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Applications of nitroalkene (4+2); cycloaddition chemistry. The asymmetric synthesis of substituted pyrrolidines and the total synthesis of mesembrine

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Title: Applications of nitroalkene (4+2); cycloaddition chemistry. The asymmetric synthesis of substituted pyrrolidines and the total synthesis of mesembrine
Author(s): Marcin, Lawrence R.
Doctoral Committee Chair(s): Denmark, Scott E.
Department / Program: Chemistry
Discipline: Chemistry
Degree Granting Institution: University of Illinois at Urbana-Champaign
Degree: Ph.D.
Genre: Dissertation
Subject(s): Chemistry, Organic
Abstract: A general route for the preparation of 2,2-disubstituted 1-nitroalkenes has been developed. Conjugate 1,4-addition of zinc cuprates (RCu(CN)ZnI) to easily obtained (E)-1-nitroalkenes, followed by trapping with phenylselenenyl bromide, and subsequent oxidative elimination afforded the corresponding 2,2-disubstituted 1-nitroalkenes in 76-88% yield as E/Z isomeric mixtures ($\sim$1.0/1.5, E/Z). 2,2-Disubstituted-1-nitroalkenes were found to undergo Lewis acid-promoted (4+2) cycloadditions with n-butyl vinyl ether to afford cyclic nitronates in 76-90% yield. The resulting nitronates were reduced with hydrogen in the presence of platinum oxide to afford 3,3-disubstituted pyrrolidines which were isolated in 70-83% yield as their N-tosyl derivatives. Similarly, cycloadditions of (E)-2-nitrostyrene with 2-substituted enol ethers provided for the stereoselective synthesis of cis- and trans-3,4-disubstituted pyrrolidines.(E)-2-Substituted 1-nitroalkenes undergo highly diastereoselective (4+2) cycloadditions with the chiral vinyl ethers derived from (R)-2,2-diphenylcyclopentanol and (1R,2S)-2-phenylcyclohexanol to afford nitronates in high yields. The resulting nitronates were reduced to afford enantiomerically enriched pyrrolidines in good yields. A series of 3-substituted pyrrolidines (71-97% ee) were prepared, as well as (3S,4R)-4-methyl-3-phenyl-N-(p-tolylsulfonyl)pyrrolidine (92% ee) and (3S,4S)-3,4-diphenylpyrrolidine (99% ee).The total synthesis of ($-$)-mesembrine was accomplished in seven steps and 19% yield from a functionalized 2,2-disubstituted 1-nitroalkene, which was prepared in six steps and 34% yield from ethyl 3-bromopropionate. The quaternary, stereogenic center of the natural product was established in 26/1 selectivity through an asymmetric (4+2) cycloaddition with a chiral vinyl ether derived from (1R,2S)-2-(1-methyl-1-phenylethyl)cyclohexanol.
Issue Date: 1996
Type: Text
Language: English
URI: http://hdl.handle.net/2142/20131
ISBN: 9780591199345
Rights Information: Copyright 1996 Marcin, Lawrence R.
Date Available in IDEALS: 2011-05-07
Identifier in Online Catalog: AAI9712369
OCLC Identifier: (UMI)AAI9712369
 

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