Preparation of aryl benzyl ketones by [1,2]-Wittig rearrangement

α -(Benzotriazol-1-yl)benzyl ethers 4a − f were readily prepared by condensation of benzotriazole, aryl aldehydes and benzyl alcohols. A one-pot reaction involving deprotonation of 4 followed by [1,2]-Wittig rearrangement and departure of the benzotriazolyl group resulted in aryl benzyl ketones 6a − f in good yields.


Introduction
The [1,2]-Wittig rearrangement 1 has been reviewed extensively. 2It is now widely accepted that the rearrangement proceeds via a radical dissociation-recombination mechanism, 3,4 with configuration retention at the migrating carbon and inversion at the Li-bearing terminus. 5ubstituted ethers 1, in which G can function as a leaving group as well as an electronwithdrawing group, eliminate group G after [1,2]-Wittig rearrangement to form the carbonyl compounds 3 (Scheme 1).Such reactions have been reported for G = cyano, 6 imidazolium and benzimidazolium 7 groups.α-(Benzotriazol-1-yl)alkyl allyl ethers have been successfully utilized in the synthesis of homoallylic ketones and alcohols via [2,3]-Wittig rearrangements. 8We now report an extension of this methodology: [1,2]-Wittig rearrangements of α-(benzotriazol-1yl)arylmethyl ethers to give aromatic ketones.

Results and Discussion
Condensation of an aromatic aldehyde, an aliphatic alcohol and benzotriazole in the presence of a catalytic amount of p-TsOH and 4Å molecular sieves in methylene chloride at room temperature as expected, 8,9 gave the α-(benzotriazol-1-yl)alkyl ethers 4a-f in 60-78% yield.
Novel ethers 4b−f were fully characterized by their 1 H, 13 C NMR spectra and elemental analyses or HRMS data.

Scheme 1
The acidic benzotriazole-activated α-proton in the α-(benzotriazol-1-yl)alkyl benzyl ethers 4a−f on treatment with LDA at -78 °C readily gives the α-lithiated intermediates 5a−f, which eliminate the benzotriazole anion to give, by [1,2]-Wittig rearrangement, the carbonyl products 6a−f in 53-63% yield.The structures of 6a−f were confirmed by 1 H and 13 C NMR spectroscopy. 1 H NMR spectra of all of the ketones 6a-f displayed a similar pattern including the disappearance of the α-proton and benzotriazolyl signals from the aromatic region.The benzylic protons in 6a-f resonated around 4.2 ppm and the 13 C NMR signal for this carbon appeared around 45 ppm.The aromatic signals in all of the ketones 6a-f experienced a negligible change in the chemical shift values from those in the 1 H and 13 C NMR spectra of starting ethers 4a-f.The disappearance of the α-carbon signal around 88 ppm and the appearance of a carbonyl signal near 197 ppm in the 13 C NMR spectra further confirmed the formation of ketones 6a-f (Scheme 2), (Table 1 General methods for the preparation of ketones from aldehydes include (i) nucleophilic addition of an organometallic reagent followed by oxidation of the secondary alcohol; 10 (ii) transformation into a carbonyl anion equivalent such as an (α-benzotriazol-1-ylalkyl)methyl ether followed by lithiation, alkylation and deprotection. 9The present two-step [1,2]-Wittig rearrangement procedure provides access to aryl benzyl ketones from an aromatic aldehyde and a benzyl alcohol.

Experimental Section
General Procedures.Melting points were determined using a Bristoline hot-stage microscope and are uncorrected. 1H NMR (300 MHz) and 13 C NMR (75 MHz) spectra were recorded on a Gemini 300 NMR spectrometer in CDCl 3 (with TMS for 1 H and chloroform-d for 13 C as the internal reference).HRMS were measured on an AEI-30 mass spectrometer.Elemental analyses were performed on a Carlo Erba-1106 instrument.THF was distilled from sodium/benzophenone and dichloromethane from calcium hydride prior to use.All of the reactions were carried out under N 2 .