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Enzymatic Cascade Reactions for the Synthesis of Chiral Amino Alcohols from L-lysine
Published on: February 16, 2018
Synthesis of chiral 1,4-oxazepane-5-carboxylic acids from polymer-supported homoserine
Petra Králová1, Barbora Lemrová2, Michal Maloň3
1Department of Organic Chemistry, Faculty of Science, Palacký University 771 46 Olomouc Czech Republic miroslav.soural@upol.cz.
Abstract:
The preparation of novel 1,4-oxazepane-5-carboxylic acids bearing two stereocenters is reported in this article. Fmoc-HSe(TBDMS)-OH immobilized on Wang resin was reacted with different nitrobenzenesulfonyl chlorides and alkylated with 2-bromoacetophenones to yield N-phenacyl nitrobenzenesulfonamides. Their cleavage from the polymer support using trifluoroacetic acid (TFA) led to the removal of the silyl protective group followed by spontaneous lactonization. In contrast, TFA/triethylsilane (Et3SiH)-mediated cleavage yielded 1,4-oxazepane derivatives as a mixture of inseparable diastereomers. The regioselectivity/stereoselectivity depended on the substitution of the starting 2-bromoacetophenones and was studied in detail. Catalytic hydrogenation of the nitro group improved the separability of the resulting diastereomeric anilines, which allowed us to isolate and fully characterize the major isomers.
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