Enones silylation

The selective cyclopropanation of the a-enone silyl enol ether 75, by methylene iodide and the zinc-silver couple 2), is remarkable. Only the double bond bearing the tri-methylsiloxy group reacted to yield the 1-trimethylsiloxy vinylcyclopropane 76 when not more than 1.1 equivalent of the Simmons-Smith reagent was used, but the bis-cyclopropanation product 77 was obtained in good yield with an excess (3 equivalents) of the cyclopropanating reagent, Eq. (24) 42). 

Three-component coupling reaction of a-enones, silyl enolates, and aldehydes by successive Mukaiyama-Michael and aldol reactions is a powerful method for stereoselective construction of highly functionahzed molecules valuable as synthetic intermediates of natural compounds [231c]. Kobayashi et al. recently reported the synthesis of y-acyl-d-lactams from ketene silyl thioacetals, a,/l-urisalu-rated thioesters, and imines via successive SbCl5-Sn(OTf)2-catalyzed Mukaiyama-Michael and Sc(OTf)3-catalyzed Mannich-type reactions (Scheme 10.87) [241]. 

Double cyclopropanation of enone silyl enol ethers by a modified Simmons-Smith procedure provides a good route to 1-cyclopropylcyclopropanols and to cyclopropyl ketones (Scheme... 

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. 

Hindered ketones and enones fail to form the ketal because of competing decomposition of the silyl reagent. 

So far, there is no conclusive evidence that a free allyl carbanion is generated from allylsilanes under fluoride ion catalysis. A hypervalent silyl anion, with the silicon still bonded to the allylic moiety, accounts equally well for the results obtained. Based on a variety of experimental results, it is in fact more likely that a nonbasic hypervalent silyl anion is involved rather than the basic free allyl carbanion first postulated14-23. When allylsilanes are treated with fluoride in the presence of enones. 1,4-addition takes place along with some 1,2-addition13. 

Table 2. 2,3-Disubstituted 1.5-Diketones form Addition of Silyl Enolates to Enones...

A very efficient method for annulations158 is based on the addition of lithium or silyl enolates to a-silylated enones as a key step. The diastereoselective 1,4-addition is followed by an aldol condensation. This procedure allows Michael additions under aprotic conditions, whereby the silyl substituent stabilizes the enolate of the Michael adduct preventing polymerization of the enone, 59 l63. 

The oxophilicity of silicon is also the driving force that allows the reaction of the same silylated reagent 29 with oxiranes [134], aldehydes and ketones [135,136], and enones [136] for yielding functionalized AT-silylphosphazenes (Scheme 31). 

Trimethylsilyl enol ethers can also be prepared by 1,4-reduction of enones using silanes as reductants. Several effective catalysts have been found,38 of which the most versatile appears to be a Pt complex of divinyltetramethyldisiloxane.39 This catalyst gives good yields of substituted silyl enol ethers (e.g., Scheme 1.2, Entry 7). 

Excellent yields of silyl enol have also been obtained from enones using B(C6F5)3 as a catalyst.40 f-Butyldimethylsilyl, triethylsilyl, and other silyl enol ethers can also be made under these conditions. 

Methyl 1-phenylthiovinyl ketones can also be used as enones in kinetically controlled Robinson annulation reactions, as illustrated by Entry 6. Entry 7 shows a annulation using silyl enol ether as the enolate equivalent. These reactions are called Mukaiyama-Michael reactions (see Section 2.6.3). 

Several examples of conjugate addition of carbanions carried out under aprotic conditions are given in Scheme 2.24. The reactions are typically quenched by addition of a proton source to neutralize the enolate. It is also possible to trap the adduct by silylation or, as we will see in Section 2.6.2, to carry out a tandem alkylation. Lithium enolates preformed by reaction with LDA in THF react with enones to give 1,4-diketones (Entries 1 and 2). Entries 3 and 4 involve addition of ester enolates to enones. The reaction in Entry 3 gives the 1,2-addition product at —78°C but isomerizes to the 1,4-product at 25° C. Esters of 1,5-dicarboxylic acids are obtained by addition of ester enolates to a,(3-unsaturated esters (Entry 5). Entries 6 to 8 show cases of... 

Silyl ketene acetals also undergo conjugate addition. For example, Mg(C104)2 and LiC104 catalyze addition of silyl ketene acetals to enones. 

In discussion of the dehydrogenation of silyl enol ethers using DDQ, Jung and Murai had proposed that DDQ abstracts a hydride producing a stabilized cation 70 which loses TMS+ to give the enone 23 (Scheme 3.31) [8]. 

Porco s route to (—)-kinamycin C (3) began with 2,5-dihydroxybenzaldehyde (38), which was elaborated to the enone 35 by the sequence shown in Scheme 3.6. Regioselective bromination [25] followed by methylation and reduction of the aldehyde function afforded the primary alcohol 39. The alcohol 39 was dearomatized by treatment with bis(acetoxy)iodobenzene, to afford the quinone monoketal 41. Transketalization with 1,3-propanediol followed by silylation of the primary alcohol generated the silyl ether 42 in 72 % yield over three steps. 

With an effective strategy for construction of the diazofluorene established, we set out to prepare the coupling partners required for synthesis of (—)-kinamycin F (6). The synthesis of the enone 117 began with meta-cresol (128, Scheme 3.23). Silylation formed the silyl ether 119 in nearly quantitative yield. Birch reduction of the silyl ether 119 formed the cyclohexadiene derivative 129 in excellent yield. Asymmetric dihydroxylation [52] of 129 occurred regioselectively to afford the... 

Exploitation of time-resolved spectroscopy allows the direct observation of the reactive intermediates (i.e., ion-radical pair) involved in the oxidation of enol silyl ether (ESE) by photoactivated chloranil (3CA ), and their temporal evolution to the enone and adduct in the following way.41c Photoexcitation of chloranil (at lexc = 355 nm) produces excited chloranil triplet (3CA ) which is a powerful electron acceptor (EKelectron-rich enol silyl ethers (Em = 1.0-1.5 V versus SCE) to the ion-radical pair with unit quantum yield, both in dichloromethane and in acetonitrile (equation 20). 

The 1,4-hydrosilylation of enones can be used as a method for the introduction of the silyl enol ether functionality, and may be accomplished with the combination of PhMe2SiH/RhH(PPh3)4 (Eq. 278),374 Et3SiH/RhCl(PPh3)3 411 (HMe2 Si)20/[CuH(PPh3) ], 455 Et3 SiH/Pt-complex,456 chloromethy ldimethy 1-... 

A further example of the trapping of the in situ generated silyl enol ether from the reduction of an enone is the conversion of an enone into an a-hydroxy ketone via oxidation of the silyl enol ether (Eq. 286).465... 

RhH(PPh3)4 efficiently isomerized fv-silylallylic alcohols to cr-silyl ketones in excellent yields, but only in the presence of an a-silyl enone as co-catalyst (Equation (13)).48... 

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