Total Synthesis of (+)-Hyperaspine, Advances Toward the Total Synthesis of Spirolucidine, and [2+2]-Photochemical Cycloadditions of2,3-Dihydro-4-Pyridones

samarium diiodide;dihydropyridone;hyperaspine;spirolucidine;2+2;photocycloaddition;azaspiro

Sahn, James Jeffrey ; Dr. Daniel Lee Comins, Committee Chair,Dr. Alex Deiters, Committee Member,Dr. Bruce Novak, Committee Member,Dr. Christian Melander, Committee Member,Sahn, James Jeffrey ; Dr. Daniel Lee Comins ; Committee Chair ; Dr. Alex Deiters ; Committee Member ; Dr. Bruce Novak ; Committee Member ; Dr. Christian Melander ; Committee Member

University:North Carolina State University

关键词: samarium diiodide;    dihydropyridone;    hyperaspine;    spirolucidine;    2+2;    photocycloaddition;    azaspiro;   

Others  :  https://repository.lib.ncsu.edu/bitstream/handle/1840.16/5539/etd.pdf?sequence=1&isAllowed=y

美国|英语

来源: null

【 摘 要 】

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.