Crystal titanium enolates

Seebach and Brenner have found that titanium enolates of acyl-oxazolidinones are added to aliphatic and aromatic nitroalkenes in high diastereoselectivity and in good yield. The effect of bases on diastereoselectivity is shown in Eq. 4.59. Hydrogenation of the nitro products yields y-lactams, which can be transformed into y-amino acids. The configuration of the products is assigned by comparison with literature data or X-ray crystal-structure analysis. 

Asymmetric aldol reactions. The chiral N-propionyloxazolidinone (1), prepared in several steps from (lR)-(—)-camphorquinone, undergoes highly diastereoselective aldol reactions with the additional advantage of high crystallinity for improving the optical purities of crude aldols. Either the lithium enolate or the titanium enolate, prepared by transmetalation with ClTi(0-(-Pr)3, reacts with aldehydes to form syn-adducts with diastereomeric purities of 98-99% after one crystallization. The observed facial selectivity is consistent with metal chelation of intermediate (Z)-enolates (supported by an X-ray crystal structure of the trapped silyl enol ether). The lithium enolate also exhibits... 

Oppolzeds sultams 1.133 are also efficient auxiliaries in asymmetric aldol reactions [209,404,407,457,1271], Boron, titanium or Sn (IV) enolates of W-pro-pionoylsultams lead stereoselectively to either enantiomeric syn aldol at -78°C. These products are easily purified by fractional crystallization (Figure 6.83). After treatment with Li0H/H202 and CH2N2, syw-P-hydroxyesters are obtained with an excellent enantiomeric excess. The drawback of this method is the need to use an excess of aldehyde to obtain good chemical yields. As in the case of oxazolidi-... 

After almost half century of intensive, fundamental, and fruitful investigations of enolate structures, there is now clear evidence indicating that enolates of groups 1, 2, and 13 metals - lithium and boron being the most relevant ones - exist as the O-bound tautomers 1 the same holds in general for silicon, tin, titanium, and zirconium enolates [4]. Numerous crystal structure analyses and spectroscopic data confirmed type metalla tautomer 1 to be the rule for enolates of the alkali metals, magnesium, boron, and silicon [5]. 

Titanium bis-enolate 19, readily available by transmetallation of the lithium enolate of acetaldehyde with dicyclopentadienyl titanium dichloride (Cp2TiCl2), was characterized by a crystal structure analysis [53, 54]. Mono-enolates of titanium and zirconium 20 were obtained analogously from Cp2Ti(Me)Cl and... 

Cp2Zr(Me)Cl, respectively. Their NMR spectra clearly reveal that the O-bond character of the enolate, indicated by the carbon-carbon double bond, is maintained in solution (Scheme 3.8) [53]. Crystal structures were also obtained for O-bound zirconium acetophenone enolate 21 [55], titanium ketone enolate 22, derived from/) r -methylacetophenone, and amide enolate 23 [56]. Whereas the latter readily added to benzaldehyde, the ketone enolate 22 (X = Ph) failed to undergo an aldol addition. This difference in reactivity was explained - based on a computational study - by a higher electron density at the methylene carbon atom in the amide compared to the ketone enolate [56]. 

Scheme 3.8 Selected structures of O-bound titanium and zirconium enolates, confirmed by crystal structure analyses.

Titanium ester enolates are not only versatile reagents for asymmetric aldol additions but also function as starters of methacrylate polymerization. A representative titanium complex 24 was characterized by crystal structure and NMR spectroscopy and reveals the monomeric O-bound enolate character. The six-coordinated titanium atom in 24 is bound to two phenolic traws-oriented oxygen atoms and two sulfur donors the remaining ligands, methyl group, and enolate moiety are c/s-configured. Upon exposure to acetone, a spontaneous aldol occurs, and the aldolate 25 thus formed was also characterized by a crystal structure. Due to its coordinative saturation, the titanium obviously does not form a chelate with the carbonyl oxygen (Scheme 3.9) [57]. 

Scheme 3.9 O-metal-bound enolate 24 and aldolate 25 with hexa

For crystal structures of 0-metal bound titanium bis- and mono-enolates of 2-methoxyacetophenone, see (a) Veya,... 

Oppolzer s auxiliary opened, in addition, an access to a/iti-configured aldol adducts 272 (Scheme 4.62). For this purpose, silyl ketene N,0-acetal 271 was prepared from propionic sultam 92, obtained as a single diastereomer, according to the NMR spectra of the crude product, and isolated as a crystalline compound it was characterized as a cis-silicon enolate by a crystal structure analysis. For the subsequent Mukaiyama aldol addition, titanium tetrachloride was found to be the optimum Lewis acid to yield the awti-diastereomers 272 in excellent diastereoselectivity. Their formation under attack of the enolate to the Re-face of the aldehyde is consistent with an open transition state 275, wherein the Lewis acid-coordinated aldehyde is located on the face opposite to the sulfonyl group (Scheme 4.62) [136b]. An alternative approach to the a fi-aldol adducts was also elaborated, based upon cA-boron enolates 267 when they are reacted with aldehydes in the presence of titanium tetrachloride, an ti-selective aldol addition occurs leading to the products 272 rather than to sy -aldols 268 that result in the absence of the Lewis acid [136c]. 

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