Metal-mediated domino

Metal-catalyzed reactions have been of major importance in synthetic organic chemistry. Over the past decade, enantio- and diastereoselective metal-mediated domino catalysis has emerged as an effective tool to construct really highly complex molecules in one-pot processes [2, 4b,d]. Among them, enantioseletcive metal-catalyzed conjugate additions (in particular, Cu-catalyzed 1,4-addition to a,P-unsaturated carbonyl compounds) have been useful components of domino reactions [4d, 5]. The generated metal enolates 2 after the additions of nucleophiles readily react with a variety of electrophiles (Scheme 11.1). Enantioselectivity of 3 depends on the first addition of nucleophiles to the P-position of the unsaturated carbonyl compounds 1. 

In addition, Kongkathip et al. reported on a synthesis of Tamiflu via a metal-mediated domino reaction and ringclosing metathesis. ... 

Besides the numerous examples of anionic/anionic processes, anionic/pericydic domino reactions have become increasingly important and present the second largest group of anionically induced sequences. In contrast, there are only a few examples of anionic/radical, anionic/transition metal-mediated, as well as anionic/re-ductive or anionic/oxidative domino reactions. Anionic/photochemically induced and anionic/enzyme-mediated domino sequences have not been found in the literature during the past few decades. It should be noted that, as a consequence of our definition, anionic/cationic domino processes are not listed, as already stated for cationic/anionic domino processes. Thus, these reactions would require an oxidative and reductive step, respectively, which would be discussed under oxidative or reductive processes. 

Beyond the numerous applications of palladium in transition metal-catalyzed domino reactions there are a lot of other metals inducing domino processes. Ihara et al. found a strategy for the enan-tioselective synthesis of (+)-equilenin catalyzed by mangan and palladium complexes,1841 Whitby et al.1851 initiated domino cyclizations on a zirconocene template and furthermore Scherf et al. generated phenantrones by a nickel-mediated one-pot domino reaction.1861... 

A model proposed for rationalizing the stereochemical outcome is also shown in Scheme 5.112. It seems plausible that the skewed structure 441, typical for transition metal BINAP complexes, has just one open space that is filled by a coordination of rhodium to the carbon - carbon bond of cyclohexenone. As a consequence, the insertion of the phenyl group then occurs from the Sf-face to the enone to give the / -rhodium complex 442 that subsequently tautomerizes to the more stable oxallyl-type enolate [205a]. It seems that a transmetallation at the stage of the enolate - from rhodium to boron enolate, as indicated in cycle B (Scheme 5.111) - doesnot occur in all these rhodium-mediated domino reactions without exception. Thus, Hayashi and coworkers produced evidence in support of a rhodium enolate as an active nucleophile in the aldol step when phenyl-9-BBN 438 was reacted with acyclic enones in the presence of [Rh(OH)-(S)-BINAP]2. In this case, the catalytic cycle is maintained by a transmetallation of the rhodium to the boron aldolate [221]. 

As a mechanistic rationale of this multicomponent Domino process, a Heck vinylation at 3-position is suggested accompanied by alkylations with Bul in both adjacent ring positions (2 and 4) mediated by transition metal activation of the C-H bonds. 

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