Reaction with metal enolates

Diethyl 5-methylcoprost-3-en-yl phosphate, 52,109 Diethyl phosphorochloridate, 50,10 reaction with metal enolates, 52,... 

The decarboxylation of allyl /3-keto carboxylates generates 7r-allylpalladium enolates. Aldol condensation and Michael addition are typical reactions for metal enolates. Actually Pd enolates undergo intramolecular aldol condensation and Michael addition. When an aldehyde group is present in the allyl fi-keto ester 738, intramolecular aldol condensation takes place yielding the cyclic aldol 739 as a main product[463]. At the same time, the diketone 740 is formed as a minor product by /3-eIimination. This is Pd-catalyzed aldol condensation under neutral conditions. The reaction proceeds even in the presence of water, showing that the Pd enolate is not decomposed with water. The spiro-aldol 742 is obtained from 741. Allyl acetates with other EWGs such as allyl malonate, cyanoacetate 743, and sulfonylacetate undergo similar aldol-type cycliza-tions[464]. 

Oppenauer oxidation of the enol ether (34) affords the corresponding 17 ketone (37) (the enol ether is stable to the basic oxidation conditions). This ketone affords the corresponding 17a-ethynyl compound on reaction with metal acetylides. Hydrolysis of the enol ether under mild conditions leads directly... 

Ketones are resistant to oxidation by dioxygen in aqueous solutions at T= 300-350 K. Transition metal ions and complexes catalyze their oxidation under mild conditions. The detailed kinetic study of butanone-2 oxidation catalyzed by ferric, cupric, and manganese complexes proved the important role of ketone enolization and one-electron transfer reactions with metal ions in the catalytic oxidation of ketones [190-194],... 

In general, the aldol reaction of an aldehyde with metal enolate creates two new chiral centers in the product molecule, and this may lead to four possible stereoisomers 2a, 2b, 2c, and 2d (Scheme 3-2 and Fig. 3-1). 

Oppenauer oxidation of the enol ether (34) affords the corresponding 17 ketone (37) (the enol ether is stable to the basic oxidation conditions). This ketone affords the corresponding 17a-ethynyl compound on reaction with metal acetylides. Hydrolysis of the enol ether under mild conditions leads directly to ethynodrel (39), an orally active progestin. This is the progestational component of the first oral contraceptive to be offered for sale. Treatment of the ethynyl enol ether with strong acid leads to yet another oral progestin employed as a contraceptive, norethindrone (40). ° In practice these and all other so-called combination contraceptives are mixtures of 1-2% mestranol... 

Asymmetric hydraxylation of lithium enolates of esters and amides.2 Hydroxylation of typical enolates of esters with ( + )- and (-)-l is effected in 75-90% yield and with 55-85% ee. The reaction with amide enolates with ( + )- and ( — )-l results in the opposite configuration to that obtained with ester enolates and with less enantioselectivity. Steric factors appear to predominate over metal chelation. 

The reaction of nitroso compounds with typical metal enolates, the nitroso aldol reaction, occurs in high yields to generate a-hydroxyamino carbonyl compounds. Exclusive iV-selectivity >99 1 is observed to give hydoroxyamino ketone in the reaction with tin enolates (Equation (70)).2... 

The use of Ln(OTf)3 in the activation of aldehydes other than formaldehyde was also investigated [18], Several examples of the present aldol reaction of silyl enol ethers with aldehydes are listed in Table 14-1. In every case, the aldol adducts were obtained in high yields in the presence of a catalytic amount of Yb(OTf)3, Gd(OTf)3, or Lu(OTf)3 in aqueous media. Diastereoselectivities were generally good to moderate. One feature in the present reaction is that water-soluble aldehydes, for instance, acetaldehyde, acrolein, and chloroacetaldehyde, can be reacted with silyl enol ethers to afford the corresponding cross aldol adducts in high yields (entries 5-7). Some of these aldehydes are commercially supplied as water solutions and are appropriate for direct use. Phenylglyoxal monohydrate also worked well (entry 8). It is known that water often interferes with the aldol reactions of aldehydes with metal enolates and that, in the cases where such water... 

Enolates are undoubtedly the most versatile intermediates for C-C, C-N, C-O bond-forming reactions [36]. Continuous progress has been made not only in fundamental operations involving these anionic species but also during the synthesis of complex natural products. Compared with metal enolates with counter cations of, e.g., B, Si, Li, Na, K, Mg, Ti, Sn, Cu, etc., aluminum enolates have found fewer apphcations, probably because no particular advantages over the other metals have been perceptible. There are, however, still intriguing aspects of novel reactivity and selectivity in the formation and reaction of aluminum enolates. Specifically, very recent development have highhghted pre-formation of Lewis acid-carbonyl complexes by use of bulky aluminum compounds as precursors of aluminum enolates the behavior of these complexes is unprecedented. 

The reaction of a-ketoesters with the tin (II) enolate of IV-acetyl-thiazolidinethione 1.123 (R=R1=H, X = S) has been earned out with an excellent enantioselectivity in the presence of chiral amine 2.13 (Figure 6.88). The reactions of a- or P-alkoxyaldehydes with metal enolates may or not be under chelation control (Cram cyclic model, 1.4.2). Reetz has shown that triisopropoxy- or tris-diethylaminotitanium enolates display a sufficiently weak Lewis acidity so as to avoid chelation control [408],... 

The only main Group III metal, other than boron, that has been utilized in the aldol reaction is aluminum, the enolates of which behave rather capriciously in terms of stereochemistry. The A1—C bond is relatively weak. However, aldol reactions with aluminum enolates derived from chiral acyl-iron complexes proceed with high asymmetric induction. 

---