Double hydroformylation reaction

SCHEME 18 Retrosynthetic analysis of quinolizidine core by double hydroformylation reaction. 

The double hydroformylation reaction was carried out under standard conditions and the bis-aldehyde-azide 53 was obtained in a yield of 76% (Scheme 21). The hydrogenolysis of the azide followed by deprotection of the primary alcohol using TBAF enabled the synthesis of (+)-lupinine with an overall yield of 15% in eight steps. 

The nickel or cobalt catalyst causes isomerization of the double bond resulting in a mixture of C-19 isomers. The palladium complex catalyst produces only the 9-(10)-carboxystearic acid. The advantage of the hydrocarboxylation over the hydroformylation reaction is it produces the carboxyUc acids in a single step and obviates the oxidation of the aldehydes produced by hydroformylation. 

If cobalt carbonylpyridine catalyst systems are used, the formation of unbranched carboxylic acids is strongly favored not only by reaction of a-olefins but also by reaction of olefins with internal double bonds ( contrathermo-dynamic double-bond isomerization) [59]. The cobalt carbonylpyridine catalyst of the hydrocarboxylation reaction resembles the cobalt carbonyl-terf-phos-phine catalysts of the hydroformylation reaction. The reactivity of the cobalt-pyridine system in the hydrocarboxylation reaction is remarkable higher than the cobalt-phosphine system in the hydroformylation reaction, especially in the case of olefins with internal double bonds. This reaction had not found an industrial application until now. 

Oxo reaction or hydroformylation reaction involves addition of a hydrogen atom and a formyl group (-CHO) to C=C double bond of an olefin making both anti—Markovnikov and Markovnikov products ... 

With regard to the structure of the olefins, tetrasubstituted olefins do not undergo hydroformylation reaction under typical reaction conditions, and olefinic substrates containing functional groups sometimes give poor yields and unexpected products. If there is no plane of symmetry in the substrate across the double bond, at least two isomeric aldehydes are obtained. Although methods for shifting the... 

To control the reaction, different precursors and ligands have been employed to gain selectively for only one aldehyde. The terminal aldehyde was obtained with ligands with bite angles near 120° and a stiff backbone, e.g., xantphos. The aldehydes with an internal double bond were obtained with a monodentate ligand, e.g., triphenylphosphine, with a selectivity of 83%. Double hydroformylation was observed with higher pressures and temperatures. 

Metal enolates have played a Umited role in the metal-catalyzed isomerization of al-kenes . As illustrated in a comprehensive review by Bouwman and coworkers, ruthenium complex Ru(acac)3 (51) has been used to isomerize a wide range of substituted double bonds, including aUylic alcohols (131), to the corresponding ketones (132) (equation 38) . The isomerization of aUylic alcohols affords products that have useful applications in natural product synthesis and in bulk chemical processes. An elegant review by Fogg and dos Santos shows how these complexes can be used in tandem catalysis, where an alkene is subjected to an initial isomerization followed by a hydroformylation reaction ... 

The virtue of the oxo synthesis lies in its applicability to a broad variety of substrates. On a laboratory scale most unsaturated carbon-carbon bonds and some heteroatom-carbon double bonds can be hydroformylated. Reaction rates vary with catalysts and reaction conditions. However, industrial importance has only been reached for 1 -olefins such as propene, butene, octene/ nonene and some se-... 

It was also reported (214) that the same hydroformylation reaction can be achieved by various rhodium(I) double bridged pyrazolate complexes of the general formula [Rh2( -pz )2(CO)2L2] (L = P(OMe)3, P(OPh)3, PPh3 Hpz = Hpz, Hmpz, or Hdmpz). Good catalytic activity was found. The latter decreases in the sequence P(OPh)3 > P(OMe)3 > PPh3 (214). The effect of the bridging pyrazolate ligand was also studied (215, 216). 

Concerning the reactions of type 2, addition of CO across double bonds can be exemplified by the hydroformylation reaction ... 

A very efficient method to transform directly an unsaturated triglyceride in polyols is to develop a hydroformylation reaction with sin gas (mixture of hydrogen/carbon monoxide), at 70-130 °C, in the presence of rhodium or cobalt catalysts [70, 71], at higher pressures (4,000-11,000 kPa). In the first step the double bonds are transformed in aldehyde groups, in high yield (reaction 17.25). 

