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Synthesis 2003(12): 1856-1868
DOI: 10.1055/s-2003-41029
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© Georg ThiemeVerlag Stuttgart · New York

Asymmetric Synthesis of β-AminoCyclohexyl Sulfonates, β-Sultams and γ-Sultones

Dieter Enders*, Stefan Wallert, Jan Runsink
Institut für Organische Chemie, Rheinisch-Westfälische Technische Hochschule, Professor-Pirlet-Straße 1, 52074 Aachen, Germany
Fax: +49(241)8092127; e-Mail: enders@rwth-aachen.de;
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Publication History

Received 3 June 2003
Publication Date:
13 August 2003 (online)

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Abstract

An efficient asymmetric synthesis of β-aminocyclohexyl sulfonates, β-sultamsand γ-sultones has been developed. The key step of thesynthesis is the Lewis acid catalyzed aza-Michael addition of theenantiopure hydrazines SAMP [(S)-1] or RAMBO [(R,R,R)-2] toalkenylcyclohexyl sulfonates 3. This leadsto β-hydrazino sulfonates 4a-k in moderate to good yields (41-85%)and diastereomeric excesses (de = 44-90%).The epimers were separated by preparative HPLC. Subsequent reductiveN-N bond cleavage with BH3·THF andprotection of the resulting amines with CbzCl gave N-Cbz-protected β-aminocyclohexylsulfonates 6a-k inmoderate to good yields (38-68% over 2 steps)and high enantiomeric excesses (ee ≥ 96%). α-Alkylationof 6 with various electrophiles afforded α-alkyl-β-aminocyclohexylsulfonates 10a-g ingood to excellent yields (67-92%) and moderateto high diastereomeric excesses (de = 71-93%).After alkylation with allyl iodide, the first asymmetric iodosultonizationwas achieved with high selectivities. Compounds 6g-k were also cyclized in a four-step synthesisto highly enantio-enriched 3-substituted-1,2-thiazetidine 1,1-dioxides (β-sultams) 9a-e.

Key words

asymmetric synthesis - Michael addition - sulfonates - β-sultams - γ-sultones - hydrazines