11042 J. Am. Chem. Soc., Vol. 122, No. 45, 2000
Yorimitsu et al.
contracting the volume of a substrate. For ionic reactions,
Barbier-type allylation of aldehydes mediated by tin is acceler-
ated in water.4 In the case of zinc, the yields of the allylated
products are improved compared to allylation in organic
solvents.5 Reactions by indium in water have also been
developed, and an efficient synthesis of (+)-3-deoxy-D-glycero-
D-galacto-nonulosonic acid (KDN) was achieved by applying
indium-mediated allylation in water starting with mannose.6
Lubineau reported that the Mukaiyama aldol reaction was carried
out in aqueous solvents without any acid catalyst.7 The crossed
aldol products showed slight syn diastereoselectivity, which was
the same as when this reaction was carried out in an organic
solvent under high pressure. Lanthanide triflate-catalyzed Mu-
kaiyama aldol reactions in water have also been actively
investigated.8
Scheme 1
On the other hand, radical reactions in water are rare in
organic synthesis9 and remain to be studied. In each case
reported, no solvent effects were observed. In general, a medium
effect in radical reactions is believed to be almost negligible,
and little attention has been paid to the solvent that is employed
for radical reactions.10 We have been exploring the usefulness
of water as a solvent in radical reactions.11 Here we wish to
report a triethylborane-induced radical cyclization reaction in
water.12 In the course of our study, a remarkable solvent effect
was observed, especially in the cyclization of allyl iodoacetate
in water. The cyclization reaction in water gave the desired
lactone in higher yield. However, in organic solvents, radical
oligomerization or polymerization predominantly occurred, and
the desired lactone was poorly obtained. The successful radical
lactonization proved unique to an aqueous medium. The results
of ab initio calculations disclosing the origin of this solvent
effect are also described.
Preparation of a Methanol Solution of Triethylborane. To
examine radical cyclization in aqueous media, we chose
triethylborane as a radical initiator,13 and a methanol solution14
of triethylborane was prepared to be handled easily. The stability
of triethylborane in methanol was checked by the examination
of the H NMR of a CD3OD solution of triethylborane. After
1
standing at ambient temperature for one month, no change was
observed in the NMR spectrum. Indeed, the solution worked
as well for a few months or longer when it was stored under
argon atmosphere.
(3) (a) Ponaras, A. A. J. Org. Chem. 1983, 48, 3866-3868. (b) Coates,
R. M.; Roger, B. D.; Hobbs, S. J.; Peck, D. R.; Curran, D. P. J. Am. Chem.
Soc. 1987, 109, 1160-1170. (c) Gajewski, J. J.; Jurayj, J.; Kimbrough, D.
R.; Gande, M. E.; Ganem, B.; Carpenter, B. K. J. Am. Chem. Soc. 1987,
109, 1170-1186. (d) Copley, S. D.; Knowles, J. J. Am. Chem. Soc. 1987,
109, 5008-5013. (e) Brandes, E.; Grieco, P. A.; Gajewski, J. J. J. Org.
Chem. 1989, 54, 515-516.
Radical Cyclization of Iodo Acetals in Aqueous Methanol
or in Water. First, we chose iodine atom-transfer15 radical
cyclization of iodo acetals in aqueous methanol in order to
establish tin-free chemistry16 (Scheme 1). For example, iodo
acetal 1a (1.0 mmol) was dissolved in aqueous methanol
(MeOH/H2O ) 3/1), and triethylborane in methanol (1.0 M,
0.1 mmol, 0.1 mL) was added to the homogeneous solution
under argon atmosphere.17 After being stirred for 2 h, the
reaction mixture was extracted and concentrated, followed by
silica gel column purification to afford the corresponding
tetrahydrofuran derivative 2a in 80% yield. This success
prompted us to perform this reaction in water, in which a
heterogeneous reaction medium was formed. Triethylborane in
methanol (1.0 M, 0.1 mmol, 0.1 mL) was added to the
suspension of 1a in water (1.0 mmol in 10 mL), and the mixture
was stirred vigorously for 2 h. An extractive workup and
(4) Nokami, J.; Otera, J.; Sudo, T.; Okawara, R. Organometallics 1983,
2, 191-193.
