Dibenzylbutyrolactones asymmetric synthesis

As the previous chapters have demonstrated, chiral auxiliaries have found a widespread application in the asymmetric synthesis of lignans. Among them, chiral oxazolidinones have been used extensively due to their ability to produce excellent diastereoselectivities in aldol as well as in numerous other reactions. For example, Kise et al. reported the use of (5)-4-isopropyl-3-(phenylacetyl)-2-oxazolidinone (141) in oxidative homocoupling reactions and its application in the asymmetric synthesis of dibenzylbutyrolactones and dibenzylbutandiols, Scheme (26) [86,87]. Treatment of 3-arylpropanoic acid derivative 142 with LDA in the presence of TiCU yielded a mixture of the dimeric compounds 143 in a ratio of 85 15 to 87 13. The major product having (R,R) configuration was converted into dibenzylbutyrolactones 145 in a three step sequence... 

Scheme (26). Asymmetric synthesis of dibenzylbutyrolactones and dibenzylbutandiols by Rise et al...

Lithiated a-amino nitriles derived from an enantiomerically pure secondary amine have been used to achieve the asymmetric synthesis of trfl 5-dibenzylbutyrolactones (scheme 10) [58]. Enantiomeric excesses of greater than 96% were obtained after removing the chiral auxiliary. When aromatic aldehydes were used as electrophiles the benzylic alcohols were obtained as a mixture of the two epimers with a diastereomeric excess of 60-75%. Addition of a chiral sulfoxide, prepared using a modified Sharpless oxidation, to butenolide has also been utilised as part of an expeditious synthesis of podophyllotoxin (scheme 11) [59]. 

As already demonstrated tra 5-dibenzylbutyrolactones are valuable as precursors for the synthesis of a wide range of lignans. For example, the keto-lactones (90) and (91), which have both been prepared by tandem conjugate addition reactions, provide key intermediates for the synthesis and asymmetric synthesis respectively of lignans of the furofuran type (scheme 30) [85,86]. 

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