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Publications (1)5.83 Total impact

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    ABSTRACT: Allenes are important compounds that exhibit axial chir-ality [1] and are present in a large number of medicinal and natural products. [2] One of the most frequently used methods for obtaining racemic allenes involves the isomerization of propargylic centers. [3] However, it is surprising that this method has rarely been used for preparing enantiomerically pure compounds, probably due to the rather poor results ob-tained in its application. Thus, the few examples reported for the synthesis of allenols using chiral auxiliaries are mini-mally successful, [4] and only moderate enantiomeric excess (ee) has been achieved with organocatalytic methods. [5] Very recently Yoshida et al. reported one of the best procedures for the synthesis of allenols (74 to 92 % ee), which is based on the method previously published by Hoppe and co-work-ers. [6] It consists of the carbolithiation of 2-OCb (OCONiPr 2) conjugated enynes in the presence of stoichiometric (À)-sparteine, followed by addition of the resulting propargylic anions to electrophiles to give the corresponding allene de-rivatives (Scheme 1 a). The key to the success of this nice transformation seems to be related to the chemical and con-figurational stability of the propargylic lithium carbanion by association with the OCb group and the (À)-sparteine, which is used in stoichiometric amounts. These results sug-gest that the main difficulty for obtaining enantiomerically enriched allenes by isomerization of compounds with chiral propargylic centers of a defined configuration is due to the configurational stabilization of the propargylic carbanion in-termediates. In recent years, we have reported that an ortho-sulfinyl group is able to provide a high configurational stabilization to differently substituted benzylic anions, allowing them to react with various electrophiles in an almost completely ste-reoselective manner. [7] From these results we hypothesized that ortho-sulfinyl benzylcarbanions containing acetylenic moieties joined to the benzyl carbon would be able to evolve in a highly stereoselective manner into enantiomeri-cally enriched allenes due to the configurational stabiliza-tion provided by the sulfinyl group (Scheme 1 b). To confirm this hypothesis, it was necessary to prepare the propargylic precursors shown in Scheme 1. The results obtained in these two fields, synthesis of alkynes and their isomerization into trisubstituted allenes, [8] are presented herein. The preparation of enantiomerically pure tertiary propar-gylic centers can be achieved by the nucleophilic addition of acetylenic residues to proper electrophiles such as enones, [9] enals, [10] nitroalkenes, [11] Meldrums acid derivatives, [12] and thioamides. [13] In all these cases, the acetylenic moiety is sup-ported by the reagent acting as nucleophile, and the electro-phile contains an electron-withdrawing group (EWG) to allow the conjugate addition (Scheme 2 a). As the acidity of the a protons to these groups could interfere with the ab-straction of the propargylic protons required for the isomeri-zation to the allene, the resulting compounds from these routes are not appropriated for our study.
    Chemistry 01/2012; · 5.83 Impact Factor