Enolate ester, chiral

Scheme 16 Diastereoselective synthesis of 2,3-diamino esters and alcohols by the addition of achiral glycine iminoester enolates to chiral M-sulfinylimines...

Following their success with chiral ketone-mediated asymmetric epoxidation of unfunctionalized olefins, Zhu et al.113 further extended this chemistry to prochiral enol silyl ethers or prochiral enol esters. As the resultant compounds can easily be converted to the corresponding a-hydroxyl ketones, this method may also be regarded as a kind of a-hydroxylation method for carbonyl substrates. Thus, as shown in Scheme 4-58, the asymmetric epoxidation of enol silyl... 

Asymmetric Hydrogenation of Enol Esters. Prochiral ketones represent an important class of substrates. A broadly effective and highly enantioselective method for the asymmetric hydrogenation of ketones can produce many useful chiral alcohols. Alternatively, the asymmetric hydrogenation of enol esters to yield a-hydroxyl compounds provides another route to these important compounds. 

The asymmetric hydrogenation of enol esters can also be catalyzed by chiral amidophosphine phosphinite catalysts derived from chiral amino acids, but the enantioselectivity of these reactions has thus far been only moderate.35... 

Amination. Three laboratories2-4 have reported use of esters of azodicarbox-ylic acid for amination of chiral substrates to provide a synthesis of optically active a-hydrazino and a-amino acids. The di-r-butyl ester is particularly useful because the diastereoselectivity improves with increasing size of the ester group, and in addition these esters are hydrolyzed by TFA at 25°. Two laboratories21 used the lithium enolates of chiral N-acyloxazolidones (2) as the chiral precursors. A typical procedure is outlined in equation (I). Thus reaction of the lithium enolate of 2... 

A different approach towards titanium-mediated allene synthesis was used by Hayashi et al. [55], who recently reported rhodium-catalyzed enantioselective 1,6-addition reactions of aryltitanate reagents to 3-alkynyl-2-cycloalkenones 180 (Scheme 2.57). In the presence of chlorotrimethylsilane and (R)-segphos as chiral ligand, alle-nic silyl enol ethers 181 were obtained with good to excellent enantioselectivities and these can be converted further into allenic enol esters or triflates. In contrast to the corresponding copper-mediated 1,6-addition reactions (Section 2.2.2), these transformations probably proceed via alkenylrhodium species (formed by insertion of the C-C triple bond into a rhodium-aryl bond) and subsequent isomerization towards the thermodynamically more stable oxa-jt-allylrhodium intermediates [55],... 

Although enol esters have a similar structure to enamides, they have proven more difficult substrates for asymmetric hydrogenation, which is evident from the significantly fewer number of examples. One possible explanation is the weaker coordinating ability of the enol ester to the metal center, as compared to the corresponding enamide. Some rhodium complexes associated with chiral phosphorous ligands such as DIPAMP [100, 101] and DuPhos [102] are effective for asymmetric hydrogenation of a-(acyloxy)acrylates. 

The self-immolative 1,3-chirality transfer from C-5 to C-3 the simple diastereoselection observed in the connection of C-2 with C-3 which results from the enol ester olefin geometry and the chair-like transition state of the [3.3]-sigmatropic rearrangement. 

S. Hanessian, P. C. Tyler, and Y. Chapleur, Reaction of lithium dimethylcuprate with confor-mationally biased acyloxy enol esters. Regio and stereocontrolled access to functionalized six-carbon chiral synthons. Tetrahedron Lett. 22 4583 (1981). 

In contrast, a-nitroalkenation adducts (298) are obtained with thermodynamic enolates of a-sub-stituted ketones or esters in addition, Fuji reports that enantioselective addition of a-subsdtuted lactone enolates to chiral nitroenamines is cation dependent with zinc affording maximum enantioselectivity.213... 

Stoichiometric and catalytic asymmetric reactions of lithium enolate esters with imines have been developed using an external chiral ether ligand that links the components to form a ternary complex.36 The method affords /i-lactams in high enantiomeric excess. 

Scheme 17 Stereodivergent synthesis of spiro- [S-lactams using ester enolates and chiral imines...

Addition to (l-acyloxy enol esters. Addition of lithium dimethylcuprate to chiral enol esters derived from carbohydrates provides access to C6 chiral synthons with four alternating and/or consecutive methyl and hydroxyl groups.21 Example ... 

Enantio-enriched enol esters - potential precursors of enantiopure a-arylalkanoic acids - have been prepared by asymmetric coupling of ketenes with aldehydes, using a chiral ferrocene bearing a dimethylaminopyridine function.20... 

The situation changes when chiral ester enolates or chiral amide enolates are alkylated. There, the half-spaces on the two sides of the enolate planes of the substrates are diastereotopic, and alkylating reagents can react from one of the sides selectively (see discussion in Section 3.4.1). Stereogenic alkylations of such enolates therefore may take place diastereo selectively. 

Addition of several lithium ester enolates to chiral 1-aminoalkyl choromethyl ketones gave the corresponding chlorohydrins which, when the solvent was completely evaporated to dryness at room temperature, underwent an intramolecular heterocyclization affording 3-hydroxyazetidinium salts 5 <02OL1299>. Azetidinium salts 5 were isolated in enantiomerically pure form, and with total or high diastereoselectivity. The degree of stereoselectivity was only moderately affected by the size of R1 in the a-amino-ketone and the substituents in the ester enolate. 

Another conventional approach, the addition of electrophiles to enolates of chiral esters, has been... 

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