New methods for synthesis of chiral 4-aryl-6-methyl-3,4-dihydrocoumarines
Summary of the Doctoral Thesis
Zigmārs Leitis, Riga Technical University, Latvia
4-Substituted oxazolidinones (Evans chiral auxiliaries) were examinated for preparation of enantiomerically enriched 3,3-diarylpropionates via conjugate 1,4-addition of aryl nucleophiles to cinnamic acid derivates. Copper/Grignard reagents and palladium or rhodium/arylboronic acids catalytic systems were used. A listof Evans auxiliaries were sythesized of a-aminoacids containing in principle different substitutements (alkyl-andphenyl-) and found out that for high selectivity is necessary p–p stacking between cinnamoil C=C and chiral auxiliary phenyl ring. Investigated influence of EDG and EWG in cinnamoil phenyl moiety and copper catalyst to 1,4-addition of arylmagnesium. In the reaction of o-disubstituted cinnamates with Grignard or arylboronic acids 3,3-diarylpropionates were not obtained; was found a new hydroarylation method using palladium catalyzed for addition of 1,3,5-trimethoxybenzene. 3,3-Diarylpropionates obtained in arylation of cinnamates were converted into 4-aryl-3,4-dihydrocoumarines via deprotecting of hydroxygroup in aryl moiety with subsequent intramolecular cyclization; diastereomeric excess obtained in addition step fully conform to enanthiomeric excess of target dihydrocoumarine. Experimentally was shown how to synthesize structurally identical molecules but with different configuration in two ways using chiral auxiliaries changing configuration in each way.
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