A R T I C L E S
Zhao et al.
Scheme 2. Oxidative Coupling toward Bond Formation
Table 1. Oxidative Carbonylation of Trialkyl-In Reagent without
ꢀ-Hydrogena
entry
1
ROH
2 (yield [%])
Ryu et al. have developed an atom transfer carbonylation
method,26–29 in which alkyl iodide was converted to acyl iodide
via a radical mechanism to achieve the carbonylations in the
presence of palladium catalyst under irradiation.30,31
1
2
3
4
1a n ) 1
1b n ) 2
1c n ) 3
1c
1c
1c
MeOH
MeOH
MeOH
EtOH
n-BuOH
t-BuOH
2a
2a
2a
2b
2c
2d
43
46
99
95
98
trace
5
6b
One of our research interests lies in coupling two nucleophiles
together in the presence of a proper catalyst and a co-oxidant
(oxidative coupling, Scheme 2, eq 1). We have recently reported
the Pd-mediated oxidative cross-coupling of Csp–Sn and
Csp3–Zn using desyl chloride (2-chloro-1,2-diphenylethone) as
the oxidant (Scheme 2, eq 2).32 Inspired by the above work,
we designed a novel type of carbonylation reaction conceptually
involving the following key steps: (1) formation of intermediate
XPd(II)CONu through the reaction of CO and a nucleophile
with Pd(II)-species generated from an oxidant and Pd(0)-species;
(2) transmetalation of Ralkyl–M to the Pd-intermediate to afford
the key intermediate Ralkyl–Pd(II)CONu, which could avoid the
difficult oxidative addition of alkyl halide over Pd(0) species;
and (3) reductive elimination to provide the final product
a The reactions were conducted with 0.5 mmol of desyl chloride, 0.6
mmol of 1, and 3 mol % PdCl2(dppf) with respect to desyl chloride in
ROH at 60 °C, with a balloon pressure of CO gas. The yield was
determined by GC. b 2e was obtained as the major product in 58%
isolated yield. 2e: 2,6-dimethyl-2,6-diphenylheptan-4-one.
carbonylations of a broad spectrum of organoindium reagents
with CO gas under very mild conditions.
Result and Discussion
Oxidative Carbonylation of Alkyl Indium Reagents. We first
set out to seek the appropriate oxidant and alkyl organometallic
species Ralkyl–M. Our previous work demonstrated that desyl
chloride efficiently promoted Pd-catalyzed Csp–Csp3 oxidative
cross-coupling reactions;32 we therefore surmised it to be a
promising candidate here. Carbonylations are usually carried
out in protic solvents, such as MeOH and EtOH. Thus, a
reasonable Ralkyl–M should exhibit a high level of tolerance
toward these protic reaction media. Organoindium reagents
(R3In, R ) alkyl, alkenyl, alkynyl, aryl), which recently have
attracted much attention for their versatile chemistry and stability
in aqueous/protic conditions,38–48 emerge as a possible Ralkyl–M
precursor. Thus, we decided to focus on investigating the
feasibility of oxidative carbonylations of organoindiums with
CO gas using desyl chloride as oxidant.
RalkylCONu with concomitant releasing of the reduced pal-
ladium(0)-species. CO is known to be good π-acceptor ligand,
so the final reductive elimination should be fast and the
competitive ꢀ-hydride elimination could possibly be suppressed.
Apparently, to realize the proposal, several practical issues
must be finely addressed. These primarily include the identifica-
tion of a catalytic system that would strongly promote the
formation of the desired intermediate Ralkyl–Pd(II)–CONu while
at the same time effectively suppressing the competing reaction
channels involving homosubstituted Ralkyl–Pd(II)–Ralkyl and
RalkylCOPd(II)–Ralkyl; and the selection of a suitable oxidant that
could promptly convert Pd(0) back to Pd(II) for further
transmetalation and render the entire process catalytic,33–37 and
that would not interfere with the reactivity of all other steps in
the catalytic cycle. Described herein is our recent discovery of
such a system that is capable of catalyzing the oxidative
The initial screening experiments employed 2-methyl-2-
phenylpropylindium(III) chloride 1a (Table 1, n ) 1), which
was readily generated from the corresponding Grignard reagent
and InCl3. The indium reagent in alcoholic solvent was mixed
with desyl chloride and then allowed to react with balloon
pressure of CO gas in the presence of a catalytic amount (3
mol %) of PdCl2(dppf). Under this condition, low conversion
of desyl chloride was observed, and the desired product was
detected only in 43% yield. Employment of a dialkyl indium
(23) Hashem, K. E.; Woell, J. B.; Alper, H. Tetrahedron Lett. 1984, 25,
4879–4880.
