Silyl enol ethers geometry

The transition state is thought to be an open structure. Assuming that a particular silyl enol ether geometry is used, the substituents will tend to occupy opposite faces of the transition state and thus give a particular diastereomer (syn-anti) preferentially. Because of the open transition state geometry, the diastereoselec-tivity is not high. 

Excellent /(-methyl selectivity is observed in the zinc chloride mediated condensation with 0-silyl enol ethers of 2-pyridinylmethyl thiopropionates109. Supposedly, chelate formation of zinc(II) with the sulfur and the nitrogen atom of the pyridinylmethyl thioester is essential for the high /(-selectivity. The geometry of the ketene acetal also seems to have some influence. 

Another interesting observation in Brunner s work was the co-production of silyl enol ethers. Often they remain unnoticed, because after aqueous workup they regenerate the starting ketone. They are important though as a clue to a mechanistic pathway as can be seen from Figure 18.15 (randomly chosen geometry, although we did keep o-bonds in cis positions). 

Stereospecific conversion of vinylsilanes to silyl enol ethers This conversion can be effected by dihydroxylation with 0s04 in combination with (CH3)3NO and pyridine followed by anti p-elimination with NaH via an a-oxidosilane. The overall process converts vinylsilanes into silyl enol ethers with preservation of the geometry of the double bond. 

Aldol reaction,6 This triflate is an effective catalyst for an aldol-type reaction between silyl enol ethers and acetals at -78°. The reaction shows moderate to high svn-selectivity regardless of the geometry of the enol ether. 

A number of other acyclic Z and E lithium enolates were quenched similarly. In all cases the stereochemistry at the enol double bond was retained, as shown by subsequent conversion into the corresponding silyl enol ether. Upon reacting the titanium enolates with aldehydes, very clean aldol addition occured (>90% conversion at —78 °C). Generally, erythro-selectivity was observed irrespective of the geometry of the enolate. Equations 64 and 65 are typical25). 

Probably the most widdy applicable conditions developed for palladium catalysts utilize silyl enol ethers.In one instance,an excellent yield of enone was ob ned using 0.5 equiv. each of palla-dium(II) acetate and p-benzoquinone in acetonitrile. The method has the advantage that the position of the double bond is determine by the geometry of the precursor silyl enol ether (Scheme 26). Palla-... 

It seems likely that the reaction proceeds through a prototropic ene reaction pathway, a pathway that has not been previously recognized as a possible mechanism in the Mukaiyama aldol condensation. Usually an acyclic antiperiplanar transition-state model has been used to explain the formation of the syn diastereomer from either ( )- or (Z)-silyl enol ethers [91]. The cyclic ene mechanism, however, now provides another rationale for the syn diastereoselectivity irrespective of enol silyl ether geometry (Sch. 32). 

Kobayashi et al. found that lanthanide triflates were excellent catalysts for activation of C-N double bonds —activation by other Lewis acids required more than stoichiometric amounts of the acids. Examples were aza Diels-Alder reactions, the Man-nich-type reaction of A-(a-aminoalkyl)benzotriazoles with silyl enol ethers, the 1,3-dipolar cycloaddition of nitrones to alkenes, the 1,2-cycloaddition of diazoesters to imines, and the nucleophilic addition reactions to imines [24], These reactions are efficiently catalyzed by Yb(OTf)3. The arylimines reacted with Danishefsky s diene to give the dihydropyridones (Eq. 14) [25,26], The arylimines acted as the azadienes when reacted with cyclopentadiene, vinyl ethers or vinyl thioethers, providing the tet-rahydroquinolines (Eq. 15). Silyl enol ethers derived from esters, ketones, and thio-esters reacted with N-(a-aminoalkyl)benzotriazoles to give the /5-amino carbonyl compounds (Eq. 16) [27]. The diastereoselectivity was independent of the geometry of the silyl enol ethers, and favored the anti products. Nitrones, prepared in situ from aldehydes and N-substituted hydroxylamines, added to alkenes to afford isoxazoli-dines (Eq. 17) [28]. Addition of diazoesters to imines afforded CK-aziridines as the major products (Eq. 18) [29]. In all the reactions the imines could be generated in situ and the three-component coupling reactions proceeded smoothly in one pot. 

