The total syntheses of (+)-crotanecine, (-)-hastanecine and (-)-rosmarinecine utilizing the tandem (4+2)/(3+2) cycloadditions of nitroalkenes
Thorarensen, Atli
This item is only available for download by members of the University of Illinois community. Students, faculty, and staff at the U of I may log in with your NetID and password to view the item. If you are trying to access an Illinois-restricted dissertation or thesis, you can request a copy through your library's Inter-Library Loan office or purchase a copy directly from ProQuest.
Permalink
https://hdl.handle.net/2142/19961
Description
Title
The total syntheses of (+)-crotanecine, (-)-hastanecine and (-)-rosmarinecine utilizing the tandem (4+2)/(3+2) cycloadditions of nitroalkenes
Author(s)
Thorarensen, Atli
Issue Date
1996
Doctoral Committee Chair(s)
Denmark, Scott E.
Department of Study
Chemistry, Organic
Discipline
Chemistry, Organic
Degree Granting Institution
University of Illinois at Urbana-Champaign
Degree Name
Ph.D.
Degree Level
Dissertation
Keyword(s)
Chemistry, Organic
Language
eng
Abstract
A short and efficient asymmetric synthesis of the pyrrolizidine necine base (${-}$)-hastanecine is described. The key reaction in the synthesis is a sequential inter (4+2) /inter (3+2) cycloaddition. The Lewis acid promoted (4+2) cycloaddition between 2-acyloxy nitroalkene 90 and chiral vinyl ether (+)-28 afforded a nitronate which underwent facile (3+2) cycloaddition with dimethyl maleate. The resulting nitroso acetal (${-}$)-96 had all the required stereocenters for (${-}$)-hastanecine. The critical unmasking of the nitroso acetal (${-}$)-96 employed a hydrogenolytic cleavage to give the 1-azabicyclo (3.3.0) octane skeleton of (${-}$)-hastanecine.
(${-}$)-Rosmarinecine 42 is the necine base portion of the pyrrolizidine alkaloid (${-}$)-rosmarinine. (${-}$)-Rosmarinecine is a representative of that group of pyrrolizidines which bear a cis relationship between adjacent stereocenters C(1), C(7) and C(7a) in addition to a highly oxygenated skeleton. (${-}$)-Rosmarinecine has been synthesized in 8 steps and 14.8% overall yield, as an illustration of a general approach for the construction of pyrrolizidines bearing this stereochemical feature. The key step in the asymmetric synthesis is a Lewis acid-promoted, tandem inter (4+2) /intra (3+2) cycloaddition between a fumaroyloxynitroalkene 165 and a chiral vinyl ether (${-}$)-29.
Numerous alkaloids contain (+)-crotanecine 36 as it necine constituent. (+)-Crotanecine which is an all cis substituted necine has been prepared in 10 steps and 10.2% overall yield. The key steps in the asymmetric synthesis is a Lewis acid-promoted, tandem inter (4+2) /intra (3+2) cycloaddition between a fumaroyloxynitroalkene 165 and a chiral propenyl ether (${-}$)-222 and a solvolytic elimination of a mesylate to install the unsaturation at C(6)-C(7).
Use this login method if you
don't
have an
@illinois.edu
email address.
(Oops, I do have one)
IDEALS migrated to a new platform on June 23, 2022. If you created
your account prior to this date, you will have to reset your password
using the forgot-password link below.