(24) Heck, R. F.; Breslow, D. S. J. Am. Chem. Soc. 1963, 85, 2779–2782.
(25) Zhou, H.; Lu, S.; Li, H.; Chen, J.; Fu, H.; Wang, H. J. Mol. Catal. A:
Chem. 1997, 116, 329–333.
(26) Ryu, I. Chem. Soc. ReV. 2001, 30, 16–25.
(27) Chatgilialoglu, C.; Crich, D.; Komatsu, M.; Ryu, I. Chem. ReV. 1999,
99, 1991–2069.
(38) Pena, M. A.; Sestelo, J. P.; Sarandeses, L. A. J. Org. Chem. 2007,
72, 1271–1275.
(39) Xue, Z.; Yang, D.; Wang, C. J. Organomet. Chem. 2006, 691, 247–
250.
(28) Ryu, I.; Sonoda, N.; Curran, D. P. Chem. ReV. 1996, 96, 177–194.
(29) Ryu, I.; Sonoda, N. Angew. Chem., Int. Ed. Engl. 1996, 35, 1051–
1066.
(40) Riveiros, R.; Rodriguez, D.; Perez Sestelo, J.; Sarandeses Luis, A.
Org. Lett. 2006, 8, 1403–1406.
(30) Fukuyama, T.; Inouye, T.; Ryu, I. J. Organomet. Chem. 2007, 692,
685–690.
(41) Croix, C.; Balland-Longeau, A.; Duchene, A.; Thibonnet, J. Synth.
Commun. 2006, 36, 3261–3270.
(31) Fukuyama, T.; Nishitani, S.; Inouye, T.; Morimoto, K.; Ryu, I. Org.
Lett. 2006, 8, 1383–1386.
(42) Pena, M. A.; Sestelo, J. P.; Sarandeses, L. A. Synthesis 2005, 485–
492.
(32) Zhao, Y.; Wang, H.; Hou, X.; Hu, Y.; Lei, A.; Zhang, H.; Zhu, L.
J. Am. Chem. Soc. 2006, 128, 15048–15049.
(43) Takami, K.; Mikami, S.; Yorimitsu, H.; Shinokubo, H.; Oshima, K.
J. Org. Chem. 2003, 68, 6627–6631.
(33) Peng, X.; Li, F.; Xia, C. Synlett 2006, 1161–1164.
(34) Pri-Bar, I.; Schwartz, J. J. Org. Chem. 1995, 60, 8124–8125.
(35) Gabriele, B.; Salerno, G.; Mancuso, R.; Costa, M. J. Org. Chem. 2004,
69, 4741–4750.
(44) Lee Phil, H.; Lee Sung, W.; Lee, K. Org. Lett. 2003, 5, 1103–1106.
(45) Perez, I.; Sestelo, J. P.; Sarandeses, L. A. J. Am. Chem. Soc. 2001,
123, 4155–4160.
(46) Lee, P. H.; Sung, S.; Lee, K. Org. Lett. 2001, 3, 3201–3204.
(47) Perez, I.; Perez Sestelo, J.; Sarandeses, L. A. Org. Lett. 1999, 1, 1267–
1269.
(36) Gabriele, B.; Mancuso, R.; Salerno, G.; Costa, M. Chem. Commun.
2003, 486–487.
(37) Kelkar, A. A.; Kolhe, D. S.; Kanagasabapathy, S.; Chaudhari, R. V.
Ind. Eng. Chem. Res. 1992, 31, 172–176.
(48) Perez, I.; Perez Sestelo, J.; Maestro, M. A.; Mourino, A.; Sarandeses,
L. A. J. Org. Chem. 1998, 63, 10074–10076.
9
9430 J. AM. CHEM. SOC. VOL. 130, NO. 29, 2008