Chelation-controlled Heck reactions

Terminal chelation controlled Heck vinylations of electron-rich amino-functionalized vinyl ethers were performed with high regioselectivity to furnish the corresponding 1-alkoxy-l,3-butadienes. Controlled microwave heating effectively accelerated these palladium catalyzed reactions and full conversion could be achieved... 

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... 

Further applications can be mentioned briefly. SAMP was used in the resolution of 4-demethoxy-7-deoxydaunomycinone/ in ee determinations (Scheme 1), as a chelate for tetracarbonylmolybdenum complexes/ in intramolecular Heck reactions, as polysilylated hydrazine, in the enantioselective synthesis of isoquinuclidines, and in the conversion of hydrazones to aldehydes and nitriles. The structure of a chiral lithium SAMP hydrazone azaenolate has been determined. In cases where SAMP did not lead to satisfactory inductions, a modified auxiliary, (S)-l-amino-2-dimethylmethoxymethylpyrrolidine (SADP), enhanced the stereochemical control. 

Scheme 1 shows the desired Heck reaction of alkoxy-DSB 1 with 2. The formation of 3 is accompanied by two destructive pathways the reductive debromination of 1 to 4 as a side reaction and the protodesilylation to 5 as a subsequent reaction. Particularly the latter limits the reaction conditions in terms of time and temperature. The phosphine is a decisive factor in this system consisting of three reactions a fine-tuning of the reaction conditions is possible via electronic and steric effects of the substituents in the phosphine electron-rich trialkylphosphines 6 and 7 strongly favor the reduction. Fast coupling reactions were observed with tris-o-tolylphosphine 8, the chelating diphosphine dppe 9 being even more efficient in terms of turnover, yield, and suppression of side reactions. Compared with Heck reactions of polycyclic or electron-deficient arenes with 2 [21, 22], the yield of 3 is only moderate. The reactivity of bromo-distyrylbenzenes 1 and 12 -14 in the coupling reaction is controlled by the substituents on the opposite side of the n-system (Fig. 1, Table 2) a compensation for the electron-donating alkoxy groups by a cyanide (13) or exchange of donors with electronically neutral alkyl side chains strongly improves the yields.

Besides the one-pot process described above, the White Reagent catalyzes a chelate-controlled oxidative Heck arylation between a wide range of a-olefins and organoborane compounds in good yields and with excellent regio-and stereoselectivities (Figure 6). Unlike other Heck arylation methods, no Pd-H isomerization is observed under the mild reaction conditions. Aryl boronic acids, styrenylpinacol boronic esters, and aryl potassium trifluoroborates (activated with boric acid) are all compatible with the general reaction conditions. 

Overview of Chelation-Controlled Mizoroki-Heck Reactions... 

Figure 7.1 Hallberg s pioneering work on chelation-controlled Mizoroki-Heck reaction.

Figure 7.2 Representative substrates for chelation-controlled Mizoroki-Heck reactions.

As is obvious from the numerous examples in previous sections, the presence of coordinating functionalities in substrate structures greatly influences the outcome of Mizoroki-Heck reactions. In this last section, we will briefly mention other representative chelation-controlled systems. 

Recently, Yahiaoui et al. developed a chelation-controlled palladium-catalyzed Heck-Mizoroki/Suzuki-Miyaura domino reaction involving metal-coordinating dimethylaminoethyl vinyl ethers and various electron-deficient and electron-rich arylboronic acids by the use of p-Bq as the oxidant [22] (Scheme 6.13). The two-carbon tethered dimethylamino moiety, which could combine with p-Bq for the stabilization of the o-alkylpalladium(II) intermediate 56 and formation of the dia-rylated products 57, is assumed to be crucial for avoiding the formation of Heck products 58. 

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