Cyclic olefin hydroformylations

Differences in reactivity have been exhibited between acyclic and different types of cyclic olefins. Vinylcyclohexene in a cobalt hydroformylation at 120°-134°C and 475-720 atm pressure gave a 65% yield of a mixture of mono- and dialdehydes (66). 

In view of the many differences noted above between the hydroformylation of olefins and epoxides, it is not surprising to find that changes in structure result in a different order of reactivity in each case. Thus for epoxides the reactivity to cobalt hydrocarbonyl is cyclohexene oxide > propylene oxide, whereas with olefins the order is terminal olefins > internal olefins > cyclic olefins (145). 

Carbonylation of cyclic amines, hydroformylation (CO-H2) of amino olefins catalyzed by metal (Pd, Ru, Rh) complexes (see 1st edition). 

These. supramolecular catalysts showed high substrate selectivity in competition hydrogenation experiments and exceptional activity in the hydroformylation reactions. In contrast to the simple methylated P-cyclodextrin previously mentioned, even internal and cyclic olefins were converted into aldehydes. Such improvements were explained with the formation of an inclusion complex at the phase boundary, with the cylodextrin host fixing the substrate in the proximity of the catalytically active metal center (Fig. 

In a related approach, Chercheja and Eilbracht [19] examined cyclic olefins together with acyclic and cyclic ketones (Scheme 5.130). Instead of monoden-tate phosphines as ligands, P(OPh)3 was used for the hydroformylation step. In general, the diastereoselectivities with cyclic substrates and reagents, respectively, were lower than those observed in the reaction of acyclic olefins and aldehydes by the Breit group (compare Scheme 5.129). 

Scheme 5.130 Domino hydroformylation-cross aldol addition of cyclic olefins with ketones.

Hydroformylation. The title conqiound serves as a ligand in the Rh-catalyzed hydroformylation reaction. Cyclic olefins and internal olefins are hydroformylated under mild conditions (eq 12)P... 

The tandem hydroformylation-Fischer indolization protocol was used in the synthesis of 2,3-disubstituted indoles. Several olefins, bearing substituents with various functional groups, as well as cyclic olefinic systems were investigated (Equations 7.20 and 7.21)... 

The variable-temperature NMR spectra help to explain the catalytic properties of the dppp complex system which were outlined previously in Table I. The reduced catalytic activity compared with the tris(triphenylphosphine) complex system is apparently due to the reduced dissociation of the cyclic complexes. For example, the 90°C spectra of Figures 3 and 13, clearly show that the ligand-exchange rate is much slower in the case of dppp. However, temperature-dependent ligand exchange of the monocyclic complex occurs and leads to cis-bisphosphine species that catalyze the hydroformylation of olefins at minimal partial pressures of CO. The hydroformylation rate of the dppp system is faster at 1 atm CO pressure than that of the dppe system. Of course, such hydroformylations are nonselective due to the cis-stereochemistry. 

A major interest for those practicing hydroformylation syntheses is the selectivity to the product desired. The factors which affect the yield of a specific aldehyde are (1) the structure of the olefinic substrate (a-olefin or internal olefin, branching, cyclic), (2) the isomers formed during the reaction (directly, with concomitant isomerization), (3) the effects of functional groups, and (4) the subsequent reactions of the product aldehyde. 

Long-chain aliphatic olefins give only insufficient conversion to the acids due to low solubility and isomerization side reactions. In order to overcome these problems the effect of co-solvents and chemically modified /i-cyclodextrins as additives was investigated for the hydrocarboxylation of 1-decene [23], Without such a promoter, conversion and acid selectivity are low, 10% and 20% respectively. Addition of co-solvents significantly increases conversion, but does not reduce the isomerization. In contrast, the addition of dimethyl-/i-cyclodextrin increased conversion and induced 90% selectivity toward the acids. This effect is rationalized by a host/ guest complex of the cyclic carbohydrate and the olefin which prevents isomerization of the double bond. This pronounced chemoselectivity effect of cyclodextrins is also observed in the hydroformylation and the Wacker oxidation of water-insoluble olefins [24, 25]. More recent studies of the biphasic hydrocarboxylation include the reaction of vinyl aromatic compounds to the isomeric arylpropanoic acids [29, 30], and of small, sparingly water-soluble alkenes such as propene [31]. 

Cyclohydrocarbonylation (CHC) is the hydroformylation of a functionalized olefin followed by concomitant intramolecular nucleophillic attack to the newly formed aldehyde moiety leading to a cyclized product. As a variant, the CHC reaction also includes an intramolecular cascade process involving the hydrocarbonylation of a functional alkene, generating an acyl-metal intermediate, which undergoes an intramolecular nucleophilic attack to give the corresponding cyclic compound. CHC reactions have been developed into sophisticated cascade reactions forming bicylic and polycyclic compounds. ... 

In 2011, Beller s group utilized an Ir hydroformylation catalyst [10] generated from Ir(acac)(COD) and a 10-fold excess of PPhg for the conversion of various terminal olefins (styrene, 3-propenylarenes, cyclic octenes. Unear a-olefins) into... 

Seok and colleagues investigated the hydroformylation of allyl alcohol with paraformaldehyde in the presence of HRh(CO)(PPh3)3 (Scheme 3.4) [14]. Similar to that found in the reaction with syngas (see Section Allyl and homoallyl alcohols in Chapter 4), the functional group in the olefinic substrate directed the regiochemistry of the reaction and a cyclic transition state between catalyst and substrate was assumed. A maximum isomeric product ratio of lib = 21 was achieved. The addition of syngas to the reaction with paraformaldehyde or an excess of phosphine inhibited the formation of the linear aldehyde. 

As a special case, the formation of hemiacetals 2 (lactolization) during the hydroformylation of hydroxy-functionalized olefins, such as allyl or homoallyl alcohols, has to be mentioned (1, Y= O, Scheme 5.70). With these substrates, the reaction occurs in an intramolecular manner. In the presence of an external alcohol, the cyclic hemiacetal can further react to give a nonsymmetric cyclic acetal 3. Hemiacetals can be subjected to hydrogenation to afford diols 4. Under reducing conditions and in the presence of amines, amino alcohols 5 are formed both are valuable building blocks in fine chemistry. Alternatively, oxidation gives lactones 6 [5]. By dehydration of hemiacetals, cychc vinyl ethers 7 are formed. The same transformation with allylamines (Y=NR) gives cyclic hemiaminals, A/ ,0-acetals, lactames, or vinyl amines. 

In contrast to the previous examples, the preferred formation of linear aldehydes was the main target in some syntheses to construct a cyclic derivative with an appropriate ring size in the next step or for simply elongating a carbon chain. The linear aldehydes are the proper intermediates for the synthesis of indolizidine alkaloids [11], the tricyclic marine alkaloid lepadiformine [12], ACE inhibitors such as MDL 27210 and its analogues [13,14], and bryostatin, a remarkably potent anticancer agent [15]. Rhodium complexes of bisphosphite ligands provide one of the best known classes of linear-selective hydroformylation catalysts for simple ot-olefins. Except for the lepadiformine intermediate, where hydroformylation was carried out in the presence of the Rh(acac)(CO)2/P(OPh)3 catalyst system, in other... 

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