Silyl enol ether palladium acetate oxidation

The oxidation of silyl enol ethers 111 with palladium(n) acetate is a convenient nnethod for the preparation of synthetically useful 2,6-disubstituted 2,3-dihydro-4-pyridones 112 <95TL(36)9449>. 

Enantioselective deprotonation can also be successfully extended to 4,4-disubstituted cyclohexanones. 4-Methyl-4-phenylcyclohexanone (3) gives, upon reaction with various chiral lithium amides in THF under internal quenching with chlorotrimethylsilane, the silyl enol ether 4 having a quaternary stereogenic carbon atom. Not surprisingly, enantioselectivities are lower than in the case of 4-tm-butylcyclohexanone. Oxidation of 4 with palladium acetate furnishes the a./i-unsaturated ketone 5 whose ee value can be determined by HPLC using the chiral column Chiralcel OJ (Diacel Chemical Industries, Ltd.)59c... 

In contrast, the closely related palladium acetate-promoted intramolecular alkylation of alkenes by tri-methylsilyl enol ethers (Scheme 4)6,7 has been used to synthesize a large number of bridged carbocyclic systems (Table 1). In principle, this process should be capable of being made catalytic in palladium(II), since silyl enol ethers are stable to a range of oxidants used to carry the Pd° -> Pd11 redox chemistry required for catalysis. In practice, catalytically efficient conditions have not yet been developed, and the reaction is usually carried out using a full equivalent of palladium(II) acetate. This chemistry has been used in the synthesis of quadrone (equation 2).8 With the more electrophilic palladium(II) trifluoroace-tate, methyl enol ethers underwent this cyclization process (equation 3).9... 

With this bicyclic intermediate available in sizeable amounts, ready advance to 111 could be conveniently accomplished prior to annulation of the second five-membered ring (Scheme XIV). 1,3-Carbonyl transposition was realized by complete eradication of the original carbonyl by Ireland s method [60] followed by allylic oxidation. Application of the Piers cyclopentannulation protocol [61] to 111 made 113 conveniently available. Introduction of a methyl group into ring B was brought about by treatment of the kinetically derived enol triflate [62] with lithium dimethylcuprate [63], Hydrolysis of 114 gave the dienone, which was directly transformed into 115 by oxidation of its silyl enol ether with palladium acetate in acetonitrile [64],... 

Some synthetic modification for Pd(II)-catalyzed oxidation of silyl enol ethers is also developed. Silyl enol ethers prepared from aldehydes and ketones are converted to the corresponding a,/3-unsaturated carbonyl compound in good yields by 10 mol % of palladium(II) acetate in the presence of 1 atm pressure of O2 in DMSO as solvent (Scheme... 

The first case of a tetrahedral palladium(O) tetraolefin complex (more exactly, Pd(diolefin)2) has been isolated in the course of the Saegusa oxidation of a silyl enol ether, aimed at the synthesis of alkaloids. Palladium acetate was used as oxidant in this reaction, and a brown compound separated from the solution, which was characterized by X-ray diffraction as 16 (Equation (5)). It decomposed upon heating to give the expected product of oxidation. This supports the accepted mechanism of Saegusa oxidation. ... 

Other metals besides palladium are also effective. Reaction of the cationic allyltetracarbonyUron complex derived from (1) or (2) with silyl enol ethers, O-sUyl ketene acetals, or allylstan-nanes, followed by oxidative decomplexation, gives the vinyl-sUane products. The process was shown to occur with near complete retention of stereochemistry (cf. eqs 4 and 5). ... 

The protection of the hemiacetal hydroxyl in step C is followed by a purification of the dominant stereoisomer. The C-6 methyl group is introduced in step C by conjugate addition of dimethylcuprate. The enolate is trapped as the silyl enol ether and oxidized to the enone by palladium acetate. The enone from step D is then subjected to a Wittig reaction. As in several of the other syntheses, the hydrogenation in step E is used to establish the configuration at C-4 and C-6. 

The protocols for the utilization of ketone-derived silyl enol ethers in Tsuji-Trost reactions were preceded by a report of Morimoto and coworkers on the enantioselective allylation of sUyl ketene acetals 88. Without external activation, they reacted with the allylic substrate 19d in the presence of the palladium complex derived from the amidine ligand 89 to give y,5-unsaturated esters 90 in moderate chemical yield but high enantiomeric excess (Scheme 5.29) [46]. Presumably, the pivalate anion hberated during the oxidative addition functions as an activator of the silyl ketene acetal. The protocol is remarkable in view of the fact that asymmetric allylic alkylations of carboxylic esters are rare. Interestingly, the asymmetric induction originates from a ligand with an uncomplicated structure. The protocol seems however rather restricted with respect to the substitution pattern of allylic component and sUyl ketene acetal. 

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