Ketones, 3-hydroxy cerium enolates

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. 

The use of lanthanide metal enolates in the aldol reaction has, to date, only been developed to a synthetically useful level in the case of cerium (Scheme S and Table 7). Stereoselectivities are no better than those of lithium enolates, but the cerium enolates of ketones woik well in crossed aldol additions to ketones (Table 7, entries 1-7) and sterically hindered aldehydes (Table 7, entries 9 and 10). Such crossed aldol reactions do not often work well with lithium enolates as enolate equilibration, retroaldolization and steric retardation of addition occur. Imamoto et al. have shown that cerium enolates (44), formed from anhydrous CeCb (1.2 equiv.) and the preformed lithium enolates of ketones in THF at -78 C, undergo such aldol reactions to give the corresponding p-hydroxy ketones (46), usually in high yield. The cerium suppresses the retroaldol reaction by efficient chelation of the aldolate (45). A similar effect is known for zinc halide mediated aldol reactions (Volume 2, (Chapter 1.8). The stereoselectivity of the... 

Cerium enolates may also be generated reductively in THF from oi-iodo or a-bromo esters in the presence of an aldehyde or ketone using cerium metal turnings and catalytic HgCk (or cerium amal-gam). This leads to a Reformatsky-type reaction (Volume 2, Chapter 1.7) producing the (3-hydroxy ester (47) as a mixture of diastereomers (equation 16). 

Cerium enolates also provide favorable routes to a-bromo-/8-hydroxy ketones, important intermediates to a,/8-epoxy ketones. 

Sodium Azide/Ammonium Cerium(IV) Nitrate. Silyl enol ethers give a-azido ketones on treament with sodium azide and anhydrous ammonium cerium(IV) nitrate in anhydrous acetonitrile (see Eq. 97).297 325 33i With a glycal, the 2-azido-1-hydroxy nitrate derivative is formed.332 Low yields due to hydrolysis of the silyl enol ether may be improved by use of the triisopropylsilyl (TIPS) derivatives,331 although with a sterically encumbered taxane-derived enol ether the TMS derivative gives higher yields than the TIPS derivative.325 The mechanism is believed to involve addition of an azide radical to the double bond. 

Cerium(III) chloride. 14, 73-77 15, 72-P-Hydroxy amides. Cerium(III) ea than the Li enolates toward ketones and >94% yield of the aldol. 

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