Development and Applications of Hydrazone-Based Transformations for the Synthesis of Allenes

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The diverse reactivity patterns, unique structural features imparted by the cumulated double bonds, and possibility of axial chirality have garnered allenes considerable attention in organic synthesis. Numerous methods have been described in the literature to afford optically active allenes starting from chiral starting materials, yet catalytic and asymmetric methods to directly synthesize chiral allenes from achiral precursors remain underdeveloped. Furthermore, few methods exist that can directly generate aliphatic allenes through mild fragment-coupling reactions. Herein we describe two elaborations of a Petasis reaction of N-sulfonylhydrazones to enable the direct synthesis of allenes. The first involves the alkynylation of aliphatic N-sulfonyl hydrazones to generate aliphatic allenes. This reaction was optimized in a high-throughput fashion by SAMDI mass spectrometry. The second project presents an organocatalytic, asymmetric boronate addition to N-sulfonyl hydrazones enabled by chiral binaphthols to access enantioenriched 2,3-allenols or 1,3-alkynyl allenes. The application of the latter methodology to the synthesis of chiral natural products is also described, in particular the exploitation of the known ability of 2,3-allenol to undergo gold-mediated cycloisomerization to enable the convergent stereocontrolled synthesis of potent anticancer and antimalarial annonaceus acetogenin natural products (+)-solamin and (+)-cis-solamin.

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  • 02/18/2019
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