Heck/aldol domino reactions

Monoprotected 3-hydroxyindan-l-ones 190 have been prepared in moderate to good yields by a new domino Heck-aldol annelation reaction involving salicylalde-hyde triflates and commercially available 2-hydroxyethyl vinyl ether (Scheme 8.45). In this one-pot transformation, which proceeds in the presence of a palladium catalyst with a bidentate Hgand, two new rings are formed [352]. 

Scheme 8.48 Domino Mizoroki-Heck/aldol reaction.

Transition metal-catalyzed transformations are of major importance in synthetic organic chemistry [1], This reflects also the increasing number of domino processes starting with such a reaction. In particular, Pd-catalyzed domino transformations have seen an astounding development over the past years with the Heck reaction [2] - the Pd-catalyzed transformation of aryl halides or triflates as well as of alkenyl halides or triflates with alkenes or alkynes - being used most often. This has been combined with another Heck reaction or a cross-coupling reaction [3] such as Suzuki, Stille, and Sonogashira reactions. Moreover, several examples have been published with a Tsuji-Trost reaction [lb, 4], a carbonylation, a pericyclic or an aldol reaction as the second step. 

Heck reactions can also be combined with anion capture processes, animations, metatheses, aldol and Michael reactions, and isomerizations. The anion capture process has also been widely used with other Pd-catalyzed transformations. Outstanding examples of many different combinations have been developed by Grigg and coworkers, though not all of them match the requirements of a domino process. All of these reactions will be detailed here, despite the fact the nature of these intermediate transformations would also have permitted their discussion in Chapter 2. 

A broad variety of special aldehydes and ketones are easily accessible by Heck-type reactions with allylic alcohols and their homologs [3]. The potential for the synthesis of carbocydic structures is illustrated by the macrocyde 11 [4] which obviously is the product of a fourfold Heck reaction (Scheme 3). A domino process consisting of a double Heck reaction followed by an intramolecular Aldol condensation leads to the annulated ring system 15 [5]. 

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