Enzyme-catalyzed Kinetic Resolution Of Racemic Electron-deficient Allenols And Its Application In Organic Synthesis

The attention of this thesis has been focused on the study of the enzyme-catalyzed kinetic resolution of electron-deficient racemic allenols and its application in organic synthesis. The whole thesis includes two parts.In the first part, the enzyme-catalyzed kinetic resolution of racemic electron-deficient 2,3-allenols was studied. Dr. Xu Daiwang in our group observed that Novozym 435 is an effective biocatalyst for the kinetic resolution of a series of racemic 1-alkyl-substituted 2,3-allenols affording highly optically active (S)-(-)-2,3-allenols and (R)-(+)-2,3-allenyl acetates in high yields and excellent ees. Dr. Xu found that the reaction of those allenols with the substitutent at 1-position beyond two carbon atoms is very slow or even does not occur. In order to obtain optically active allenols with the substitutent at 1-position beyond two carbon atoms, Novozym 435-catalyzed kinetic resolution of 1-ethenyl or 1-ethynyl-substituted electron-deficient 2,3-allenols was studied. Novozym 435 is also an efficient biocatalyst for the kinetic resolution of racemic 1-ethenyl or 1-ethynyl-substituted 2,3-allenols. Based on this observation, we paid our attention to the Novozym 435-mediated kinetic resolution of 1-methyl, ethyl, ethenyl or ethynyl substituted-2-EWG-substituted 2,3-allenols (EWG=electron-withdrawing group). We introduced methoxycarbonyl, phenylsulfonyl, diphenylphosphinyl or diethyl phosphate to substrates and fortunately, we synthesized optically active 2-phenylsulfonyl or methoxycarbonyl substituted 2,3-allenols. However the reaction failed to afford the optically active 2-diphenylphosphinyl or diethyl phosphonyl substituted product due to the highly steric hindrance between the substrate and enzyme.In the second part, the coupling-cyclization reaction of the prepared optically active 2,3-allenols was studied. Dr. Gao Wenzhong in our group found that Pd(II) catalysts can catalyze the coupling-cyclization reaction of a-allenols in the presence of allylic halides in DMA at room temperature to provide five-membered 2,5-dihydronfurans. Futher experimental results showed that the transformation proceeds via a Pd(â…¡)-catalyzed pathway. From this way, the above prepared optically active electron-deficient 2,3-allenols can be easily converted to optically active 3-allyl-substituted 2,5-dihydrofurans.