Achiral hydrogenation catalysts

Fig. 12.21 Chiral and achiral Rh-catalysts employed for the hydrogenation of styrene.

As with most chiral atropisomeric ligands, resolution or enantioselective synthesis is requisite. Mikami developed a novel ligand-accelerated hydrogenation catalyst in which the chirality of an atropos but achiral triphos-Ru complex could be controlled by chiral diamines. Using (S)-dm-dabn as controller, a single diastereomeric triphos-Ru complex was obtained through isomerization of the (R)-triphos-Ru complex in dichloroethane at 80°C (Scheme 26.1) [36]. 

Another series of achiral iridium catalysts containing phosphine and heterocyclic carbenes have also been tested in the hydrogenation of unfunctionalized alkenes [38]. These showed similar activity to the Crabtree catalyst, with one analogue giving improved conversion in the hydrogenation of 11. 

Hydrosilylation can be applied to alkenes, alkynes, and aldehydes or ketones. A wide range of metal compounds can be used as a catalyst. The most common and active ones for alkenes and alkynes are undoubtedly based on platinum. Hydrosilylation of C-0 double bonds gives silyl ethers, which are subsequently hydrolysed to their alcohols. The reaction is of interest in its enantioselective version in organic synthesis for making chiral alcohols, as the achiral hydrogenation of aldehydes or ketones does not justify the use of expensive silanes as a reagent. 

The present procedure involving homogeneous catalysis is operationally simple and takes advantage of the easy availability of 2-(l -hydroxyalkyl )-acrylic esters. A two-step procedure Involving kinetic resolution of the racemic starting material with an optically active hydrogenation catalyst, followed by a further reduction with an achiral catalyst, leads to diastereomerically pure products in 4. 97t ee. 

The reaction actually produces a mixture of the primary amine and the correspond ing formyl derivative, but the amine product is exclusively isolated after the crude product is treated with H Cl (Scheme 7.3). As of this writing, the method provides low yields and ee for cyclic aromatic substrates, for example, 1 indanone (6% yield, no ee reported, chiral Ru catalyst) [11b]. Regarding aliphatic ketones, for example, 2 octanone (44% yield, 24% ee, chiral Ru catalyst [lla[ or 37% yield with an achiral Rh catalyst [11b]). The same authors have recently made inroads concerning the use of aromatic ketones and molecular hydrogen [12], although the transfer hydrogenation method presented here appears to be superior as of now. 

All the iron [6.5.6]-P-N-N-P hydrogenation catalysts require activation by an external base. The catalytic profile for achiral complex 32 showed that there is an induction period before rapid catalysis takes place for the TH of acetophenone in basic isopropanol. Unexpectedly, reacting 32 with sodium isopropoxide in either benzene or isopropanol yields the pentadentate ferraaziridine complex 39, which was isolated and structurally characterized (Scheme 10).> This unusual complex is diamagnetic, with... 

An alternative enzyme/transition metal combination employs transfer hydrogenation catalysts that are capable of racemizing secondary alcohols. The racemization procedure temporarily converts the alcohol into an achiral ketone, which is reduced back to the racemic alcohol. Coupling this racemization procedure to an enzyme-catalyzed acylation reaction affords a dynamic resolution process (Fig. 9-12). Several enzyme/transition metal combinations have been shown to be effective for these reactions, although ruthenium complexes 1-3 appear to be especially effective for the in situ racemization of the alcohol. The product esters are not prone to racemization under the reaction conditions. Early results employing transfer hydrogenation catalysts to effect the racemization of alcohols required the use of added ketone 21, 22. However, it was subsequently shown that added ketone was not required when appropriate transition metal complexes were used as catalysts. Furthermore, the use of 4-chlorophenyl acetate as the acyl donor afforded improved results. 

SELECTED EXAMPLES OF ACHIRAL HOMOGENEOUS HYDROGENATION CATALYSTS... 

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