Synthesis and steredivergent conversion of 4-amino-1,2-butanediols to pyrrolidines.
Thobejane, Nkwane Donald
Thobejane, Nkwane Donald
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Abstract
In this study, a stereo divergent 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
2018-06-01
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Tshwane University of Technology
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Keywords
Stereodivergent, Pyrrolidines, Diastereoselective, Homoallylic amines, Cyclodehydration