Stereochemistry asymmetric hydroformylation

Optically active aldehydes can be obtained by asymmetric hydroformylation of olefinic substrates when at least one asymmetric carbon atom is formed either by addition of a formyl group or of a hydrogen atom to an unsaturated carbon atom (Scheme 1, reactions (1) and (2)). In the case of trisubstituted olefins, two new asymmetric carbon atoms can form due to the cis stereochemistry of the reaction10), in the absence of isomerization, the formation of only one epimer is expected. 

The enantioselective hydrocyanation of alkenes has the potential to serve as an efficient method to generate optically active nitriles, as well as amides, esters, and amines after functional group interconversions of the nitrile group. As in asymmetric hydroformylation, asymmetric hydrocyanation requires control of both regiochemistry and stereochemistry because simple olefins tend to generate achiral terminal nitrile products. The hydrocyanation of norbomene will give a single constitutional isomer and was studied initially. However, modest enantioselectivities were obtained, and the synthetic value is limited. ... 

To illustrate the practical use of this asymmetric hydroformylation, Huang and co-workers completed the synthesis of 7 -exo-norbornylamine in an overall yield of 71% from the starting olefin, with full retention of stereochemistry induced in the hydroformylation step (Scheme 14.22). ... 

In the hydroformylation reaction, V, the situation is even worse. Here there is no definite stereochemistry between the phosphine ligand and the metal. One of the reactants, carbon monoxide, competes so well with the phosphine for sites on the metal that it is difficult to insure that the chiral agent is present when the new asymmetric center is formed. 

Of at least as great importance to the chemistry of PX3 compounds as the electronic factors are steric factors.6 Indeed these may be more important or even dominant in determining the stereochemistries and structures of compounds Steric factors also affect rates and equilibria of dissociation reactions and the stereochemistry of phosphine ligands is the prime factor in many highly selective catalytic reactions of phosphine complexes, such as hydroformylation and asymmetric hydrogenation. 

---