Aryl ketone synthesis via tandem orthoplatinated triarylphosphite-catalyzed addition reactions of arylboronic acids with aldehydes followed by oxidation

Article abstract of DOI:10.1021/jo101469s

Tandem orthoplatinated triaryl phosphite-catalyzed addition reactions of arylboronic acids with aldehydes followed by oxidation to yield aryl ketones is described. 3-Pentanone was identified as a suitable oxidant for the tandem aryl ketone formation reaction. By using microwave energy, aryl ketones were obtained in high yields with the catalyst loading as low as 0.01%.

Full text of DOI:10.1021/jo101469s

pubs.acs.org/joc
complexes and, more recently, Ru(II) complexes7 have been
Aryl Ketone Synthesis via Tandem Orthoplatinated
Triarylphosphite-Catalyzed Addition Reactions of
Arylboronic Acids with Aldehydes Followed by
Oxidation
reported to catalyze this type of addition reactions. In our
laboratory, we’re interested in employing readily available
anionic four-electron donor-based (type I) metalacycles,9 a
large family of cyclic organometallic compounds, as cata-
lysts for such addition reactions.10,11 In this context, we have
recently documented type I palladacycle-catalyzed addition
reactions of arylboronic acids with carbonyl-containing
compounds.10b,c We have also employed type I platinacycle
1 as the catalyst for the addition reactions of arylboronic
acids with aldehydes.10a To further the use of these readily
Yuan-Xi Liao and Qiao-Sheng Hu*
Department of Chemistry, College of Staten Island and the
Graduate Center of the City University of New York,
Staten Island, New York 10314
qiaosheng.hu@csi.cuny.edu
Received July 26, 2010
(3) Selected examples of Pd(II)-catalyzed 1,2-addition of arylboronic
acids with aldehydes: (a) Kuriyama, M.; Ishiyama, N.; Shimazawa, R.;
Shirai, R.; Onomura, O. J. Org. Chem. 2009, 74, 9210–9213. (b) Yamamoto,
T.; Iizuka, M.; Takenaka, H.; Ohta, T.; Ito, Y. J. Organomet. Chem. 2009,
694, 1325–1332. (c) Yu, A.; Cheng, B.; Wu, Y.; Li, J.; Wei, K. Tetrahedron
Lett. 2008, 49, 5405–5407. (d) Kuriyama, M.; Shimazawa, R.; Shirai, R. J.
Org. Chem. 2008, 73, 1597–1600. (e) Qin, C.; Wu, H.; Cheng, J.; Chen, X.;
Liu, M.; Zhang, W.; Su, W.; Ding, J. J. Org. Chem. 2008, 73, 4102–4107. (f)
Nishikata, T.; Kiyomura, S.; Yamamoto, Y.; Miyaura, N. Synlett 2008,
2487–2490. (g) Francesco, I. N.; Wagner, A.; Colobert, F. Eur. J. Org. Chem.
2008, 34, 5692–5695. (h) Kuriyama, M; Shimazawa, R.; Enomoto, T.; Shirai,
R. J. Org. Chem. 2008, 73, 6939–6942. (i) Liu, G.; Lu, X. Tetrahedron 2008,
64, 7324–7330. (j) Lin, S.; Lu, X. J. Org. Chem. 2007, 72, 9757–9760. (k) Qin,
C.; Wu, H.; Cheng, J.; Chen, X.; Liu, M.; Zhang, W.; Su, W.; Ding, J. J. Org.
Chem. 2007, 72, 4102–4107. (l) Liu, G.; Lu, X. J. Am. Chem. Soc. 2006, 128,
16504–16505. (m) Suzuki, K.; Arao, T.; Ishii, S.; Maeda, Y.; Kondo, K.;
Aoyama, T. Tetrahedron Lett. 2006, 47, 5789–5792. (n) Yamamoto, T.; Ohta,
T.; Ito, Y. Org. Lett. 2005, 7, 4153–4155.
