Silyl enol ethers, oxidative functionalization

Sn(OTf)2 can function as a catalyst for aldol reactions, allylations, and cyanations asymmetric versions of these reactions have also been reported. Diastereoselective and enantioselective aldol reactions of aldehydes with silyl enol ethers using Sn(OTf)2 and a chiral amine have been reported (Scheme SO) 338 33 5 A proposed active complex is shown in the scheme. Catalytic asymmetric aldol reactions using Sn(OTf)2, a chiral diamine, and tin(II) oxide have been developed.340 Tin(II) oxide is assumed to prevent achiral reaction pathway by weakening the Lewis acidity of Me3SiOTf, which is formed during the reaction. 

In all of the cyclization reactions, Moeller has found only a small difference between the use of alkyl and silyl enol ethers. Since both styrenes and enol ethers have similar oxidation potentials, even the styrene moiety could function as the initiator for oxidative cyclization reactions. The anodic oxidation of simple styrene type precursors leads to low yields of cyclized products so that enol ether moiety seems to be the more efficient initiator for intramolecular anodic coupling reactions [93]. 

Oxygen at the heterocyclic sulfur atom has been functionalized in two ways (1) by a TMSOTf-catalyzed Pummerer reaction in the presence of a silyl enol ether (Scheme 95) <1998TL9131> or (2) by reductive removal of the oxygen using Ac20/Zn/cat. 4-dimethylaminopyridine (DMAP) <1996SL885>. The formation of 1,3-dithiane from 1,3-dithiane 1-oxide proceeds efficiently in 95% yield (Equation 70). 

Perhaps the most useful type of alkene substrates for these reactions are enol ethers, enol esters and vinyl sulfides. Silyl enol ethers have excellent electron-donor properties, with an ionization potential of about 8 eV and an oxidation potential in various solvents of approximately 1.0-1.5 V vs SCE161. These compounds are easily synthesized by reaction of an enolate with a chlorosilane. (A very recent report synthesized a variety of silyl enol ethers with extremely high stereochemical yield, using the electrogenerated amidate of 2-pyrolidinone as the base.)162 An interesting point is that the use of oxidative or reductive cyclization reactions allows carbonyl functionalities to be ambivalent, either oxidizable or reducible (Scheme 65)163. 

The DFT study of the 3 + 2-cycloaddition between ketene and TV-silyl-, IV-germyl-, and TV-stannyl-imines shows that the TV-germylimine reaction is a two-step process the TV-stannylimine reaction is a competition between two- and three-step processes whereas the TV-silyl process follows a three-step process44 A new and convenient synthesis of functionalized furans and benzofurans based on 3 + 2-cycloaddition/oxidation has been reported. The cyclization of cyclic 1,3-bis-silyl enol ethers (48) with l-chloro-2,2-dimethoxyethane (49), via a dianion, produced 5,6-bicyclic 2-alkylidenetetrahydrofurans (50), which are readily oxidized with DDQ to 2,3-unsubstituted benzofurans (51) (Scheme 13)45 The Evans bis(oxazoline)-Cu(II) complex catalyses the asymmetric 1,3-dipolar cycloaddition of a -hydroxyenones with nitrones to produce isoxazolidines.46 The... 

A catalytic route using a manganese (III) complex has been developed for a-hydroxylation of ketones avoiding the use of water or a protic solvent mixtures of a-hydroxyketones and their silyl derivatives were formed in excellent yield. By using a chiral pyrrolidine-based manganese (III) complex as catalyst, asymmetric oxidation was effected, with enantiomeric excess varying from 14 to 62% [30], Another kind of a-functionalized ketones resulted from silyl enol ethers which after the addition of IOB.BF3 were treated with triethyl phosphite a-ketophosphonates were obtained in this way [31] ... 

The stemona alkaloid stemonamide (49) was synthesized starting from a-stannyl acetate 47 and 2-stannyl pyrrolidine 48. The oxidative coupling of stannyl acetate 47 with acetylenic silyl enol ether affords the functionalized C-7 unit which corresponds to the side arm of the pyrrolidine ring. Then, introduction of the C-7 unit to the pyrrolidine ring is performed by the oxidative generation of acyliminium ion. The carbon skeleton of stemonamide was thus constructed efficiently as shown in Scheme 19 by employing organotin compounds. ... 

Others [180,260]). In general, enol radical cations may be obtained from either direct oxidation of stable ends or by selective oxidation of the enol tautomer of the keto/enol equilibrium. In addition it has been outlined that enol radical cations offer an access to a-carbonyl radical chemistry. Other enol systems like silyl enol ethers, enol esters and enolates similarly may open up after oxidation the chemistry of a-carbonyl radical or a-carbonyl cation intermediates, whereas enol ether oxidative a-functionalization reactions work by another route. 

