An efficient and flexible asymmetric synthesis of various protected anti-1,2-sulfanyl amines bearing two adjacent stereogenic centres is described. Key steps are the diastereoselective α-alkylation of α-sulfanylated acetaldehyde-SAMPhydrazones with various electrophiles and subsequent nucleophilic 1,2-addition of organocerium reagents to the hydrazone CN double bond. The resulting hydrazines were converted into the title compounds with excellent diastereo-
A s y m m e t r i c S y n t h e s i s o f 1 , 2 -a n t i t e r t -B u t y l s u l f a n y l A m i n e s Abstract: A flexible diastereo-and enantioselective synthesis of various 1,2-anti tert-butylsulfanyl amines 5a-e is described. As starting material SAMP-hydrazone (S)-2 was obtained from 2-(bromomethyl)-1,3-dioxolane (1) in a three-step procedure. a-Alkylation with various electrophiles, followed by 1,2-addition to the C-N double bond and removal of the auxiliary by cleavage of the N-Nbond results in the title compounds in excellent diastereomeric and enantiomeric excesses (de, ee ³ 96%).In recent years chiral vic-alkylsulfanyl amines became a focus of interest as N,S-chelates in asymmetric catalysis. 1 Since the sulfur atom becomes a stereocentre when coordinated to a metal, they reveal another potential than their N, N-and N,O-counterparts. 2 Compared to the popular 1,2-amino alcohol ligands, 3 there has been little research on the synthesis of enantiopure 1,2-thioether amines. Some ex-chiral-pool 1a,4 and diastereoselective syntheses 5 have been reported for this class of compounds but to the best of our knowledge there is only one asymmetric synthesis of an N-acetyl methylsulfanyl amine 6 described. Our synthetic strategy employing the SAMP/RAMP-hydrazone methodology 7 provides a flexible route to the desired title compounds and gives access to both anticonfigured enantiomers.The concept of a-alkylation of SAMP/RAMPhydrazones 7a followed by 1,2-addition 7b and reductive N-N bond cleavage 8 has been demonstrated by our group in various applications. 9 We now report an extension of our previous protocol concerning the tolerance of an alkylsulfanyl moiety in the system. The starting material is readily obtained in 74% yield from commercially available 2-(bromomethyl)-1,3-dioxolane (1) by a three step sequence in multigram scale (Scheme 1). 10
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