Stereoselective synthesis of spiro[5.5]undecane derivatives via biocatalytic [5+1] double Michael additions

• A novel d-aminoacylase (DA)-catalyzed double Michael addition.
• The specific catalytic effect of DA was demonstrated by control experiments.
• Five spiro[5.5]undecane derivatives were prepared in moderate yield.
• Only the cis isomers were obtained in all the cases.

A novel enzymatic, promiscuous protocol of d-aminoacylase (DA)-catalyzed [5+1] double Michael addition was developed herein, for the synthesis of (hetero)spiro[5.5]undecane derivatives in moderate yields. It is notable that almost only the cis isomers were obtained through this biocatalytic methodology in all the cases according to their 1H and 13C NMR spectra. It is the first report on hydrolase-catalyzed double Michael addition in organic solvent.

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