Nitroalkene (4+2) cycloadditions of achiral and chiral vinyl ethers. The stereochemical consequence of the Lewis acid promoter and studies toward the total synthesis of (+)-pretazettine
Schnute, Mark Edward
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Permalink
https://hdl.handle.net/2142/22403
Description
Title
Nitroalkene (4+2) cycloadditions of achiral and chiral vinyl ethers. The stereochemical consequence of the Lewis acid promoter and studies toward the total synthesis of (+)-pretazettine
Author(s)
Schnute, Mark Edward
Issue Date
1995
Doctoral Committee Chair(s)
Denmark, Scott E.
Department of Study
Chemistry
Discipline
Chemistry
Degree Granting Institution
University of Illinois at Urbana-Champaign
Degree Name
Ph.D.
Degree Level
Dissertation
Keyword(s)
Chemistry, Organic
Language
eng
Abstract
Chiral enol ether dienophiles derived from (1R,2S)-($-$)-2-phenylcyclohexanol and (R)-($-$)-2,2-diphenylcyclopentanol (($-$)-6 have been found to provide high levels of asymmetric induction in tandem inter (4+2) /intra (3+2) nitroalkene cycloadditions. Either enantiomeric series of tandem cycloaddition/hydrogenolysis product is available from the chiral auxiliary of a single absolute configuration by judicious selection of the Lewis acid promoter, Ti(Oi-Pr)$\sb{2}$Cl$\sb{2}$ (98% ee, ($-$)) or methylaluminum bis-(2,6-diphenylphenoxide) (MAPh) (93% ee, (+)). Propenyl ethers derived from ($-$)-6 undergo endo-selective (4+2) cycloadditions (2.3/1-8.2/1) in the presence Ti(Oi-Pr)$\sb2$Cl$\sb2$, however, exoselective (4+2) cycloadditions (10.2/l-54.8/l) are observed in the presence of MAPh.
2-(Acyloxy)vinyl ethers undergo regioselective (4+2) cycloadditions with nitroalkenes (promoted by SnCl$\sb4$) to afford substituted 5-acetoxy nitronates in good yields (68%-91%). The endo/exo selectivity in the cycloadditions has been found to be dependent on the nitroalkene substitution; 2-aryl-1-nitroalkenes provided exclusively exo cycloadducts while 2-cyclohexyl-1-nitroethene afforded predominately endo cycloadducts (12/1). The resulting nitronates can be elaborated to N-tosyl-4-substituted-3-hydroxypyrrolidines by hydrogenolysis (160 psi of H$\sb2$/PtO$\sb2$) or to bicyclic $\alpha$-hydroxy lactams by (3+2) cycloaddition followed by hydrogenation (14.7 psi of H$\sb2$/Raney nickel). A chiral 2-acetoxyvinyl ether derived from ($-$)-6 has been employed in the cycloaddition-hydrogenation sequence to prepare an optically active N-tosyl-3-hydroxypyrrolidine in high enantiomeric excess (96% ee). The strategy of nitroalkene (4+2) cycloadditions employing 2-acetoxyvinyl ethers as dienophiles has been explored toward the total synthesis of the Amaryllidaceae alkaloid (+)-pretazettine.
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