Enols regioisomeric

Another preparative method for the enone 554 is the reaction of the enol acetate 553 with allyl methyl carbonate using a bimetallic catalyst of Pd and Tin methoxide[354,358]. The enone formation is competitive with the allylation reaction (see Section 2.4.1). MeCN as a solvent and a low Pd to ligand ratio favor enone formation. Two regioisomeric steroidal dienones, 558 and 559, are prepared regioselectively from the respective dienol acetates 556 and 557 formed from the steroidal a, /3-unsaturated ketone 555. Enone formation from both silyl enol ethers and enol acetates proceeds via 7r-allylpalladium enolates as common intermediates. 

When the aldol reaction is carried Wt under thermodynamic conditions, the product selectivity is often not as high as under kinetic conditions. All the regioisomeric and stereoisomeric enolates may participate as nucleophiles. The adducts can return to reactants, and so the difference in stability of the stereoisomeric anti and syn products will determine the product composition. 

There has been little study of the stereoselectivity of the reaction under acidic conditions. In the absence of a coordinating Lewis acid, there is no preference for a cyclic transition state. When regioisomeric enols are possible, acid-catalyzed reactions tend to proceed through the more substituted of the enols. This reflects the predominance of this enol. (See Section 7.2.)... 

Certain starting materials may give rise to the non-selective formation of regioisomeric enolates, leading to a mixture of isomeric products. Furthermore a ,/3-unsaturated carbonyl compounds tend to polymerize. The classical Michael procedure (i.e. polar solvent, catalytic amount of base) thus has some disadvantages, some of which can be avoided by use of preformed enolates. The CH-acidic carbonyl compound is converted to the corresponding enolate by treatment with an equimolar amount of a strong base, and in a second step the a ,/3-unsaturated carbonyl compound is added—often at low temperature. A similar procedure is applied for variants of the aldol reaction. 

From intermediate 12, the path to periplanone B (1) is short but interesting. Enolization of 12 with lithium bis(trimethylsilyl)amide at -78 °C, followed by sulfenylation using Trost s reagent,12 affords a 16 1 mixture of regioisomeric monosulfenylated ketones favoring intermediate 17. The regioselectivity displayed in this reaction is... 

Deprotonation of the corresponding carbonyl compound is a fundamental method for the generation of enolates, and we discuss it here for ketones and esters. An unsymmetrical dialkyl ketone can form two regioisomeric enolates on deprotonation. 

Ketone imine anions can also be alkylated. The prediction of the regioselectivity of lithioenamine formation is somewhat more complex than for the case of kinetic ketone enolate formation. One of the complicating factors is that there are two imine stereoisomers, each of which can give rise to two regioisomeric imine anions. The isomers in which the nitrogen substituent R is syn to the double bond are the more stable.114... 

Besides direct nucleophilic attack onto the acceptor group, an activated diene may also undergo 1,4- or 1,6-addition in the latter case, capture of the ambident enolate with a soft electrophile can take place at two different positions. Hence, the nucleophilic addition can result in the formation of three regioisomeric alkenes, which may in addition be formed as E/Z isomers. Moreover, depending on the nature of nucleophile and electrophile, the addition products may contain one or two stereogenic centers, and, as a further complication, basic conditions may give rise to the isomerization of the initially formed 8,y-unsaturated carbonyl compounds (and other acceptor-substituted alkenes of this type) to the thermodynamically more stable conjugated isomer (Eq. 4.1). 

An unsymmetrical dialkyl ketone can form two regioisomeric enolates on deprotonation ... 

For many ketones, stereoisomeric as well as regioisomeric enolates can be formed, as is illustrated by entries 6, 7, and 8 of Scheme 1.3. The stereoselectivity of enolate formation, under conditions of either kinetic or thermodynamic control, can also be controlled to some extent. We will return to this topic in more detail in Chapter 2. 

Molander and Siedem have reported the reaction of l-methoxy-l,3-bis(trimethylsilylo-xy)-buta-l,3-diene, the bis(trimethylsilyl) enol ether of methyl acetoacetate, with 1,4- and 1,5-dicarbonyl species under the influence of trimethylsilyl triflate. Two regioisomeric oxabicyclo[3.2.1]octane products are formed (Scheme 83)194. Use of 4- or 5-ketoacyl silanes as the dicarbonyl species can result in a reversal of the sense of regioselectivity. 

Hydration of 2-butyne-l,4-diols (1). Treatment of 1 with acetic anhydride and pyridine (25°) results in acetylation of the less hindered hydroxyl group. When treated with AgC104, the monoacetate (2) is converted into the enol acetate of a dihydro-3(2H (-furanone (3, equation I). The regioisomeric dihydro-3(2H)-furanone is formed by hydration of 1 with Hg(OAc)2-Nafion-H preferentially (equation II).1... 

The two carbons of the triple bond are similarly but not identically substituted in 2-heptyne, CH3C=CCH2CH2CH2CH3. Two regioisomeric enols are formed, each of which gives a different ketone. 

Only one enolate can be generated from aldehydes or their aza analogs, from symmetric ketones or their aza analogs, or from carboxylic esters or carboxylic amides. For the moment we are ignoring the possibility that two stereoisomers, E- and Z-enolates, may occur for each of these enolates. On the other hand, constitutionally isomeric (regioisomeric) enolates may be derived from unsymmetrical ketones and from their aza analogs if they contain acidic H atoms... 

Fig. 13.23. O-Sulfonylations of regioisomeric ketone eno-lates to give an enol trifLate (regarding the regiocontrol of the enolate formations cf. the discussion of Figure 13.11) ...

This deprotonation may reform the ketone enolate that was the intermediate en route to the Michael adduct. However, the regioisomeric ketone enolate also can be formed. Figures 13.71-13.74 show such enolate isomerizations B — D, which proceed via the intermediacy of a neutral Michael adduct C. This neutral adduct is a 1,5-diketone in Figure 13.71, a 5-ketoaldehyde in Figure 13.72, and a 5-ketoester in Figure 13.73. 

Formation of the possible regioisomeric silyl enol ether... 

In a model reaction used to support the structure identification of a neutral polyaza cleft for enolate complexations, the disubstituted dihydropyrrolo[2,3-/i]quinoline (51) was prepared by alkylation of 7-bromo-5,6,7,8-tetrahydro-8-quinolone with ethyl 3,3-diamino-2-propenoate (Equation (24)) <91JA9687>. The regioisomeric residence of the two substituents in this product was supported by 13C—13C shift-correlated NMR spectroscopy. 

Ketones are unique because they can have enolizable protons on both sides of the carbonyl group. Unless the ketone is symmetrical, or unless one side of the ketone happens to have no enolizable protons, two regioisomers of the enolate are possible and alkylation can occur on either side to give regioisomeric products. We need to be able to control which enolate is formed if ketone alkylations are to be useful. 

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