Synthetic studies towards the total synthesis of (-)-Cephalotaxine
Abstract
Synthetic studies towards the total synthesis of ($-$)-Cephalotaxine are described. The key chemical transformations involved are: (1) intramolecular Heck reaction to establish the cis C3,4 stereochemistry; (2) regioselective p-alkoxy benzylic ether cleavage by BBr$\sb3$; (3) TsOH$\cdot$H$\sb2$O promoted intra-molecular lactone formation from 6.2; (4) alkylative isomerization of vinyl sulfones under basic phase-transfer catalyst conditions; and (5) Pd (0) promoted intramolecular amination to construct the azabicycle of the target with complete regio- and stereocontrol and to set the stage for the future intramolecular reductive amination upon deprotection of thioacetal and p-methoxybenzyl group. Earlier model studies led to the discovery of several new vinyl sulfone based methodologies: (1) Regiospecific silver (I) promoted, palladium (0) -catalyzed intramolecular addition of aryl iodide to vinyl sulfone; (2) A highly efficient synthesis of $\beta$-substituted 6 and 7-membered ring enones via carbon alkylation of $\gamma$-methoxy allylsulfonyl anions; (3) A facile synthesis of $\beta$-cyclopentenylsubstituted dienones and trienones; (4) Conversion of vinyl sulfones to regiospecifically functionalized trisubstituted olefins; (5) Regiospecific alkylative isomerization of vinyl sulfones under PTC conditions in a system capable of undergoing anion-promoted $\beta$-elimination; and (6) Palladium (0) -catalyzed intramolecular allylic amination using allyl sulfones as the substrates to construct spiro-fused azabicycle. The scope and limitations of these methodologies are described.
Degree
Ph.D.
Advisors
Fuchs, Purdue University.
Subject Area
Organic chemistry
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