Chiral tetralins via asymmetric inverse electron demand cycloaddition of heteroaromatic salts with dienophiles having stereogenic centers.
Item
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Title
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Chiral tetralins via asymmetric inverse electron demand cycloaddition of heteroaromatic salts with dienophiles having stereogenic centers.
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Identifier
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AAI9207060
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identifier
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9207060
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Creator
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Choudhury, Anusuya.
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Contributor
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Adviser: Richard W. Franck
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Date
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1991
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Language
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English
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Publisher
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City University of New York.
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Subject
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Chemistry, Organic | Chemistry, Biochemistry
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Abstract
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The asymmetric cycloaddition reactions of isoquinolinium salts with a wide variety of chiral dienophiles (modified version of the Bradsher cycloaddition) to which the stereogenic center was attached in the form of ethers, orthoesters and acetals have been examined. Very high asymmetric induction (95+%) has been achieved for the case of chiral trans-2-phenyl cyclohexyl vinyl ether with excellent chemical yield. In order to avoid the difficulty of removing the chiral auxiliary which remains as a secondary ether in the cycloadduct in the case of chiral vinyl ethers, the chiral othoesters having a C2 axis were used, permitting the facile removal of the chiral auxiliary. But the face discrimination was not high. A sugar derived chiral vinyl acetal exhibits very high face control resulting in an enantiomerically pure compound.;Our configurational assignments are based on the comparison of the CD spectra of the products with CD's of tricylic tetralins prepared from sugars of known configuration.;Cycloaddition of chiral ketene acetal dienophiles having complex substitution patterns, afford after work-up, highly functionalized tetralins with a masked hydroxy methylene substituent as a hemiacetal, a tertiary hydroxyl function at the position corresponding to 9-position of anthracyclines and a chemically manipulable 2,4 dinitrophenylamino group, matching the 7-position requirement of anthracyclines with a facile removal of the chiral auxiliary. The attempted effort to convert the cyclic acetal to lactone (which would give the required ester moiety at 10-position by regioselective opening) resulted in the rupture of C-C bond forming a tetralone derivative. Though the cycloaddition of these dienophiles and the subsequent manipulations were highly encouraging, we could not get an optically pure dienophile. A dienophile starting from optically active threonine was designed, the cycloaddition of which gave a mixture of diastereomers. The uniqueness and the beauty of this cycloaddition lies in the simultaneous creation of a tertiary hydroxyl group and the hydroxy alkyl side chain at 9-position during cycloaddition with the hydrolysis of the chiral director without additional effort.;In summary, we have achieved a practical synthetic route towards enantiomerically pure tetralins with absolute stereocontrol, which are building blocks for the AB ring synthon of anthracyclines.
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Type
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dissertation
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Source
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PQT Legacy CUNY.xlsx
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degree
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Ph.D.
