Design of a second generation MIDA boronate: iterating c(sp3) based Suzuki cross couplings

Small molecules have had a tremendous positive impact on human health and society in general. Despite this, small molecule synthesis is still a time and cost intensive process practiced primarily by highly trained specialists. Inspired by the impact of general, automated synthesis platforms for peptides and other biomolecules, we have pioneered iterative cross coupling (ICC) as an analogous platform for small molecules. Enabled by both a building block based synthesis strategy and a general purification protocol, our group has designed and built a small molecule synthesizer. We have demonstrated the ability of this synthesizer to access a wide variety of small molecules, including natural products, pharmaceuticals, and materials components. Further, the synthesizer is able to access complex, polycyclic, C(sp3) rich natural products through the use of the “linear-to-cyclized” strategy wherein linear precursors are prepared on the machine in an automated fashion and then manually cyclized. Given the ubiquity of stereogenic C(sp3) carbons in natural products, the ability to stereospecifically couple secondary alkyl fragments iteratively would be highly enabling. However, all currently known methods for such transformations require conditions which hydrolyze MIDA boronates (aqueous base, high heat, strong base, etc.). In this thesis I describe the development of a second generation iminodiacetic acid ligand for boronic acids which is refractory to hydrolysis and has enabled the first examples of coupling unactivated, secondary alkyl boronic acids in the context of an iterative cross coupling cycle.

Name thesis:degree_name

M.S.

Level thesis:degree_level

Thesis

Discipline thesis:degree_discipline

Chemistry

Grantor

University of Illinois at Urbana-Champaign

Year dc:date

2017

Author dc:creator

• Schmidt, Michael Joseph

Contributors dc:contributor

• Burke, Martin D.

• Suzuki
• coupling
• cross coupling
• MIDA boronate
• iteration
• automation

Statement dc:rights

• Copyright 2016 Michael Schmidt

Language dc:language

en

Handle dc:identifier

http://hdl.handle.net/2142/95599

OAI identifier oai:identifier

oai:www.ideals.illinois.edu:2142/95599