Chlorosulfides are often used for vicinal functionalization of alkenes. Silyl enol ethers can react with a-chloromethyl phenyl sulfides (5) in the presence of ZnBr2 or TiCU to give the corresponding -keto sulfide, which could be easily transfonned into the a-methylene ketone via sulfide oxidation to sulfoxide, followed by pyrolytic elimination (Scheme 23). 

Reaction with ei,fi-Unsaturated Sulfoxides. The reaction of TMSI with a, -unsaturated sulfoxides in chloroform at ambient temperature is a mild, efficient, and general method for the preparation of carbonyl compounds (eq 63). The proposed reaction mechanism is shown in eq 63. Formation of a strong oxygen-silicon bond is followed by reduction of the sulfur function and oxidation of iodide to iodine, the latter precipitating in chloroform. The trimethylsiloxy anion attacks the unsaturated carbon linked to the sulfur function, which leaves the substrate, allowing the formation of the sUyl enol ether species. Finally, hydrolysis converts the silyl enol ether into the carbonyl compound. ... 

This is a synthetically valuable process, as illustrated by the hypervalent iodine-mediated oxidative nucleophilic substitution of 269 with the silyl enol ether 271, leading to the highly functionalized naphthoid cyclohexa-2,4-dienone 272 (Scheme 3.113), which is an important intermediate product in the synthesis of aquayamycin-type angucyclinones [343,344],... 

Vinyl siloxonium ion 14 also serves as an important intermediate en route to conjugate adducts of unsaturated carbonyl compounds. For example, treatment of cyclohexenone (13) with reactive silyl electrophiles affords y-functionalized silyl enol ethers 15 and 16 suitable for subsequent synthetic transformations (eq 4). The temporary silicon tether (TST) strategy has been updated (2010) by an excellent review focusing upon metal-mediated reactions. The inception of this strategy is attributable to Nishiyama and Itoh who reported the radical cycUzation of acyclic bromomethyl silyl ethers to sUoxanes and their subsequent oxidation to 1,3-diols. Shortly thereafter, the group of Gilbert... 

Indeed, photoredox catalysis with Ru polypyridine complexes has emerged as a powerful tool for redox reactions including formation of carbon-carbon bonds based on oxidation of sp C-H bonds via single-electron-transfer (SET) processes. Results that are closely related to those shown in Schemes 33,34, and 35, where the carbon-carbon bond formation resulted from the benzyUc sp C-H oxidative activation in the presence of BuOOH, have been recently reported for the regioselective functionalization of tetrahydroisoquinolines with cyanide and a variety of nucleophiles arising from ketones, nitroalkanes, allyltrimethylsilane, silyl enol ethers, 1,3-dicarbonyl compounds under photocatalytic conditions [67-70] as illustrated in Scheme 62 [67]. Other applications of Ru(bipy)3Cl2 in photocatalytic cycUzation reactions involving carbon-carbon btmd formation have appeared [71, 72]. 

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. 

This chapter covers preparations of organosilicon reagents and their use in organic synthesis. Because many books, book sections,and reviews are already available on these topics and only a limited space is available here, this chapter focuses on the reactions that involve cleavage of C-Si bonds for C-C bond formation, aldol reactions of silyl enol ethers, and oxidation of C-Si bonds. Therefore, topics concerning carbonyl reduction and the protection of functional groups, such as hydroxy with organosilanes, are not included in this chapter. 

Silyl enol ethers are a class of electron-rich, nonaromatic compounds that easily form reactive radical cations on one electron oxidation. The silyl enol ether functional group is closely related to the carbonyl function and consequently, syntheses of silyl enol ethers generally make use of enolates. In addition, silyl enol ethers can be described as masked enols or enolates since their reactions often yield ketones. A number of oxidation reactions of silyl enol ethers making use of oxygen or oxygen-containing reagents such as peroxides, peracids (known as Rubottom oxidation), dioxirane, osmium tetraoxide, or triphenyl phosphite ozonide have been described in the literature. In all cases either a-hydroxy-ketones or the silyl enol ether epoxides are formed. 

Before describing one of the most important synthetic aspects, i.e., the addition to carbon-carbon double bonds (see Sections 10.5 and 10.6), we will briefly discuss functionahzation reactions leading to a-heterosubstituted carbonyl compounds. However, although several of the oxidation reactions of silyl enol ethers with oxygen-containing compounds lead to a-hydroxy-carbonyl compounds as a-carbonyl functionalization, radical cations are not involved in these reactions. ... 

In their search for conformationally biased mimics of mannopyranosylamines, A. Vasella and co-workers planned to synthesize compounds that would inhibit p-mannosidases. In order to construct the bicyclo[3.1.0]hexane framework, a five-membered 0-silylated A/,A/-dimethyl-amino alcohol was synthesized. Oxidation of the tertiary amine with mCPBA yielded 83% of the A/-oxide, which was subsequently subjected to the Cope elimination to give 69% of the desired benzyl enol ether. Cyclopropanation of this enol ether gave rise to the highly functionalized bicyclic skeleton. 

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