nucleophiles such as the thioester 4f (entry 6) and the
oxazolidinone 16 reported in eq 4. However, this procedure
is not suitable for the hydroxylation of R-bromocarboxylic
acid derivatives; see the discussion of the mechanism (vide
infra) for an explanation.
Table 1. Radical Hydroxylation of Iodides 4 According to Eq
2.
Two possible mechanisms for the transformation are
depicted in Figure 1. Reaction of triethylborane with oxygen
gives ethyl radicals, which abstract the iodine atom8 from
the radical precursor 4 to furnish an enolate radical 6.
Reaction of this radical with oxygen gives the peroxyl radical
7. In the first mechanism (A), 7 reacts with Et3B to furnish
8 and to propagate the chain by formation of an ethyl radical.
The peroxyborane 8 is reduced with the second equivalent
(3) For conversion of halides to alcohols with oxygen in the presence of
tin derivatives, see: Nakamura, E.; Inubishi, T.; Aoki, S.; Machii, D. J.
Am. Chem. Soc. 1991, 113, 8980-8982. Nakamura, E.; Imanishi, Y.;
Machii, D. J. Org. Chem. 1994, 59, 8178-8186. Nakamura, E.; Sato, K.;
Imanishi, Y. Synlett 1995, 525-526. Sawamura, M.; Kawaguchi, Y.; Sato,
K.; Nakamura, E. Chem. Lett. 1997, 705-706. Moutel, S.; Prandi, J.
Tetrahedron Lett. 1994, 35, 8163-8166. Mayer, S.; Prandi, J. Tetrahedron
Lett. 1996, 37, 3117-3120. Takahashi, T.; Tomida, S.; Doi, T. Synlett 1999,
644-646. Yoshida, M.; Ohkoshi, M.; Aoki, N.; Ohnuma, Y.; Iyoda, M.
Tetrahedron Lett. 1999, 40, 5731-5734. Kittaka, A.; Tsubaki, Y.; Tanaka,
H.; Nakamura, K. T.; Miyasaka, T. Nucleosides Nucleotides 1996, 15, 97-
107. A related process with tetraphenyldistibine: Barrett, G. M.; Melcher,
L. M. J. Am. Chem. Soc. 1991, 113, 8177-8178. Organocobalt compounds
react with oxygen via a radical mechanism: Okamoto, T.; Oka, S. J. Org.
Chem. 1984, 49, 1589-1594. Bhandal, H.; Pattenden, G.; Russell, J. J.
Tetrahedron Lett. 1986, 27, 2299-2302. Patel, V. F.; Pattenden, G.
Tetrahedron Lett. 1987, 28, 1451-1454. Patel, V. F.; Pattenden, G. J. Chem.
Soc., Perkin Trans. 1 1990, 2703-2708. Mayer, S.; Prandi, J.; Bamhaoud,
T.; Bakkas, S.; Guillou, O. Tetrahedron 1998, 54, 8753-8770. Punniya-
murthy, T.; Bhatia, B.; Iqbal, J. J. Org. Chem. 1994, 59, 850-853.
Alkylmercuric halides react with oxygen in the presence of NaBH4: Hill,
C.; Whitesides, G. M. J. Am. Chem. Soc. 1974, 96, 870-876. For reactions
of radicals with oxygen under oxidative conditions, see: Yoshida, J.;
Nakatani, S.; Sakaguchi, K.; Isoe, S. J. Org. Chem. 1989, 54, 3383-3389.
Colombo, M. I.; Signorella, S.; Mischne, M. P.; Gonzales-Sierra, M.;
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H.; Kurosawa, K. Heterocycles 1998, 48, 465-480. Ohshima, T.; Sodeoka,
M.; Shibasaki, M. Tetrahedron Lett. 1993, 34, 8509-8512. Cossy, J.;
Belotti, D.; Bellosta, V.; Brocca, D. Tetrahedron Lett. 1994, 35, 6089-
6092. Nair, V.; Nair, L. G.; Mathew, J. Tetrahedron Lett. 1998, 39, 2801-
2804. Boto, A.; Freire, R.; Hernandez, R.; Suarez, E.; Rodriguez, M. S. J.
Org. Chem. 1997, 62, 2975-2981. Reaction of radicals with oxygen is a
key step in lipid autoxidation; for a review, see: Porter, N. A. Acc. Chem.
Res. 1986, 19, 262-268. For related synthetic applications, see: Beckwith,
A. L. J.; Wagner, R. D. J. Chem. Soc., Chem. Commun. 1980, 485-486.
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124. For miscellaneous reactions of radicals with oxygen, see: Fukunishi,
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6756.
a
General procedure: The iodide (0.5 mmol) was placed in two-necked
flask under an oxygen atmosphere. After introduction of CH2Cl2 (0.5 mL),
the solution was cooled at -50 °C, and a 1 M solution of Et3B in 1,2-
dichloroethane (1 mL, 1 mmol) was added over 5 h using a syringe pump.
The needle used for the addtion of Et3B was placed into the reaction mixture
to avoid oxidation of Et3B before the reaction took place. At the end of the
addition, MeOH (0.5 mL) was added followed by Me2S (0.2 mL). After
being stirred for 15 min, the solution was filtered through silica gel (Et2O).
The filtrate was concentrated, and the crude alcohol was purified by flash
b
chromatography. 1:1 mixture of diastereomers
(eq 2). Different R-iodo acid derivatives were investigated
and results are summarized in Table 1.
(4) Reaction of alkyl radicals with aminoxyl radicals such as TEMPO
represents also an indirect way of radical oxygenation: Ollivier, C.; Chuard,
R.; Renaud, P. Synlett 1999, 807-809 and references therein.
(5) The rate constant for the reaction of radicals with oxygen have been
measured. In all systems investigated, this rate is bigger than 109 M-1 s-1
:
Maillard, B.; Ingold, K. U.; Scaiano, J. C. J. Am. Chem. Soc. 1983, 105,
5095-5099.
(6) Brown, H. C.; Midland, M. M. Angew. Chem., Int. Ed. Engl. 1972,
11, 692-700. Nozaki, K.; Oshima, K.; Utimoto, K. J. Am. Chem. Soc. 1987,
109, 2547-2549.
(7) Guindon has observed a similar Et3B-oxygen-initiated low-yielding
radical hydroxylation process with tertiary R-iodoesters: Guindon, Y.;
Gue´rin, B.; Chabot, C.; Ogilvie, W. J. Am. Chem. Soc. 1996, 118, 12528-
12535.
(8) The rate constant of iodine atom transfer from ethyl iodoacetate to
primary alkyl radicals is 2.6 × 107 M-1 s-1: Curran, D. P.; Bosch, E.;
Newcomb, M. J. Org. Chem. 1989, 54, 1826-1831. The rate constant of
the corresponding bromine atom transfer (2.7-7 × 104 M-1 s-1) is too
slow to compete with the direct reaction of ethyl radicals with oxygen.
This explains the failure of the hydroxylation process with R-bromocar-
boxylic acid derivatives.
R-Iodoamides, -esters, -thioesters, and -lactones are hy-
droxylated in 69-88% yield. The use of 2 equiv of Et3B is
necessary to reach high yields. Traces of hydroperoxides are
occasionally isolated; therefore, a preventive reductive treat-
ment with dimethyl sulfide is done before workup. Interest-
ingly, the reaction gives good yields with tertiary iodides
(entries 4 and 5) as well as with substrates sensitive to
1420
Org. Lett., Vol. 1, No. 9, 1999