ABSTRACT
Substituted arenes flanked by two bulky triethylsilyl groups were regiospecifically lithiated at the 5-position with nBuLiâ PMDTA at 25 °C. The resulting aryllithiums reacted with a broad range of electrophiles such as ketones, isocyanates, Weinreb amides, allyl bromides, and CO2 at 25 °C. These bis-silylated arenes were then converted in simple reaction sequences into silyl-free tetrasubstituted arenes. This remote lithiation was extended to 2,6-bis(triethylsilyl)pyridine as well as 3,3'-bis(triethylsilyl)biphenyl.
ABSTRACT
Sinoracutine is a recently isolated alkaloid with unusual stereochemical and biological properties. It features an unprecedented tetracyclic 6/6/5/5 skeleton that bears an N-methylpyrrolidine ring fused to a cyclopentenone. Interestingly, both enantiomers of sinoracutine have been independently isolated from the same plant, yet the molecule does not appear to occur as a racemate. Here, we present a short synthesis of (-)-sinoracutine that relies on a highly diastereoselective Pauson-Khand reaction and a Mandai-Claisen reaction to install the quaternary stereocenter. Our work establishes the absolute configuration of the levorotatory isomer and suggests that the optical purity of sinoracutine varies in nature due to its gradual racemization. Experimental evidence supports this proposal, and a plausible mechanism for the racemization is provided.