The structure written for I is satisfactory for olefins which can have only internal or only terminal double bonds (ethylene, propylene, cyclohexene). We find, however, that although internal olefins are thermodynamically more stable than terminal olefins under reaction conditions, the products obtained in the hydroformylation reactions are largely derived by addition to the terminal carbons. For example, the distribution of alcohols secured from 1-pentene and 2-pentene is about the same 13, 14), 50-55% of n-hexanol, 35-40% of 2-methylpentanol-l, and 10% of 2-ethylbutanol-l. In each case the chief product can be obtained only by the addition of the formyl group to the No. 1 carbon atom. If we assume that hydroformylation occurs only at the double bond, we may ask how it is possible to form a straight-chain aldehyde from an internal olefin. 

The hydroformylation reaction is the formal addition of formaldehyde across a C-C double bond (Scheme 8.3). 

Terminal n-alkenes undergo hydroformylation reactions most rapidly followed by internal n-alkenes, while branched olefins react least rapidly. The greater number of alkyl groups that are bonded to the carbon atom which forms the double bond, the slower the reaction course. The mechanism of the reaction for the cobalt, rhodium, or manganese [MnH(CO)5] catalyst is basically the same. The proper catalysts are metal hydrido carbonyls. 

Control of selectivity, chemo-, regio-, and stereoselectivity, is the most important problem in the hydroformylation reaction. As far as chemoselectivity is concerned such competitive reactions as isomerization, double bond hydrogenation and aldehyde hydrogenation occur under hydroformylation conditions. 

This section deals with substrate-controUed stereoselective hydroformylation, since asymmetric hydroformylation is covered in chapter 5. The stereoselectivity of the hydroformylation reaction is the result of the cis addition of the proton and the formyl group to the less hindered face of the double bond [41]. The presence of heteroatoms in the substrate causes chelation, so the stereoselectivity can be controlled, (see section 6.5). 

The problem of the chemoselectivity is associated with the drastic reactions conditions usually employed in the hydroformylation reaction. Thus, the consecutive hydrogenation of unsaturated aldehyde gives aldehydes or alcohols [111, [112] (Figure 48). No products of double hydroformylation are obtained. 

Hydroformylation can be highly tolerant of functional groups. An azide, normally highly reactive towards transition metals, can survive. This property has been exploited in a synthesis of the pyridine alkaloids anaba-sine 4.158 and nicotine 4.159 from the same hydroformylation reaction (Scheme 4.58). Another approach to both of these alkaloids can be found in Chapter 8, Schemes 8.76 and 8.77. Double hydroformylation of the azido diene 4.160 gave the bis-aldehyde 4.161 (Scheme 4.59). Tandem azide reduction and double reductive amination then gave the indolizidine alkaloid, lupinine 4.162. ... 

To achieve double hydroformylation, appropriate reaction conditions have to be identified. Thus, in a two-step sequence using, in the first step, a phosphine-modified rhodium complex and, in the second step, a cobalt catalyst was claimed... 

The double bonds in aromatic hydrocarbons cannot be hydroformylated. Thus, aromatics like benzene, toluene, and xylene can be used as solvents for the hydroformylation reaction even under extreme conditions without themselves being reacted. 

It is assumed that in the first step the metal hydrocarbonyl is added across the double bond of the starting material, analogous to the hydroformylation reaction (1). 

Bidentate ligands were used by Alper and coworkers. The bis(diphenylphospino-methyl)amine ligands were prepared on primary amine-terminated PAMAM dendrons on silica as well as polyamido dendrons on polystyrene via the double Mannich-like reaction with formaldehyde and diphenylphosphine (Scheme 15.36a). " Subsequently, Alper and coworkers subjected the dendronized ligand-decorated supports to complexation with rhodium and palladium precursors in order to prepare active catalysts for a number of important chemical transformations (Scheme 15.36b). Initially, the dendronized rhodium catalysts were tested in the hydroformylation reaction and carbonylative ring expansion of... 

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