Tandem orthoplatinated triaryl phosphite-catalyzed ad-
dition reactions of arylboronic acids with aldehydes
followed by oxidation to yield aryl ketones is described.
3-Pentanone was identified as a suitable oxidant for the
tandem aryl ketone formation reaction. By using micro-
wave energy, aryl ketones were obtained in high yields
with the catalyst loading as low as 0.01%.
(4) (a) Bouffard, J.; Itami, K. Org. Lett. 2009, 11, 4410–4413. (b) Zhou,
L.; Du, X.; He, R.; Ci, Z.; Bao, M. Tetrahedron Lett. 2009, 50, 406–408. (c)
Yamamoto, K.; Tsurumi, K.; Sakurai, f.; Kondo, K.; Aoyama, T. Synthesis
2008, 3585–3590. (d) Arao, T.; Kondo, K.; Aoyama, T. Tetrahedron Lett.
2007, 48, 4115–4117. (e) Takahashi, G.; Shirakawa, E.; Tsuchimoto, T.;
Kawakami, Y. Chem. Commun. 2005, 1459–1461. (f) Hirano, K.; Yorimitsu,
H.; Oshima, K. Org. Lett. 2005, 7, 4689–4691.
(5) (a) Zheng, H.; Zhang, Q.; Chen, J.; Liu, M.; Cheng, S.; Ding, J.; Wu,
H.; Su, W. J. Org. Chem. 2009, 74, 943–945. (b) Tomita, D.; Kanai, M.;
Shibasaki, M. Chem. Asian J. 2006, 1, 161–166.
(6) Zou, T.; Pi, S.-S.; Li, J.-H. Org. Lett. 2009, 11, 453–456.
(7) Yamamoto, Y.; Kurihara, K.; Miyaura, N. Angew. Chem., Int. Ed.
2009, 48, 4414–4416.
(8) Jia, X.; Fang, L.; Lin, A.; Pan, Y.; Zhu, C. Synlett 2009, 495–499.
(9) Recent reviews of metalacycles: (a) Dupont, J.; Consorti, C. S.;
Spencer, J. Chem. Rev. 2005, 105, 2527–2572. (b) Beletskaya,I.P.;Cheprakov,
A. V. J. Organomet. Chem. 2004, 689, 4055–4082. (c) Bedford, R. B. Chem.
Commun. 2003, 1787–1796. (d) Newkome, G. R.; Puckett, W. E.; Gupta, V. K.;
Kiefer, G. E. Chem. Rev. 1986, 86, 451–489.
(10) (a) Liao, Y.-X; Xing, C.-H.; He, P.; Hu, Q.-S. Org. Lett. 2008, 10,
2509–2512. (b) He, P.; Lu, Y.; Dong, C.-G.; Hu, Q.-S. Org. Lett. 2007, 9, 343–
346. (c) He, P.; Lu, Y.; Hu, Q.-S. Tetrahedron Lett. 2007, 48, 5283–5288.
(11) (a) Yu, A.; Cheng, B.; Wu, Y.; Li, J.; Wei, K. Tetrahedron Lett. 2008,
49, 5405–5407. (b) Bedford, R. B.; Betham, M.; Charmant, J. P. H.; Haddow,
M. F. A.; Orpen, G.; Pilarski, L. T.; Coles, S. J.; Hursthouse, M. B.
Organometallics 2007, 26, 6346–6353. Also see: (c) Gibson, S.; Foster,
D. F.; Eastham, G. R.; Tooze, R. P.; Cole-Hamilton, D. J. Chem. Commun.
2001, 779–780.
(12) For recent general reviews on tandem reactions: (a) Tietze, L. F.;
Rackelmann, N. Pure Appl. Chem. 2004, 76, 1967–1983. (b) Nicolaou, K. C.;
Montagnon, T.; Snyder, S. A. Chem. Commun. 2003, 551–564. (c) Parsons,
P. J.; Penkett, C. S.; Shell, A. J. Chem. Rev. 1996, 96, 195–206. (d) Tietze, L. F.
Chem. Rev. 1996, 96, 115–136.
