Enantioselective catalytic hydrogenation, alkylation

The synthesis of the C20—C26 fragment started with a 4-alkylation of methyl aceto-acetate. The first stereocentre was introduced by enantioselective catalytic hydrogenation with Noyori s (S)-binap rhodium complex (cf. p. 102f.). Stereoselective Fr ter-Seebach alkylation with allyl bromide introduced the second stereooentre in 90% yield (cf. p. 27). Stereospecific introduction of the stereocentres C24 and C25 was achieved by a chelation controlled addition of an allylstannane to an aldehyde (see p. 66 f.). After some experimentation with Lewis acid catalysts and reaction conditions a single diastereomer of the desired configuration was ob-... 

Although they are often considered as poorer ligands than diphosphines, they lead also to very efficient and attractive enantioselective catalytic systems as exemplified here. As recent examples, diphosphinites 19 and 20 have been involved successfully in hydrogenation of olefins (mostly itaconate derivatives and enamides, up to > 99.9 % ee) ([84-89] and functionalized ketones (21) (up to 86 % ee) [90], hydrocyanation (19) [91], standard Pd-mediated allylic alkylation (20) [92] (up to 86% ee) [93], and Diels-Alder reaction between a,/l-enals and dienes (eq. (4) 99 % ee) [94]. 

Norton and coworkers found that catalytic enantioselective hydrogenation of the C=N bond of iminium cations can be accomplished using a series of Ru complexes with chiral diphosphine ligands such as Chiraphos and Norphos [68], Even tetra-alkyl-substituted iminium cations can be hydrogenated by this method. These reactions were carried out with 2 mol.% Ru catalyst and 3.4—3.8 bar H2 at room temperature in CH2C12 solvent (Eq. (39)). 

Table 34.4 Selected results for the enantioselective hydrogenation of N-alkyl imines and enamines (for structures, see Fig. 34.7) Catalytic system, reaction conditions, enantioselectivity, productivity and activity.

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