Total Synthesis of (+)-Hyperaspine, Advances Toward the Total Synthesis of Spirolucidine, and [2+2]-Photochemical Cycloadditions of 2,3-Dihydro-4-Pyridones

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Title: Total Synthesis of (+)-Hyperaspine, Advances Toward the Total Synthesis of Spirolucidine, and [2+2]-Photochemical Cycloadditions of 2,3-Dihydro-4-Pyridones
Author: Sahn, James Jeffrey
Advisors: Dr. Daniel Lee Comins, Committee Chair
Dr. Alex Deiters, Committee Member
Dr. Bruce Novak, Committee Member
Dr. Christian Melander, Committee Member
Abstract: The ladybug alkaloid, (+)-hyperaspine, was synthesized in 6 steps and 21% overall yield. Utilizing Cs2CO3 and CH2Br2, a novel entry into the 3,4,4a,5-tetrahydropyrido[1,2-c][1,3]oxazin-6(1H)-one ring system was developed. The synthesis showcases a stereoselective dissolving-metal reduction, which provided the requisite equatorial alcohol that was rapidly advanced to the natural product. Significant progress has been made towards the total synthesis of the Lycopodium alkaloid, spirolucidine. Implementing a convergent approach to the natural product, zone A was synthesized and united with zone B. Subsequent elaboration of the A-B fragment afforded the N-Boc derivative for an impending ortho-lithiation. Additionally, the racemic, desmethyl zone C was prepared from its carboxylic acid precursor via the Barton ester. Finally, the Negishi cross-coupling reaction was investigated for the union of racemic, desmethyl zone C with a zone B surrogate. The intramolecular [2+2]-photochemical cycloaddition of 2,3-dihydro-4-pyridones proceeded in good yield with excellent stereocontrol. When the photoadducts were treated with SmI2, different mechanistic pathways ensued. The lower homologue underwent a dual ring opening/reduction, rendering a cis 2,6-disubstituted piperidinol. Exposure of the higher homologue to SmI2 resulted in homolytic β-cleavage, which afforded an azaspiro[5.5]undecane.
Date: 2009-01-05
Degree: PhD
Discipline: Chemistry
URI: http://www.lib.ncsu.edu/resolver/1840.16/5539


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