(13) Aryl ketones are common structural units for a number of natural
products. For examples, see: (a) Deng, Y.; Chin, Y.-W.; Chai, H.; Keller,
W. J.; Kinghorn, A. D. J. Nat. Prod. 2007, 70, 2049. (b) Pecchio, M.; Solis,
P. N.; Lopez-Perez, J. L.; Vasquez, Y.; Rodriguez, N.; Olmedo, D.; Correa,
M.; San Feliciano, A.; Gupta, M. P. J. Nat. Prod. 2006, 69, 410. (c) Zhang, C.;
Ondeyka, J. G.; Herath, K. B.; Guan, Z.; Collado, J.; Platas, G.; Pelaez, F.;
Leavitt, P. S.; Gurnett, A.; Nare, B.; Liberator, P.; Singh, S. B. J. Nat. Prod.
2005, 98, 611. (d) Iijima, D.; Tanaka, D.; Ogamino, T.; Ishikawa, Y.;
Nishiyama, S. Tetrahedron Lett. 2004, 45, 5469. (e) Katoh, T.; Ohmori, O.;
Iwasaki, K.; Inoue, M. Tetrahedron 2002, 58, 1289. (f) Storm, J. P.; Andersson,
C.-M. J. Org. Chem. 2000, 65, 5264.
Transition-metal-catalyzed addition reactions of organo-
boron reagents with aldehydes have emerged as useful tools
in organic synthesis.1-8 Several transition-metal catalysts
including Rh(I)/(II),1,2 Pd(II),3 Ni(0),4 Cu(II),5 and Fe(III)6
(1) For recent reviews on Rh(I)-catalyzed addition reactions of arylboro-
nic acids with carbonyl containing compounds: (a) Glorius, F. Angew.
Chem., Int. Ed. 2004, 43, 3364–3366. (b) Hayashi, T.; Yamasaki, K. Chem.
Rev. 2003, 103, 2829–2844. (c) Fagnou, K.; Lautens, M. Chem. Rev. 2003,
103, 169–196. and references cited therein.
(2) Selected examples of Rh-catalyzed 1,2-addition of arylboronic acids
with aldehydes: (a) Xing, C.-H.; Liu, T. ;-P.; Zheng, J. R.; Ng, J.; Eposito,
M.; Hu, Q.-S. Tetrahedron Lett. 2009, 50, 4953–4957. (b) Trindade, A. F.;
Gois, P. M. P.; Veiros, L. F.; Andre, V.; Duarte, M. T.; Afonso, C. A. M.;
Caddick, S.; Cloke, F. G. N. J. Org. Chem. 2008, 73, 4076–4086. (c) Tuerkmen,
H.; Denizalti, S.; Oezdemir, I.; Cetinkaya, E.; Cetinkaya, B. J. Organomet.
Chem. 2008, 693, 425–434. (d) Gois, P. M. P.; Trindade, A. F.; Veiros, L. F.;
Andre, V.; Duarte, M. T.; Afonso, C. A. M.; Caddick, S.; Cloke, F. G. N.
Angew. Chem., Int. Ed. 2007, 46, 5750–5753. (e) Arao, T.; Suzuki, K.; Kondo,
K.; Aoyama, T. Synthesis 2006, 3809–3814. (f) Suzuki, K.; Ishii, S.; Kondo, K.;
Aoyama, T. Synlett 2006, 648–650. (g) Duan, H. F.; Xie, J.-H.; Shi, W.-J.;
Zhang, Q.; Zhou, Q.-L. Org. Lett. 2006, 8, 1479–1481. (h) Jagt, R. B. C.;
Toullec, P. Y; de Vries, J. G.; Feringa, B. L; Minnaard, A. J. Org. Biomol.