(5) (a) Petrier, C.; Luche, J. L. J. Org. Chem. 1985, 50, 910-912. (b)
Einhorn, C.; Luche, J. L. J. Organomet. Chem. 1987, 322, 177-183.
(6) (a) Li, C.-J.; Chan, T.-H. Tetrahedron Lett. 1991, 32, 7017-7020.
(b) Chan, T.-H.; Li, C.-J. J. Chem. Soc., Chem. Commun. 1992, 747-748.
(7) (a) Lubineau, A. J. Org. Chem. 1986, 51, 2142-2144. (b) Lubineau,
A.; Meyer, E. Tetrahedron 1988, 44, 6065-6070.
(8) Kobayashi, S.; Hachiya, I. J. Org. Chem. 1994, 59, 3590-3596. For
review, see: Kobayashi, S. Synlett 1994, 689-701.
(9) (a) Minisci, F. Synthesis 1973, 1-24. (b) Yamazaki, O.; Togo, H.;
Nogami, G.; Yokoyama, M. Bull. Chem. Soc. Jpn. 1997, 70, 2519-2523.
(c) Breslow, R.; Light, J. Tetrahedron Lett. 1990, 31, 2957-2958. (d) Jang,
D. O. Tetrahedron Lett. 1998, 39, 2957-2958. (e) Maitra, U.; Sarma, K.
D. Tetrahedron Lett. 1994, 35, 7861-7862.
(10) (a) Curran, D. P.; Porter, N. A.; Giese, B. Stereochemistry of Radical
Reactions; VCH Verlagsgesellschaft mbH.: Weinheim, 1996. (b) Giese,
B.; Kopping, B.; Go¨bel, T.; Dickhaut, J.; Thoma, G.; Kulicke, K. J.; Trach,
F. Org. React. 1996, 48, 301-856.
(11) (a) Nakamura, T.; Yorimitsu, H.; Shinokubo, H.; Oshima, K. Synlett
1998, 1351-1352. (b) Yorimitsu, H.; Wakabayashi, K.; Shinokubo, H.;
Oshima, K. Tetrahedron Lett. 1999, 40, 519-522. (c) Yorimitsu, H.;
Shinokubo, H.; Oshima, K. Chem. Lett. 2000, 104-105.
(15) (a) Curran, D. P. Synthesis 1988, 417-439; 489-513. (b) Curran,
D. P.; Chen, M.-H.; Kim, D. J. Am. Chem. Soc. 1986, 108, 2489-2490.
(16) For recent review. Baguley, P. A.; Walton, J. C. Angew. Chem.,
Int. Ed. Engl. 1998, 37, 3072-3082.
(17) The reaction was performed in a reaction flask equipped with a toy
balloon that was filled with argon. Oxygen, which is necessary to produce
an ethyl radical from triethylborane, could penetrate the balloon easily, and
the concentration of oxygen in the balloon reached 10% after 12 h.
Alternatively, air could be introduced with a syringe (2 mL) every 30 min
(3 times) after an addition of triethylborane when the flask was kept strictly
under argon atmosphere.
(12) A part of this work was reported: Yorimitsu, H.; Nakamura, T.;
Shinokubo, H.; Oshima, K. J. Org. Chem. 1998, 63, 8604-8605.
(13) (a) Nozaki, K.; Oshima, K.; Utimoto, K. J. Am. Chem. Soc. 1987,
109, 2547-2548. (b) Nozaki, K.; Oshima, K.; Utimoto, K. Tetrahedron
Lett. 1989, 30, 923-933.
(14) An attempt to prepare a homogeneous aqueous solution of Et3B
resulted in failure. Et3B floated on the water.