Author's School

Graduate School of Arts & Sciences

Author's Department/Program

Chemistry

Language

English (en)

Date of Award

Summer 9-3-2013

Degree Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Chair and Committee

Vladimir Birman

Abstract

In the context of enantioselective nucleophilic acyl substitution, there are 3 types of processes depending where chirality is present: Type I, where the nucleophile: alcohol or amine) gets resolved, Type II, where chirality resides in the leaving group, and Type III, where a chiral acyl donor is attained in enantioenriched form. All these transformations can be used to physically separate enantiomers from a racemate in the presence of an asymmetric acylation catalyst and thus can be termed as "kinetic resolutions" or KR. Considerable progress has been done in the Type I transformation, where chiral alcohols, thiols, and amines are achieved with great selectivities via asymmetric enzymatic and non-enzymatic acylation. KR of chiral acyl donors: Type III) has also been accomplished using both enzymatic and non-enzymatic modes of catalysis. However, Type II process has only been reported enzymatically.

Since 2003 our group has developed 4 consecutive generations of amidine-based catalysts: ABCs) that have engaged in a variety of enantioselective acylation transformations, mostly Type I: KR of various alcohols and lactams: and thiolactams) via asymmetric acylation) and Type III: enantioselective alcoholysis of α-substituted acids and azlactones) processes.

As a contribution and an extension to enantioselective, catalytic, nucleophilic acyl substitution study with ABCs, my work has left a mark in all three types of processes discussed above. An unprecedented KR of N-acyl-β-lactams via enantioselective alcoholysis: Type III) has been achieved with great results. The established protocol leads to preparation of β-amino acids derivatives in enantioenriched form. Equally unique in this transformation is the mode of action of ABCs, where for the first time the nucleophilic attack of our catalysts on chiral acyl donors was in itself highly enantioselective - a phenomenon in contrast to usual behavior of ABCs in previously studied processes in our lab. Similarly novel, or at least conceptually, was the accomplishment of the first asymmetric de-acylation: Type II) process reported to date using non-enzymatic acyl transfer catalyst in the form of asymmetric alcoholysis of N-acyl-thiolactams. The KR poses an alternate route to obtaining enantioenriched thiazolidin-2-thiones and oxazolidine-2-thiones. And last but not least, the first enantioselective N-acylation of β-lactams: a Type I process) has been obtained with acceptable to good selectivities. This method complements the enantioselective alcoholysis of N-acyl-β-lactams, since it achieves unscathed enantioenriched β-lactams.

Comments

Permanent URL: http://dx.doi.org/10.7936/K7S46Q0Q

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