Silylenol ethers

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

Recently, Narasaka and co-workers have found that Tnitroalkyl radicals are generated by oxidadon of nci-nitroanions vrith CAN, and they undergo the intermolecidar addidon to electron-rich olefins. For example, when oxidadon is carried out in the presence of silylenol ethers, fi-nitroketones are formed in good yield. fi-Nitroketones are readily converted into u vrith base ("see Secdon 7.3, as shovm in Eq. 5.43. 

For example, using (/ )-5-trimethylsilyl-2-cyclohexenone as the chiral Michael acceptor, optically active m // .v-3.5-disubstituied cyclohexanones 1 are obtained via a Lewis acid catalyzed addition of silylenol ethers or ketene acetals. 

The titanium(IV) chloride catalyzed addition of silylenol ethers to 2-substituted cyclopen-tenones stereoselectively yields tnmv-cyclopcntanoncs45 4h. 

Eu(fod)3 and SnCU-catalyzed heterocycloadditions of o-silylenol ethers deriving from cyclic ketones [113]... 

Reaction of the N,0-acetal 1554 with the silylenol ether of cyclohexanone 107 a in the presence of TiCU generates the cation 1555, which affords 43% of the cych-zation product 1556 and 27% of the seco product 1557 [73] (Scheme 9.42). 

Table 3.2 Solvent and temperature dependence in the reaction of DDQ with a silylenol ether.

The third cycloaddition substrate explored the feasibility of a vinyl nitro functionality as an activated dipolarophile (98, Scheme 1.9c). Preparation of nitroalkene oxidopyridinium betaine 98 began with silylenol ether 92, which was treated with methoxydioxolane in the presence of Lewis acid catalyst, TrC104, to afford keto dioxolane 93 in 58 % yield [47]. Ketone 93 then underwent a-nitration by treatment with /-BuONCL and KOt-Bu to provide nitro ketone 84 (91 %), which was then converted to the nitroalkene functionality via reduction under Luche conditions to... 

The silylative conversion of a ketone or aldehyde to silylenol ether developed by Marshall, Ireland and Danishevsky produces a reactive diene which can participate in Diel-Alder or Claisen rearrangements. 

The above three examples involved reactions where the electron transfer takes place from the metal to the organic substrate. The reverse scenario can also be used in radical reactions via oxidative generation of cationic radical species, which can undergo coupling reactions. Kurihara et al. have used chiral ox-ovanadium species as a one-electron transfer oxidant to silylenol ethers in a hetero-coupling process [165]. Treatment of 246 with a catalyst prepared in situ from VOCI3/chiral alcohol/MS 4 A followed by addition of 247 provided the coupling product 248 (Scheme 63). 8-Phenyl menthol 251 was found to be... 

Scheme 6.88 Silylenol ethers and silyl keteneacetals that were used to trap the cyclic allene 417. The [2+ 2]-cycloadducts such as 435 were converted into products of the type 436.

Similar results were obtained when diphenylnitrenium ion was trapped with various silylenol ethers and silyl ketene acetals (e.g., 116). In these experiments, a distribution of N-(117), p- (118), and o- (119) adducts were generated (Fig. 13.55). The ortho adducts underwent a cyclization reaction, producing an indolone derivative. 

The use of DAMgBr 39 in Et20/HMPA/TMSCPEt3N leads to the thermodynamic enolates or silyl enol ethers. This methodology is one of the best direct regiospecific preparations of thermodynamic silylenol ethers from unsymmetric cyclic ketones. 

Krafft and Holton have found that bromomagnesium diisopropylamide (BMDA) in an ethereal solution may be used in conjunction with the system TMSCl/EtsN/HMPA to prepare thermodynamic silylenol ethers. Reaction times of 8-12 h at 25 °C are required for the complete conversion to trimethylsilyl enolates (equation 67). 

The effectiveness of magnesium enolates as nucleophilic agents limits the interest of the reaction. With less substituted substrates (R = H), the aldol reaction is faster than the sily-lation. Moreover, due to solubility limitations, the authors are unable to determine whether the high thermodynamic kinetic ratio of silylenol ethers obtained accurately represents the magnesium enolate composition. Nonetheless, this method is an excellent procedure to selectively prepare the thermodynamic silylenol ether from an unsymmetrical ketone. ... 

