Silyl enol ethers cyclization

In the prostaglandin synthesis shown, silyl enol ether 216, after transmetaJ-lation with Pd(II), undergoes tandem intramolecular and intermolecular alkene insertions to yield 217[205], It should be noted that a different mechanism (palladation of the alkene, rather than palladium enolate formation) has been proposed for this reaction, because the corresponding alkyl enol ethers, instead of the silyl ethers, undergo a similar cyclization[20I],... 

Pd(II)-catalyzed cyclization of the siloxyhexatriene 34 offers a cyclohexe-none annulation method. The Pd enolate 35, formed by transraetallation of the silyl enol ether with Pd(II), is an intermediate which undergoes intramolecular eWo-alkene insertion. Then Pd(II) is regenerated to give 36, and finally cyclohexenone is formed[38]. 

The final example concerns cyclization of a silyl enol ether, connected to yet another carbon atom. The (.Ej-enol ether 23 appears to be converted with high stereoselectivity into the aldehyde 24 in 70- 90% yield, while the (Z)-enol ether 23 affords the epimeric aldehyde 25 in similar yield and selectivity164. 

An efficient two-step annelation of functionalized orthoesters with trimethyl-silyloxyfuran derivatives has been reported that produces bicyclo[3. .0]lactones. ° The reaction in Scheme 7 shows an example in which the initial condensation between silyl enol ether and orthoester is followed by the radical cyclization reaction under standard conditions. It is worth underlining the complete diastereocontrol in which three contiguous stereocenters are generated in one step with >95% stereoselectivity. 

As discussed in Chapter 9, various nucleophiles can be introduced at the ortho position of nitroarenes via the VNS process. This provides a useful strategy for the synthesis of indoles. One of the most attractive and general methods of indoles and indolinones would be the reductive cyclization of a-nitroaryl carbonyl compounds (Eq. 10.54). The VNS and related reactions afford a-nitroaryl carbonyl compounds by a simple procedure. For example, alkylation of 4-fluoronitrobenzene with a lactone silyl enol ether followed by reductive cyclization leads to tryptophols (Eq. 10.55).73... 

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. 

This method can also be applied to silyl enol ethers of homologous unsaturated ketones as well as of unsaturated aldehydes or esters [85-87]. While unmodified unsaturated esters give only the corresponding aldehydes without cyclization under tandem hydroformylation/aldol reaction conditions, the corresponding silylated ester enolates smoothly cyclize in a tandem hy-droformylation/ Mukaiyama aldol reaction (Scheme 32) [85-87]. 

Different nucleophiles such as methanol, allylsilanes, silyl enol ethers, trimethylsilyl-cyanide, and arenes can be used in this process [62]. When the sulfide itself contains an unsaturated or aromatic fragment and the process is carried out in the absence of a nucleophile, an intramolecular anodic sub-stitution/cyclization might occur [61-63]. Methyl esters of 2-benzothiazolyl-2-alkyl or aryl-acetic acid, oxidized in MeOH/Et4 NCIO4 or H2SO4 in the presence of CUCI2, form 2,2-dimethoxy products (Eq. 7) [64]. 

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]. 

Mattay et al. examined the regioselective and stereoselective cyclization of unsaturated silyl enol ethers by photoinduced electron transfer using DCA and DCN as sensitizers. Thereby the regiochemistry (6-endo versus 5-exo) of the cyclization could be controlled because in the absence of a nucleophile, like an alcohol, the cyclization of the siloxy radical cation is dominant, whereas the presence of a nucleophile favors the reaction pathway via the corresponding a-keto radical. The resulting stereoselective cis ring juncture is due to a favored reactive chair like conformer with the substituents pseudoaxial arranged (Scheme 27) [36,37]. 

Scheme 27 Regioselective and stereoselective cyclization of unsaturated silyl enol ethers.

