Arylation chelation effects

The benzoic acid derivative 457 is formed by the carbonylation of iodoben-zene in aqueous DMF (1 1) without using a phosphine ligand at room temperature and 1 atm[311]. As optimum conditions for the technical synthesis of the anthranilic acid derivative 458, it has been found that A-acetyl protection, which has a chelating effect, is important[312]. Phase-transfer catalysis is combined with the Pd-catalyzed carbonylation of halides[3l3]. Carbonylation of 1,1-dibromoalkenes in the presence of a phase-transfer catalyst gives the gem-inal dicarboxylic acid 459. Use of a polar solvent is important[314]. Interestingly, addition of trimethylsilyl chloride (2 equiv.) increased yield of the lactone 460 remarkabiy[3l5]. Formate esters as a CO source and NaOR are used for the carbonylation of aryl iodides under a nitrogen atmosphere without using CO[316]. Chlorobenzene coordinated by Cr(CO)j is carbonylated with ethyl formate[3l7]. 

The reactivity order Ni>Pd>Pt has been found for the oxidative addition of aryl halides. Steric and electronic properties, and the numbers of L as well as chelate effects, play an important role [65, 194—196]. For example, Pd(0) complexes of basic chelating phosphines react substantially more easily with chlorobenzenes than their nonchelating analogues (see Section 18.2.4) [2, 100, 196]. 

Proton nmr halide anion titrations reveal that the ethyl- [79], propyl-[80] and butyl- [81] linked derivatives (Fig. 43) form complexes of 1 1 stoichiometry in acetonitrile solution. Stability constant determinations suggest that the ethyl derivative [79] exhibits selectivity for the chloride anion in preference to bromide or iodide. As the chain length increases, so the selectivity for chloride decreases and also the magnitude of the stability constant which is evidence for an anionic chelate effect with the chloride anion. Receptors containing larger aryl [81], [83], [84] and alkylamino spacers [85] (Fig. 43) form complexes of 2 1 halide anion receptor stoichiometry. 

Even the sterically hindered 2,6-disubstituted aryl iodide 443 is carbonylated smoothly to give 445. Alkyl iodide present in the alcoholic component 444 remains intact under the carbonylation conditions. This carbonylation reaction is a key reaction in the synthesis of zearalenone (446) [216]. Optimal conditions for technical synthesis of the anthranilic acid derivative 448 from bromide 447 has been studied, and it has been found that A-acetyl protection of 447, which has a chelating effect, is important [217]. Cheaply available chlorides are rather inert [13]. The carbonylation of chloride 449 in the presence of DBU and Nal gives the amide 450 [218],... 

In regard to electronic effects, the aryl group prefers to add to the more positive carbon of the double bond. A chelation effect may be operative in the arylation of allylic alcohols in which the phenyl adds to the more substituted carbon of the double bond. 

Regioselective Reactions. An important attribute of DIBAL is its capacity to react regioselectively. Acetal cleavage is a classical example of this property, which finds its source in electronic, steric, and/or chelation effects. The reduction of aryl-1,2-ethanediol benzylidene acetals is controlled mainly by electronic effects a change in electron donating capacity of the aryl moiety changes the regioselectivity of the reaction (eq 43).4 ... 

One of the more fascinating applications of the chelating effect is the stereoselective synthesis of 2-aryl-3-sullinyl-2,5-dihydrofurans (Scheme 14). The high stereocontrol is attributed to the Pd(ll) coordination with the dimethylamino group and the subsequent selective presentation of the tr-adduct during the insertion step (de = 70-88%). Consistent with this scenario, Heck arylations of non-amino-containing 4-arylsulfinyl-2,3-dihydrofurans resulted predominantly in the opposite diastereomers (de = 34-56%). 

Portnoy, M., Ben-David, Y. andMUstein, D. (1993) Clarification of aremarkable chelate effect leads to palladium-catalyzed base-free arylation. Organometallics, 12, 4734-5. 

Ben-David, Y, Portnoy, M., Gozin, M. and Milstein, D. (1992) Palladium-catalyzed vinylation of aryl chlorides. Chelate effect in catalysis. Organometallics, 11, 1995-6. 

One of the more fascinating applications of the chelating effect is the stereoselective synthesis of 2-aryl-3-sullinyl-2,5-dihydrofurans (Scheme The high stereocontrol... 

Although chelating aryl diphosphine ligands are effective for hydrogenating dehydroamino acids with high stereoselectivity, minor changes in the composition of the substrate can drastically lower the enantiomeric excess. The best results are obtained for the following structures ... 

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