J. Am. Chem. Soc. 2001, 123, 3137-3138
3137
Scheme 1
Triethylborane-Induced Radical Reaction with
Schwartz Reagent
Kazuya Fujita, Tomoaki Nakamura, Hideki Yorimitsu, and
Koichiro Oshima*
Department of Material Chemistry
Graduate School of Engineering, Kyoto UniVersity
Yoshida, Sakyo-ku, Kyoto 606-8501, Japan
Scheme 2
ReceiVed September 1, 2000
Since the 1970s, hydrozirconation of alkynes and alkenes with
bis(cyclopentadienyl)zirconium chloride hydride (Cp2Zr(H)Cl,
Schwartz reagent) has been extensively studied and is widely used
in organic synthesis.1,2 Scope and limitations have been well
investigated owing to the outstanding usefulness of Cp2Zr(H)Cl
as a hydrozirconation reagent. Carbonyl compounds such as
aldehydes, ketones, carboxylic acids, and esters are reduced to
alcohols with Cp2Zr(H)Cl because of its strong hydridic character.
Imines and nitriles are also converted into the corresponding
amines and aldehydes, respectively.2 However, the issue of the
reaction with organic halides remains obscure. Little attention has
been paid to the reaction of Cp2Zr(H)Cl with organic halides.1,3
Here we describe a novel type of reaction with Cp2Zr(H)Cl.
Reduction of halides with Cp2Zr(H)Cl proceeded smoothly via a
radical process, which is similar to reduction with n-Bu3SnH, in
the presence of triethylborane as an initiator.4
4 would abstract hydrogen from Cp2Zr(H)Cl to provide the
product 2 and regenerate the zirconium(III) species.
The reaction in Scheme 1 did not complete without Et3B. After
being stirred for 1.5 h, 2 was obtained in 24% yield and 1a was
recovered (68%). Moreover, no product was obtained in the
presence of a radical scavenger, 2,2,6,6-tetramethylpiperidine-N-
oxyl. These observations support the radical mechanism in
Scheme 2. It is also notable that â-alkoxy elimination did not
take place in the Cp2Zr(H)Cl-mediated reaction. 3-Methyl-2-
buten-1-ol or 9-methyl-6-oxa-4,8-decadien-1-ol was not detected
in the reaction mixture. Therefore, a mechanism involving
bromine-zirconium exchange followed by intramolecular carbo-
zirconation would be improbable.9 Last, the reaction conditions
were also applicable to the reduction of 1-bromoadamantane,
which is difficult to debrominate via an ionic process such as
SN2 reaction, to provide adamantane quantitatively.
The use of Cp2Zr(H)Cl, prepared in situ from Cp2ZrCl2 and
Red-Al [NaAlH2(OCH2CH2OCH3)2],1 was also effective for the
radical reaction. Various halides were examined, and the results
are summarized in Table 1.10 The stereochemistry of the products
is again highly suggestive of the 3-oxa-5-hexenyl radical inter-
mediates.7,11 It is worth noting that Cp2Zr(H)Cl is a comparable
hydrogen donor with n-Bu3SnH. The less reactive benzylic radical
resulting from cyclization of 7a can abstract hydrogen from Cp2-
Zr(H)Cl to afford 8. However, the reactivity toward organic
halides of Cp2ZrCl proved to be inferior to that of the tin-centered
radical. Chloro acetal 7d was not a good substrate. The cyclized
product 9 was obtained in 46% yield even at elevated temperature.
Although the allylic ether of o-iodophenol 11a was a suitable
substrate to construct the dihydrobenzofuran skeleton, a bromo
We chose halo acetals5 1a and 1b as model substrates.
Treatment of 1a (0.5 mmol) with Cp2Zr(H)Cl (1.5 mmol) in the
presence of Et3B (0.5 mmol)6 in THF (5 mL) at 25 °C for 3 h
provided the cyclized product 2 in 89% yield. Iodo acetal 1b also
afforded 2 in 82% yield. Interestingly, the stereochemical outcome
of 2 was quite similar to that in the previous report of radical
reaction mediated by EtMgBr in THF at 25 °C.7 In addition, the
reduction of 1a and 1b with n-Bu3SnH, instead of Cp2Zr(H)Cl,
afforded 2 with the same selectivity. Therefore, the structure of
the transition state of radical cyclization would be the same in
all of these reactions including the Cp2Zr(H)Cl-mediated reaction.
