Functional Group-Directed Hydroformylation

Functional group-directed hydroformylation. Phosphine and phosphite moieties in olefinic substrates exert strong directing effects on the regioselectivity of hydroformylation. For example, hydroformylation of 4-(diphenylphosphino)-l-butene (32) catalyzed by Rh2(OAc)4/4PPh3 gives branched aldehyde 33, which subsequently is reduced to provide the corresponding alcohol 34 as the sole product (Eq. 16)." Under the same conditions, 1-hexene affords the linear alde-... 

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]. 

Alternatively, substrate control of diastereoselectivity can rely on attractive catalyst substrate interactions. This requires in general special functional groups which allow for a directed hydroformylation, which is summarized in Sect. 6 (vide infra). 

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. 

Functionalized olefins can be classified in two groups the <5-fimctionalized olefins in which the functional group is not directly branched on the double bond but on an alkyl chain of the olefin as in the case of oct-7-en-l-al or linoleic alcohol, and the a-functionalized olefins in which the functional group is directly branched on the double bond as in the case of methyl acrylate or phenyl vinyl ether. The results described for these two groups will be discussed separately. Hydroformylation of water-soluble olefins in two-phase system with water-insoluble catalysts is far beyond the scope of this chapter and will not be discussed here (1, 2]. 

In addition, reactions of many olefins containing electron-withdrawing functional groups at the C=C bond react to form branched substitution products. Examples of these reactions catalyzed by rhodium-carbonyl complexes modified by PPhj are shown in Scheme i7.i4.55.io6-"3 Directed hydroformylations, such as that in Equation 17.16, have also been studied. ... 

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. 

Functional groups can be utilized for directing the regioselectivity of the C-C bond formation. Recent work by Breit and Reek [33] provided evidence that, in particular, carboxylic acid groups are powerful regiodirecting groups in supramolecular catalyst-substrate assemblies, which allow even iso-selective hydroformylation of both internal and terminal olefins. 

Ricinoleic acid contains a hydroxyl function at a stereogenic carbon atom. Such additional functional groups may interact with transition-metal catalysts causing directing effects or lead to their deactivation. In the hydroformylation of ethyl ricinoleate, the formed aldehydes are converted immediately into cyclic ethers by acetalization and subsequent dehydration (Scheme 6.87) [36]. 

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