Bordeau and coworkers have described an efficient and stereoselective synthesis of kinetic silylenol ethers. Less highly substituted silylenolates are regiospecifically prepared in high yield, around room temperature under kinetic conditions, from unsymmetric cyclic ketones and [(DA)2Mg] in THF/heptane (equation 68). 

An important reaction of silylenol ethers is their use as enolate equivalent in Mukaiyama aldol additions. An example of the synthetic utility of this reaction with a magnesium enolate as starting reagent is shown below. 

A stereoselective synthesis of all E retinal, via a condensation of a Cio chloroacetal with (3-eyelogerany 1 sulfone was described by Julia et al. [29]. The chloroacetal was reacted with the silylenol ether, using TiCl4/Ti(OMe)4, to give in 63% yield, the chloromethoxyacetal derivative as a mixture of E Z isomers (80/20). The aldehyde was converted in 97% yield into the corresponding acetal with HC(OMe)3 and camphorsulfonic acid in methanol, Fig. (6). 

Aldol reactions of aldehydes with cycloakanones were performed in ionic liquids and catalyzed by FeCl3-6H20 [32]. Mukaiyama aldol reactions of silylenol ethers with aldehydes can be carried out in aqueous media however, among several Lewis acidic catalysts investigated, iron compounds were not the optimal ones [33], If silyl ketene acetals are applied as carbon nucleophiles in Mukaiyama aldol reactions, cationic Fe(II) complexes give good results. As catalysts, CpFe(CO)2Cl [34] and [CpFe(dppe) (acetone)] BF4 [35] [dppe = l,2-bis(diphenylphosphano)ethane] were applied (Scheme 8.8). No diastereomeric ratio was reported for product 26a. 

An interesting observation that lends some credit to the above-proposed mechanism comes from the reaction of allylsilane 171 with various aldehydes 174 in the presence of Et2 A1C1. This reaction afforded for the first time, the silylenol ether 177 as a single double-bond isomer. When 177 was further treated with Et2OBF3 in the presence of a second equivalent of aldehyde 174, smooth formation of 173 ensued, indicating that 177 is a plausible intermediate in the transformation of 171 to 173 (Scheme 13.62). 

Hypervalent iodine oxidation reactions of unsaturated compounds such as a,/ -unsaturated compounds, alkynes, and silylenol ethers afford the important substructures of several natural products. 

Scheme4.72. Reaction of epoxides with allyl silanes, allyl stannanes, and silylenol ethers [297, 308, 309, 328].

The iminium salts of 2,3-dihydropyridines are far more stable than the free bases and have been used extensively in the synthesis of alkaloids. N-Benzyl iminium salt 26, formed from the Polonovski-Potier reaction of V-oxide 25, was transformed into enol ether 27, which is a synthon for the unstable AT-benzvl-l, 2-dihvdropyridine 28 (Scheme 5) <2004LOC168>. The same transformation on a similar iminium salt has been used in the formation of macrocyclic marine alkaloids <1995TL2059>. Carbon nucleophiles, such as the silylenol ethers of esters, have been shown to undergo 1,2-addition rather than 1,4-addition to 2,3-dihydropyridinium salts <1999T14995>. 

Reaction of the benzylic bromide 1195 with silylenol ether 1196 in the presence of TBAI and Gingras salt ([//-If 111 ][I h SnF2]) affords the isochroman-4-one 1197 in poor yield. The product can be explained by the 1,2-addition of the enolate to the top side chain, followed by nucleophilic substitution of the benzylic bromide (Equation 459) <2000CEJ3887>. 

Conversion of thiochromones into 4-silyloxybenzothiopyrylium triflates 352 facilitates the 1,2-addition of nucleophiles across the S=C bond. Of course, the process corresponds to an overall 1,4-addition to the thiochromone. For example, reaction with silylenol ethers, readily derived from an enolizable ketone, affords the thiochroman-based 1,5-diketone or a silylenol ether derivative <1996SL182>. In like manner, allyltri- -butyltin yields the 2-(2-propenyl)-4-silyloxy-2//-l-benzothiopyran <2001T1005> and 1-morpholinocyclopentene affords the 2-(2-oxocyclopentyl) derivative (Scheme 78) <1997J(P1)2807>. 

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