arylboronates in the
presence of a ruthenium catalyst furnished the corresponding
ketimines in high yields for a short reaction time; the resulting
ketimines were readily converted to ketones by hydrolysis.
With these observations at hand, we investigated the scope of
the coupling reactions of 1 and 2 (Table 2).{ The electronic effect
of the 4-substituent in 1 and 2 had no significant influence on
reactivity, and the corresponding diaryl ketones were obtained in
good yields after hydrolysis in most cases except for 2d (entries
The transition metal-catalyzed reactions involving a C–H bond
cleavage have opened up a new methodology for the addition of
relatively inert C–H bonds to C–C multiple bonds.1 In particular,
the chelation-assisted hydroacylation of 1-alkene or alkyne is one
of the most promising ways for transforming aldehydes to ketones
in which the resulting ketones are aryl-alkyl or alkyl-alkyl ketones.2
However, direct synthesis of aryl-aryl ketone from aldehydes (or
corresponding imines) has been rarely developed. One of the
more notable direct syntheses of aryl-aryl ketones (as reported
by Suggs et al.) is the stoichiometric reaction of the
iminoacylrhodium(III)-hydride complex with benzoyl chloride
yielding diphenyl ketimine.3 Relevant catalytic approaches are
the Heck type reaction between aldehydes (or aldimines) and aryl–
metal species generated from oxidative addition of aryl halide to
transition metals,4 or the reaction of a,b-unsaturated aldehydes
with boronic acids.5,6 Here we wish to report the ruthenium-
catalyzed coupling of aldimines with arylboronates for the synthesis
of aromatic ketimines, which form ketones upon hydrolysis
(Scheme 1).
Table 1 Additive effects on the Ru-catalyzed coupling of 1a with 2aa
Yieldb (%) of
Entry
Additives
3a
6a
7a
1
2
3
4
a
none
cyclohexene
61
63
94
83
13
13
4
22
24
1
methyl vinyl ketonec
1-cyclohexenone
10
5
Reaction conditions: 1a (0.216 mmol), 1.2 equiv. of 2a, 5 mol% 5,
100 mol% additive, 0.2 ml solvent mixture at 150 uC (bath temp.)
b
c
for 1 hour. Determined by GC based on 1a. Small amount of
addition product of MVK with 2a (, 4%) was also observed.
Pic 5 3-picolin-2-yl.
In our initial experiments, when the reaction of 1a (R = Ph) with
2a (Ar = Ph) was carried out in the presence of 5 mol% Ru3(CO)12
(5)7 in acetone–1,4-dioxane solvent mixture (w/w 5 1 : 1) at 150 uC
for 1 h, ketimine of benzophenone (3a) was obtained in a 61%
yield along with 6a (13%) and 7a (22%), determined by GC
(Table 1, entry 1).8 Attempts to avoid the formation of 6a and 7a,
reduced forms of 1a and 3a, have failed under various reaction
conditions.9 However, addition of methyl vinyl ketone (MVK)
dramatically suppressed the formation of 6a and 7a without
affecting the yield of 3a (entry 3). Other olefins such as cyclohexene
Table 2 Scope of the Ru-catalyzed coupling of 1 with 2a,b
Entry R of 1
Ar of 2
Ph (2a)
4-MeOC6H4 (2b) 82 (91)
Isolated yieldc (%) of 4
1
2
3
Ph (1a)
1a
1a
85 (94)
(4aa)
(4ab)
(4ac)
(4ad)
(4ae)
(4af)
(4ag)
(4ah)
(4bb)
(4cb)
4-MeC6H4 (2c)
2-MeC6H4 (2d)
4-FC6H4 (2e)
4-ClC6H4 (2f)
3-ClC6H4 (2g)
4-BrC6H4 (2h)
75 (86)
18 (28)
86 (93)
84 (96)
86 (94)
74 (88)
71 (86)
88 (94)
4
5
1a
1a
6
7
1a
1a
8
1a
9
10
a
4-MeOC6H4 (1b) 2b
4-CF3C6H4 (1c) 2b
Scheme 1
Reaction conditions: 1 (0.216 mmol), 1.2 equiv. of 2, 5 mol% 5,
1 equiv. of MVK, 0.2 ml solvent mixture at 150 uC (bath temp.) for
1 hour. Small amounts of 6 (, 4%), 7 (, 2%) and addition
b
{ Electronic supplementary information (ESI) available: characterization
of new compounds. See http://www.rsc.org/suppdata/cc/b4/b415810e/
*junch@yonsei.ac.kr
product of MVK with 2 (, 4%) were also observed before
hydrolysis. GC yield of 3 based on 1 is given in parentheses.
