Reversibility titanium enolates

With titanium enolates it was found that use of excess (3 equiv.) of the titanium reagent reversed facial selectivity of oxazolidinone enolates.140 This was attributed to generation of a chelated TS in the presence of the excess Lewis acid. The chelation rotates the oxazolidinone ring and reverses the facial preference, while retaining the Z-configuration syn diastereoselectivity. 

Asymmetric aldol reactions5 (11, 379-380). The lithium enolate of the N-propionyloxazolidinone (1) derived from L-valine reacts with aldehydes with low syn vs. anti-selectivity, but with fair diastereofacial selectivity attributable to chelation. Transmetallation of the lithium enolate with ClTi(0-i-Pr)3 (excess) provides a titanium enolate, which reacts with aldehydes to form mainly the syn-aldol resulting from chelation, the diastereomer of the aldol obtained from reactions of the boron enolate (11, 379-380). The reversal of stereocontrol is a result of chelation in the titanium reaction, which is not possible with boron enolates. This difference is of practical value, since it can result in products of different configuration from the same chiral auxiliary. 

These four examples do not seem to comply with a consistent mechanistic model. The dilithioprolinol amide enolate in Scheme 5.31a is attacked on the enolate Si face, in accord with the sense of asymmetric induction observed in alkylations of this enolate [166,167]. On the other hand, the structurally similar dilithiovalinol amide enolate, while being attacked on the same face (as expected), reverses top-icity. Furthermore, the S,S-pyrrolidine enolate in Scheme 5.31c is attacked from the Si face by Michael acceptors, but from the Re face by alkyl halides [168] and acid chlorides [169]. The titanium imide enolate in Scheme 5.31d adds Michael acceptors from the Si face, consistent with the precedent of aldol additions of titanium enolates (c/. Table 5.4, entry 2, [88]). An intramolecular addition (Scheme 5.3le) seems to follow a clear mechanistic path [165] the Si face is attacked by the electrophile, and the cis geometry of the product implicates intramolecular complexation of the acceptor carbonyl. This coordination of the acceptor carbonyl is probably a function of the metal recall the lithium ester enolates illustrated in Scheme 5.30c and d, but also metal chelation in titanium aldol additions (Table 5.4, entry 2). 

Nerz-Stormes M, Thornton ER. Asymmetric aldol reactions. Use of the titanium enolate of a chiral N-acyloxazolidinone to reverse diastereofacial selectivities. J. Org. Chem. 1991 56 (7) 2489-2498. 

The stereoselectivity of this reaction also depends on the titanium reagent used to prepare the enolate.104 When the substituent is benzyloxy, the 2,2 -anti-2,3-syn product is preferred when ( -PrO)TiCl3 is used as the reagent, as would be expected for a chelated TS. However, when TiCl4 is used, the 2,2 -syn-2,2-syn product is formed. A detailed explanation for this observation has not been established, but it is expected that the benzyloxy derivative would still react through a chelated TS. The reversal on use of TiCl4 indicates that the identity of the titanium ligands is also an important factor. 

The addition of acetate-derived, achiral lithium enolates to monoprotected a-amino aldehydes is controlled by chelation, and leads to a modest stereochemical preference in favor of the 3,4-syn configuration (Table 1, entry a). 18 The formation of the 3, A-syn-product is enhanced by the use of acetate-derived silyl ketene acetals and the addition of titanium(IV) chloride or tin(IV) chloride to the reaction mixture (Table 1, entries b and c). 22-23 The same enolates add stereoselectively to A2 A-dibenzyl a-amino aldehydes but with diastereomeric ratios in favor of the Felkin-Ahn 3,4-anti-product (Table 1, compare entries a and d, and b and f). 22-24 Reverse stereocontrol is observed in the presence of a Lewis acid such as tita-nium(IV) chloride, but the yield is low (Table 1, entry e). 24 ... 

Silyl enol ethers undergo reaction with carbonyl compounds promoted by Lewis acids, but especially titanium tetrachloride. The reaction is thought to proceed via a titanium chelate which inhibits the reverse aldol process and the regiochemical integrity of the starting silyl enol ether is retained (Scheme 102).373... 

Fujisawa et al. [89] have reported the stereodivergent synthesis of spiro-[S-1 act a ms 64, 65 (Scheme 17) by reaction of lithium or titanium ester enolates 62 with single chiral imines 63 by taking advantage of different coordination states of the enolate metals. Almost complete reversal of the diastereofacial-discrimination with respect to the C-4 of the (3-lactam skeleton has been attained in this reaction coupled with flexibility in the selection of the enolates and ready removal of the chiral auxiliary. 

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