Stereodefined enolates

Stereodefined enol acetates of ketones can readily be synthesized by palladium-catalyzed cross-coupling reactions of arylboron compounds with enol acetates of a-bromo ketones (Eq. (70)) [113]. 

A new catalytic elimination/isomerization pathway of stereodefined enol triflates capable of providing the corresponding functionalized, highly substituted, 1,3-dienes in synthetically useful yields has been discovered. Preliminary mechanistic studies support a distinct catalytic pathway that rationalizes the stark reactivity differences between E and Z enol triflates through stereoisomeric cationic vinyl palladium(II) complexes. 

Acetylenic ethers 7 can be hydrozirconated, and subsequent iododezirconation leads to (fc)-iodo enol ethers 8 (Scheme 4.4) [18], These species undergo efficient Sonogashira couplings to give (E)-enynes, which are ultimately converted to stereodefined dienol ethers. These dienes have proven useful in studies of diastereoselective cycloaddition reactions with singlet oxygen, where R in 8 is a nonracemic auxiliary (e. g., menthyl) (Procedure 3, p. 140). 

The Denmark phosphoramide organocatalyst has recently been applied in the first catalytic, diastereoselective, and enantioselective crossed-aldol reaction of aldehydes [86]. It is worthy of note that such controlled stereoselective selfcondensation of aldehydes has previously found no general application, because of many side-reactions, e.g. polyaldolization, and dehydration of the products. Several previously developed solutions have limitations. In a first step the Denmark group developed a procedure for generation of stereodefined trichlorosilyl enolates of aldehydes with high geometrical purity. Use of these geometrically pure (Z) and... 

Davies used Sml2 and D20 to carry out a highly diastereoselective conjugate reduction of benzylidene diketopiperazine templates en route to (2S3R)-dideuteriophenylalanine.57 The new stereocentres arise from diastereoselective protonation of a Sm(III) enolate and the protonation of a stereodefined organosamarium intermediate (Scheme 4.46).58... 

So, the combination of the isomerization process described in Scheme 33 with the elimination reaction described in Scheme 29 would lead to an efficient preparation of stereodefined metalated zirconocene complexes 95 from simple unsaturated enol ether 94 (Scheme 34). 

Although stereoselective formation of enolates from acyclic ketones with bases such as LDA is rather difficult, stereodefined boron enolates are more readily accessible. In the Mukaiyama method, an ethyl ketone is treated with a dialkylboron triflate and a tertiary amine, usually i-Pr2NEt. The resultant Z-(0) boron enolates (also known as enol borinates) are believed to be formed under kinetic control by deprotonation of the Lewis acid-complexed substrate. Brown and co-workers have shown that E- 0) boron enolates may be prepared by treatment of ethyl ketones with dicyclohexylboron chloride in the presence of Et3N. ... 

A study on stereodefined boryl enolates that employed both pure (Z)- and ( )-dialkylboryl enolates has been carried out by Masamune et al Hooz reaction involving a-diazocarbonyi compounds (Scheme 3) and a trialkylborane provides exclusively (0)-alkenyloxyboranes, which can be isomerized cleanly to the corresponding Z(0)-isomers.- The Z((9)-dibutylboryl enolates (17) react with various aldehydes exhibiting uniformly high syn selectivities (syn.anti > 95 5), while the corresponding (0)-isomers (18) are converted into the anti aldol products with somewhat lower selectivities (Scheme 15). 

Isatins have served as valuable precursors for the preparation of oxindoles bearing amino functionality at stereodefined C3. In a report from the Emiua group, isatin derived oxime 91 (Scheme 25) was transformed to the urea derivative 92 which underwent a diastereoselective alkylation at C3 to afford the /-menthol adduct 93 (94 6 dr) [59]. Lithium counterions proved to be more effective than potassium ions for achieving diastereocontrol of the enolate alkylation a mechanism has been suggested involving lithium ion chelation between the oxindole enolate of 92, the carbonyl of the urea fimctionality at C3, and the carbonyl of the menthyl ester electrophile. 

R > R ) fonns phosphonium enolate 122. Addition of this enolate to a second molecule of ketene occurs with facial selectivity as depicted in 124 to yield stereodefined intermediate 123, which after cycUzation and release of the catalyst furnishes the optically enriched p-lactone. 

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