c
This journal is ß The Royal Society of Chemistry 2005
Chem. Commun., 2005, 1185–1187 | 1185

View Article Online
1–10). The reaction of 2d with 1a was sluggish, probably owing to
the unfavourable steric interaction (entry 4). For the coupling of
aliphatic aldimine with 2, aminal was used as an imine precursor of
aliphatic aldehyde, in which aldimine 1 and 2-amino-3-picoline is
dissociated from aminal above 100 uC (Scheme 2).10 When the
reaction of aminal with 2 was carried out, it was found that
secondary as well as primary alkyl aminals gave the corresponding
ketone in moderate yields irrespective of the electronic effect of the
4-substituent in 2 (Table 3).
ruthenium metal center yielding the iminoacylruthenium(II)-
hydride species (B).12 A hydride attack of B on acetone leads
to the isopropoxy iminoacyl ruthenium(II) species (C).
Transmetallation of C with 2 gives the iminoacylruthenium(II)-
aryl species (D).13 And subsequent reductive elimination of D
furnishes ketimine 3, which is hydrolyzed by H2O to give the
corresponding ketone 4.
In summary, we developed the coupling reaction of aldimines
with arylboronates using the chelation protocol. This transforma-
tion represents a new catalytic reaction for the synthesis of
aromatic ketones. More detailed mechanistic studies and improved
applications are under way.
From the mechanistic point of view, the following mechanism
can be suggested for the direct addition of aryl–metal species to
imine followed by b-hydrogen elimination (Scheme 3).4(b)–(d),6,11
Alternatively, as far as aldimines of 2-amino-3-picoline are
concerned,12 the chelation-assisted C–H bond cleavage of 1 by 5
might take place. Thus we have a preference for the following
mechanism for the coupling reaction of 1 with 2, though other
reaction pathways cannot be ruled out (Scheme 4). The first step
might be an oxidative addition of the C–H bond in 1 into the
This work was supported by the National Research Laboratory
(NRL) (2000-N-NL-01-C-271) Program administered by the
Ministry of Science and Technology and CBMH.
Young Jun Park, Eun-Ae Jo and Chul-Ho Jun*
Department of Chemistry and Center for Bioactive Molecular Hybrid
(CBMH), Yonsei University, Seoul, 120-749, Korea.
E-mail: junch@yonsei.ac.kr; Fax: 08 02 364 7050; Tel: 08 02 2123 2627
Notes and references
{ Representative Procedure: A screw-capped pressure vial (1 mL) was
charged with 0.216 mmol of 1, 6.9 mg (0.0108 mmol) of Ru3(CO)12 (5),
0.259 mmol of 2 and 15.1 mg (0.216 mmol) of methyl vinyl ketone and the
reaction mixture was dissolved in 0.2 ml of a 1,4-dioxane–acetone mixture
(w/w 5 1 : 1). It was stirred in an oil bath that was preheated to 150 uC for
1 h. After the reaction, the resulting mixture was hydrolyzed using 10 ml of
1 M HCl and THF mixture solution for 12 h and then purified by column
chromatography (SiO2, n-hexane : ethyl ether 5 10 : 1) to afford the
corresponding ketones.
Scheme 2
Table 3 Scope of the Ru-catalyzed coupling of aminal with 2a
Entry
R of aminal
2
Isolated yield (%) of 4
1
2
3
4
a
n-C5H11 (1d)
1d
Cy (1e)
1e
2b
2e
2b
2e
47 (58)
46 (60)
55 (67)
51 (60)
(4db)
(4de)
(4eb)
(4ee)
1 For reviews: (a) A. E. Shilov and G. B. Shul’pin, Chem. Rev., 1997, 97,
2879; (b) G. Dyker, Angew. Chem., Int. Ed., 1999, 38, 1698; (c)
