Event Information
Regioselective, Asymmetric a,a-Bisalkylation of Ketones via N-Amino Cyclic Carbamate Chiral Auxiliaries: Methodology Development and Application to the Total Synthesis of both (+) and (-)-Stigmolone and Apratoxin D
- Abstract:
The a-alkylation of ketones is a transformation of central importance to organic synthesis. Our lab recently introduced the N-amino cyclic carbamate (ACC) chiral hydrazide auxiliaries, which affect asymmetric ketone a-alkylation in high yield and with excellent stereoselectivity, via the derived hydrazones. A unique feature of ACCs is their ability to control the regioselectivity of deprotonation through what we have termed Complex Induced Syn-Deprotonation. We will describe several projects relating to the development and synthetic application of ACCs.
We have employed ACCs in the development of the first method for the regiocontrolled asymmetric a,a-bisalkylation of ketones, which proceeds in excellent yield and with >99:1 diastereoselectivity. This method was also extended to the asymmetric a,a,a',a'-tetraalkylation of ketones, enabled by the development of a mild, epimerization-free LDA-mediated isomerization of the a,a-bisalkylated ACC hydrazones.
Additionally, we will discuss three synthetic applications of the ACC a,a-bisalkylation methodology. We successfully applied our method to the asymmetric formal syntheses of both (+)- and (–)-stigmolone, as well as two approaches to the polyketide fragment of the novel cyclic depsipeptide apratoxin D, resulting in the completion of its first asymmetric total synthesis.
Ph.D. Dissertation Defense Examination Seminar
Departmental Seminar