Chem. 2006, 4, 773–775. (i) Chen, J.; Zhang, X.; Feng, Q.; Luo, M.
J. Organomet. Chem. 2006, 691, 470–474. (j) Son, S. U.; Kim, S. B.; Reingold,
J. A.; Carpenter, G. B.; Sweigart, D. A. J. Am. Chem. Soc. 2005, 127, 12238–
12239. (k) Huang, R.; Shaughnessy, K. H. Chem. Commun. 2005, 4484–4486.
(l) Imlinger, N.; Mayr, M.; Wang, D.; Wurst, K.; Buchmeiser, M. R. Adv.
Synth. Catal. 2004, 346, 1836–1843. (m) Moreau, C.; Hague, C.; Weller, A. S.;
Frost, C. G. TetrahedronLett. 2001, 42, 6957–6960. (n) Pourbaix, C.; Carreaux,
F.; Carboni, B. Org. Lett. 2001, 3, 803–805. (o) Batey, R. A.; Thadani, A. N.;
Smil, D. V. Org. Lett. 1999, 1, 1683–1686.
6986 J. Org. Chem. 2010, 75, 6986–6989
Published on Web 09/17/2010
DOI: 10.1021/jo101469s
r
2010 American Chemical Society

Liao and Hu
JOCNote
TABLE 1. Tandem Platinacycle 1-Catalyzed Reaction of p-Tolualdehyde
with p-Tolylboronic Acid Followed by Oxidation a
We began our study with the identification of a suitable
oxidant for the oxidation step for type I platinacycle 1-
catalyzed tandem reaction with p-tolualdehyde as the sub-
strate and p-tolylboronic acid as the nucleophile. Our results
are summarized in Table 1. We first used air as the oxidant
for the oxidation step. We found that although the addition
reaction proceeded smoothly to yield the alcohol under
air at 90-100 °C in 2 h, the oxidation of the alcohol to
ketone was very sluggish and only 3% of ketone was
observed (Table 1, entries 1 and 2). As acetone has been
well-established as an oxidant for secondary alcohol
oxidation,14a,b we seek to use it as the oxidant. We found
indeed more ketone product (49%) was formed, which was
promising (Table 1, entry 3). However, one drawback of
using acetone as the oxidant was that the aldol condensation
between p-tolualdehyde and acetone under the reaction
conditions occurred significantly. Because the aldol conden-
sation is known to be sensitive to steric hindrance, we
reasoned that increasing the steric hindrance of the ketone
oxidants might overcome this side reaction issue. We thus
tested 2-butanone and 3-pentanone as the oxidants. We
found although the aldol condensation can still be observed
for 2-butanone (Table 1, entry 4), 3-pentanone was an
excellent oxidant, with almost no aldol condensation be-
tween aldehyde and 3-pentanone being observed (Table 1,
entry 5). By using 3-pentanone as the oxidant, we then tested
other bases for the reaction, and found K3PO4 was the most
effective base (Table 1, entries 5-7). Higher yields were
observed for the ketone formation with the use of larger
amounts of K3PO4, and the best results were obtained by
using 3 equiv of K3PO4 (Table 1, entries 5 and 8-10). We
further found that the oxidation step was influenced by the
reaction temperature and time. Lowering the temperature
from 90 to 80 °C led to a decreasing yield of ketone (Table 1,
entry 11). Lengthening the reaction time led to more ketone
formation (Table 1, entry 12).
