Hydroformylation functionalized alkenes

The regioselectivity of the hydroformylation of alkenes is a function of many factors. These include inherent substrate preferences, directing effects exerted by functional groups as part of the substrate, as well as catalyst effects. In order to appreciate substrate inherent regioselectivity trends, alkenes have to be classified according to the number and nature of their substitution pattern (Scheme 3) [4]. 

Most recently new applications for substrate-controlled branched-selective hydroformylation of alkenes substituted with inductively electron-with drawing substituents have emerged. A recent example is the hydroformylation of acrylamide with a standard rhodium/triphenylphosphine catalyst, which yields the branched aldehyde exclusively (Scheme 4) [40]. Reduction of the aldehyde function furnishes 3-hydroxy-2-methylpropionamide, which is an intermediate en route to methyl methacrylate. 

Many chiral diphosphine ligands have been evaluated with regard to inducing enantioselectivity in the course of the hydroformylation reaction [25,26]. However, a real breakthrough occurred in 1993 with the discovery of the BI-NAPHOS ligand by Takaya and Nozaki [65]. This was the first efficient and rather general catalyst for the enantioselective hydroformylation of several classes of alkenes, such as aryl alkenes, 1-heteroatom-functionalized alkenes, and substituted 1,3-dienes, and is still a benchmark in this area [66,67]. But still a major problem in this field is the simultaneous control of enantio-... 

The limitations of hydroformylation reactions in water are the same as those of hydrogenation reactions, i.e. the poor solubility of the substrates (see Section 8.2.1). While aqueous-organic biphasic hydroformylation works well for alkenes with chain lengths up to C7, the solubility of longer chain alkenes is too low for viable processes. Although simple alkenes are poorly soluble, many functional alkenes have solubilities in water that are sufficiently high to avoid mass transfer problems, but at the same time this can impede separation. 

Rhodium complexes of the phosphine-functionalized carbosilane dendrimers are active for the hydroformylation of alkenes. The influence of the flexibility of the dendritic backbone on the catalytic performance was characterized by comparing dendritic ligands 84a-84c (conditions toluene, 80°C, 20 bar CO/H2) 49). 

Functionalized Alkenes Asymmetric hydroformylation of functionalized alkenes can serve as a useful method for the syntheses of polyfunctionalized intermediates to biologically... 

Hydroformylation of alkenes by homogenous rhodium catalysts has attracted the attention of researchers for functionalization of complex molecules [42,43]. Al-Abed et al. [44] recently... 

Bulky diphosphites not only express a high selectivity toward 1-alkenes [255] but also for less reactive internal [256] and functionalized alkenes. Recently DSM and Du Pont reported on a ligand (24) which has a high regio- and chemoselectivity for the hydroformylation of methyl 3-pentenoate [253]. The synthesis of monophenols containing bulky substituents (25) is described in patents from Mitsubishi [257]. High yields with 1-alkenes and l/b ratios up to 20 are reported. 

Although the broad applicability of the hydroformylation in homogeneous medium has been demonstrated without ambiguity, the scope of biphasic catalysis for the hydroformylation of functionalized alkenes remains to be investigated. Indeed, there are relatively few examples in the literature related to hydroformylation of such substrates. Furthermore, most of the work described so far has been devoted to the hydroformylation of d-functionalized alkenes (the functional group is not di-... 

Recently, rhodium/poly(enolate-co-vinyl alcohol-co-vinyl acetate) catalysts have been developed for the biphasic hydroformylation of aliphatic alkenes and applied to the selective hydroformylation of functionalized alkenes [16], Although the conversions were low (< 25%), excellent selectivities for the hydroformylation of n-bu-tyl vinyl ether and methyl 3,3-dimethylpenten-4-onate can be achieved with such water-soluble polymer-anchored rhodium catalysts. For instance, the hydroformylation of methyl 3,3-dimethylpenten-4-onate gives only the linear aldehyde. 

