Imide enolates diastereoselective synthesis

Imide enolates derived from (5)-valinol and (15,2/f)-norephe-drine and obtained by either LDA or Sodium Hexamethyldisi-lazide deprotonation (eq 24) exhibit complementary and highly diastereoselective alkylation properties. Mild and nondestructive removal of the chiral auxiliary to yield carboxylic acids, esters, or alcohols contributes to the significance of this protocol in small-and large-scale synthesis. ... 

The most general protocol (eq 10) has therefore been based on potassium hexamethyldisilazide (KHMDS) as the base addition of trisyl azide at —78 °C and then acetic acid at the same temperature. Excellent levels of diastereoselectivity are ohsCTved with most substrates and the method has been used widely in the enantioselective synthesis of a-amino acids from chiral iniides. Chemoselective azidation of an imide enolate in the presence of an ester function has been demonstrated (eq 11). The product distribution is nevertheless finely balanced, as discovered with the respective dimethyl and dihenzyl ethers of the 3,5-substituted phenylacetyl imide (3) (eq 12). ... 

The synthesis of e.p. a-[ " C ]amino acids through diastereoselective homologation of protected acyclic or cyclic homochiral glycine building blocks (Figure 11.62) by alkylation of their enolates is a valuable alternative to the electrophilic a-amination of chiral a-unsubstimted imide enolates ". ... 

In the synthesis of ionomycin published in 1990, the Evans group provided a convincing acid test of their auxiharies in several alkylation and aldol addition steps. Just one of those, the preparation of the alcohol 72, that was required as C-13 to C-16 fragment of ionomycin, may serve as an Ulustrative example, shown in Scheme 4.13. The hthium enolate of imide 48 was alkylated with cinnamyl bromide in a highly diastereoselective manner. The a-branched imide 71 thus obtained was reduced to the alcohol 72 that, after conversion into the primary iodide 15 (Scheme 4.3), served as electrophile in Evans prolinol procedure for chain elongation en route to ionomycin [12b]. 

So far only one example for the successful use of acetals in diastereoselective a-functionalization of chiral isotopically labeled imides has been published. Though this reaction was performed with carbon-13 material, there is little doubt that it is also applicable in carbon-14 synthesis. The titanium enolate prepared from (45)-4-benzyl-3-[(2R)-2-[ C, H3]methylpropionyl]-l,3-oxazolidin-2-one (111) reacted with trioxane to afford the corresponding a-hydroxymethyl derivative 112 in 83% yield and >96%... 

Other uses of oxazinone enolates have been described by Williams, including the boron enolate 60, in the synthesis of diaminopimelic acid (62), the penultimate precursor of the essential amino acid i.-lysine (Scheme 10.8) [59], Acylated derivatives of Oppolzer s camphor sultam 63 can readily be alkylated in a highly diastereoselective fashion (Scheme 10.9) [60]. Thus, the imide derived from the condensation of 63 and 64 undergoes enolization and subsequent alkylation to furnish protected amino acid derivatives with high selectivity (cf 65, dr > 99 1) [61],... 

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