Asymmetrische Synthese von Beta-Aminosulfonaten, Beta-Sultamen und Gamma-Sultonen
type: CreativeWork
description: An efficient asymmetric synthesis of beta-amino-cyclohexyl sulfonates, beta-sultams and gamma-sultones has been developed. The key step of the synthesis is the Lewis acid (zinkbromide) catalyzed aza-Michael addition of the enantiopure hydrazines (S)-1-amino-2-methoxymethyl-pyrrolidine (SAMP) or (R,R,R)-2-amino-3-methoxymethyl-2-azabicyclo[3.3.0]-octane (RAMBO) to alkenyl-cyclohexyl sulfonates. This leads to beta-hydrazino sulfonates in moderate to good yields (41-85%) and diastereomeric excesses (de = 44-90%). The epimers were separated by preparative chirale HPLC. Subsequent reductive N-N bond cleavage with BH3*THF and protection of the resulting amines with benzyloxycarbonyl-chloride (CbzCl) gave N-Cbz-protected beta-amino-cyclohexyl sulfonates in moderate to good yields (38-68% over 2 steps) and high enantiomeric excesses (ee > 96%). Alpha-alkylation of the N-Cbz-protected sulfonates with various electrophiles lead to alpha-alkyl-beta-amino-cyclohexyl sulfonates in good to excellent yields (67-92%) and moderate to high diastereomeric excesses (de = 71-93%). After alkylation with allyliodide, the first asymmetric iodosultonisation was achieved with high selectivites (de > 96%). The N-Cbz-protected beta-amino-cyclohexyl sulfonates were also cyclized in a 4 step synthesis to highly enantioenriched 3-substituted-1,2-thiazetidine 1,1 dioxides (beta-sultams). The reaction sequence starts with the cleavage of sulfonic esters to the corresponding sulfonic acids, followed by chlorination to yield N-Cbz-protected beta-amino-sulfonyl chlorides. After deprotection of the amino group and cyclization, the beta-sultams were obtained in excellent enantiomeric purity (ee > 96%).
abstract: An efficient asymmetric synthesis of beta-amino-cyclohexyl sulfonates, beta-sultams and gamma-sultones has been developed. The key step of the synthesis is the Lewis acid (zinkbromide) catalyzed aza-Michael addition of the enantiopure hydrazines (S)-1-amino-2-methoxymethyl-pyrrolidine (SAMP) or (R,R,R)-2-amino-3-methoxymethyl-2-azabicyclo[3.3.0]-octane (RAMBO) to alkenyl-cyclohexyl sulfonates. This leads to beta-hydrazino sulfonates in moderate to good yields (41-85%) and diastereomeric excesses (de = 44-90%). The epimers were separated by preparative chirale HPLC. Subsequent reductive N-N bond cleavage with BH3*THF and protection of the resulting amines with benzyloxycarbonyl-chloride (CbzCl) gave N-Cbz-protected beta-amino-cyclohexyl sulfonates in moderate to good yields (38-68% over 2 steps) and high enantiomeric excesses (ee > 96%). Alpha-alkylation of the N-Cbz-protected sulfonates with various electrophiles lead to alpha-alkyl-beta-amino-cyclohexyl sulfonates in good to excellent yields (67-92%) and moderate to high diastereomeric excesses (de = 71-93%). After alkylation with allyliodide, the first asymmetric iodosultonisation was achieved with high selectivites (de > 96%). The N-Cbz-protected beta-amino-cyclohexyl sulfonates were also cyclized in a 4 step synthesis to highly enantioenriched 3-substituted-1,2-thiazetidine 1,1 dioxides (beta-sultams). The reaction sequence starts with the cleavage of sulfonic esters to the corresponding sulfonic acids, followed by chlorination to yield N-Cbz-protected beta-amino-sulfonyl chlorides. After deprotection of the amino group and cyclization, the beta-sultams were obtained in excellent enantiomeric purity (ee > 96%).
author: Wallert, Stefan
language: ger
keywords: info:eu-repo/classification/ddc/540, Sulfonate, Aminogruppe, Asymmetrische Synthese, Sultame, Schutzgruppe, Sultone, Chemie, Michael-Addition, Aminosulfonat, Sulton, Sultam
date published: 2003
date modified: 2026-07-30T19:42:39Z
provider: RWTH Aachen University
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: Publikationsserver der RWTH Aachen University