Silylative cyclopentenones

Silyl enol ethers of alkenyl methyl ketones can be efficiently cyclized to cyclopentenones and cyclohexenones by treating them with stoichiometric amounts of palladium acetate244 an example indicating the elaboration of this approach to the synthesis of a reduced benzoxepinone derivative, and the suggested244 mechanism of the reaction, are depicted in Scheme 174. 

The alkyl allenyl ethers whose chemistry has been discussed are readily prepared and are useful for the synthesis of diverse cyclopentenones, as racemates or in enan-tiomerically enriched form. It is worth noting that silyl allenyl ethers allow entry into a distinct mechanistic manifold [16]. Triisopropylsilyloxyallene 47 can be deprotonat-... 

The reaction of (trialkylsilyl)vinylketenes with nucleophilic carbenoid reagents, such as sulfur ylides and diazo compounds, has been used for synthesis of substituted cyclopentenones by stereoselective 4 + 1-annulation (Scheme 12). The strategy relies on the remarkable ability of silyl substituents to stabilize ketenes and suppress their tendency to undergo dimerization and 2 - - 2-cycloaddition. 

As shown in Scheme 11, the alkynylcyclopropanol to cyclopentenone rearrangement of these compounds proceeds smoothly in most cases. Interestingly, the reactions of the silyl ethers of the exo-isomers 29 c and 29 d proceed much faster than those of the corresponding ezzdo-isomers 28 c, d, and the reaction goes to completion within several hours in refluxing THE This clear differ-... 

The reactions of various l-(l-alkynyl)cyclopropanols were examined using 5-10 mol% of Co2(CO)8 and 10 mol% of tri(o-isopropylphenyl) phosphite. 1-Phenylethynylcyclopropanol (11b), as well as the alkyl- or silyl-substituted derivatives, gave the corresponding 3-substituted 2-cyclopentenones in good to high yields (Scheme 13). 

Oxidation of (15,47 )-4-/ert-butyldimethylsilyloxy-2-cyclohexenol (see p400) and subsequent silyl group removal gave 4-hydroxy-2-cyclopentenone (1) of known R configuration55. 

The Nazarov reaction [196] is a conrotatory electrocyclization involving four electrons over a five-carbon span. Usually, a more highly substituted cyclopentenone is obtained. However, contrathermodynamic products may be generated by placing a silyl group at the p-position of a bare vinyl moiety in the cross-conjugated dienone [197]. The acceptor facilitates and controls the regiochemistry of the cyclization process. 

A similar coupling with a,p-unsaturated acid chlorides provides p-silyl divinyl ketones (Nazarov reagents). These ketones cyclize in the presence of a Lewis acid, particularly BF3 etherate, to cyclopentenones, generally with retention of the silyl group. 

Bernadi and Scolastico, and later Evans in a more effective manner, indicated that the enantioselective addition reaction using silyl enol ethers can be catalyzed by Lewis acidic copper(II) cation complexes derived from bisoxazolines [38-40]. In the presence of the copper complex (S,S)-14 (10 mol %), silyl enol ethers derived from thioesters add to alkylidenemalonates or 2-alkenoyloxazo-lidone in high ees (Scheme 12). Bernadi, Scolastico, and Seebach employed a titanium complex derived from TADDOL for the addition of silyl enol ethers to nitroalkenes or 2-cyclopentenone [41-43], although these are stoichiometric reactions. 

Full details42 have been published on the conversion of enynes into iminocyclopentenes using a titanium precatalyst in the presence of BuLi and TESCN (equation 9) the resulting iminocyclopentenes can be hydrolysed to cyclopentenones or reduced to allylic silyl-amines. In a related protocol43, the tandem insertion of TMSCN and alkenes, alkynes, ketones or isocyanates into zirconacyclo-pentanes or -pentenes leads to cyclopentylamines carrying an a-alkyl, -alkenyl, -1-hydroxyalkyl or -carboxamide substituent, respectively (equation 9). 

Michael addition.1 This ketene silyl acetal undergoes Michael addition to a,fl-enones in acetonitrile in the absence of a Lewis acid to afford the corresponding O-silylated Michael adduct in high yield. These O-silyl enolates undergo site-specific electrophilic substitution. This sequence was used for vicinal dialkylation of cyclohexanone (equation I) and of cyclopentanone. It is particularly useful for synthesis of methyl jasmonate and related compounds from cyclopentenone. 

