Asymmetric aldol

Extensive investigations have been directed toward the development of chiral ester enolates that might exhibit practical levels of aldol asymmetric induction. Much of the early work in this area has been reviewed (111). In general, metal enolates derived from chiral acetate and propionate esters exhibit low levels of aldol asymmetric induction that rarely exceed 50% enantiomeric excess. The added problems associated with the low levels of aldol diastereoselection found with most substituted ester enolates (cf. Table 11) further detract from their utility as effective chiral enolates for the aldol process. Recent studies have examined the potential applications of the chiral propionates 121 to 125 in the aldol condensation (eq. [94]), and the observed erythro-threo diastereoselection and diastere-oface selection for these enolates are summarized in Table 31. For the six lithium enolates the threo diastereoselection was found to be... 

Carbonyl compounds reacting with compounds or enones by the aldol Asymmetric synthesis ch41... 

The reduction of the pre-fuctionalized, usually through the referred in the previous chapter aldols, asymmetric 5-hydroxy-3-ketoesters (72) can lead directly to functionalized 1,3-diols. This transformation can be achieved either by chemical reduction or by biotransformation. Since the Noyori reduction [72] is not only one of the most prominent and applied catalytic reductions but also highly applicable to P-keto esters, it was investigated by Shao et al. [73]. They used chiral ester 72 and performed Noyori reduction using both enantiomers of DINAR It was realized that the chiral... 

Asymmetric Aldol Condansations with Chiral Auxilaries-... 

A useful catalyst for asymmetric aldol additions is prepared in situ from mono-0> 2,6-diisopropoxybenzoyl)tartaric acid and BH3 -THF complex in propionitrile solution at 0 C. Aldol reactions of ketone enol silyl ethers with aldehydes were promoted by 20 mol % of this catalyst solution. The relative stereochemistry of the major adducts was assigned as Fischer- /ir o, and predominant /i -face attack of enol ethers at the aldehyde carbonyl carbon atom was found with the (/ ,/ ) nantiomer of the tartaric acid catalyst (K. Furuta, 1991). 

Acetoxy-l,7-octadiene (40) is converted into l,7-octadien-3-one (124) by hydrolysis and oxidation. The most useful application of this enone 124 is bisannulation to form two fused six-membered ketonesfl 13], The Michael addition of 2-methyl-1,3-cyclopentanedione (125) to 124 and asymmetric aldol condensation using (5)-phenylalanine afford the optically active diketone 126. The terminal alkene is oxidi2ed with PdCl2-CuCl2-02 to give the methyl ketone 127 in 77% yield. Finally, reduction of the double bond and aldol condensation produce the important intermediate 128 of steroid synthesis in optically pure form[114]. 

Asymmetric aldol reaction promoted by chiral oxazaborolidinone 97YGK313. 

Comparison witli tlie Hajos-Parrisb asymmetric version of tlie Robinson annulation [81] iSdieme 7.25iaj) shows tlie following distinct differences between tlie two metliods. Firstly, tlie cydoalkenone in tlie CuiOTf)2/ligand 18-catalyzed procedure is tlie Midiael acceptor, whereas tlie cydoalkanone is tlie Midiad donor in tlie proline-mediated annulation. Secondly, tlie asymmetric induction occurs in tlie 1,4-addition step in tlie new metliod, in contrast to tlie asymmetric aldol-cydization in tlie Hajos-Parrisb procedure. 

The enantiomers are obtained as a racemic mixture if no asymmetric induction becomes effective. The ratio of diastereomers depends on structural features of the reactants as well as the reaction conditions as outlined in the following. By using properly substituted preformed enolates, the diastereoselectivity of the aldol reaction can be controlled. Such enolates can show E-ot Z-configuration at the carbon-carbon double bond. With Z-enolates 9, the syn products are formed preferentially, while fi-enolates 12 lead mainly to anti products. This stereochemical outcome can be rationalized to arise from the more favored transition state 10 and 13 respectively ... 

An enantioselective aldol reaction may also be achieved with non-chiral starting materials by employing an asymmetric Lewis acid as catalyst ... 

For example in the so-called Mukaiyama aldol reaction of an aldehyde R -CHO and a trimethylsilyl enol ether 8, which is catalyzed by Lewis acids, the required asymmetric environment in the carbon-carbon bond forming step can be created by employing an asymmetric Lewis acid L in catalytic amounts. 

Scheme 3.20. Proposed mechanism of asymmetric nitro-aldol reactions catalyzed by LLB, LLB-II, or LLB-LI nitronate...

The synthetic problem is now reduced to the enantioselective construction of the two sectors of cytovaricin, intermediates 6 and 7, and it was anticipated that this objective could be achieved through the application of asymmetric aldol, alkylation, and epoxi-... 

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