Carbonyl ylides zaragozic acids

Toward the synthesis of zaragozic acids, a novel family of fungal metabolites that has been shown to be picomolar competitive inhibitors of squalene synthease, Hodgson s group and Hashimoto s group have used cyclic carbonyl ylide formation/[3 + 2]-cycloaddition approach. " In Hashimoto s synthesis, the 2,8-dioxabicyclo[3,2,l]octane core... 

The carbonyl ylide generated from metal carbene can also add to C=0 or C=N bonds. The [2 + 3]-cycloaddition of carbonyl ylide with G=0 bond has been used by Hodgson and co-workers in their study toward the synthesis of zaragozic acid as shown in Scheme n 27a,27d Recently, a three-component reaction approach to syn-a-hydroxy-f3-amino ester based on the trapping of the carbonyl ylide by imine has been reported.The reaction of carbonyl ylide with aldehyde or ketone generally gives l,3-dioxolanes. Hu and co-workers have reported a remarkable chemoselective Rh2(OAc)4-catalyzed reaction of phenyl diazoacetate with a mixture of electron-rich and electron-deficient aryl aldehydes. The Rh(ii) carbene intermediate reacts selectively with electron-rich aldehyde 95 to give a carbonyl ylide, which was chemospecifically trapped by the electron-deficient aldehyde 96 to afford 1,3-dioxolane in a one-pot reaction (Equation (12)). 

Intermolecular cycloaddition also proceeds smoothly. The 2,8-dioxabicyclo-[3,2.1]octane core system 379 of zaragozic acid 380 was constructed by the intramolecular carbonyl ylide formation from 376 catalysed by Rh2(OAc)4, followed by intermolecular 1,3-dipolar cycloaddition of the electron-deficient dipolarophile 377 as shown by 378 as a single diastereomer out of four possible diastereomers [124],... 

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