Asymmetrische Synthese von Beta-Aminosulfonaten, Beta-Sultamen und Gamma-Sultonen

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%).

Grantor dc:publisher

Publikationsserver der RWTH Aachen University

Year dc:date

2003

Author dc:creator

• Wallert, Stefan

Contributors dc:contributor

• Enders, Dieter

• info:eu-repo/classification/ddc/540
• Sulfonate
• Aminogruppe
• Asymmetrische Synthese
• Sultame
• Schutzgruppe
• Sultone
• Chemie
• Michael-Addition
• Aminosulfonat
• Sulton
• Sultam

Statement dc:rights

• info:eu-repo/semantics/openAccess

Language dc:language

ger

Identifier

https://publications.rwth-aachen.de/search?p=id:%22RWTH-CONV-120946%22

OAI identifier oai:identifier

oai:publications.rwth-aachen.de:59135