Ring closure Wadsworth-Emmons

Another highlight of the period under review is the report of the total synthesis of the tricyclic alkaloid fawcettimine (22) (Scheme 2).9 Lewis-acid-catalysed Diels-Alder addition of butadiene to 2-allyl-5-methylcyclohex-2-enone provided the ds-octalone (23), which was modified as indicated to give the dialdehyde (24). After considerable experimentation, conditions were defined which led to regioselective ring-closure in the desired direction. The unsaturated aldehyde was treated directly with the Wadsworth-Emmons reagent to provide... 

The ether derivatives 0,0,0-trimethylkorupensamine A (248) and B have both been synthesised by a route which commenced with a lengthy sequence to the biaryl 249 from 3,5-dimethylanisole (ref. 95) (Scheme 32). Reduction of 249 with LiAlHa and oxidation gave aldehyde 250 which upon Wadsworth-Emmons-Homer extension, reduction and Sharpless asymmetric epoxidation provided epoxide 251 and the corresponding atropisomer in almost equal amounts which were separated by silica gel chromatography. The derived alcohol 252, obtained by mesylation of 251 and in situ reduction, was then converted into the acetamide 253 by displacement with azide under Mitsunobu conditions followed by reduction and acetylation. Ring closure followed by stereoselective reduction then yielded 0,0,0-trimethylkorupensamine A (248). The synthesis of 0,0,0-triraethylkorupensamine B was accomplished in a similar manner using the atropisomer of 251 obtained in the epoxidation step. 

Scheme 6.20). This methodology has got its own significance to construct the macrocycle as an alternative to a Horner-Wadsworth-Emmons macrocyclization or a more conventional Yamaguchi macrolactonization for ring closure. 

Vares and Rein have developed a powerful approach to tetrahydrofurans where they coupled an asymmetric Homer-Wadsworth-Emmons (HWE) reaction with a Pd-catalyzed ring closure to generate cis- and tran -tetrahydrofuran derivatives (Schemes 76 and 77) [82]. From weso-dialdehyde 289, asymmetric HWE gave E-alkene isomer 291 with high levels of diastereoselectivity. Aldehyde reduction was followed by pivaloyl migration to afford cyclization precursor 292 in 63 % yield. Pd-catalyzed ir-allyl formation and cyclization proceeded with overall retention of stereochemistry to give 2,5-cis-tetrahydrofuran 293 in 76 % yield. 

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