Consecutive hydroformylation-aldol reaction

The reaction provides better yields with cyclic secondary amines than with acychc ones [ 107]. 

SUylenol ethers such as 184 also undergo the hydroformylation-aldol reaction to give the sUylated aldol adducts 185 in good yields through a sequence of reactions involving the hydroformylation of the alkene and the intramolecular Mukaiyama type aldol reaction. [108]. Best results were achieved using the trimethylsilyl group. 

Different reaction products are obtained if the hydroformylation of the unsturated ketone 183 is carried out in the presence of amines. With secondary amines the hydroaminomethylation of the double bond is observed, leaving the carbonyl group unaffected. 

In the presence of benzylamine, ketone 183 is converted into the aminoketone 186 by alkene hydroformylation, imine formation and aldol reaction. Under more drastic hydroformylation conditions the reaction of 183 with benzylamine leads to the amine 187, which results from a mechanism similar to those above including reductive amination of the ketone moiety. 

Using bulkier primary amities such as isopropyl- or cyclohexylamine, no aldol reaction is observed and, instead, heterocycles of type 188 are generated via alkene hydroformylation, double amine condensation and rednctive 

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Figure 46. Consecutive hydroformylation-aldol reactions in the presence of amines...

The aldol reaction is probably one of the most important reactions in organic synthesis. In many industrially important hydroformylation processes selfcondensation of aldehydes is observed. Sometimes this consecutive reaction is favored as in the production of 2-ethyl hexanol. But synthetic applications of tandem hydroformylation/aldol reactions seem to be limited due regiose-lectivity problems of a mixed aldol reaction (Scheme 28). However, various tandem hydroformylation/intramolecular mixed aldol reactions have been described. 

The desired reaction in catalytic hydroformylation is the addition of carbon monoxide and dihydrogen to the olefin substrate usually to obtain aldehyde. To some extent, however, concurrent reactions of the olefin (substrate) such as hydrogenation, isomerization, and special carbonylations, and consecutive reactions of the aldehyde product such as hydrogenation to alcohol, aldol reaction, trimer-ization, and formate formation take place under the reaction conditions of hydroformylation, which affect both yield and selectivity of the aldehyde products. For an example of product composition obtained using an unmodified cobalt catalyst in the BASF process, see Table 3. 

When the hydroformylation is carried out in an alkaline reaction medium, the aldehydes formed as primary products undergo aldolization and, consecutively, hydrogenation. Thus the addition of, e.g., KOH (2 mol/g at Co) or a tertiary alkylamine leads to 2-ethylhexanol with yields up to 85 %, starting from propene. The formation of by-products like C4/4/4-acetal can be controlled by proper choice of the alkalinity and its source [188, 189]. 

Other Aldehyde Consuming Side Reactions. Beside consecutive hydrogenation and hydroformylation of the aldehyde product, other reactions as well can cause the lowering of the aldehyde yield in olefin hydroformylation. Especially in hydroformylation with unmodified cobalt catalyst, aldol formation from the aldehyde product is one of the sources of several high boiling components. 

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