Cyclic acetal templates for the stereoselective synthesis of 2,5-disubstituted tetrahydrofurans (THF's).
Item
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Title
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Cyclic acetal templates for the stereoselective synthesis of 2,5-disubstituted tetrahydrofurans (THF's).
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Identifier
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AAI9720158
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identifier
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9720158
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Creator
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Zhang, Huiping.
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Contributor
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Adviser: David R. Mootoo
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Date
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1997
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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, Pharmaceutical
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Abstract
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The use of cyclic acetals as templates for the stereoselective synthesis of 2,5-disubstituted tetrahydrofuran (THF) was investigated. The study centered on the iodoetherification of hydroxyalkenes which were embedded in C6 allylated 2,3-dideoxy pyranoside or in 5,6-O-isopropylidene alkene substrates. The reactions were performed in wet {dollar}\rm CH\sb2Cl\sb2{dollar} or CH{dollar}\sb3{dollar}CN using iodonium perchlorate (IDCP).;In part II, the reactions of C6 allylated 2,3-dideoxy-gluco and galacto-pyranosides are discussed. The effect of aglycone structure and alkene substitution was evaluated. High cis stereoselectivity ({dollar}>{dollar}10/1 c/t) was achieved in good yield (78-91%) with trityl pyranoside alkenes. A transition state model was proposed to rationalize the observed stereoselectivity. This assumed a preferred chair like reactive conformation involving the four carbon atoms of the eventual THF ring. More substituted pyranoside substrates (galacto, gluco, and manno) were also investigated. Excellent cis stereoselectivity and high yields were obtained in galacto series. The gluco and manno systems also gave good yield but with moderate to low stereoselectivity. The application of these results to the synthesis of complex polyether is discussed.;The iodocyclization of 5,6-O-isopropylidene alkenes is described in Part III. These templates gave the trans 2,5-disubstituted THF's in extremely high stereoselectivity and in excellent yields (88-95%). This stereoselectivity is complementary to results achieved with the trityl pyranosides templates.;The trans 2,5-disubstituted THF methodology was applied to the synthesis of THF containing acetogenins. A chiral building block whose structure is primed for elaboration into a variety of naturally mono and bis-THF acetogenins, was prepared in a concise and straightforward procedure. The synthesis was carried out in 8 steps and in 46% overall yield from 4-benzyloxybutanal. It capitalizes on the enantioselectivity and regioselectivity of the Sharpless asymmetric dihydroxylation and the high trans selective iodoetherification of 5,6-O-isopropylidene alkenes.
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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.