The plausible reaction mechanism is shown in Scheme 2 in
analogy with the case of n-Bu3SnH. An ethyl radical, generated
from Et3B by the action of a trace amount of oxygen, would
abstract hydrogen homolytically from Cp2Zr(H)Cl to give a
zirconium(III) radical species (Cp2ZrCl). A single electron
transfer8 from Cp2ZrCl to 1 gives the radical anion of 1. A halide
ion is immediately liberated as Cp2ZrClX (X ) Br or I) and the
resulting carbon-centered radical 3 cyclizes to afford 4. The radical
(1) (a) Hart, D. W.; Schwartz, J. J. Am. Chem. Soc. 1974, 96, 8115-8116.
(b) Wailes P. C.; Weigold, H. J. Organomet. Chem. 1970, 24, 405-411.
(2) For review: (a) Labinger, J. A. In ComprehensiVe Organic Synthesis;
Trost, B. M., Fleming, I., Heathcock, C. H., Eds.; Pergamon Press: New York,
1991; Vol. 8, Chapter 3.9. (b) Negishi, E.; Takahashi, T. Aldrichim. Acta
1985, 18, 31-47. (c) Schwartz, J.; Labinger, J. A. Angew. Chem., Int. Ed.
Engl. 1976, 15, 333-340.
(3) (a) Tam, W.; Rettig, M. F. J. Organomet. Chem. 1976, 108, C1-C4.
(b) Gibson, T. Organometallics 1987, 6, 918-922. (c) Buchwald, S. L.;
LaMaire, S. J.; Nielsen, R. B.; Watson, B. T.; King, S. M. Tetrahedron Lett.
1987, 28, 3895-3898. In these reports, little discussion on the reduction of
organic halides was found.
(8) A single electron transfer from Zr(III) species to alkyl halide is
proposed: (a) William, G. M.; Gell, K. I.; Schwartz, J. J. Am. Chem. Soc.
1980, 102, 3660-3662. (b) William, G. M.; Schwartz, J. J. Am. Chem. Soc.
1982, 104, 1122-1124. (c) Barden, M. C.; Schwartz, J. J. Org. Chem. 1997,
62, 7520-7521. A single electron transfer from a trivalent titanium complex
to organic halides is suggested: (d) Liu, Y.; Schwartz, J. Tetrahedron 1995,
51, 4471-4482.
(9) A recent study on the PhLi-initiated cyclization of olefinic alkyl iodides
suggests that â-alkoxy elimination may be the result of rapid expulsion of
the allyloxy anion from an electron-rich iodine ate complex prior to completion
of the lithium-iodine exchange reaction. See: Bailey, W. F.; Carson, M. W.
J. Org. Chem. 1998, 63, 9960-9967.
(10) Simple alkyl halides were also reduced to the corresponding hydro-
carbons: 1-bromoadamantane (89%, 5 h), 2-bromododecane (94%, 5 h),
1-bromododecane (93%, 3 h), 1-chloroadamantane (88%, 17 h), and 1-chlo-
rododecane (73%, 40 h).
(4) Nozaki, K.; Oshima, K.; Utimoto, K. J. Am. Chem. Soc. 1987, 109,
2547-2548.
(5) (a) Ueno, Y.; Chino, K.; Watanabe, M.; Moriya, O.; Okawara, M. J.
Am. Chem. Soc. 1982, 104, 5564-5566. (b) Stork, G.; Mook, R., Jr.; Biller,
S. A.; Rychnovsky, S. D. J. Am. Chem. Soc. 1983, 105, 3741-3742.
(6) When a catalytic amount of Et3B (10 mol %) was used, 2 was obtained
in 56% yield and 1a (39%) was recovered after the reaction mixture was
stirred for 1.5 h.
(11) (a) Manganese-ate complex-mediated reaction in THF at 0 °C: Inoue,
R.; Nakao, J.; Shinokubo, H.; Oshima, K. Bull. Chem. Soc. Jpn. 1997, 70,
2039-2049. (b) Tri-2-furanylgermane-mediated reaction in THF at 25 °C:
Nakamura, T.; Yorimitsu, H.; Shinokubo, H.; Oshima, K. Synlett 1999, 1415-
1416. (c) Hypophosphorus acid-mediated reaction in ethanol at 25 or 78 °C:
Yorimitsu, H.; Shinokubo, H.; Oshima, K. Chem. Lett. 2000, 104-105.
(7) Inoue, A.; Shinokubo, H.; Oshima, K. Org. Lett. 2000, 2, 651-653. In
this report, the reaction proceeded via an atom transfer process. The products
were 2 (48%, diastereomer ratio ) 67/33) and its isopropenyl analogue (36%,
65/35).
10.1021/ja0032428 CCC: $20.00 © 2001 American Chemical Society
Published on Web 03/13/2001