Asymmetric synthesis of chiral β-alkynyl carbonyl and sulfonyl derivatives via sequential palladium and copper catalysis† †Electronic supplementary information (ESI) available. See DOI: 10.1039/c6sc01724j Click here for additional data file.
نویسندگان
چکیده
We present a full account detailing the development of a sequential catalysis strategy for the synthesis of chiral b-alkynyl carbonyl and sulfonyl derivatives. A palladium-catalyzed cross coupling of terminal alkyne donors with acetylenic ester, ketone, and sulfone acceptors generates stereodefined enynes in high yield. These compounds are engaged in an unprecedented, regioand enantioselective copper-catalyzed conjugate reduction. The process exhibits a high functional group tolerance, and this enables the synthesis of a broad range of chiral products from simple, readily available alkyne precursors. The utility of the method is demonstrated through the elaboration of the chiral b-alkynyl products into a variety of different molecular scaffolds. Its value in complex molecule synthesis is further validated through a concise, enantioselective synthesis of AMG 837, a potent GPR40 receptor agonist.
منابع مشابه
Asymmetric synthesis of chiral cycloalkenone derivatives via palladium catalysis† †Electronic supplementary information (ESI) available: Detailed experimental procedures and copies of NMR spectra and HPLC chromatograms. See DOI: 10.1039/c3sc53250j Click here for additional data file.
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متن کاملAsymmetric synthesis of chiral β-alkynyl carbonyl and sulfonyl derivatives via sequential palladium and copper catalysis.
We present a full account detailing the development of a sequential catalysis strategy for the synthesis of chiral β-alkynyl carbonyl and sulfonyl derivatives. A palladium-catalyzed cross coupling of terminal alkyne donors with acetylenic ester, ketone, and sulfone acceptors generates stereodefined enynes in high yield. These compounds are engaged in an unprecedented, regio- and enantioselectiv...
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A synthesis of the bioactive indolocarbazole alkaloid K-252c (staurosporinone) via a sequential C–H functionalisation strategy is reported. The route exploits direct functionalisation reactions around a simple arene core and comprises of two highly-selective copper-catalysed C–H arylations, a coppercatalysed C–H amination and a palladium-catalysed C–H carbonylation, which build up the structura...
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