Catalytic enantioselective synthesis of quaternary carbon stereocentres.

Quaternary carbon stereocentres-carbon atoms to which four distinct carbon substituents are attached-are common features of molecules found in nature. However, before recent advances in chemical catalysis, there were few methods of constructing single stereoisomers of this important structural motif. Here we discuss the many catalytic enantioselective reactions developed during the past decade for the synthesis of single stereoisomers of such organic molecules. This progress now makes it possible to incorporate quaternary stereocentres selectively in many organic molecules that are useful in medicine, agriculture and potentially other areas such as flavouring, fragrances and materials

Palladium-Catalyzed Cascade Approach to 12-(Aryl)indolo[1,2- c ]quin­azolin-6(5 H )-ones

A straightforward one-pot approach to the synthesis of challenging 12-arylindolo[1,2-c]quinazolin-6(5H)-ones is described. Starting from readily available o-(o-aminophenylethynyl)trifluoroacetanilides, palladium-catalyzed aminoarylation of the triple bond with ArI, ArBr, and ArN2 +BF4 – is followed by cyclization of the resulting N-trifluoro­acetyl-2-(o-aminophenyl)-3-aryl indole. This sequential reaction provides the title compounds by means of a rare elimination of trifluoromethane

Pd-catalyzed enantioselective aerobic oxidation of secondary alcohols: Applications to the total synthesis of alkaloids

Enantioselective syntheses of the alkaloids (-)-aurantioclavine, (+)-amurensinine, (-)-lobeline, and (-)- and (+)-sedamine are described. The syntheses demonstrate the effectiveness of the Pd-catalyzed asymmetric oxidation of secondary alcohols in diverse contexts and the ability of this methodology to set the absolute configuration of multiple stereocenters in a single operation. The utility of an aryne C-C insertion reaction in accessing complex polycyclic frameworks is also described

Indolo[2,3-a]quinolizidines and derivatives: Bioactivity and asymmetric Synthesis

Corynantheine alkaloids with a tetracyclic indole[2,3-a]-quinolizidine motif are an important issue in academia and in the life science industries due to their broad bioactivity profile. In particular, the main biological effects described for indoloquinolizidines include analgesic, anti-inflammatory, antihypertensive, and antiarrhythmic activities, as well as inhibition of multiple ion channels, affinity for opioid receptors, and activity against Leishmania. For that reason, in the last decades, numerous efforts have been invested in the development of novel synthetic strategies to obtain the indole[2,3-a]-quinolizidine system. This review focuses on the synthetic methodologies developed to target the most important alkaloids of this family, and highlights the potential use of these alkaloids or analogs to treat several diseases, ranging from cancer to neurodegenerative disorders

Palladium-Catalyzed Cross-couplings of Lithium Arylzincates with Aromatic Halides. Synthesis of Analogues of Isomeridianin G and Evaluation as GSK- 3 Inhibitors

International audienceSeveral analogues of Isomeridianin G have been synthesized using as a key step palladium-catalyzed crosscoupling reactions of lithium triorganozincates. The latter have been prepared by deprotonative lithiation followed by transmetalation using ZnCl2*TMEDA (1/3 equiv)

ppm Pd-catalyzed, Cu-free Sonogashira couplings in water using commercially available catalyst precursors.

A new catalyst that derives from commercially available precursors for copper-free, Pd-catalyzed Sonogashira reactions at the sustainable ppm level of precious metal palladium under mild aqueous micellar conditions has been developed. Both the palladium pre-catalyst and ligand are commercially available, bench stable, and highly cost-effective. The catalyst is applicable to both aryl- and heteroaryl-bromides as educts. A wide range of functional groups are tolerated and the aqueous reaction medium can be recycled. An application to a key intermediate associated with an active pharmaceutical ingredient (ponatinib) is discussed

Formal total syntheses of classic natural product target molecules via palladium-catalyzed enantioselective alkylation

Pd-catalyzed enantioselective alkylation in conjunction with further synthetic elaboration enables the formal total syntheses of a number of “classic” natural product target molecules. This publication highlights recent methods for setting quaternary and tetrasubstituted tertiary carbon stereocenters to address the synthetic hurdles encountered over many decades across multiple compound classes spanning carbohydrate derivatives, terpenes, and alkaloids. These enantioselective methods will impact both academic and industrial settings, where the synthesis of stereogenic quaternary carbons is a continuing challenge

Synthesis of indoles via palladium-catalyzed annulation of aryl chlorides and internal alkynes

Thesis (S.M.)--Massachusetts Institute of Technology, Dept. of Chemistry, 2005.Includes bibliographical references (leaves 34-35).A palladium-catalyzed preparation of 2,3-disubstituted indoles from commercially available and relatively inexpensive reagents, o-chloroacetanilide and internal alkynes, is reported. The system is efficient in delivering 2,3-disubstituted indoles in good to excellent yield with a high level of regioselectivity in most cases. Alkynes with alkyl, aryl, alkenyl, and trialkylsilyl substituents are compatible with this methodology.by Daemian David Dussault.S.M