As far as is known, the only industrial application of the water-soluble catalyst for the hydroformylation of 5 -functionalized alkenes has been developed by Kura-ray [17]. In this process, 7-octen-l-al is hydroformylated into nonane-1,9-dial, a precursor of nonene-l,9-diol, by using a rhodium catalyst and the monosulfonated tri-phenylphosphine as water-soluble ligand in a 1 1 sulfolane/water system. At the completion of reaction, the aldehydes are extracted from the reaction mixture with a primary alcohol or a mixture of primary alcohol and saturated aliphatic hydrocarbon (cf. Section 6.9). 

In contrast with the first class of functionalized alkenes, immobilization of the catalyst in aqueous phase results in an enhancement of the catalytic activity [19]. Indeed, it has been observed that the hydroformylation rates of arylic esters having high solubility in water were much higher in biphasic systems than those observed under comparable homogeneous conditions. Except for 2-ethylhexyl acrylate, the initial rate was increased by a factor of 2.4, 12, 2.8, and 14 for methyl, ethyl, butyl, and 2-ethoxyethyl acrylate, respectively (see Figure 1) [20]. One of the most intriguing features is that the hydroformylation rates for ethyl and butyl acrylates in biphasic medium were respectively higher than and comparable with those observed with methyl acrylate. Actually, the water-solubilities of ethyl and butyl acrylates (18.3 and 2.0 g L-1 at 20 °C, respectively) are lower than that of methyl acrylate (59.3 g L-1 at 20°C). 

The behavior of functionalized alkenes depends strongly on the proximity of the functional group relative to the double bond to be hydroformylated. The few examples described so far reveal that most of the principles used for the hydroformylation of unfunctionalized alkenes can be applied. However, unusual results can be observed with a-functionalized alkenes, i.e., with acrylates. The formation of reactive nonchelated species has been suggested as an explanation of this behavior. Such a phenomenon should probably be generalized to other alkenes bearing functional groups in a suitable position, but experiments still remain to be done under biphasic conditions to confirm this hypothesis. 

The results of asymmetric hydroformylation are described here for individual substrate types such as normal open chain and cyclic alkenes, styrene and other alkenylaromatics, dienes, functionalized alkenes and alkynes. Earlier extensive compilations of results concerning this subject are found in several monographs and reviews31 45,54,104,105, l21,177,178,180,, 81. 

Table VH. Hydroformylation of Unsaturated Halogen Compounds Table VIH. Hydroformylation of Un.saturated Nitrogen Compounds Table IX. Hydroformylation of Other Functionalized Alkenes. ...

Functionalized alkenes. Regioselective hydroformylation of functionalized alkenes has been extensively studied. The rhodium complex with... 

Even though the hydroformylation of alkenes is an important reaction for the functionalization of unsaturated compounds with enormous potential, the above mentioned examples already show the limitations of using molecularly enlarged catalysts in combination with membrane filtration the hydroformylation reaction is typically performed at elevated temperature (40-80 °C) as well as under a syngas... 

A more sophisticated (3-cyclodextrin-based catalytic system combining different functions in the same molecule was also conceived. Rhodium complexes of multi-component ligands featuring a chelating diphosphine covalently linked to the upper riin of P-cyclodextrin (Fig. 6) were used as catalysts for the hydrogenation and the hydroformylation of alkenes in water-organic two-phase systems. 

Highly regioselective hydroformylation of functionalized alkenes has been studied. The rhodium complex with BIPHEPHOS efficiently catalyzes the regioselective hydroformylation of a variety of functionalized terminal alkenes, giving the corresponding aldehydes (Scheme 2-3). ... 

X = MeC(O), MeOC(O), BzOC(O), Et2NC(0), (EtO)2CH. (CH2CO)2N n = Oto8 Scheme 2-3. Highly regioselective hydroformylation of functionalized alkenes. 

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. ... 

Hydroformylation ofless reactive internal and functionalized alkenes. 

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