Robinson annulation, anionic cyclizations

Anionic domino processes are the most often encountered domino reactions in the chemical literature. The well-known Robinson annulation, double Michael reaction, Pictet-Spengler cyclization, reductive amination, etc., all fall into this category. The primary step in this process is the attack of either an anion (e. g., a carban-ion, an enolate, or an alkoxide) or a pseudo anion as an uncharged nucleophile (e. g., an amine, or an alcohol) onto an electrophilic center. A bond formation takes place with the creation of a new real or pseudo-anionic functionality, which can undergo further transformations. The sequence can then be terminated either by the addition of a proton or by the elimination of an X group. 

It is well known that the tricarbonylchromium-complexed benzylic anions and cations are stabilized due to overlapping between d-orbital of the chromium and p-orbital of the benzylic carbon [1]. Tricarbonylchromium complexes of a-te-tralone and a-indanone having a carbonyl group at the side chain underwent a deprotonation of the exo-benzylic protons by treatment with base to give the stereo-controlled tricyclic compounds (Eqs. 1 and 2) [2]. In these cases, Robinson annulation products were formed in less than 10% yield. Also, base treatment of benzyl ether chromium complex having a chlorine at the side chain 3 gave cyclization product as a diastereomeric mixture (Eq. 3) [3]. 

This reaction has been extended to the Michael Addition on a,)0-unsaturated nitrile by temporarily chelating the Grignard reagent to y-hydroxy unsaturated nitrile. An alternative route involving a free-radical )0-alkylation of nonactivated carbon atoms and subsequent anionic cyclization has been developed as a complementary route of the Robinson annulation. In addition, this reaction has been modified to occur under antibody catalysis" or with the combination of a lithium enolate with aluminum tris(2,6-diphenylphenoxide). Further modifications include the Robinson annulation in supercritical C02, the reaction promoted by K2CO3 under ultrasound,and the solid-supported reaction under microwave irradiation. ... 

Scheme 8.63. A representation of the Robinson annulation process. The initial addition of the enolate anion to the a,P-imsaturated ketone represents a Michael reaction. Subsequent cyclization with loss of water is an aldol reaction.

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See also in sourсe #XX -- [ ]

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