A-Skytanthine

The homochiral f -branched carboxylic acids (13 or enf-13 Table 1) have been used for the synthesis of a variety of natural products21 such as California red scale pheromone,14 a-skytanthine,22 the southern com rootworm pheromone,15 and norpectinatone.16 Pure (5)-3-trichloromethylbutyric acid (a structural subunit of some sponge metabolites) was prepared via conjugate addition of ClaCMgCl to the chiral cro-tonate (16) followed by hydrolysis (Scheme S).23... 

Scheme 10. Oppolzer and co-workers synthesis of (+)-a-skytanthine (184) and (+)-8-skytanthine (33) (191).

Thus, Cid and Pombo-Villar have also described the synthesis of (-)-a-skytanthine (201) and (+)-epi-dihydrotecomanine (202) from the common intermediate 200 (195). Treatment of200with (4-toluenesulfonyl)hydrazide and in situ reduction with sodium cyanoborohydride afforded the piperi-done 203 in 44% yield. Debenzylation with Li-NH3 followed by reduction of the lactam 204 [which is formally an aza-analog of (+)-isoiridomyrmecin (205)] with UAIH4 gave 206, and iV-methylation under Eschweiler-Clarke conditions afforded (-)-a-skytanthine (201) (Scheme 12) (195). 

The Mitsunobu reaction has been used by It6 and co-workers as a key step in the synthesis of unnatural (+)-a-skytanthine (184) (196). The chiral amide 210 (197) was subjected to an aza-Claisen rearrangement, and the resulting amide 211 was reduced with LiAlU to afford the amine 212 in 80% yield. A hydroboration-oxidation sequence led to a mixture of amino alcohols 213, which was heated at 100°C for 24 h in the presence of cyanomethylene-trimethylphosphorane (CMMP) to yield a 92 8 mixture of cis- and rrans-fused isomers 214 and 215 in 81% yield from 212. 

Another type of rearrangement involving 1,5-asymmetric induction is the ketene aza-Claisen rearrangement, used in the stereoselective synthesis of intermediate 16, a common precursor for the synthesis of monoterpene alkaloids (-)-a-skytanthine, (-)-jV-demethyl-<5-skytamhine, and (+ )-epidihydrotecomanine 649. 

Miscellaneous Reactions. - p-Toluenesulfonaraide undergoes Mitsunobu-type reactions in the presence of alcohols and cyanomethylenetriphenyl-phos-phorane (56) to give predominantly mono-N-alkylation products. This reaction has also been applied to the synthesis of cyclic ethers from diols and cyclic amines from amino alcohols and to carbon-carbon bond formation. Examples of cyclic amine synthesis include that of (+)-a-skytanthine (57). A comparative study of the reactions of active methine compounds (58) as nucleophiles using... 

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