Noyori-type three-component reaction

The dendrobatid alkaloid 251F 213 (Figure 12.4) was isolated from the skin exudates of a Columbian dendrobatid poison frog, Minyobates bombetes [105]. The asymmetric total synthesis of this molecule has been reported by Aube and co-workers [106], The synthesis featured a Noyori-type three-component reaction to access an advanced bicyclopentenone intermediate, and also included a tandem ROM/RCM reaction sequence and a Schmidt rearrangement as key steps. 

An asymmetric total synthesis of the alkaloid dendroba-tid 251 F 192 using a Noyori-type three-component reaction was described by Aube and coworkers (Scheme 6.26) [55]. 1,4-Cuprate addition to enone 189 is achieved from the exo-face, and subsequent aldol condensation results in the formation of only one diastereoisomer 191 in 65% yield. Dendrobatid 251 F 192 is achieved in only six further steps. 

Shibasaki and coworkers have used the Noyori-type three-component reaction in the synthesis of the fused poly heterocycle garsubellin A 195 (Scheme 6.27) [56]. The chiral cyclohexenone 193 reacts with methylmagnesium bromide, followed by trapping of the enolate with isopropan-aldehyde. The key intermediate 194 is isolated in 61% yield and diastereomeric ratio of 4 1. 

SCHEME 6.26 Noyori-type three-component reaction in the total synthesis of dendrobatid 251 F 192. 

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