Isopropylidenetriphenylphosphorane

[16666-80-1]  · C21H21P  · Isopropylidenetriphenylphosphorane  · (MW 304.39)

(highly reactive phosphorus ylide used in natural product alkene formation1-3 and gem-dimethylcyclopropane formation4)

Physical Data: red-colored ylide in solution.

Solubility: sol THF, DMSO, toluene, diethyl ether. Drying: the precursor phosphonium salt should be vacuum dried before use to drive off any residual water.

Preparative Methods: prepared in situ from commercially available isopropyltriphenylphosphonium iodide or bromide and an appropriate base. An isopropyltriphenylphosphonium bromide-sodium amide instant ylide5 pre-mix is also available.

Handling, Storage, and Precautions: should be used immediately after formation. Most ylide solutions slowly decompose with time.

Wittig Reaction.

Many natural products have an alkene terminus substituted with two methyl groups, and isopropylidenetriphenylphosphorane (1) has proven ideal for its construction. Terpenoids,1 pheromones,2 and other natural products3 with this substitution pattern have successfully been synthesized using this reagent (eq 1).

Tetrasubstituted alkene natural products have been obtained when isopropylidenetriphenylphosphorane reacts with cyclic ketones6 (eq 2) and benzophenone.7 Very few Wittig reagents are sufficiently reactive to allow formation of tetrasubstituted alkenes, and even the highly reactive (1) will fail to couple with hindered ketones.8 Oxaphosphetanes are the only observable intermediates in the reactions of (1) with aldehydes9 and ketones.10 A single-electron transfer (SET) mechanism has been offered for oxaphosphetane formation in the reaction of both aldehydes11 and ketones7,8b with (1).

Wittig reaction with (1) also occurs with lactols12 to give alkenes, with acyl chlorides to give allenes,13 with isocyanates to give ketenimines,14 and with imidates to give azadienes.15 With this phosphorane, 1,2,3-tricarbonyl compounds give alkenes at the reactive central carbon,16 and (cyclobutadienecarbaldehyde)irontricarbonyl gives a (vinylcyclobutadiene)iron tricarbonyl complex.17 Isopropylidenetriphenylphosphorane reacts with Borane-Dimethyl Sulfide to give a triphenylphosphine-monoalkylborane adduct, which can undergo hydroboration reactions.18 The reagent can react sequentially with an anhydride and an alkyllithium to generate alkenes (eq 3).19

Cyclopropane Formation.

Isopropylidenetriphenylphosphorane can add to activated double bonds, such as a,b-unsaturated esters, to give gem-dimethylcyclopropanes after elimination of triphenylphosphine.20 If an aldehyde is also present in the conjugated p-system, the Wittig reaction can compete with the cyclopropanation reaction (eq 4).4 The initial lithium halide-betaine complex can decompose directly to the dienoic ester, which undergoes no further reaction. Addition of a second equivalent of (1) to the lithium halide-betaine complex allows cyclopropane formation to occur. Ratios of the dienoic ester and the cyclopropane are solvent and base dependent.

Tandem cyclopropanations can occur with dienoic esters.21 Racemic,22 chiral,23 and deuterated24 chrysanthemic acid esters are readily prepared with isopropylidenetriphenylphosphorane. 2-Metallo-2-nitropropanes afford gem-dimethylcyclopropanes in comparable yields.25 Other methods to introduce a gem-dimethylcyclopropane structure include replacement of bromine in gem-dibromocyclopropanes26 and the reaction of chromium(II) salts and 2,2-dibromopropane with alkenes;27 however, disposal of heavy metal salts is necessary with these alternative methods. The highly reactive isopropylidenetriphenylphosphorane has been shown to react with a triene to give a cyclopropane in 75% yield.28


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18. Bestmann, H. J.; Röder, T.; Sühs, K. CB 1988, 121, 1509 (CA 1989, 110, 154 350r).
19. (a) Shen, Y.; Liao, Q. JFC 1990, 47, 137. (b) Shen, Y.; Qiu, W. TL 1987, 28, 449.
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Thomas J. Fleck

The Upjohn Company, Kalamazoo, MI, USA



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