With 3-pentanone as the oxidant and K3PO4 as the base,
we tested other aldehydes and arylboronic acids for this
platinacycle 1-catalyzed tandem ketone formation, and our
results are listed in Table 2. As shown in Table 2, good yields
were obtained for aromatic aldehydes bearing electron-
donating or electron-withdrawing substituents (Table 2, en-
try 1-17). Impressively, we found that aliphatic aldehydes
were suitable substrates for the tandem reactions, and alkyl
aryl ketones were obtained in good yields (Table 2, entry
18-21). It should be mentioned that, to our knowledge, these
represent the first examples of direct access to aryl alkyl
ketones from alkyl aldehydes with arylboronic acids via the
tandem addition-oxidation reaction. We also found phe-
nylboronic acids bearing a CH3 or CH3O group were better
reagents than F-containing phenylboronic acid as a lower
yield was observed with 4-fluorophenylboronic acid as the
reagent (Table 2, entry 22). Since platinacycle 1 could
catalyze the addition reaction of arylboronic acids with
aldehydes with the catalyst loading of 0.05%,10a we also
tested the tandem reaction at lower catalyst loadings. We
found that reducing the catalyst loading influenced the
oxidation step. By extending the reaction time to 18 h, the
catalyst loading could be reduced to 0.2% with good isolated
yield (Table 2, entry 23). Further lowering the catalyst
loading led to a very slow formation of ketone (Table 2,
entry 24).
entry
oxidant (mL)
none
air
base (equiv)
convb (%)
A/Bb
1
2
3
4
5
6
7
8
9
K3PO4 (3)
K3PO4 (3)
K3PO4 (3)
K3PO4 (3)
K3PO4 (3)
K2CO3 (3)
Cs2CO3 (3)
K3PO4 (2)
K3PO4 (1)
K3PO4 (0)
K3PO4 (3)
K3PO4 (3)
100
100
100
100
100
86
15
78
67
0
100/0
97/3
acetone (0.2)
51/49 c
80/20 d
50/50
42/58
0/100
95/5
2-butanone (0.2)
3-pentanone (0.2)
3-pentanone (0.2)
3-pentanone (0.2)
3-pentanone (0.2)
3-pentanone (0.2)
3-pentanone (0.2)
3-pentanone (0.2)
3-pentanone (0.2)
97/3
10
11
12
100
100
65/35e
15/85 f
aReaction conditions: aldehyde (1.0 eqiuv), p-tolylboronic acid (2.0
equiv), toluene and oxidant (1 mL), base, 90-100 °C. bRatio based on
GC-MS. c43% of aldol condensation product from aldehyde with
acetone was observed. d13% of aldol condensation product from
aldehyde with acetone was observed. eReaction temperature: 80 °C.
fReaction time: 7 h.
available, air-stable type I metalacycles as addition catalysts
for organic synthesis, we became interested in combining
type I metalacycle-catalyzed addition reactions with other
bond-forming reactions in a sequential or tandem fashion. In
particular, we’re interested in combining such addition reactions
with the secondary alcohol oxidation process to access aryl
ketones.12,13 Two groups have recently studied such additions
followed by an oxidation reaction sequence.14,15 Genet and
Darses reported the preparation of diaryl ketones from Rh(I)-
catalyzed addition of aldehydes with potassium trifluoro-
(organo)borates14a,b or arylboronic acids14c followed by an
oxidation reaction. Wu reported a one-pot synthesis of diaryl
ketones via palladium-catalyzed reaction with arylboronic acids
with aldehydes, in which 2 equiv of aldehydes was required.15
While these protocols are useful for diaryl ketone synthesis,
there are drawbacks associated with them, e.g., high catalyst
loading, requirement of 2 equiv of aldehydes, and/or limited
substrate scope. Based on the consideration that low catalyst
loading such as 0.05% have been achieved for type I platina-
cycle-catalyzed addition reaction of arylboronic acids with
aldehydes,10a we reasoned that if a suitable oxidant for the
oxidation step could be identified, a highly efficient ketone
synthesis protocol could be developed. Herein, we report our
results on such tandem type I platinacycle-catalyzed addition of
arylboronic acids with aldehydes followed by oxidation for the
synthesis of aryl ketones. In addition, we also report a micro-
wave-assisted aryl ketone synthesis with shortened reaction time
and low catalyst loading.
