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Synlett 2002(2): 0337-0339
DOI: 10.1055/s-2002-19777
LETTER
© Georg Thieme Verlag Stuttgart · New York

Radical Cyclization Reactions with a Zirconocene-Olefin Complex as an Efficient Single Electron Transfer Reagent

Kazuya Fujita, Hideki Yorimitsu, Koichiro Oshima*
Department of Material Chemistry, Graduate School of Engineering, Kyoto University, Yoshida, Sakyo-ku, Kyoto 606-8501, Japan
Fax: +81(75)7534863; e-Mail: oshima@fm1.kuic.kyoto-u.ac.jp;
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Publication History

Received 15 November 2001
Publication Date:
02 February 2007 (online)

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Abstract

A zirconocene-olefin complex induced reductive radical cyclization of β-haloalkyl allyl acetals in THF. This complex served as a single electron transfer reagent to promote the cyclization. Furthermore, the reaction in DME afforded tetrahydrofuranylmethylzirconium species effectively.

Key words

cyclizations - electron transfer - halo acetals - radical reactions - zirconocene-olefin complex

    References

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8

Formation of mixtures of 2f-2k and their unsaturated analogues (3f-3k) could be explained by disproportionation of tertiary radical or secondary radical resulting from cyclizations of 1f-1k. Namely, we guess that these alkyl radicals do not recombine with the zirconocene-olefin complex.

9

In addition to these results, no product was obtained in the presence of a radical scavenger such as 2,2,6,6-tetramethylpiperidine-N-oxyl.

10

The formation of 9 could be confirmed by quenching the reaction mixture with DCl in place of HCl. However, deuterium was not completely incorporated (54%). Therefore, we do not exclude the path of hydrogen abstraction from THF.

11

Given this pathway, the reactions should proceed with only one equiv of the zirconocene-olefin complex. However, in this case, two equimolar amounts of ”Cp2Zr(II)" is required in order to obtain reasonable yields of the cyclization products.

12

We assume that the alkyl radical species resulting from cyclizaton of 1e would abstract hydrogen less efficiently from DME than from THF and that most of them recombine with the zirconocene-olefin complex.

13

Typical Experimental Procedure for Cyclization Reaction in DME: Cp2ZrCl2 (585 mg, 2.0 mmol) and n-BuLi (1.5 M in hexane, 2.7 mL, 4.0 mmol) were mixed in DME at 0 °C under argon and were stirred for 1 h at 0 °C to form a zirconocene-olefin complex. A solution of bromo acetal 1e (297 mg, 1.0 mmol) in DME (2 mL) was added to the reaction mixture at 0 °C. The temperature was then raised to ambient temperature, and the stirring was continued for 3 h to yield the alkyl zirconium species 10. The mixture was poured into deuterochloric acid (10 mL, 1 M) and stirred for 30 min. The resulting products were extracted with hexane for three times. The combined organic layer was dried over Na2SO4 and concentrated in vacuo. Silica gel column purification (hexane:ethyl acetate = 10:1) of the crude oil provided 11 (152 mg, 0.70 mmol) in 70% yield with 94% deuterium incorporation. Spectroscopic data for 11 (mixture of diastereomers, 68:32): IR(neat): 3061, 3026, 2932, 2872, 1736, 1497, 1450, 1250, 1148, 1022, 991, 951, 897, 872, 733, 702 cm-1; 1H NMR (CDCl3): δ = 1.25-2.00 (m, 5 H), 2.52-2.88 (m, 2 H), 3.41 (dt, J = 2.7, 10.4 Hz, 0.32 H), 3.59-3.68 (m, 1 H), 3.72-3.91 (m, 2.36 H), 4.17 (dt, J = 1.2, 8.1 Hz, 0.32 H), 5.03 (d, J = 3.3 Hz, 0.32 H), 5.27 (d, J = 3.9 Hz, 0.68 H), 7.13-7.32 (m, 5 H); 13C NMR (CDCl3), for major isomer: δ = 19.39, 22.98, 32.90 (t, J = 19.4 Hz), 36.47, 42.29, 60.84, 69.75, 101.92, 126.17, 128.48, 128.52, 140.13. For minor isomer: δ = 20.56, 22.28, 38.19 (t, J = 19.1 Hz), 39.25, 43.65, 64.20, 73.47, 102.08, 126.21, 128.35, 128.52, 139.98. Found: C, 76.38; H + D, 8.56%. Calcd for C14H17DO2: C, 76.68; H + D, 8.73%.

15

A solid CuCN was used in this system Replacement of a solid CuCN2 LiCl slightly reduced the yield.