Creation of C2-Symmetric Molecules using An Asymmetric Dihydroxylation and Its Application

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Since chiral C_2-symmetric molecules play an important role in an asymmetric synthesis, much attention has increasingly been focused on their asymmetric synthesis. We describe a promising route to C_2-symmetric tetraols involving the Sharpless asymmetric dihydroxylation (AD) of symmetric terminal dienes and its application to the synthesis of C_2-symmetric chiral amines the representative of chiral auxiliaries of wide use.The precedent established by the Sharpless group suggested that enantiomeric excess in the case of terminal olefins might be modest (more or less 80% ee). In a symmetrical diene such as the twin olefins conjoined, we anticipate that the stereoselectivity might be improved based on the following consideration : The first AD reaction produces the major and minor enantiomers (diols). Since each enantiomer undergoes the second AD reaction with essentially the same enantiofacial selectivity as in the first AD reaction, three tetraol products result ; a C_2-symmetry compound 1, a meso compound, and ent-1. The overall consequence is that most of the AD reaction resulting from the undesired enantiofacial attack leads to the meso compound. Very little of the mirror image compound ent-1 is formed, and therefore the enantiomeric purity of the major C_2-symmetry product 1 will be high. Based on these consideration, the C_2-symmetric teraols are prepared indeed in high enantiomeric purities from dienes (1,5-hexadiene, 1,6-heptadiene, and ally1 ether). Subsequently, the tetraols are transformed into C_2-symmetric OMICRON-protected alpha, alpha'-bishydroxymethylpyrrolidines, piperidines, and morphorine. Interestingly, we found that medium-pressure chromatography on silica gel of pyrrolidines and piperidines with modest enantioselectivity resulted in efficient enantiomeric fractionation.