An interestingly short total synthesis of quadrone was developed by Kende and coworkers who made application of Pd(II)-mediated cycloalkenylation of silyl enol ethers (Scheme LV) Their point of departure was 609 which was converted directly to 610, Reaction of this silyl enol ether with palladium acetate in acetonitrile gave predominantly 6JI which could be cyclized to 612. From this intermediate, it was possible to prepare the known keto acid. 

Halogen shifts have been found for tungsten, with assumed formation of iodovinylidenes in reactions of 1-iodo-l-alkynes with W(CO)5(thf) en route to cyclization of 2-(iodoethynyl)styrenes to naphthalenes and of iodo-alkynyl silyl enol ethers [147], while more substantial confirmation is found in Mn =C=C(I)CH (OR)2 (CO)2Cp [R = Me, Et (OR)2 = 0(CH2)30], of which the XRD structure of Mn =C=C(I)CH(OMe)2 (CO)2Cp was determined [148]. 

Utilization of Pentacarbonyi Vinyiidem Complexes of Croup 6 Metals for Synthetic Reactions 175 Table 5.2 Stoichiometric and catalytic cyclization of co-acetylenic silyl enol ethers."... 

This reaction in the presence of base was applied to a tandem cyclization. When bis-alkynyl silyl enol ether 93a was irradiated in toluene in the presence of 10 mol % W(CO)6 and DABCO with 1 equiv of H2O, the expected tricyclic ketone 94a was obtained in 80% yield. The five-membered substrate 93b also gave the corresponding tricyclic ketone 94b having the basic carbon skeleton of the cedranes. Thus we can prepare synthetically useful tricyclic compounds utilizing this W (CO)5(L)-catalyzed tandem cyclization in the presence of DABCO [25c] (Scheme 5.29). 

Scheme 5.29 Tandem cyclization of bis-alkynyl silyl enol ethers.

Cycloheptanes.— The C-1—C-2 bond in -y-thujaplicin is essentially single, Co"-/3-thujaplicin-amine complexes have been described, and thermodynamic data on the U -/3-thujaplicin complex have been calculated. The biomimetic cyclization of the silyl enol ether (191) to karahanaenone (192), using methyl-aluminium bis(trifluoroacetate) is almost quantitative (192) is also synthesized by thermolysis followed by desilylation of the silyl enol ether (193) which is readily available from l-bromo-2-methyl-2-vinylcyclopropane and isobutyraldehyde. Dehalogenation of 3-bromo-l-iodo-3-methylbutan-2-one with Zn-Cu couple on alumina in the presence of isoprene yields (192) and minor amounts of the isomers (194) and (195) however, dehalogenation with Fc2(CO)9 favours (195). Acetolysis of karahanaenol tosylate yields anticipated p-menthane derivatives and no filifolene. ... 

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. 

While normal Knorr conditions involve initial N-C bond formation, the overall reaction can also be accomplished under conditions which begin with C-C bond formation. Condensation of the dimethyl ketal of acetamidoacetone with silyl enol ethers give adducts which cyclize to pyrroles (Scheme 49) <88S38l). 

In contrast, the closely related palladium acetate-promoted intramolecular alkylation of alkenes by tri-methylsilyl enol ethers (Scheme 4)6,7 has been used to synthesize a large number of bridged carbocyclic systems (Table 1). In principle, this process should be capable of being made catalytic in palladium(II), since silyl enol ethers are stable to a range of oxidants used to carry the Pd° -> Pd11 redox chemistry required for catalysis. In practice, catalytically efficient conditions have not yet been developed, and the reaction is usually carried out using a full equivalent of palladium(II) acetate. This chemistry has been used in the synthesis of quadrone (equation 2).8 With the more electrophilic palladium(II) trifluoroace-tate, methyl enol ethers underwent this cyclization process (equation 3).9... 

The mechanism of the trimethylsilyl enol ether cyclization may involve formation of a palladium enol-ate which adds to the double bond. However, another mechanism is also possible involving attack of a palladium(II)-alkene complex upon the silyl enol ether double bond. 

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. 

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. 

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... 

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