Enones, 367. enolates

The intermediate enolate or enol ether from the initial reduction of an enone may be alkylated in situ (Eq. 281).455 / -Substituted cyclopentenones may be asymmetrically reduced and alkylated459 (see section on asymmetric reductions of enones). Enolates may also be trapped with an aldehyde in a reductive aldol condensation of an enone with an aldehyde,455 permitting a regioselective aldol condensation to be carried out as shown in Eq. 282.455 This class of reductive aldol condensation reactions can also occur in a cyclic manner (Eq. 283).460... 

Conjugate addition of H2O, ROH or AcOH to enones and enone enolates can be catalysed by (MeCN)2 PdCl2458,459. Palladium-catalysed addition of stabilized C-nucleophiles, such as RCH(CN)2 to allenes, has been reported. The reaction proceeds under essentially neutral conditions regio- and, in some instances, stereo-selectively460. 

From Simmons-Smith Cyclopropanation of a-Enone Enol Ethers... 

In a related case, Maier and coworker [153] have recently also demonstrated that vinylogous enolates can enter into a cross-coupling step. However, the final products of Pd-catalyzed reactions of the hexahydro naph-thalenone and aryl bromides or iodides in the presence of cesium carbonate and tetraalkylammonium bromide in DMF at room temperature are 7-aryltetralones 208 (Scheme 85). This process can be readily interpreted as a Pd-catalyzed /-selective arylation of the thermodynamic enone enolate with a concomitant dehydrogenation-aromatization of the initial crosscoupling product. 

Enol carbonates. O-Acylation is accomplished by rapid addition of ketone enolates, which are generated with NaH-TMEDA in refluxing THF, to chloroformate esters at 0 C. Aryl and a,/3-enone enolates are better prepared with NaN(SiMe3)2-TMEDA at -78°. 

Dienic Enol Triflates. Enone enolates generated from epoxyketones are also reactive with 2-PyrNTf2 to provide dienic enol triflates in good yield (eq 10). 

Scheme 52 Tandem copper-NHC-catalysed ECA of Grignard reagents to a-substituted cyclic enone/enolate trapping by Alexakis [87, 88] (all ee s measured after recrystallisation)...

The resulting radieal (144)" reaeted with alkenes to give (145). [Ir(dF(CF3)ppy)2(dthhpy)] acted as excellent visihle-light photocatalyst for the intramolecular and intermolecular [2 + 2] cycloaddition of alkenes, styrenes, enones, enolates, enol ethers, haloalkenes, and allenes. ... 

Oxidation of silylenol ethers and enol carbonates to enones... 

In the presence of a double bond at a suitable position, the CO insertion is followed by alkene insertion. In the intramolecular reaction of 552, different products, 553 and 554, are obtained by the use of diflerent catalytic spe-cies[408,409]. Pd(dba)2 in the absence of Ph,P affords 554. PdCl2(Ph3P)3 affords the spiro p-keto ester 553. The carbonylation of o-methallylbenzyl chloride (555) produced the benzoannulated enol lactone 556 by CO, alkene. and CO insertions. In addition, the cyclobutanone derivative 558 was obtained as a byproduct via the cycloaddition of the ketene intermediate 557[4I0]. Another type of intramolecular enone formation is used for the formation of the heterocyclic compounds 559[4l I]. The carbonylation of the I-iodo-1,4-diene 560 produces the cyclopentenone 561 by CO. alkene. and CO insertions[409,4l2]. 

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. 

The decarboxylation-allylation of allyl enol carbonates proceeds smoothly[450]. The isomeric enol carbonates 699 and 701 of the enone 698 undergo regiospecific allylation, giving the regioisomers 700 and 702 selectively. 

Ailyl enol carbonates derived from ketones and aldehydes undergo Pd-cat-alyzed decarboxylation-elimination, and are used for the preparation of a, /3-unsaturated ketones and aldehydes. The reaction is regiospecific. The regio-isomenc enol carbonates 724 and 726, prepared from 723, are converted into two isomeric enones, 725 and 727. selectively. The saturated aldehyde 728 can be converted into the a,/3-unsaturated aldehyde 730 via the enol carbonate 729[459]. 

The Pd enolates also undergo intramolecular Michael addition when an enone of suitable size is present in the allyl d-keto ester 744[465]. The main product is the saturated ketone 745, hut the unsaturated ketone 746 and ally-lated product 747 are also obtained as byproducts. The Pd-catalyzed Michael... 

Conversion of PGA2 to the highly sensitive PGC2 was accomplished by deconjugation of the enone system by formation of the y-extended enolate using rm-alkoxide as base and a-protonation by pH 4 buffer. 

Metal-ammonia solutions reduce conjugated enones to saturated ketones and reductively cleave a-acetoxy ketones i.e. ketol acetates) to the unsubstituted ketones. In both cases the actual reduction product is the enolate salt of a saturated ketone this salt resists further reduction. If an alcohol is present in the reaction mixture, the enolate salt protonates and the resulting ketone is reduced further to a saturated alcohol. Linearly or cross-conjugated dienones are reduced to enones in the absence of a proton donor other than ammonia. The Birch reduction of unsaturated ketones to saturated alcohols was first reported by Wilds and Nelson using lithium as the reducing agent. This metal has been used almost exclusively by subsequent workers for the reduction of both unsaturated and saturated ketones. Calcium has been preferred for the reductive cleavage of ketol acetates. 

Reduction of a conjugated enone to a saturated ketone requires the addition of two electrons and two protons. As in the case of the Birch reduction of aromatic compounds, the exact order of these additions has been the subject of study and speculation. Barton proposed that two electrons add initially giving a dicarbanion of the structure (49) which then is protonated rapidly at the / -position by ammonia, forming the enolate salt (50) of the saturated ketone. Stork later suggested that the radical-anion (51), a one electron... 

Reversible electron addition to the enone forms the radical anion. Rate determining protonation of the radical anion occurs on oxygen to afford an allylic free radical [Eq. (4b) which undergoes rapid reduction to an allylic carbanion [Eq. (4c)]. Rapid protonation of this ion is followed by proton removal from the oxygen of the neutral enol to afford the enolate ion [Eq. (4c)]. 

Protonation of the a-carbanion (50), which is formed both in the reduction of enones and ketol acetates, probably first affords the neutral enol and is followed by its ketonization. Zimmerman has discussed the stereochemistry of the ketonization of enols and has shown that in eertain cases steric factors may lead to kinetically controlled formation of the thermodynamically less stable ketone isomer. Steroidal unsaturated ketones and ketol acetates that could form epimeric products at the a-carbon atom appear to yield the thermodynamically stable isomers. In most of the cases reported, however, equilibration might have occurred during isolation of the products so that definitive conclusions are not possible. 

If the equilibrium were established rapidly, reduction of the free ketone as it formed would result in a substantial loss of product. Lithium enolates are more covalent in character than are those of sodium and potassium and consequently are the least basic of the group. This lower thermodynamic basicity appears to be paralleled by a lower kinetic basicity several workers have shown that lithium enolates are weaker bases in the kinetic sense than are those of sodium and potassium." As noted earlier, conjugated enones... 

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