Synthesis of chiral furanoside diphosphinite and thioether-phosphinite compounds derived from d-(+)-xylose. Application as ligands in asymmetric catalytic processes

Identificador:  TDX:858

Handle: https://hdl.handle.net/20.500.11797/TDX858

Autores:  Guimet Vila, Eugeni

Resumen:
In the last years, the growing demand of enantiomerically pure compounds (pharmacs, agrochemicals, additives...) has captured the interest of asymmetric catalysis. Asymmetric processes catalyzed by chiral transition-metal complexes have found many applications in this field. In this context, the synthesis of new chiral ligands is important to develop good catalytic systems in asymmetric catalysis. Carbohydrates have many advantages: they are readily available, are highly functionalized and have several stereogenic centers. This enables series of chiral ligands to be synthesized in the search for high activities and selectivities for each particular reaction.This thesis has focused on the synthesis of compounds derived from D-(+)-xylose and their application as ligands of chiral homogeneous catalyst in four asymmetric industrial processes: hydrogenation, allylic substitution, 1,4-addition and hydroformylation. Thus, new diphosphinite and thioeter-phosphinite compounds have developed (figure 1). Diphosphinites have the opposite configuration at C-3 (two backbones are xylofuranoside and ribofuranoside). Thioether-phosphinites have a thiother moiety at C-5 bearing substituents with different steric and electronic properties. Figura 1. Compounds synthetized from D-(+)-xylose.After the introduction (chapter 1) and the objectives (chapter 2), chapter 3 contains the synthesis and characterization of the two families of compounds. This chapter also discusses the characterization of their Rh(I) and Ir(I) catalytic precursors and their application in the asymmetric hydrogenation of prochiral olefins.Diphosphinite and thioether-phosphinite compounds have been synthesized from the corresponding alcohols. The reaction of diols with chlorodiphenylphosphine in the presence of pyridine and 4-(dimethylamino)-pyridine has provided the corresponding phosphinite ligands. The reaction of thioether-alcohols with chlorodiphenylphosphine in the presence of pyridine and 4-(dimethylamino)-pyridine has provided the corresponding thioether-phosphinite ligands. Diol and thioether-alcohol intermediates have been prepared on a large scales from D-(+)-xylose using standard procedures. Diphosphinites and thioether-phosphinites have been characterized by 1H, 13C and 31P and 13C-1H i 31P-1H MNR spectroscopy.The reaction of these compounds with [M(cod)2]BF4 (M = Rh and Ir, cod = 1,5-ciclooctadiene) has led to [M(cod)(P-P)]BF4 and [M(cod)(P-SR)]BF4 (P-P = diphosphinite and P-SR = thioether-phosphinite) complexes. These complexes have been characterized by 1H, 13C and 31P and 13C-1H i 31P-1H MNR spectroscopy.The characterization of M/diphosphinite complexes has showed that all, except Ir/diphosphinite complex with xylofuranoside backbone, have only one isomer. The characterization of M/thioether-phosphinite complexes has indicated that only one diastereomer, with pseudoaxial location of the sulfur substituents, is present in solution. Adding hydrogen to the iridium complexes has given cis-dihydridoiridium(III) complexes with pseudoaxial location of the sulfur substituents.The M/diphosphinite and M/thioether-phosphinite systems have been tested as chiral catalysts in the asymmetric hydrogenation of prochiral olefins. Enantiomeric excesses of up to 81% with moderate to high activities have been obtained with M/diphosphinite systems. Our results have shown that enantioselectivity is dependent on the absolute configuration of the C-3 stereocenter of the carbohydrate bakcbone, on the metal source and on the substrate. Enantiomeric excesses of up to 96% with good activities have been obtained with M/thioether-phosphinite systems. Our results have shown that enantioselectivity depends on the steric properties of the substituent in the thioether moiety, the metal source and the substrate structure.Chapter 4 reports the use of dihosphinite and thioether-phoshinite compounds as ligands in the palladium-catalyzed asymmetric allylic substitution reactions (alkylation and amination) of hindered linear and unhindered cyclic substrates. The use of diphosphinite ligands has provided good activity but low enantioselectivity (ee's up to 31%). Our results have indicated that the absolute configuration at carbon C-3 of the carbohydrate backbone controlles the sense of enantioselectivity and that the nucleophilic attack takes place trans to the phosphinite moiety attached to C-5. The Pd/thioether-phosphinite systems have led to best activities and enantioselectivities (ee's up to 93%) than the Pd/diphosphinite systems. Our results have shown that enantiomeric excesses depend on the steric properties of the substituent in the thioether moiety and the structure of substrate. Our results have showed that the nucleophilic attack takes place trans to the phosphinite moiety attached to C-3. Moreover, these ligands are more actives in allylic alkylation than allylic amination.Chapter 5 contains the application of diphosphinite and thioether-phoshinite compounds as ligands in the asymmetric copper-catalyzed asymmetric 1,4-addition to 2-cyclohexenone. Good enantioselectivities (ee's up to 72%), high activities (TOF > 1225 mol product x (mol catalytic precursor x h)-1) and excellent regioselectivities in 1,4 product (100%) have been obtained. Our results show that activity and selectivity (chemo- and enantioselectivity) depend strongly on the type of functional group at C-5 position of the carbohydrate backbone, the steric properties of the substituent in the thioether moiety, the catalyst precursor and the alkylating agent. The best enantioselectivities have been obtained with Cu/thioether-phosphinite system containing isopropyl substituent. However, activity is better with Cu/diphosphinite systems. The use of AlEt3 as alkylating agent has led to better activities but worse enantioselectivities than the use of ZnEt2.Chapter 6 discuss the application of diphosphinite compounds as chiral auxiliares in the rhodium-catalyzed asymmetric hydroformylation of vinyl arenes. These catalytic systems have led to high regioselectivities in the branched aldehyde (99%) and moderate enantiomeric excesses (up to 63%). The results have shown a remarkable substrate effect on enantioselectivity. Thus, the presence of para-methoxy and naphthyl substituents in the substrate has a positive effect on enantioselectivities. For the first time, the structure in solution of the species formed under hydroformylation conditions with diphosphinite ligands has been determined. The characterization of these rhodium complexes by NMR techniques and in situ IR spectroscopy have shown that the hydridorhodium dicarbonyl species exist in one diastereosiomeric equatorial-equatorial form. However, this strong coordination preference does not allow high enantioselectivity.