Silyl enol ethers conversion into enolates

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... 

Chromene acetals 39 are accessible from 2-vinyl-substituted phenols via the allylic acetals 38 through oxypalladation of benzyloxypropa- 1,2-diene and a subsequent Ru-catalysed RCM. 2-Substituted chromenes can be derived from the acetals 39 by conversion into the 1-benzopyrylium salts which are then trapped by nucleophiles (Scheme 26) <00TL5979>. In a like manner, 2-aIkoxychromans have been converted into various 2-substituted chromans by sequential treatment with SnCl4 and a silyl enol ether <00TL7203>. 

In 1978, Saegusa and coworkers discovered that silyl enol ethers can be converted into a,b-unsaturated ketones and aldehydes by Pd" [193]. In the presence of 0.5 equivalents of BQ, substoichiometric Pd(OAc)2 (0.5 equiv) effects nearly quantitative conversion of the substrate into product in acetonitrile (Eq. 51). Attempts to lower the catalyst loading further results in longer reaction times as well as increased yields of saturated carbonyl by-product. 

Stereospecific conversion of vinylsilanes to silyl enol ethers This conversion can be effected by dihydroxylation with 0s04 in combination with (CH3)3NO and pyridine followed by anti p-elimination with NaH via an a-oxidosilane. The overall process converts vinylsilanes into silyl enol ethers with preservation of the geometry of the double bond. 

A number of other acyclic Z and E lithium enolates were quenched similarly. In all cases the stereochemistry at the enol double bond was retained, as shown by subsequent conversion into the corresponding silyl enol ether. Upon reacting the titanium enolates with aldehydes, very clean aldol addition occured (>90% conversion at —78 °C). Generally, erythro-selectivity was observed irrespective of the geometry of the enolate. Equations 64 and 65 are typical25). 

This sequence transforms acyclic ketones and aldehydes into a-methylene ketones and a-methyl-a,)5-unsaturated ketones and aldehydes It has been illustrated by the synthesis of eucarvone, ( )-nuciferal and ( )-manicone This ring-opening of chlorosiloxycyc-lopropanes with ClSiMea elimination appears to be a practical route to Z or a,)5-ethylenic aldehydes and ketones depending on the stereochemistry of the reactants. For example, conversion in MeOH-NEta at 20°C of the 2-chloro-2-methyl-3-pentyl-l-trimethylsiloxycyclopropanes (derived from the addition of the chloromethylcarbene to the E and Z silyl enol ethers of n-heptanal) leads either to or Z 2-methyl-oct-2-enal (equation 65). ... 

Previously difficult substitution reactions of 1,3-dithietan 1,1,3,3-tetroxide (50) are now possible. The formation of the silyl derivative (51) (see Scheme 8), its conversion into the dithieten (52), followed by the addition of electrophiles forms the substitution products. The dithieten (52) can be considered as the first enol ether of a sulphone. The transient benzothiet (53) has been prepared by the thermolysis of (54), its structure having been confirmed by i.r. and photoelectron spectroscopy. ... 

Tyrosinase initiates conversion of phenol into o-benzoquinone, which forms Diels-Alder adducts. Employment of oxygen instead of other cooxidants in the oxidative cyclization of compounds containing a silyl enol ether and alkenyl side chain is desirable. ... 

A Lewis acid-promoted, IMDA cycloaddition between an electron-poor pyrone and an electron-rich silyl enol ether was used to prepare the A ring. The requisite triene 12 was synthesized from alcohol 13 and chlorodiisopropylsilyl enol ether 14. Subsequent ZnBr2-promoted cyclization of 12 allowed slow conversion to the Diels-Alder adducts 15 and 16 in 46% and 12% yields, respectively (Scheme 10-4). The major, endo adduct 15 was subsequently elaborated into fluoroalkyl-vitamin Dj analog 10. 

Trimethylsilyl enol ethers of acyltrimethylsilanes. These useful silanes (3) can be prepared from benzenethiol esters (1) by conversion into the silyl enol ethers... 

In the reaction with the primary alkyl hahde, the boot is on the other foot as there will be a good reaction with the hthium enolate but no reaction with the more stable silyl enol ethers. Lewis acid won t help here either as primary cations are unstable. Prehminary conversion into a hthium enolate or a naked enolate (using fluoride ion) would be better. 

In some reactions (difluoroiodo)arenes can be used as general oxidizing reagents. For example, Koser and coworkers applied a difluoroiodotoluene/phosphoric acid mixture as a reagent for direct conversion of silyl enol ethers into tris-ketol phosphates 166 (Scheme 3.69) [217]. 

Aldol reaction between a silyl enol ether and an aromatic or aliphatic aldehyde can be catalysed by tetrabutylammonium fluoride ketones and epoxides are not attacked by the enolates derived in this manner. Directed cross-aldol reactions have now been carried out by conversion of a methyl ketone into the intermediate (15) using 9-trifluoromethylsulphonyl-9-borabicyclo[3,3,l]nonane and t-amine prior to reaction with the second carbonyl compound. ... 

A simple conversion of 11-deoxy-PGE2 into PGA2 through reaction of the silyl enol-ether (70) with Pb(OAc) and subsequent desilylation has been described by Crabbe. ... 

More importantly, some silylating reagents used for protection of functional groups with active hydrogen atoms can react with carbonyl fragments with the formation of trimethylsilyl (TMS) derivatives of enols. If such unpredictable mode of derivatization is undesirable, all carbonyl fragments should be protected before silylation, for example, by conversion into alkoxyimino groups (alkyl ethers of oximes, see below). 

Conversion of silyl enol ethers into corresponding oc,(3-eneones using stoichiometric amounts of palladium acetate ... 

The silicon-containing Grignard reagents (27) and (28) are alkylated in high yield in the presence of Cu salts. The conversion of vinyl silanes via the epoxide into silyl enol ethers prompts the recognition of these reagents as examples of the two nucleophilic synthons for acetaldehyde (Scheme 23). 

A useful sequence has been described for the conversion of aldehydes and ketones, via their silyl enol ethers, into a-methyl-a, -unsaturated aldehydes or ketones (Scheme 36). When applied to cyclic ketones, the products are a-methylcycloalkenones with one extra carbon atom in the ring. ... 

The method becomes even more attractive, as the formation and subsequent conversion of the ketenes can be carried out in a one-pot procedure. For this purpose, the sterically demanding BHT esters like 155 are deprotonated to give the ester enolate 156. Upon addition of the alkyllithium compound (R Li) and warming up to room temperature, elimination occurs under formation of ketene 153b that is immediately converted into ketone enolate 154b. The highly selective formation of the cis-diastereomer has been proven by conversion into the silyl enol ether 157 (Scheme 2.45) [153]. 

There are several methods that are useful in particular cases and special substrates for enolate formation. Although most of these protocols found no application in asymmetric synthesis, some are briefly mentioned. Nonenolizable or slowly enolizable carboxylic esters, thioesters, or amides are converted into ketone enolates by treatment of a combination of allylmagnesium chloride and LDA or n-butyllithium. The twofold addition of the Grignard reagent is suppressed by rapid in situ deprotonation. As illustrated in Scheme 2.56, the enolate 185a forms with remarkable diastereoselectivity as proven by conversion into the silyl enol ether 185b [175]. 

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