Diastereoselection extended enolates

The fact that (Z)-lithium enolatcs generally display a higher simple diastereoselectivity giving. vyn-aldols compared to (E)-enolates affording nn/i-aldols is a challenge to the Zimmer-man-Traxler model, and has become the source of extended speculation. 

The enolate of the 1,4-adduct, obtained after the stereoselective Michael addition step, as discussed in the previous sections, may be quenched in situ with various electrophiles. The fact that additional stereogenic centers may be formed via such tandem Michael addition/quench-ing procedures, giving products with high diastereoselectivity in many cases, extends the scope of these methods substantially. Furthermore these procedures occasionally offer the possibility of reversing the syn/anti diastereoselection. In the next sections pertinent examples of diastereoselective inter- and intramolecular quenching reactions will be discussed. 

Rovis and co-workers further extended the scope of the reaction to the enantio-and diastereoselective cyclisation of a,P-disubstituted Michael acceptors 137. The high diastereoselectivity of the process relies on selective protonation of the resnltant enolate after conjugate addition. It was found that HMDS (formed dnring deprotonation of the triazolium salt pre-catalyst) was detrimental to the... 

This reaction sequence has been extended to lithium enolates. The deprotonation of the aminoester 54 with LDA followed by a transmetalation with zinc bromide in ether furnishes a zinc enolate, which readily adds to the double bond providing the proline derivative 55 in high diastereoselectivity (Scheme 23) . ... 

This methodology can be extended to alkylation of (3-silyl-a-alkyl enolates the diastereoselectivity is dependent on the size of the a-alkyl substituent, decreasing as the size of the alkyl group is increased (equation I). 

The extended cyclic enolate derived from a simple pyrrol-3-en-2-one (butenolac-tam) has been deuterated at the 5-position with very high diastereoselectivity if the (g) nitrogen atom carries a a-methyl-p-methoxybenzyl group (de > 99 l).27 A similar diastereoselective protonation has been observed in a pyrrol-3-en-2-one formed by dearomatizing cyclization of a pyrrole. 

The aldol-type condensation can be extended to carbonyl equivalents such as the 4-acetoxy-2-azetid-inone (93) or similar a-acetoxylactams. The condensation of (93) with the chiral tin(II) enol ether (94) has been used in a highly diastereoselective synthesis of chiral carbapenems. 

The utility of the tetraacetyl glucopyranosyl auxiliary has been extended to diastereoselective functionalizations of glycosyl enol ether derivatives. 1 Hydrogenation of 257 affords an 84 16 epimeric mixture predominantly 258, while the lactone 259 is hydrogenated wi 50-65% d.e. to 260 as major product. 

The use of the cyclitol, L-quebrachitol, as chiral auxiliary for ketone alkylation has been extended to additions of silyl enol ethers and silyl enol esters, providing a-hydroxyacid precursors, 269 with d.e. > 98% in most cases (Scheme 56). [Grignard, alkylithium and allylsilane additions to this substrate, Vol. 26, p. 319, ref. 93]. The same a-keto esters bearing this L-quebrachitol auxiliary undergo diastereoselective [3+2] cycloadditions with allylsilanes, providing a route to chiral functionalized tetrahydrofurans 270. ... 

The main stereoselective MBFTs for the synthesis of spirocyclic acetals or aminals involve the activation of a C-C triple bond to form an intermediate cyclic enol ether. The method disclosed above for the synthesis of a-heteroatom-substituted spirocen-ter (see Section 9.3.3, Scheme 9.18) [34] was next extended by the same authors to the synthesis of spiroacetals. They simply used salicyladehyde as starting aldehyde, but the transformation was not diastereoselective anymore [43]. This problem of stereoselectivity was recently solved by Gong and coworkers, who employed a gold(I)/chiral Brpnsted acid catalysis to do so [44], The chroman spiroacetals were obtained in excellent yields (67-97%) and with high stereoselectivities (up to 95% ee, up to 25 1 dr) (Scheme 9.24). This reaction resulted in the formation of three new single bonds and two stereogenic centers. 

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