Bicyclic silyl enol ethers

Jauch, J. Stereochemistry of the Rubottom oxidation with bicyclic silyl enol ethers synthesis and dimerization reactions of bicyclic a-hydroxy ketones. Tetrahedron 1994, 50,12903-12912. 

The silyl enol ethers 209 and 212 are considered to be sources of carbanions. and their transmetallation with Pd(OAc)2 forms the Pd enolate 210. or o.w-tt-allylpalladium, which undergoes the intramolecular alkene insertion and. 1-elimination to give 3-methylcyclopentenone (211) and a bicyclic system 213[199], Five- and six-membered rings can be prepared by this reaction[200]. Use of benzoquinone makes the reaction catalytic. The reaction has been used for syntheses of skeletons of natural products, such as the phyllocladine intermediate 214[201], capnellene[202], the stemodin intermediate 215[203] and hir-sutene [204]. 

Similarly, tandem hydroformylation/aldol sequences can be applied to the formation of bicyclic and spirocyclic compounds. Thus silyl enol ethers of 3-vinyl and 3-allyl cycloalkanones give ring anellated products (Scheme 33) [86,87]. 

Auto-tandem hydroformylation-cyclization, catalyzed by [RhCl(cod)]2, enables expansion of the organic skeleton of unsaturated silyl enol ethers (Scheme 10). Linear aldehydes generated in the hydroformylation step subsequently undergo Rh-catalyzed, intramolecular Mukaiyama aldol addition. Bicyclic ketones are also accessible from cyclic silyl enol ethers. 

Bicyclic ketones, also, have been prepared intramolecularly from silyl enol ethers. Six-membered rings are formed more easily in these reactions than in the reactions forming monocyclic products, described earlier.38... 

Modification of these procedures by using only catalytic amounts of the cyano compound dicyanonaphthalene (DCN) allowed the cyclization of silyl enol ethers to bicyclic compounds in good yield (equation 38)178. 

Bridged and spirocyclic bicycloalkenones. The conversion of silyl enol ethers to a,/J-enones by Pd(OAc)2 (8, 378) can result in cyclization to bicyclic systems when applied to silyl enol ethers of cyclohexanones bearing an alkenyl side chain a or y to the carbonyl group. Although the factors favoring cyclization are not fully defined, this cyclization offers a route to a variety of bridged and spirocyclic systems.1... 

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... 

Substitution of the acetate group at the C-3 position of the /3-sultam 105 can occur by reaction with silyl enol ethers in the presence of zinc iodide or zinc chloride. When the diazo compound is used, after desilylation with tetrabutyl-ammonium fluoride (TBAF), photochemical cyclization gives the bicyclic /3-sultam 106 as a mixture of two cis/ fra -diastereoisomers. When silyl enol ethers derived from cyclic ketones are used, the substitution product is stabilized by a retro-Michael-type reaction leading to open-chained sulfonamides 107 (Scheme 31) <1997LA1261>. 

Substrates containing an electron-rich double bond, such as enol ethers and enol acetates, are easily oxidized by means of PET to electron-deficient aromatic compounds, such as dicyanoanthracene (DCA) or dicyanonaphthalene (DCN), which act as photosensitizers. Cyclization reactions of the initially formed silyloxy radical cation in cyclic silyl enol ethers tethered to an olefinic or an electron-rich aromatic ring, can produce bicyclic and tricyclic ketones with definite stereochemistry (Scheme 9.14) [20, 21]. 

Quite recently a modification of the carbene addition reaction has been published and applied to the synthesis of phoracantholide I (11/88) [70]. The silyl enol ether 11/85 prepared from ( )-8-nonanolide underwent addition of chlorocarbene to give the intermediate bicyclic adduct 11/86, which rearranged into an E/Z-mixture of a,/J-unsaturated lactones 11/87 by heating. Phoracantholide I (11/88) was formed by hydrogenation of the latter, Scheme 11/12. 

Another TiCU-mediated electrophilic annulation using acetal stannane (48) has also been developed recently. As an example, the silyl enol ether of 2-methylcyclohexanone has been shown to form the as-fused bicyclic alcohol (49) in reasonable yield with this tin reagent (equation 42). ... 

Craig, D, Munasinghem, V R N, Stereoselective template-directed C-glycosidation. Synthesis of bicyclic keto oxetanes via intramolecular cyclization reactions of (2-pyridylthio)glycosidic silyl enol ethers, J. Chem. Soc., Chem. Commun., 901-903, 1993. 

The diethylzinc/diidomethane system has also been used for the cyclopropanation of silyl enol ethers to give access to functionalized bicyclic systems, e.g. cyclopropanation of 17 occurred selectively at the enol ether moiety, and the product could be converted to a perhydroin-dene. ... 

Several annulation procedures based on this rearrangement have been developed. Linearly fused bicyclic ring systems, e.g. 19 and 20, were prepared in good yield by thermolysis and subsequent hydrolysis of vinylcyclopropanes functionalized with silyl enol ethers. ... 

Bridged bicyclic ketones 7 are obtained by the Cope rearrangement of silyl enol ethers or lithium enolate anions derived from ent/o-vinylcyclopropanes 4. i 11 The corresponding exo-isomers of 5 require flash-vacuum pyrolysis at temperatures in the range of 250-500°C to... 

Disubstituted furans with different functionalities were synthesized through an acid-catalyzed elimination reaction of 2-alkylidenetetrahydrofurans, in turn, prepared via the cyclization of 1,3-bis-silyl enol ethers with l-chloro-2,2-dimethoxyethane with high regioselectivity <05EJOC2074>. 2-Substituted furans and bicyclic furans can also be... 

With this bicyclic intermediate available in sizeable amounts, ready advance to 111 could be conveniently accomplished prior to annulation of the second five-membered ring (Scheme XIV). 1,3-Carbonyl transposition was realized by complete eradication of the original carbonyl by Ireland s method [60] followed by allylic oxidation. Application of the Piers cyclopentannulation protocol [61] to 111 made 113 conveniently available. Introduction of a methyl group into ring B was brought about by treatment of the kinetically derived enol triflate [62] with lithium dimethylcuprate [63], Hydrolysis of 114 gave the dienone, which was directly transformed into 115 by oxidation of its silyl enol ether with palladium acetate in acetonitrile [64],... 

Intramolecular C-glycosylation by a silyl enol ether leads to bicyclic acyloxe-... 

---