alkynes · asymmetric catalysis · nucleophilic substitution · propargylic substitution · transition metalsThe nucleophilic substitution of allylic substrates under the catalysis of transition metals has been investigated extensively; [1] however, somewhat surprisingly, the corresponding catalytic propargylic substitution was not studied in much detail until recently. The Nicholas reaction, which involves the nucleophilic substitution of cobalt-complexed propargylic alcohols, enables the incorporation of a wide range of functionalities through the use of various nucleophiles, but has the drawback that a stoichiometric amount of the metal complex is used.[2] There is thus a need for a catalytic propargylation process. Several issues need to be considered in the development of such a reaction: 1) the type of nucleophiles that can be used; 2) restrictions in terms of the propargylic substrate (terminal/internal, aliphatic/aromatic); 3) whether or not the hydroxy functionality requires prior activation; 4) the risk of competing allene formation; 5) possibilities for development of an asymmetric version. We discuss herein the recent developments in this area, with a special focus on asymmetric processes. Organocatalytic methods are not covered, but have been reviewed recently by Kabalka and Yao. [3] One of the earliest transition-metal-catalyzed propargylic substitution reactions described was the copper-catalyzed propargylation reaction reported in 1994 by Murahashi and co-workers, [4] who examined several copper catalysts in the reaction between propargylic phosphates and amine nucleophiles (Scheme 1). Copper(I) chloride was found to give the best results. With this catalyst, propargylic amines were formed in high yields. The reaction is limited to terminal alkynes, but allows the use of both aliphatic and aromatic amines.Nishibayashi and co-workers studied the corresponding asymmetric copper-catalyzed propargylation reaction by using copper(I) triflate together with chiral diphosphine ligands.[5] A variety of aniline derivatives were screened as nucleophiles. The product was formed with up to 89 % ee with chloro-substituted N-methylaniline (Scheme 2). Aliphatic amine nucleophiles could also be used, although the enantioselectivity was lower in this case. The reaction is limited to terminal propargylic acetates with aromatic substituents; the attempted use of an aliphatic propargylic acetate was not successful.Simultaneously with this account, van Maarseveen and co-workers reported the use of chiral bisoxazoline (pybox) ligands and copper catalysis in propargylic amination reactions.[6] Four different copper complexes as well as eight pybox ligands were screened in the propargylic substitution of terminal propargylic acetates with aniline derivatives. Copper(I) iodide in conjunction with ligand 2 gave the best results: The substitution product was formed with up to 88 % ee (Scheme 3). The nature of the base was found to be important not only for the reaction rate, but also for the stereoselectivity. Diisopropylamine ...
Ein Platz in der Ruhmeshalle: Bis kürzlich stand die Titelreaktion im Schatten der katalytischen allylischen Substitution, doch nun wurden für propargylische Substitutionen effiziente Verfahren entwickelt, die durch verschiedene Übergangsmetalle katalysiert werden können (siehe Bild). Zu den neueren Errungenschaften zählen kupferkatalysierte asymmetrische propargylische Aminierungen. Nu = Nucleophil.
Metal carbonyl stabilized cationic species react with a wide range of nucleophiles under mild conditions, and have thus found many synthetic applications. In this Perspective, we describe the utility of iron carbonyl dienyl cations in solution and solid phase parallel synthesis, and in the development of a new synthetic route towards oseltamivir phosphate (Tamiflu). We also discuss the solid phase version of the Nicholas reaction, employing cobalt carbonyl stabilized propargylic cations, and giving access to substituted alkynes.
N e w R o u t e t o N a t u r a l C a m p t o t h e c i n t h r o u g h I s o m ü n c h n o n e C y c l o a d d i t i o nAbstract: A novel approach to camptothecin by [3+2] cycloaddition of an isomünchnone intermediate is described.
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