V. Ritleng, C. Sirlin and M. Pfeffer, Chem. Rev., 2002, 102, 1731; (d)
F. Kakiuchi and S. Murai, Acc. Chem. Res., 2002, 35, 826; (e)
F. Kakiuchi and N. Chatani, Adv. Synth. Catal., 2003, 345, 1077.
2 For reviews: (a) C.-H. Jun, C.-W. Moon and D.-Y. Lee, Chem. Eur. J.,
2002, 8, 2423; (b) C.-H. Jun and J. H. Lee, Pure Appl. Chem., 2004, 76,
577. For articles: (c) D.-Y. Lee, B.-S. Hong, E.-G. Cho, H. Lee and
C.-H. Jun, J. Am. Chem. Soc., 2003, 125, 6372; (d) C.-H. Jun, H. Lee,
J.-B. Hong and B.-I. Kwon, Angew. Chem., Int. Ed., 2002, 41, 2146; (e)
M. C. Willis and S. Sapmaz, Chem. Commun., 2001, 2558; (f)
M. C. Willis, S. J. McNally and P. J. Beswick, Angew. Chem., Int.
Ed., 2004, 43, 340.
Same as in Table 2: aminal (0.216 mmol) was used instead of 1.
Scheme 3
3 J. W. Suggs and S. D. Cox, Organometallics, 1982, 1, 402.
4 (a) T. Satoh, T. Itaya, M. Miura and M. Nomura, Chem. Lett., 1996,
823; (b) T. Ishiyama and J. F. Hartwig, J. Am. Chem. Soc., 2000, 122,
12043; (c) C. Krug and J. F. Hartwig, J. Am. Chem. Soc., 2002, 124,
1674; (d) C. Krug and J. F. Hartwig, J. Am. Chem. Soc., 2004, 126,
2694; (e) Y. C. Huang, K. K. Majumdar and C. H. Cheng, J. Org.
Chem., 2002, 67, 1682.
5 Z. Wang, G. Zou and J. Tang, Chem. Commun., 2004, 1192.
6 During the process of reviewing this manuscript, a rhodium-catalyzed
cross-coupling reaction for the synthesis of diaryl ketones from aromatic
aldehydes and ArBF3K has been reported, see: M. Pucheault, S. Darses
and J.-P. Genet, J. Am. Chem. Soc., 2004, 126, 15356.
7 Other catalysts such as Rh(PPh3)3Cl, Ru(PPh3)3Cl2,
RuHCl(CO)(PPh3)3, Pd(OAc)2 and Pd(PPh3)2Cl were ineffective except
for RuH2(CO)(PPh3)3, albeit in low yield (57% GC yield) as compared
with 5.
8 (a) The direct conversion of aldehydes to ketones using the chelation-
assisted catalytic system of 5 and 2-amino-3-picoline (in situ generation
of the aldimine) was unsuccessful, because 2-amino-3-picoline is
supposed to react with 5 to give an inactive complex during the
reaction, see: J. A. Cabeza, Eur. J. Inorg. Chem., 2002, 1559; (b) In the
absence of acetone, the yield of 3a was decreased (47% GC yield) and
severe reduction of 1a also took place; (c) Boronic acids were also
Scheme 4 Proposed mechanism for the coupling of 1 with 2.
1186 | Chem. Commun., 2005, 1185–1187
This journal is ß The Royal Society of Chemistry 2005

View Article Online
applicable, but yields were approximately 20% lower compared with
those of 2.
11 For an aryl–RhI bond insertion into aldimine yielding amines, see:
M. Ueda and N. Miyaura, J. Organomet. Chem., 2000, 595, 31.
12 For the ruthenium-carbonyl complex-catalyzed C–H bond activation,
see: C. H. Jun, H. Lee, J.-B. Park and D.-Y. Lee, Org. Lett., 1999, 1,
2161.
13 For a similar transmetallation of alkoxo ruthenium species with an
organoboron reagent, see: (a) F. Kakiuchi, S. Kan, K. Igi, N. Chatani
and S. Murai, J. Am. Chem. Soc., 2003, 125, 1698; (b) F. Kakiuchi,
M. Usi, S. Ueno, N. Chatani and S. Murai, J. Am. Chem. Soc., 2004,
126, 2706.
9 When only 1a was stirred in dioxane–acetone mixture with 5 (5 mol%)
at 150 uC for 1 hour, 7a, a reduced form of 1a, was observed in 25% GC
yield. One of the possible explanations for the formation of these
reduced forms of 1 and 3 may be a water-gas shift reaction producing
molecular hydrogen, H2. However, we observed comparable results
even under anhydrous conditions. For a similar observation, see:
ref. 4(b).
10 J. W. Suggs, J. Am. Chem. Soc., 1979, 101, 489.
This journal is ß The Royal Society of Chemistry 2005
Chem. Commun., 2005, 1185–1187 | 1187