Chemistry Letters Vol.32, No.10 (2003)
899
ester 2a in low yield (11%) with recovery of 1a (82%).
CO
Organic phase
Finally, we investigated the radical carbonylation of 1-io-
dooctane (1c) in an ethanol/water system in the absence of
any surfactants (Eq 1), since it was reported that radical-medi-
ated, reductive cyclization of organic halides with phosphinic
acid proceeded well in this mixed solvent.4,6 It was unexpected-
ly found that ꢀ-keto carboxylic acid 4c was formed via double
carbonylation along with the formation of singly carbonylated
product 3c. Although the yield was still low and the precise
mechanism is unclear, this is, to the best of our knowledge,
the first observation of radical-mediated double carbonylation.8
Stabilization of radical intermediates by the highly polar solvent
system might give rise to this unprecedented reaction. Further
optimization of the reaction conditions as well as theoretical
and mechanistic studies of this novel double carbonylation are
now under investigation.
O
O
P
O
P
AIBN
RI
R
–
–
R
H
O
∆
O
H
H
O
RI
I
1
P
H
–
O
I
O
O
O
RI
–
–
OH
R
OR
R
R
R
O
2
CTAB
CTAB
CTAB
O
P
O
P
O
–
O
P
OH
–
–
–
–
O
–
H
O
I
O
O
O
H
3
H
H
Aqueous phase
Figure 1.
iodine atom transfer from the alkyl iodide.2 The acid iodide
readily hydrolyzes to a carboxylate that can provide a carboxyl-
ic acid or an ester via attack to the alkyl iodide. This mechanism
explains our observation shown in Table 2 that alkyl iodides
with less hydrophobic or bulkier alkyl groups tend to give acids
rather than esters. High hydrophobicity of carboxylates would
suppress their transfer to the aqueous phase leading to esters,
while the bulkiness of alkyl iodides would prevent the attack
by carboxylates.
According to the proposed mechanism, phosphinic acid and
AIBN act as radical initiators, meaning that both may be re-
duced to catalytic amounts in principle. Thus, further optimiza-
tion of the reaction conditions was pursued using iodocyclohex-
ane (1e) as a substrate (Table 3). Indeed, reduction of the
amounts of phosphinic acid, NaHCO3, and AIBN was attained
(Entries 1–4), and acid 3e was obtained in high yield (82%) un-
der the conditions shown in Entry 4. Control experiments with-
out using phosphinic acid (Entry 5) or AIBN (Entry 6) clearly
showed that the combination of both reagents was essential
for the radical initiation. On the other hand, reduction of the
amount of CTAB or CO pressure resulted in significant de-
crease of the yield of 3e (Entries 7 and 8). Carbonylation of
1-iododecane (1a) under the optimized conditions for 1e gave
AIBN (0.3 equiv.)
H3PO2 (5 equiv.)
O
NaHCO3 (7 equiv.)
OH
+
+
n-C8H17
(1)
1c CO
(50 atm)
3c
16%
EtOH/H2O (2/1)
75 °C, 15 h
4c
13%
O
In summary, we have demonstrated the first example of rad-
ical carbonylation of alkyl iodides in aqueous media. Single car-
bonylation of alkyl iodides was found to proceed smoothly us-
ing phosphinic acid as a radical initiator in the presence of a
surfactant in water as the sole solvent. Furthermore, radical-
mediated double carbonylation was observed for the first time
by performing the reactions in an ethanol/water system. It
should be noted that these novel results have been obtained
not in standard organic solvents but in aqueous media.
This work was partially supported by CREST and SORT,
Japan Science Technology Coporation (JST) and a Grant-in-
Aid for Scientific Research from Japan Society of the Promo-
tion of Science.
References and Notes
1
For organotin-mediated radical carbonylation, see: a) Review: I. Ryu
and N. Sonoda, Angew. Chem., Ind. Ed. Engl., 35, 1050 (1996).
b) I. Ryu, K. Kusano, A. Ogawa, N. Kambe, and N. Sonoda, J. Am.
Chem. Soc., 112, 1295 (1990).
Table 3. Further optimization of carbonylation of 1e
2
For radical carbonylation via iodine atom transfer initiated by irradi-
ation or tin or silyl radicals, see: a) Review: I. Ryu, Chem. Soc. Rev.,
30, 16 (2001). b) K. Nagahara, I. Ryu, M. Komatsu, and N. Sonoda, J.
Am. Chem. Soc., 119, 5465 (1997). c) I. Ryu, K. Nagahara, N. Kambe,
N. Sonoda, S. Kreimerman, and M. Komatsu, Chem. Commun., 1998,
1953.
O
Reagents
I
+
CO
(50 atm)
OH
H2O
75 ˚C, 15 h
1e
3e
3
4
5
6
‘‘Organic Synthesis in Water,’’ ed. by P. Grieco, Blackie Academic
Press, London (1998).
Reagents/equiv.
Yield/%a
Rec.
A recent review on radical reactions in aqueous media, see: H.
Yorimitsu, H. Shinokubo, and K. Oshima, Synlett, 2002, 674.
A review on chemistry of acyl radicals, see: C. Chatgilialoglu, D.
Crich, M. Komatsu, and I. Ryu, Chem. Rev., 99, 1991 (1999).
Phosphinic acid was first utilized in water by Jang for radical-mediat-
ed reduction of organic halides and later by Oshima, et al. in aqueous
ethanol, see: a) D. O. Jang, Tetrahedron Lett., 37, 5367 (1996).
b) H. Yorimitsu, H. Shinokubo, and K. Oshima, Chem. Lett., 2000,
104. c) H. Yorimitsu, H. Shinokubo, and K. Oshima, Bull. Chem.
Soc. Jpn., 74, 104 (2001). See also Ref. 4.
Use of surfactants in radical reactions: H. Nambu, G. Anilkumar, M.
Matsugi, and Y. Kita, Tetrahedron, 59, 77 (2003) and references cited
therein.
The addition of an acyl radical to CO has been considered to be most
difficult, see: I. Ryu, H. Kuriyama, S. Minakata, M. Komatsu, J.-Y.
Yoon, and S. Kim, J. Am. Chem. Soc., 121, 12190 (1999).
Entry
H3PO2 NaHCO3 AIBN CTAB 3e
1ed
1b
2
3
4
5
6
7
8c
5
1
7
3
0.3
0.3
0.3
0.1
0.1
—
0.2
0.2
0.2
0.2
0.2
0.2
0.1
0.2
70
63
76
82
0
0
0
0
0.5
0.5
—
0.5
0.5
0.5
2.5
2.5
2.5
2.5
2.5
2.5
0
59
26
39
20
0
7
8
0.1
0.1
30
59
1
aYields were determined by H NMR analysis using naphtha-
lene as an internal standard. bSee Table 2, Entry 5. cUnder
CO (30 atm). Recovered starting material.
d
Published on the web (Advance View) September 1, 2003; DOI 10.1246/cl.2003.898