(14) (a) Chuzel, O.; Alexander Roesch, A.; Jean-Pierre Genet, J.-P.;
Darses, S. J. Org. Chem. 2008, 73, 7800–7802. (b) Mora, G.; Darses, S.;
Genet, J.-P. Adv. Synth. Catal. 2007, 349, 1180–1184. (c) Pucheault, M.;
Darses, S.; Genet, J.-P. J. Am. Chem. Soc. 2004, 126, 15356–15357. Also see:
(d) Imlinger, N.; Wurst, K.; Buchmeiser, M. R. J. Organomet. Chem. 2005,
690, 4433–4440.
(15) Qin, C.; Chen, J.; Wu, H.; Cheng, J.; Zhang, Q.; Zuo, B.; Su, W.;
Ding, J. Tetrahedron Lett. 2008, 49, 1884–1888.
J. Org. Chem. Vol. 75, No. 20, 2010 6987

Liao and Hu
JOCNote
TABLE 2. Orthoplatinated Triaryl Phosphite 1-Catalyzed Formation
of Diaryl Ketones from Aldehydes and Arylboronic Acidsa
TABLE 3. Microwave-Assisted, Platinacycle 1-Catalyzed Addition
Reactions of Arylboronic Acids with Aldehydes a
ratio of
C/D/Ec
entry
T (°C), time (min.)
additive
convb (%)
1
2
3
4
5
6
7
8
9
90, 30
100, 30
120, 30
140, 30
90, 60
160, 60
90, 30; 160, 30
90, 30; 160, 30
90, 30; 160, 30
96
97
97
99
99
99
100
100
100
96:4:0
94:5:1
85:9:6
74:16:10
69:27:0d
24:65:0e
11:84:0f
10:86:0g
14:85:0h
acetone
acetone
acetone
2-butanone
3-pentanone
aReaction conditions: aldehydes (1.0 equiv), arylboronic acids
(2.0 equiv), 4 (0.05%), toluene (1 mL), K3PO4 (3.0 equiv), microwave
(100 °C, 45 min, 160 °C, 45 min). bBased on 1HNMR. cBased on
d
e
GC-MS analysis. 4% of 4-phenyl-3-buten-2-one was oberved. 10%
of 4-phenyl-3-buten-2-one was oberved. f5% of 4-phenyl-3-buten-2-one
was oberved. g4% of 1-phenyl-1-penten-3-one was oberved. h1% of
2-methyl-1-phenyl-1-penten-3-one was oberved.
temperatures for reactions under microwave irradiation
could be much higher than that of reactions being heated
by conventional methods such as heating in oil bath.16,17 We
surmised that due to the temperature difference between
microwave-assisted reactions and reactions being heated by
conventional methods, carrying out such tandem addition-
oxidation reactions under microwave irradiation might need
lower catalyst loading and require shorter reaction time
compared to the same reaction being heated under conven-
tional heating methods. We first tested microwave-assisted
platinacycle 1-catalyzed reaction of benzaldehyde with
p-methoxyphenylboronic acid with 0.05% catalyst loading.
We found without additionally added oxidants such as
acetone, benzaldehyde served as the oxidant for the ketone
formation and low yields of the ketone product were ob-
served (Table 3, entries 1-4). Significantly, the addition
reactions were observed to be completed in 30 min, which
was much shorter than the time required for this addition
reaction being heated under oil-bath heating.10a We next
tested the use of acetone as the oxidant for the reaction. We
found while the addition reaction occurred smoothly at
90 °C, only 27% of ketone was observed (Table 3, entry 5),
suggesting that a higher reaction temperature and/or longer
reaction time would be needed to achieve higher yields of
ketones. We thus tested the reaction at 160 °C. We found that
although the amount of the ketone was increased, 10% of the
aldol condensation product of acetone with aldehyde was
observed (Table 3, entry 6). We next conducted the tandem
reaction with ramped temperatures: 90 °C for 30 min for the
addition reaction and 160 °C for 45 min for the oxidation
reaction. We found less aldol condensation byproduct was
formed (Table 3, entry 7). We also tested the use of 2-buta-
none and 3-pentanone as oxidants with such a gradient
temperature setting and found 3-pentanone gave the best
result (Table 3, entries 7-9).
