Silyl enol ethers stereoselective formation

If there is no other interaction, the reaction proceeds through an acyclic TS and steric factors determine the amount of syn versus anti addition. This is the case with BF3, where the tetracoordinate boron-aldehyde adduct does not offer any free coordination sites for formation of a cyclic TS. Stereoselectivity increases with the steric bulk of the silyl enol ether substituent R1.50... 

The preparation of silyl enol ethers and enol acetates may afford mixtures of isomers, however, these can be separated prior to cleavage. Usually the preparation of silyl enol ethers or enol acetates proceeds via one of the base-catalyzed deprotonations described previously and conditions can be applied which favor the formation of one isomer (vide supra). Thus, regio- and stereoselectivity can be achieved. An extensive review of the synthetic uses, including the preparation and reactions, of silyl enol ethers is available32. 

Scheme 7.26 Regioselective and stereoselective formation of oxetanes in the PB reactions of silyl enol ethers.

The nucleophilicity of silyl enol ethers has been examined. Base-induced formation of the enolate anion generally leads to a mixture of (E)- and (Z)-isomers, and dialkyl amide bases are used in most cases. The (EjZ ) stereoselectivity depends on the structure of the lithium dialkylamide base, with the highest EjZ) ratios obtained with LiTMP-butyllithium mixed aggregates in THF. ° The use of LiHMDS resulted in a reversal of the (E/Z) selectivity. In general, metallic (Z) enolates give the syn (or erythro) pair, and this reaction is highly useful for the diastereoselective synthesis of these products. 

To avoid complications with the reactive enolates and to preserve the stereochemistry it has proven practical to employ the derived silyl enol ethers, formed by trapping the enolates with chlorotrialkyl-silane instead of the enolates themselves. The rearrangement of the silyl enol ethers takes place under mild conditions, too, often at room temperature, and exhibits all the characteristics of 3,3-sigmatropic rearrangements, namely high stereoselectivity in the formation of double bonds and stereocenters. 

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 Diels-Alder was successful20 129 but now the methyl group in the SW comer needs to be added by conjugate addition and that requires an enone. Oxidation of the silyl enol ether 130, prepared by kinetic enolate formation with LDA, with catalytic Pd(OAc)2 and benzoquinone as the stoichiometric oxidant gave the required enone 131 in 57% yield. Addition of Me2CuLi was stereoselective to give 132 and the synthesis of mevinolin completed. 

A stereoselective construction of 1,3-diol systems is based on the reaction of lactol acetates with allylsilanes or silyl enol ethers. Formation of the product is subject to 1,3-asymmetric induction by one or more substituents in the ring. Note that BFj OEt2 is not a suitable catalyst. 

Total syntheses of racemic muscarine and allomuscarine were achieved by Pirrung and DeAmicis 11), who used a new approach to formation of the stereoselectively substituted tetrahydrofuran nucleus (Scheme 8). The key step in this procedure was the stereospecific photochemical ring expansion of a cyclobutanone derivative. The cycloaddition of silyl enol ether with methylchloroketene generated by zinc dechlorination of 2,2-dichloropropionyl chloride followed by reductive removal of the halogen produced the methylsiloxycyclobutanone intermediate. Irradiation of the... 

The treatment of an ester (or lactone) with a base and a silyl halide or trillate gives rise to a particular type of sUyl enol ether normally referred to as a silyl ketene acetal. The extent of O- versus C-silylation depends on the structure of the ester and the reaction conditions. The less-bulky methyl or ethyl (or 5-tert-butyl) esters are normally good substrates for O-silylation using LDA as the base. Acyclic esters can give rise to two geometrical isomers of the silyl ketene acetal. Good control of the ratio of these isomers is often possible by careful choice of the conditions. The f-isomer is favoured with LDA in THF, whereas the Z-isomer is formed exclusively by using THF/HMPA (1.24). Methods to effect stereoselective silyl enol ether formation from acyclic ketones are less well documented. ... 

CAB 3a is also an excellent catalyst (20 mol%) for the Mukaiyama condensation of simple enol silyl ethers of achiral ketones with various aldehydes. Furthermore, the reactivity of aldol-type reactions can be improved without reducing the enantioselec-tivity by using 10-20 mol% of 3c. Enantioselectivity can also be improved without reducing the chemical yield by using 20 mol% of 3b. The 3-catalyzed aldol process allows for the formation of adducts in a highly diastereo- and enantioselective manner (up to 99% ee) under mild reaction conditions [41a, cj. These reactions are catalytic, and the chiral source is recoverable and reusable (Equation 41). The observed high syn selectivities, together with their lack of dependence on the stereoselectivity of the silyl enol ethers, in 3-catalyzed reactions are fully consistent with Noyori s TMSOTf-catalyzed aldol reactions of acetals, and thus may reflect the acyclic extended transition state mechanism postulated in the latter reactions. 

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