Heck hetero

Microwave-assisted Heck reaction of (hetero)aryl bromides with N,N-dimethyl-2-[(2-phenylvinyl)oxy]ethanamine, using Herrmann s palladacycle as a precatalyst, yielded the corresponding /3-(hetero)arylated Heck products in a good EjZ selectivity (Scheme 79) [90]. The a/yd-regioselectivity can be explained by the chelation control in the insertion step. This selectivity is better than 10/90 when no severe steric hindrance is introduced in the (hetero)aryl bromides. The process does not require an inert atmosphere. There is evidence that a Pd(0)/Pd(II)- and not Pd(II)/Pd(IV)-based catalytic cycle is involved. Similarly, other j6-amino-substituted vinyl ethers such as... 

The Suzuki-Miyaura and Heck reactions were recently also reported under conventional heating conditions [39,40]. A variety of 3-chloro pyrazinones were reacted with commercially available (hetero)aryl boronic acids or the alkyl-9-BBN derivatives under either classical or slightly modified Suzuki conditions to generate the 3-substituted analogues, however having the drawback of longer reaction times of up to 12 h of reflux. 

As Scheme 23 illustrates, DMF reacts with POCI3 to form Vilsmeier reagent 158. Aryl-Pd-I species 159, generated by the oxidative addition of iodotoluene 160 to Pd(0) species, reacts with the reagent 158 to yield chloroiminium ion 162 via an adduct 161 through a hetero-Heck-type reaction mechanism, and liberates H-Pd-I species. Finally, the hydrolysis of chloroiminium ion 162 gives amide 163. 

Many further important natural product syntheses are covered by the aforementioned review. Particularly noteworthy amongst them are Hudlicky s syntheses of conduramines [522] and (+)-lycoricidine [523] since they employ enantioselective microbial oxidations of halobenzenes as source of chirality. Racemic lycoricidine has also been prepared by Martin et al. this synthesis exhibits an interesting Heck cyclisation as key step in addition to the hetero Diels-... 

An intriguing showcase for polycyclizations based upon hetero-domino reactions is outlined in Scheme 30, where the catalyst 89 gives rise to the formation of a mixture of indolone skeletons 92-94 with a preference for the generation of tetracycle 94 as a result of an intramolecular allylic substitution-Heck sequence. 

The remarkable affinity of the silver ion for hahdes can be conveniently applied to accelerate the chiral palladium-catalyzed Heck reaction and other reactions. Enantioselectivity of these reactions is generally increased by addition of silver salts, and hence silver(I) compounds in combination with chiral ligands hold much promise as chiral Lewis acid catalysts for asymmetric synthesis. Employing the BINAP-silver(I) complex (8) as a chiral catalyst, the enantioselective aldol addition of tributyltin enolates (9) to aldehydes (10) has been developed." This catalyst is also effective in the promotion of enantioselective allylation, Mannich, ene, and hetero Diels-Alder reactions. 

Whether the reaction is inter- or intramolecular, the Heck reaction generates vinyl(hetero)arenes or dienes from an alkene and a (hetero)aryl or alkenyl halide [130]. This reaction has great versatility and is applicable to a wide range of aryl and alkene species. Mechanistically, the Heck reaction varies from that depicted in Fig. 4.3. While the oxidative addition of the halogen species occurs, the transmetalation step is replaced by the coordination of the alkene. This is followed by a migratory insertion which essentially substitutes for the cross-coupling step. The product is released not by a reductive elimination, but by a 3-hydride elimination sequence (Fig. 4.5). 

An extension of the palladium(0) catalyzed direct arylation reactions was reported by Lautens et al. in 2005. Based on the Catellani reaction [32], a direct intramolecular arylation of indole (C2) followed ort/m-alkylation, via a norbor-nene-mediated tandem aromatic alkylation/Heck reaction (Scheme 17) [33]. An analogous process was later developed for thiophenes and furans, allowing formation of a range of interesting hetero-aryl polycyclic products (Scheme 17) [34]. 

IMI has also developed a general route for the synthesis of homo- and hetero-disubstituted benzophenones such as 4,4 -difluorobenzophenone (DFBP), 4,3 -di-fluorobenzophenone, and 4,4 -diphenoxybenzophenone (DPOBP). These substituted benzophenones are important materials, with a variety of uses as specialty monomers (for polyether ketones and polyarylene ether ketones) and pharmaceutical intermediates. These benzophenones are prepared by utilizing Heck technology in conjunction with an oxidative cleavage reaction. 

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