aReaction conditions: aldehydes (1.0 equiv), arylboronic acid (2.0
equiv), 1% platinacycle 1, 3-pentanone/toluene (1:4, 1 mL), K3PO4 (3.0
equiv), 90-100 °C. bIsolated yields. c1.5 equiv of ArB(OH)2 was used.
d88% conversion was observed for the oxidation step. eThe aldol
condensation product of acetone with p-chlorobenzaldehyde was the
major product. fCatalyst loading: 0.2%. Reaction time: 18 h. gCatalyst
loading: 0.1%. Reaction time: 24 h. 49% of (p-methoxyphenyl)-
phenylmethanol was observed.
To further decrease the catalyst loading, we turned our
attention to use microwave energy for the tandem reaction as
(16) (a) Kappe, C. O.; Dallinger, D.; Murphree, S. S. Practical Microwave
Synthesis for Organic Chemists: Strategies, Instruments and Protocols; Wiley-
VCH: Weinheim, 2009. (b) Larhed, M., Olofsson, K., Eds. Microwave
Methods in Organic Synthesis. Springer: Berlin, 2006. (c) Microwaves in
Organic Synthesis, 2nd ed.; Loupy, A., Ed.; Wiley-VCH: Weinheim, 2006.
(d) Kappe, C. O.; Stadler, A. Microwaves in Organic and Medicinal Chem-
istry; Wiley-VCH: Weinheim, 2005. (e) Lidstrom, P., Tierney, J. P., Eds.
Microwave-Assisted Organic Synthesis; Blackwell Publishing: Oxford, 2005.
(17) (a) Polshettiwar, V.; Varma, R. S. Acc. Chem. Res. 2008, 41, 629–639.
(b) Dallinger, D.; Kappe, C. O. Chem. Rev. 2007, 107, 2563–2591.
(c) Roberts, B. A.; Strauss, C. R. Acc. Chem. Res. 2005, 38, 653–661.
6988 J. Org. Chem. Vol. 75, No. 20, 2010

Liao and Hu
JOCNote
TABLE 4. Microwave-Assisted, Platinacycle 1-Catalyzed Reactions of
Arylboronic Acids with Aldehydes for Ketone Synthesis a
tandem addition-oxidation protocols for the synthesis of aryl
ketones competes favorably with these reported methods.
In summary, we have demonstrated that type I platinacycle 1-
catalyzed addition reactions of arylboronic acids with aldehydes
can be combined with the oxidation of alcohol process in
tandem fashion to access aryl ketones. 3-Pentanone was identi-
fied as a suitable oxidant for the oxidation of alcohol step.
By using microwave energy, platinacycle 1-catalyzed addition
followed by oxidation could be realized with low catalyst
loading, as low as 0.01%. Our study provides an efficient
method to synthesize aryl ketones. Our future work will be
directed to explore other tandem/sequential reactions involving
the addition reaction of arylboronic acids with aldehydes as part
of the reaction sequence.
