Hydroformylation linear-regioselective

Two recent exemplary applications in organic synthesis employing either a rhodium(l)/BlPHEHOS or a rhodium(I)/XANTPHOS catalyst to achieve a linear-regioselective hydroformylation of terminal aUcenes are summarized in Schemes 10 and 11. The hydroformylation of an aldehyde allylation product has served as a key step diu ing the course of a synthesis of a BC-ring subunit of the anticancer agent bryostatin (Scheme 10) [55]. 

Much progress has been made on regioselective hydroformylation of terminal alkenes in favor of the linear product. In particular bidentate phosphine or phosphite ligands, which have a natural bite angle 9 of about 110°, will favor the linear product. The most successful ligand types are BISBI [49, 50], BIPHEPHOS [51,52], and XANTPHOS systems (Scheme 8) [53]. 

Recently, a new bidentate hemispherical chelating bisphosphite ligand based on a calixarene backbone has been designed for linear selective hydroformylation of alkenes (Scheme 9) [54], Excellent levels of regioselectivity have been observed, and even the intrinsic branched-selective hydroformylation of styrene could be overruled by this system. However, the system suffers from low catalytic activity. 

As demonstrated by Hoffmann and coworkers, hydroformylation can also be combined with an allylboration and a second hydroformylation, which allows the formation of carbocycles and also heterocycles [213]. A good regioselectivity in favor of the linear aldehyde was obtained by use of the biphephos ligand [214]. Reaction of the allylboronate 6/2-76 having an B-configuration with CO/H2 in the presence of catalytic amounts of Rh(CO)2(acac) and biphephos led to the lactol 6/2-80 via 6/2-77-79 (Scheme 6/2.17). In a separate operation, 6/2-80 was oxidized to give the lactone 6/2-81 using tetrabutyl ammonium perruthenate/N-methylmorpholine N-oxide. 

The mechanism of the hydroformylation reaction suggests that aldehyde regioselectivity is determined in the hydride addition step, which converts the five-coordinated H(alkene)-Rh(CO)L2 into either a primary or a secondary four-coordinated (alkyl)Rh(CO)L2. For the linear rhodium alkyl species, this... 

A typical feature of hydroformylation is the fact that both sides of the double bond are in principle reactive, so only ethene yields propanal as a single product. From propene, two isomers are formed linear or normal butanal and 2-methylpropanal (branched or iso product). With longer chain 1-alkenes, the isomerization of the double bond to the thermodynamically more favored internal positions is possible, yielding the respective branched aldehydes (Fig. 1). Frequently, terminal hydroformylation is targeted because of the better biodegradability of the products. Thus, not only stability, activity, and chemoselectivity of the catalysts are important. A key parameter is also the regioselectivity, expressed by the n/i ratio or the linearity n/(n+i). 

Although early catalysts were based on cobalt, nowadays, rhodium catalysts are preferred because they require lower pressure and afford higher chemo- and regioselectivity [1,2]. In recent years, extensive research into the production of only linear aldehydes has provided impressive results. The application of phosphines with a wide bite angle in the rhodium catalyzed hydroformylation of terminal alkenes enable the regioselectivity to be almost totally controlled [3]. Branched selective hydroformylation, al-... 

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