Synthesis and stereodivergent conversion of 4-amino-1,2 butanediols to pyrrolidines.
Thobejane, Nkwane Donald
Thobejane, Nkwane Donald
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Abstract
In this study, a stereodivergent synthetic strategy for pyrrolidines based on a diastereoselective ring closing reaction (cyclodehydration) of 4-amino-1,2-butanediols was investigated. The target pyrrolidines were obtained via a four (4) step synthetic plan. Initially, commercially available aldehydes were converted into imines in high yields (90-98%) via the Schiff base reaction. The imines were then allylated to give homoallylic amines in high yields (70-85%) using allyl magnesium bromide.
The homoallylic amines were oxidized using Upjohn dihydroxylation method utilizing catalytic osmium tetroxide; when successful this method gave inseparable mixtures of amino-diol diastereomers in poor yields (39-45%). However, during this dihydroxylation good stereoselectivity was observed in a 3:1 ratio, in favour of syn-4-amino-1,2-butanediols. The amino-diols were later converted into pyrrolidines in moderate yields (51-90%) using the tin-mediated cyclodehydration/sulfonylation protocol. The conversion of anti-amino diols also gave a side product of anti-4-amino-2-hydroxytosylates (10%).
A key unexpected finding was that under the Upjohn method the majority of the homoallylic amines were oxidized directly to pyrrolidines, instead of the 4-amino-1,2-butanediols. The yields were moderate (51-59%), but the mechanism of cyclization via an in situ ring opening of the incipient osmate ester presents a shorter route to the target pyrrolidine molecules. The diastereomeric ratios (syn/anti) of 2:1 was obtained in favour of the syn-pyrrolidines.
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Submitted as partial fulfilment of the requirements for the degree, Magister Technologiae: Chemistry in the Department of Chemistry, Faculty of Science at the Tshwane University of Technology.
Date
2018-06-02
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Tshwane University of Technology
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Keywords
Cyclodehydration, Stereodivergent, Amino-diol, Diastereoselective, Cyclization