Experimental Section
Typical Procedure for Platinacycle 1-Catalyzed Reactions of
Arylboronic Acids with Aldehydes for Ketone Synthesis. To a vial
containing 2-methoxybenzaldehyde (0.25 mmol), 4-methoxy-
phenylboronic acid (0.50 mmol), K3PO4 (0.75 mmol), and 1
(1 mol %) were added toluene (0.80 mL) and 3-pentanone
(0.20 mL). After the mixture was stirred at 90-100 °C for
4-10 h, the reaction was extracted by CH2Cl2. Column chro-
matography on silica gel with ethyl acetate/hexane (v/v = 1:10)
afforded the ketone product 2-methoxyphenyl 4-methoxyphe-
nyl ketone: 1H NMR (CDCl3, 600 MHz) δ 7.81 (d, J = 7.2 Hz,
2H), 7.44 (t, J = 7.8 Hz, 1H), 7.32 (d, J = 7.8 Hz, 1H), 7.03 (t,
J = 7.2 Hz, 1H), 6.99 (d, J = 7.8 Hz, 1H), 3.86 (s, 3H), 3.74 (s,
3H); 13C NMR (CDCl3, 150 MHz) δ 195.0, 163.5, 157.0, 132.3,
131.4, 130.7, 129.3, 129.2, 120.4, 113.4, 111.3, 55.6, 55.4.
Typical Procedure for Microwave-Assisted Platinacycle 1-
Catalyzed Reactions of Arylboronic Acids with Aldehydes for
Ketone Synthesis. To a 10-mL pressure vial containing 4-methoxy-
benzaldehyde (0.50 mmol), 4-methoxyphenylboronic acid
(1.0 mmol), K3PO4 (0.50 mmol), and platinacycle 1 (0.05 mol %)
were added toluene (1.6 mL) and 3-pentanone (0.4 mL). After the
mixture was irradiated by microwave at 100 °C for 45 min and then
irradiated at 160 °C for another 45 min, the reaction was quenched
by adding a small amount of water. Extraction with CH2Cl2 and
column chromatography on silica gel with ethyl acetate/hexane
(v/v = 1:10) afforded the product, bis(4-methoxyphenyl) ketone:
1H NMR (CDCl3, 600 MHz) δ 7.78 (4H, d, J = 7.2 Hz), 6.96 (4H,
d, J =7.2 Hz), 3.88 (3H, s);13C NMR (CDCl3, 150 MHz): δ194.4,
162.8, 132.2, 130.7, 113.4, 55.4.
aReaction conditions: aldehydes (1.0 equiv), arylboronic acids
(2.0 equiv), 1 (0.01-0.05%), toluene/3-pentanone (4/1,1 mL), K3PO4
(1.0 equiv), microwave (100 °C, 45 min; 160 °C, 45 min). bIsolated yields.
c1.5 equiv of ArB(OH)2 was used. d7% of aldol condensation product of
3-pentanone with benzaldehyde was observed. e50% of aldol condensa-
tion product of 3-pentanone with p-chlorobenzaldehyde was observed.
fMicrowave (100 °C, 60 min; 160 °C, 60 min).
With 0.05% catalyst loading of platinacycle 1 and 3-pen-
tanone as the oxidant, we examined other arylboronic acids
and aldehydes. Good to high yields were observed for all
arylboronic acids/aldehydes tested (Table 4, entries 1-10)
except for 4-fluorophenylboronic acid (Table 4, entry 11).
We further attempted to lower the catalyst loading and found
with even 0.01% catalyst loading the tandem reaction still
occurred efficiently (Table 4, entries 9-13). Compared to the
reported ketone preparation via tandem Rh(I)- and Pd(II)-
catalyzed addition reactions followed by oxidation,14,15 which
required high catalyst loading, limited substrate scope, and/or
extra equivalent of aldehydes, our platinacycle 1-catalyzed
Acknowledgment. We gratefully thank the NSF (CHE-
0719311) and NIH (1R15 GM094709) for funding. Partial
support from the PSC-CUNY Research Award Program is
also gratefully acknowledged. We thank Frontier Scientific,
Inc. for its generous gifts of arylboronic acids.
Supporting Information Available: General procedures and
characterizations of tandem platinacycle-catalyzed addition
followed by oxidation reactions. This material is available free
of charge via the Internet at http://pubs.acs.org.
J. Org. Chem. Vol. 75, No. 20, 2010 6989