We report Pd-catalyzed annulations
of in situ generated strained
cyclic allenes. This methodology employs aryl halides and cyclic allene
precursors as the reaction partners in order to generate fused heterocyclic
products. The annulation proceeds via the formation of two new bonds
and an sp3 center. Moreover, both diastereo- and enantioselective
variants of this methodology are validated, with the latter ultimately
enabling the rapid enantioselective synthesis of a complex hexacyclic
product. Studies leveraging transition metal catalysis to intercept
cyclic allenes represent a departure from the more common, historical
modes of cyclic allene trapping that rely on nucleophiles or cycloaddition
partners. As such, this study is expected to fuel the development
of reactions that strategically merge transition metal catalysis and
transient strained intermediate chemistry for the synthesis of complex
scaffolds.
Strained cyclic allenes are a class of in situ-generated fleeting intermediates that, despite being discovered more than 50 years ago, has received significantly less attention from the synthetic community compared to related strained intermediates. Examples of trapping strained cyclic allenes that involve transition metal catalysis are especially rare. We report the first annulations of highly reactive cyclic allenes with in situ-generated π-allylpalladium species. By varying the ligand employed, either of two isomeric polycyclic scaffolds can be obtained with high selectivity. The products are heterocyclic and sp 3 -rich and bear two or three new stereocenters. This study should encourage the further development of fragment couplings that rely on transition metal catalysis and strained cyclic allenes for the rapid assembly of complex scaffolds.
This chapter describes a convenient method for the removal of tetrabutylammonium salts from desilylation reactions. One especially useful reagent for the removal of silyl protecting groups is tetrabutylammonium fluoride. The solubility of this reagent in organic solvents, as well as its chemoselectivity, has contributed to its frequent usage in the removal of silyl protecting groups. The chapter presents some of the important points to be considered, the conditions that need to be maintained, characterization data, and the reagents required, as well as the techniques used and the equipment setup that are vital to carrying out the process. It also describes the hazards associated with working with chemicals and the ways to deal with these hazards.
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