Synthesis Using Palladium Allyl Chemistry

The element most widely used today in oiganic synthesis is palladium. Not only do we have the catalytic palladium allyl chemistry mentioned above but there is also a wide range of Pd coupling reactions available (Section 9.6) Pd reactions are very tolerant of functionality and give predictable products. ... 

A different approach to the cephalotaxine ring system also used tf-allyl palladium chemistry (Scheme 9.49). " Tetramethylguanidine (TMG), which is a stronger base than triethylamine by at least two orders of magnitude, was found to be the base of choice for the cyclization of allylic sulfone 9.171. The sulfone leaving group was also essential to the synthesis of the earlier intermediate 9.170 by allowing alkylation to introduce the aminopropyl side chain. ... 

Allyl- and vinylsilane chemistry was one of the first areas of reagent synthesis impacted by CM methodology. Allylsilanes are commonly employed in nucleophilic additions to carbonyl compounds, epoxides, and Michael acceptors (the Sakurai reaction) vinylsilanes are useful reagents for palladium-coupling reactions. As the ubiquitous application of CM to this substrate class has recently been described in several excellent reviews, this topic will not be discussed in detail, with the exception of the use of silane moieties to direct CM stereoselectivity (previously discussed in Section 11.06.3.2). 

Sulfoximines are versatile reagents for diastereoselective and asymmetric synthesis. They continue to find many synthetic applications as both nucleophilic and electrophilic reagents. While the nucleophilic character of sulfoximine reagents has been well exploited,1 the use of the sulfoximine group as a nucleofuge is more recent and adds to the synthetic use of these compounds. The palladium(0)-catalyzed chemistry of allylic sulfoximines and the use of chiral sulfoximines as ligands in catalytic asymmetric synthesis are areas of recent development that have potentially useful applications. Further work is required to understand the factors that determine the diastereoselection and the stereochemical outcomes of these reactions. These studies will result in enhanced product diastereo- and enantioselectivities and make these reagents even more attractive to the wider synthetic chemistry community. 

Several new routes involve formation of one carbon-carbon bond in pre-formed substrates. Palladium-catalyzed cyclization of /3-hydroxyenamine derivatives has been employed in a route to substituted pyrroles and 4,5,6,7-tetrahy-droindoles with multiple substituents by formation of the C-3-C-4 bond as the key feature, as illustrated by construction of the molecule 534 (Equation 146) <2006T8533>. Zinc perchlorate-catalyzed addition of alcohols to the nitrile functionality of a-cyanomethyl-/3-ketoesters, followed by annulation gave access to a series of substituted ethyl 5-alkoxypyrrole-3-carboxylates <2007T461>. Similar chemistry has also been used for synthesis of a related set of pyrrole-3-phosphonates <2007T4156>. A study on preparation of 3,5,7-functionalized indoles by Heck cyclization of suitable A-allyl substituted 2-haloanilines has also appeared <2006S3467>. In addition, indole-3-acetic acid derivatives have been prepared by base induced annulation of 2-aminocinnamic acid esters (available for instance from 2-iodoani-lines) <2006OL4473>. 

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