Addition to Enolizable Ketones

5 Diastereoselectivities associated with reactions of 88 will be discussed in Section D.II. 

Grignard-type addition to the sterically hindered ketone 92 is a challenge because 

Unfortunately, 6 and 63 as well as the zirconium reagent 61 also fail. Based on the observation that reagents containing two methyl groups are more reactive and less  

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Azide addition to enolizable ketones is regiospecific and may be considered as a 1,3-dipolar cycloaddition occurring at the double bond of the enolate, similar to the addition of azides to electron-rich olefins. However, a stepwise reaction appears more probable because glycosyl azides exhibit anomerism when they react with activated methylene compounds, thus indicating the presence of a triazene intermediate.264 On the other hand, the formation of the triazene intermediate may be considered as a limited case of 1,3-dipolar cycloaddition where one of the bonds is formed completely before the other one starts,2 such a limited case being observed for the Diels-Alder reaction.265... 

Aldol Additions to Ketones. Traditionally, cerium enolates or the Reformatsky-type reaction have been employed to achieve high-yielding aldol additions to enolizable ketones. In this regard, methyl trichlorosilyl ketene acetal provides a reliable alternative for the synthesis of tertiary -hydroxy esters. In the absence of a Lewis base promoter, the aldol additions of 1 to ketones are too slow to be synthetically useful. On the contrary, with pyridine A-oxide as catalyst, methyl trichlorosilyl ketene acetal reacts smoothly with nearly all classes of ketones (7) (Scheme 1). Good yields of the tertiary alcohol products (8) are obtained (eq 4), table 2 from aromatic (entries 1-2 and 4—6), hetereoaromatic (entry 3), olefinic (entries 7-8), acetylenic (entries 9-10), and aliphatic (entries 11-14) ketones. The only poorly performing substrate is 2-tetralone (7o), which affords a 45% yield of the addition product and returns 45% of unreacted starting material, most likely from competitive enolization. 

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