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Synlett 2009(7): 1077-1080  
DOI: 10.1055/s-0028-1088222
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

Direct Conversion of Aldehydes and Ketones to Allylic Halides by a NbX5-[3,3] Rearrangement

Fraser F. Fleming*, P. C. Ravikumar, Lihua Yao
Department of Chemistry and Biochemistry, Duquesne University, Pittsburgh, PA 15282-1530, USA
Fax: +1(412)3965683; e-Mail: flemingf@duq.edu;
Further Information

Publication History

Received 8 January 2009
Publication Date:
20 March 2009 (online)

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Abstract

Sequential addition of vinylmagnesium bromide and NbCl5, or NbBr5, to a series of aldehydes and ketones directly provides homologated, allylic halides. Transposition of the intermediate vinyl alkoxide is envisaged through a metalo-halo-[3,3] rearrangement with concomitant delivery of the halogen to the terminal carbon. The [3,3] rearrangement is equally effective for the conversion of a propargyllic alcohol to the corresponding allenyl bromide.

Key words

niobium pentachloride - niobium pentabromide - alkyl halides - halogenation - rearrangements

    References and Notes

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6

A control experiment in which non-1-en-3-ol was treated with vinylmagnesium bromide led only to recovered alcohol establishing that the bromomagnesium alkoxide does not participate in a bromo-[3,3] rearrangement.

10

Dry NbCl5 powder was weighed in a glovebox and transferred directly to the reaction flask under a blanket of dry nitrogen.

12

Distillation provided chloride 4a in 84% yield with trace impurities not previously observed in the crude product. Purification on SiO2 or alumina resulted in poor mass recovery with considerable modification of the SiO2 indicating that the reactive electrophile had alkylated the SiO2 support.

15

The use of excess KH ensures the absence of a proton source.

18

Vinylmagnesium bromide is far superior to vinylmagnesium chloride.

20

Addition-Chlorination-Sulfide Displacement; General Procedure A THF solution of vinylmagnesium bromide (0.7 M solution) was added to a 10 ˚C, THF solution (0.75-0.85 M) of the aldehyde or ketone. After 15 min 1,4-dioxane (4 volumes relative to THF) and solid NbCl5 (1.2 equiv) were added sequentially. After 10 min the reaction mixture was poured into 2 M HCl, extracted with EtOAc, and the combined organic extract was then washed with brine and dried (Na2SO4). A THF solution (0.2 M) of the crude, essentially pure allylic chloride was added to a 10 ˚C, THF suspension of NaH (2.0-2.5 equiv) to which had been added thiophenol (2.0-2.5 equiv). The reaction mixture was allowed to warm to r.t. over 16 h, poured into an aq NaOH soln (2% by weight) and then extracted with EtOAc. The combined organic extract was washed with brine, dried (Na2SO4), and concentrated under reduced pressure to furnish an oily residue that was purified by radial chromatography to furnish the pure sulfide.

21

Performing the addition-rearrangement-sulfenylate displacement with piperonal proceeded in 20% yield with the minor reaction components exhibiting spectral data consistent with acetal cleavage.