Stereoselective Mukaiyama-Michael reactions, Heathcock et alJ have investigated the syn anti stereoselectivity in the reaction of twelve silyl enol ethers with a variety of acyclic and cyclic enones catalyzed by TiCh or SnCh. Preliminary results suggest that the stereoselectivity is independent of the geometry of the silyl enol ether, and that silyl enol ethers derived from aliphatic ketones show a preference for (2n /-addition ranging from 1.5 1 to 10 1. The preference for a/ift-addition is even higher in the case of (Z)-silyl enol ethers of aromatic ketones (10 1 to >20 1). However, high 5y/i-selectivity is observed with acyclic -butyl enones. 

Introduction and stereochemical control syn,anti and E,Z Relationship between enolate geometry and aldol stereochemistry The Zimmerman-Traxler transition state Anti-selective aldols of lithium enolates of hindered aryl esters Syn-selective aldols of boron enolates of PhS-esters Stereochemistry of aldols from enols and enolates of ketones Silyl enol ethers and the open transition state Syn selective aldols with zirconium enolates The synthesis of enones E,Z selectivity in enone formation from aldols Recent developments in stereoselective aldol reactions Stereoselectivity outside the Aldol Relationship A Synthesis ofJuvabione A Note on Stereochemical Nomenclature... 

The aldol reaction is often used to make enones by dehydration of the aldol itself, a reaction which often occurs under equilibrating aldol conditions, but has to be induced in a separate step when lithium enolates or silyl enol ethers are used. In general one has to accept whatever enone geometry results from the dehydration, and this is usually controlled by thermodynamics, particularly if enone formation is reversible. Simple enones such as 46 normally form as the E isomer but the Z isomer is difficult to prepare. When the double bond is exo to a ring, e.g. 47, the E isomer is again favoured, but other trisubstituted double bonds have less certain configurations. 

Enol ester formation from crotonaldehyde gives the expected / -selectivity 66. Now the silyl enol ether is formed from this ester, also with the expected double bond geometry. The product 67 has three alkenes each is conjugated with at least one oxygen atom. 

The geometry of the silyl enol ether has only a slight influence on the stereochemistry of the Mukaiyama-Michael addition. For example, the Z silyl enol ether in entry 5 (Table 10) provides a 35 65 (syn/anti) mixture of diastereomers. With the corresponding E silyl enol ether (entry 25), a 23 77 (syn/anti) mixture of diastereomers results. 

In some instances, particularly when a dependence of the stereochemistry on the double-bond geometry of either the acceptor or donor is observed, it appears likely that the stereochemistry-determining step is the initial conjugate addition. The stereochemical consequences of Lewis-acid-mediated additions of silyl enol ethers (116) and allylsilanes (117,118) have frequently been rationalized by open-extended transition states. Similar pathways seem likely with the Mukaiyama-Michael addition (vide infra) (77,79). 

Additions of enol silanes to p-alkoxy aldehyde (85 equation 25) are reported in Table 17. High selectivity (chelation control) was obtained with TiCU via complex (78 entries 1, 2). The same preference for isomers (86) and (87) was obtained with BF3 via complex (80), which simulates chelation. The influence of chelation on simple stereoselection is also evident in the reactions of achiral aldehydes (90) and (92) with silyl enol ethers (Z)-(91) and ( )-(93), which are usually moderately anti selective in their reactions with aldehydes incapable of chelation high syn selectivity was obtained irrespective of the enol ether geometry (equations 26 and 27). - ... 

When the alkenyl component is an O-terf-butyldimethylsilyl (TBDMS) enol ether, another anomaly occurs independent of enol ether geometry, the anti product is favored (Scheme 6.8) [62]. With trimethylsilylpropargyl ethers, the anti selectivity is 95-98%, making this reaction an excellent route for the preparation of anti 1,2-diols. In these cases, transition structures similar to Figure 6.6c and d are operative, the dominant influence being mutual repulsion between the carbanion substituent, R, and the 0-silyl group. 

Scheme 6.8. The [2,3]-Wittig rearrangement of silyl enol ethers is anti selective independent of carbanion substituent and double bond geometry [62].

Yamamoto s CAB catalysts (7.16) (see Section 8.1) have also been used in catalytic aldol reactions. This reaction is stereoconvergent as either geometry of silyl enol ether (7.18) affords syn selectivity in the product (7.19) indicating that the reaction proceeds via an open anticHnal transition state with the minimum of steric interactions between the aldehyde substituent and a-substituent of the enol ether, as depicted in Figure 7.2. ... 

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