Unfunctionalized ketones

Simple unfunctionalized ketones such as aryl alkyl ketones 36 can be olefinated by ynolates to provide tetrasubstituted olefins 37-42 in good to excellent yield (Fig. 12) [56]. While the Wittig and the Horner-Emmons reagents are not suitable reagents for this type of olefination, especially for ferf-butyl phenyl ketone (43), the ynolate affords the corresponding olefin 41 in 74% yield (Fig. 13). Ynolates are actually much better reagents for the olefination of ketones than the conventional 

This olefination strategy has been used by Kobayashi to synthesize globostellatic acid analogs, an antiangiogenic triterpene derivative from the marine sponge Stelletta globostellata (Fig. 14) [57]. Thus ketone 44 is olefinated by ynolate to yield the tetrasubstituted olefin 45. 

---

The asymmetric hydrogenation of unfunctionalized ketones is a much more challenging task than that of functionalized ketones [3 j, 115]. Many chiral catalysts which are effective for functionalized ketones do not provide useful levels of enantioselectivity for unfunctio-nalized ketones, due to a lack of secondary coordination to the metal center. Zhang demonstrated the enantioselective hydrogenation of simple aromatic and aliphatic ketones using the electron-donating diphosphane PennPhos, which has a bulky, rigid and well-defined chiral backbone, in the presence of 2,6-lutidine and potassium bromide [36]. 

I.4.2.I. Aromatic Ketones Although phosphine-Ru(II) dichlorides are poor catalysts for hydrogenation of unfunctionalized ketones [162b,255], a remarkably high reactivity emerges when the Ru compounds are further complexed with a 1,2-diamine ligand. Thus trans-... 

In contrast to unfunctionalized ketones, Wilkinson-type catalysts are quite effective in the hydrogenation of 2-oxo esters. With in situ catalysts consisting of [Rh(cod)Cl]2 2 and a proline derived chelate phosphane BPPM 3l4, quantitative hydrogenation of 2-oxo esters to (7 )-2-hydroxy esters was achieved. Dry benzene or dry tetrahydrofuran as solvent were superior to alcohols usually used in hydrogenation reactions with Wilkinson-type catalysts. While methyl 2-oxopropanoate was reduced to methyl (R)-2-hydroxypropanoate in only 66% eel5, propyl and 2-methylpropyl 2-oxopropanoate gave the (R)-alcohols with 76% and 71 % ee, respectively (Table 2)15,10. 

The hydrogenation of a-amino ketones results in the formation of a-aminoalkanols which are biologically important compounds, e.g., adrenergic drugs. In contrast to unfunctionalized ketones, a-amino ketones can be catalytically reduced with high enantioselectivity (Table 6), indicating that chelation within the catalyst is a necessary prerequisite. 

For hydrogenation of unfunctionalized ketones the only efficient solid catalyst is Ni [13]. Catalyst pretreatment conditions are similar to those used for catalysts in the hydrogenation of /6-ketoesters. A major difference is the application of pivalic acid in greater than stoichiometric amounts during the hydrogenation reaction. This additive, with sufficient Na" ions, enhanced the ee from 2 to 80-85% in the reduction of a variety of 2-alkanones. 

As noted previously, one of the most dramatic advances in asymmetric hydrogenation over the past tu o decades has been the development of ruthenium catalysts for the hydrogenation of ketones. Tltese hydrogenations can be divided into the hydrogenation of "functionalized" ketones and "unfunctionalized" ketones. "Functionalized" ketones... 

Figure 15.13. Noyori s catalyst for the hydrogenation of unfunctionalized ketones.

---