Michael A. Calter
This thesis presents the development of new methodologies and the conservation of enantiopurity throughout reduction reaction sequence.
The first work was an extension of a previously developed asymmetric IFB reaction of α-tosyloxy aldehyde as electrophile and dimedone as a nucleophile. This reaction produced the corresponding C-alkylation product, in the form of a hemiacetal product that was isolated in moderate yield. This product was transformed into chiral dihydrofuran via the reduction of the aldehyde with sodium borohydride. The best enantiomeric excess (21%) was achieved by phenyl naphthyl bis QD catalyst.
The second project presents progress made towards the asymmetric total synthesis of the natural product Aflatoxin M1. α-bromopyruvate and 3, 5-dimethoxy phenol was submitted to the typical reaction conditions, to get the IFB product. This reaction provides the core of the Aflatoxin type natural product.
In the third project, an IFB product is a result of the reaction between hydroxyl coumarin as a nucleophile and 3-bromo-1-phenylpropane-1,2-dione as an electrophile. Enantioselectivity is achieved using cinchona alkaloid pyrimidinyl catalysts. The best chiral catalysts to date, which provided 29% enantiomeric excess of R- enantiomer, is (Quinidine) 2 Pyr [2-(2-phenyl -6-methoxy pyridine), 5-phenyl]. IFB reaction creates one stereocenter and also forms one of the rings in the natural product, (+) - Gmelinol.
Formation of the IFB product, gives rise to tetrasubstituted olefin. Reduction of IFB product results in three different products that can be useful precursor for the 2 synthesis of Gmelinol. Various attempts at hydrogenation of olefin were carried out that did not produce expected product. Conversely, this process originated some byproducts that drawn the attention to a new trajectory, starting from the IFB to the fully reduce IFB product. The goal here was to conserve percent enantiomeric excess (ee) for each step till the last reduction step; is accomplished. It was found that the secondary hydroxyl group needs to be protected to conserve enantiomeric excess. The unprotected secondary alcohol falls off to form an achiral furan, which then leads to racemic product. The conservation of % ee was accomplished throughout the reduction/elimination sequence.
Bhatawdekar, Prachiti, "Conservation of Enantiomeric Excess Throughout a Multistep Reduction / Elimination Reaction Sequence Starting with an Interrupted Feist-Bénary Product" (2019). Dissertations. 104.
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