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

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

• For recent applications in synthesis, see:
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• Initial reagent screening with high-valent metals identified TiCl₄, ZrCl₄, NbCl₄, and NbCl₅ as being effective. NbCl₅ provided the greatest conversion with the minimal solvent cleavage. For the strong M-O bond energy in this series, see:
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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.