Triethyl orthoformate hydroformylation

The cA-PtCl2(diphosphine)/SnCl2 constitutes the system mostly used in catalyzed hydroformylation of alkenes and many diphosphines have been tested. In the 1980s, Stille and co-workers reported on the preparation of platinum complexes with chiral diphosphines related to BPPM (82) and (83) and their activity in asymmetric hydroformylation of a variety of prochiral alkenes.312-314 Although the branched/normal ratios were low (0.5), ees in the range 70-80% were achieved in the hydroformylation of styrene and related substrates. When the hydroformylation of styrene, 2-ethenyl-6-methoxynaphthalene, and vinyl acetate with [(-)-BPPM]PtCl2-SnCl2 were carried out in the presence of triethyl orthoformate, enantiomerically pure acetals were obtained. 

A big problem in asymmetric hydroformylation is that the chiral aldehyde products may be unstable and may undergo racemization during the reaction. This problem is even more serious for the Pt catalyst systems, which are usually plagued by slow reaction rates. Stille et al.121 tackled this problem by using triethyl orthoformate to trap the aldehyde products as their diethyl acetals and consequently increased the product ee values significantly. 

SCHEME 52. Hydroformylation by PtCl2(bppm)-SnCl2 in the presence of triethyl orthoformate. 

The hydroformylation of styrene in triethyl orthoformate is slower than that observed in benzene, but a 98% ee is obtained, since racemization of the product acetal does not occur. Hydrolysis of the acetal to the aldehyde can be accomplished without racemization. A number of other substrates are hydroformylated in the presence of triethyl orthoformate. The reactions are slower, but with all substrates tried except norbomene, enantiomerically pure products can be obtained. 

One of the difficulties in achieving high enantioselectivity in asymmetric hydroformylation is the propensity of chiral 2-arylpropanal to racemize under the reaction conditions. Accordingly, if the chiral aldehyde can be converted to a less-labile derivative in situ, higher enantioselectivity might be anticipated. In fact, when the asymmetric hydroformylation of styrene and its derivatives catalyzed by PtCl2(BPPM)/SnCl2 was carried out in triethyl orthoformate, the... 

The two metals that have been found to give encouraging conversions and selectivities for the hydroformylation of styrene are platinum and rhodium. The platinum-based catalytic system uses tin chloride as a promoter. It also uses triethyl orthoformate as a scavenger that reacts with the aldehyde to form the acetal. By removing it as soon as it is formed, any further degradative reactions of the aldehyde are avoided. The chirality in these reactions is induced by the use of optically active phosphorus ligands. With the best platinum catalyst, branched and linear aldehydes are produced in about equal proportion, but the former has an e.e. of >96%. 

Carbonylation of aromatic olefins also provides an attractive route to profens. The key issues in the hydroformylation reaction (cf. Section 2.1.1 and Scheme 4) are the branched/normal selectivity and the configurational stability of the branched aldehydes. When the Pt -catalyzed asymmetric reaction is performed with triethyl orthoformate, the aldehyde product is immediately removed as... 

An exception is norbornene, which after 84% conversion in the presence of PtCl2/SnCl2/(—)-BPPM gives exclusively < .TO-2-formylbicyclo[2.2.1]heptane with 98.7% aldehyde selectivity and 60 % ee12. The product can be converted to the corresponding carboxylic acid upon oxidation without loss of enantiomeric purity. If the hydroformylation reaction is carried out in triethyl orthoformate as solvent, the aldehyde is trapped as the acetal. Thus, higher temperatures with higher conversions and yields can be applied without racemization of the product. 

Preferentially, acetals were obtained by the Kalck group in the rhodium-catalyzed hydroformylation- acetalization reaction of (l/J,4/ )-isolimonene in the presence of triethyl orthoformate (Scheme 5.76) [64]. The reaction with P-pinene gave a mixture of diastereomeric acetals. Increasing temperatures forced the... 

The initial rate of Co2(CO)g-catalyzed cyclohexene hydroformylation, triethyl orthoformate carbonylation, and CoH(CO)4 formation from Co2(CO)g and H2 is reduced by the addition of dinitrogen, argon, or xenon. It is assumed that the additional gas competes with one or more reactants for a coordinatively unsaturated site responsible for their activation, thus affecting the reaction rate [1]. 

Polymer (46) with SnCl2 catalyzed hydroformylation of styrene in a mixture of benzene and triethyl orthoformate in 98% ee, but only 22% conversion was attained in 10 d (Scheme 18), compared with 98% ee and 100% conversion in < 150 h using the soluble analogue of (46). The triethyl orthoformate converted the product aldehyde to an enantiomerically stable acetal, whereas the aldehyde racemized slowly under reaction conditions. Since the reaction proceeds much faster in benzene than in triethyl orthoformate, polymer (46) might be used in a flow reactor with benzene as solvent, continuous separation of aldehyde, and recycling of the styrene. 

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