Three-component domino approach

Scheme 17.2 A three-component domino approach for the synthesis of quinolinones using [bmimJPFg...

In 1987, Vaultier and coworkers [27] developed a combination of a [4+2] cycloaddition of a bora-1,3-diene to provide an allylborane, which then reacts with an aldehyde to give a highly functionalized alcohol. The Lallemand group, as well as Hall and colleagues, has recently used this procedure. In an approach for the synthesis of the antifeedant natural product clerodin (4-83), Lallemand and coworkers performed a three-component domino reaction of 4-80, 4-81 and methyl acrylate to give 4-82 (Scheme 4.18) [28]. 

Later, the same authors established a similar three-component domino reaction providing a divergent approach to 40 examples of fused pyrroles (Scheme 12.40) [61]. The reaction proceeded as a domino [3+2] heterocychzation to afford fused pyrroles 103 in 65-86% yields through an aUyhc amination. On the contrary, using 57 with R=carboxymethyl group, an intermolecular arylation took place with formation of 104. 

Tie1996a Tietze, L.F., Hippe, T. and Steinmetz, A., Solid-Phase Three-Component Domino Reactions. Combinatorial Approach to Substituted 3,4-Dihydro-2H-pyrans, Synlett, (1996) 1043-1044. 

Domino Michael/aldol addition processes unquestionably represent the largest group of domino transformations. Numerous synthetic applications - for example, in natural product synthesis as well as for the preparation of other bioactive compounds - have been reported. Thus, the procedure is rather flexible and allows the use of many different substrates [12]. In this process it is possible, in theory, to establish up to two new C-C-bonds and three new stereogenic centers in a single step. For example, Collin s group developed a three-component approach. 

Recently, Larock and coworkers used a domino Heck/Suzuki process for the synthesis of a multitude of tamoxifen analogues [48] (Scheme 6/1.20). In their approach, these authors used a three-component coupling reaction of readily available aryl iodides, internal alkynes and aryl boronic acids to give the expected tetrasubsti-tuted olefins in good yields. As an example, treatment of a mixture of phenyliodide, the alkyne 6/1-78 and phenylboronic acid with catalytic amounts of PdCl2(PhCN)2 gave 6/1-79 in 90% yield. In this process, substituted aryl iodides and heteroaromatic boronic acids may also be employed. It can be assumed that, after Pd°-cata-lyzed oxidative addition of the aryl iodide, a ds-carbopalladation of the internal alkyne takes place to form a vinylic palladium intermediate. This then reacts with the ate complex of the aryl boronic acid in a transmetalation, followed by a reductive elimination. 

It should be also noted that, in a very recent publication, Liu and coworkers were successful in applying microwave radiation within their domino approach towards the synthesis of pyrrolo[2,l-fc]quinazoline alkaloids such as deoxyvasicinone, 8-hy-droxydeoxyvasicinone, mackinazolinone and isaindigotone, which exhibit a promising broad spectrum of biological activities. In the case of isaindigotone, the authors were able to extend their strategy to a three-component procedure, which comprises the domino conversion of anthranilic acids and Boc-protected amino acids into the tricyclic core skeleton [43]. 

Rolfe A, Young K, Hanson PR. Domino Heck-Aza-Michael reactions a one-pot, sequential three-component approach to l,l-dioxido-l,2-benzisothiazoline-3-acetic acid. Eur. J. Org. Chem. 2008 31 5254-5262. 

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