Transmetallation of silyl enol ethers of ketones and aldehydes with Pd(II) generates Pd(II) enolates, which are usefull intermediates. Pd(II) enolates undergo alkene insertion and -elimination. The silyl enol ether of 5-hexen-2-one (241) was converted to the Pd enolate 242 by transmetallation with Pd(OAc)2, and 3-methyl-2-cyclopentenone (243) was obtained by intramolecular insertion of the double bond and -elimination [148], Formally this reaction can be regarded as carbopalladation of alkene with carbanion. Preparation of the stemodin intermediate 246 by the reaction of the silyl enol ether 245, obtained from 244, is one of the many applications [149]. Transmetallation and alkene insertion of the silyl enol ether 249, obtained from cyclopentadiene monoxide (247) via 248, afforded 250, which was converted to the prostaglandin intermediate 251 by further alkene insertion. In this case syn elimination from 250 is not possible [150]. However, there is a report that the reaction proceeds by oxypalladation of alkene, rather than transmetallation of silyl enol ether with Pd(OAc)2 [151]. 

Pd(OAc)2 to give the cyclohexenone 256. In clavulone synthesis, only the silyl enol ether in 257 reacts with Pd(OAc)2 to give the enone 258 [153]. The dehydrogenation can be carried out with a catalytic amount of Pd(OAc)2 using benzoquinone as the reoxidant. Cyclopentenone (260) is prepared from cyclopentanone (259) by using a supported Pd catalyst under 02 atmosphere [154], The enone 261 is converted to the dienone 263 via the dienol silyl ether 262 [155],... 

Trialklysilyl groups control the course of the Nazarov cyclization.78 80 For example, the presence of the trimethylsilyl substituent in 80a results in the exclusive formation of the less stable cyclopentenone isomer 8178 (Scheme 12) arising from desilylation of the P-trimethylsilyl carbenium ion intermediate 82, whereas in the absence of the silyl substituent in 80b the thermodynamically more stable cyclopentenone 83 is obtained. 

In an unconventional cyclopentenone synthesis, Negishi cyclised vinyllithiums derived from the 1-iodo- 1-silyl alkenes 103 onto preformed lithium carboxylate salts.57 He later found58 that amides 104 function in this reaction rather better than the carboxylate salts, and that the silyl substituent is not necessary for cyclisation. Nitriles, on the other hand, fail to cyclise. 

Vinyllithiums of type 663 (R2 = R3 = H) reacted with primary alkyl bromides, carbonyl compounds, carbon dioxide, DMF, silyl chlorides, stannyl chlorides, disulfides and phenylselenyl bromide142,970-979. Scheme 173 shows the synthesis of dihydrojasmone 669 from the corresponding 1,4-diketone. a-(Phenylsulfanyl)vinyllithium 665, prepared from phenyl vinyl thioether, reacted with hexanal and the corresponding adduct 666 was transformed into its acetoacetate. This ester 667 underwent a Carrol reaction to produce the ketone 668, which was transformed into the cyclopentenone 669 by deprotection either... 

Treatment of 1,3-dicarbonyl compounds with DBP in a methoxide/methanol system affords 2-alkyl-4-[(phenylsulfonyl)methyl]furans, where reaction proceeds by Initial addition-elimination on the vinyl sulfone moiety. In contrast, silyl enol ethers in the presence of silver tetrafluoroborate resulted in products derived from Sn2 displacement at the allylic site.11 Anions derived from 1,3-dicarbonyls substituted at the C-2 position are found to induce a complete reversal in the mode of ring closure.12 The major products obtained are 3-[(phenylsulfonyl)methyl]-substituted cyclopentenones. The internal displacement reaction leading to the furan ring apparently encounters an unfavorable Ai -interaction in the transition state when a substituent group is present at the 2-position ol the dicarbonyl compound. This steric Interaction is not present in the transition state leading to the cyclopentenone ring. 

Methyl-2-eyclopentenones. Enol silyl ethers of 3-butenyl methyl ketones such as 1 and 3 are cyclized exclusively to 2-cyclopentenones (2,4) in the presence of palladium(II) acetate (1 equiv.) at room temperature with deposition of Pd(0). 

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