The Application of Trimethylsilyl Diazomethane to the Synthesis of Optically Active Pyrazolines and Related Studies

Citation

Mish, Michael Robert (2001) The Application of Trimethylsilyl Diazomethane to the Synthesis of Optically Active Pyrazolines and Related Studies. Dissertation (Ph.D.), California Institute of Technology. doi:10.7907/s6ej-q525. https://resolver.caltech.edu/CaltechTHESIS:03252014-083524220

Abstract

The 1,3-dipolar cycloadditions of trimethylsilyl diazomethane with camphorsultam-derived acrylates are reported as a means for the efficient synthesis of optically active pyrazolines. Trimethylsilyl diazomethane is a safe, commercially available diazoalkane which provides Δ¹-pyrazolines 1n good yield and diastereoselectivity when camphorsultam-derived acrylates are used as the reaction dipolarophiles . These initial cycloadducts are subsequently converted to stable, characterizable Δ²-pyrazolines upon desilylation.

A manifold of reactions that can be applied to these Δ²-pyrazolines has been developed which includes pyrazoline reduction, N-N bond reduction, addition to the pyrazoline C=N by mild carbon nucleophiles, and both solvolytic and reductive chiral auxiliary removal. Additionally, it has been demonstrated that the pyrazoline reduction products can take part in peptide coupling reactions that allow for the pyrazolidines to serve as proline-like molecules. The development of this methodology is a general solution to the problem of highly substituted, functionalized pyrazoline synthesis. Importantly, the pyrazolines thus provided have been demonstrated to be amenable to reactions that add to their value as synthetic intermediates.

Thesis Files