Olefin structures heterocyclic synthesis, intramolecular

The following discussion focuses on the synthesis of aromatic heterocycles where a key palladium- or copper-catalyzed aryl halide (or equivalent) amination, etherification or thioetherification process is employed. Annulative routes utilizing anilines and related compounds with alkynes (Larock type) are also considered. Routes that do not lead to aromatic products or that rely on the functionalization of preexisting heterocycles have been discounted. Similarly, the synthesis of heterocycles via TT-allylpalladium chemistry or intramolecular cyclization of palladium Tr-olefin and TT-alkyne complexes is not featured. The discussion is structured predominantly around the type of bond being formed (C—N, C—O, or C—S) and is classified further by heterocycle type. Intramolecular and intermolecular C—X bond formations as well as tandem catalytic processes leading to aromatic heterocycle products are all discussed. 

A number of intramolecular cycloadditions of alkene-tethered nitrile oxides, where the double bond forms part of a ring, have been used for the synthesis of fused carbocyclic structures (18,74,266-271). The cycloadditions afford the cis-fused bicyclic products, and this stereochemical outcome does not depend on the substituents on the alkene or on the carbon chain. When cyclic olefins were used, the configuration of the products found could be rationalized in terms of the transition states described in Scheme 6.49 (18,74,266-271). In the transition state leading to the cis-fused heterocycle, the dipole is more easily aligned with the dipolarophile if the nitrile oxide adds to the face of the cycloolefin in which the tethering chain resides. In the trans transition state, considerable nonbonded interactions and strain would have to be overcome in order to achieve good parallel alignment of the dipole and dipolarophile (74,266). 

In 1993, Murai reported the reactions of aryl ketones witti ethylene and vinylsilanes to form the product from the addition of the C-H bond ortho to the carbonyl group to the olefin (Equation 18.49). This finding led to subsequent work on the addition of the C-H bonds of a variety of aromatic groups to a series of olefins. Catalysts that react under milder conditions than the original ones and extensions of the C-H activation to intramolecular cyclizations to form heterocyclic structures have made this reaction capable of being used in the synthesis of complex molecules. For example, alkylated diterpe-noids and (+)-lithospermic acid (Equations.18.50 and 18.51) have been synthesized using directed hydroarylation. ... 

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