Lithium active chelated

The results of this study suggest that optically active chelated lithium reagents may be used generally for asymmetric synthesis according to the scheme ... 

Oxo esters are accessible via the diastereoselective 1,4-addition of chiral lithium enamine 11 as Michael donor. The terr-butyl ester of L-valine reacts with a / -oxo ester to form a chiral enamine which on deprotonation with lithium diisopropylamide results in the highly chelated enolate 11. Subsequent 1,4-addition to 2-(arylmethylene) or 2-alkylidene-l,3-propanedioates at — 78 °C, followed by removal of the auxiliary by hydrolysis and decarboxylation of the Michael adducts, affords optically active -substituted <5-oxo esters232 (for a related synthesis of 1,5-diesters, see Section 1.5.2.4.2.2.1.). In the same manner, <5-oxo esters with contiguous quaternary and tertiary carbon centers with virtually complete induced (> 99%) and excellent simple diastereoselectivities (d.r. 93 7 to 99.5 0.5) may be obtained 233 234. 

A Indole, when treated with one equivalent of sodaniide and then with benzenesulfonyl chloride, gives l- pheny sutronyl)indole. The A -sulfonyl substituent activates the H-2 to deprotonation by butyl-lithium and stabilizes the lithium derivative by chelation. This oriho lithiation process facilitates subsequent acetylation at this site by acetyl chloride, affording 2-acetyl-l-(phenylsulfonyl)indole (Scheme 7,11). 

I he keto function in compound 10 is reduced with lithium aluminum hydride in THF to a secondary alcohol. In the course of this reaction one of the melhoxy groups in the ortho-position is also cleaved. It appears reasonable to explain this by an oriho effect the alcohol group forms an intermediate alkoxyaluminum hydride complex 37 that coordinates with one of the methoxy groups, which is thereby activated toward nucleophilic attack by hydride. A chelate complex protects the product from cleavage of the second ortho-methoxy group. 

Scheme 4.74 complete reversal of regioselectivity is observed when highly basic lithium amides are used as nucleophiles. Activation of the benzylic C-O bond by chelate formation of Li+ with the oxirane and the carbonyl group has been proposed as a possible reason for this unexpected reversal of regioselectivity [332]. 

Eberhardt and co-workers (12, 13) found that lithium alkyls are active toward the telomerization of ethylene and benzene when a tert-amine or chelating diamine, such as sparteine or N.N.JV. Af -tetramethylenethy-lenediamine (TMEDA), is used [Eqs. (1)—(3)]. 

Anti diastereoselectivity gives the optically active (S)-p-hydroxy ester while syn diastereoselectivity leads to the (/ )-P-hydroxy ester, via a chelated six-membered transition state (eq 3). Since the anti intermediate is more stable, the (S)-P-hydroxy ester predominates under thermodynamic conditions (Table 1, entry 1). Higher diastereoselectivity is achieved by changing the counterion from lithium to a more chelating one such as zinc (Table 1, entry 2). On the other hand, in order to obtain diastereoselection under kinetic control, zirconium enolates (prepared by treating the lithium enolate with Dichlorobis(cyclopentadienyl)zirconium) are used, leading to the (/ )-p-hydroxy ester (Table 1, entry 3) in high yield. 

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