Coupling of silyl enol ethers

The first promising asymmetric aldol reactions through phase transfer mode will be the coupling of silyl enol ethers with aldehydes utilizing chiral non-racemic quaternary ammonium fluorides,1371 a chiral version of tetra-n-butylammonium fluoride (TBAF). Various ammonium and phosphonium catalysts were tried138391 in the reaction of the silyl enol ether 41 of 2-methyl-l-tetralone with benzaldehyde, and the best result was obtained by use of the ammonium fluoride 7 (R=H, X=F) derived from cinchonine,1371 as shown in Scheme 14. 

Coupling of silyl enol ethers or boron enolates with Co2(CO)6-stabilized carbocations, generated via Lewis acid treatment of the appropriate propargyl ethers or aldehydes (aldol reaction), via the Nicholas reaction has been used to obtain large, highly strained, ring ketones. 

Oxidative coupling of silyl enol ethers as a useful synthetic method for carbon-carbon bond formation has been known for a long time. Several oxidants have been successfully applied to synthesize 1,4-diketones from silyl enol ethers, e.g. AgjO [201], Cu(OTf)2 [202], Pb(OAc)4 [203] and iodosobenzene/BFj EtjO [204]. Although some of these reagents above are known to react as one-electron oxidants, the potential involvement of silyl enol ether radical cations in the above reactions has not been studied. Some recent papers, however, have now established the presence of silyl enol ether radical cations in similar C-C bond formation reactions under well-defined one-electron oxidative conditions. For example, C-C bond formation was reported in the photoinduced electron transfer reaction of 2,3-dichIoro-1,4-naphthoquinone (98) with various silyl enol ethers 99 [205], From similar reactions with methoxy alkenes [206,207] it was assumed that, after photoexcitation, an ion radical pair is formed. 

Oxidative cyclization. The one-electron oxidant converts a silyl enol ether into electron acceptor. Interaction with a nucleophilic moiety in the same molecule leads to cyclized product. Unsymmetrical coupling of silyl enol ethers is also realized. 

Lewis acid catalyzed aldol coupling of silyl enol ethers with substituted cyclohexanone acetals showed an excellent preference for equatorial attack (95-l(X)%). In accord with this general rule, additions of a silyl enol ether to equatorially or axially substituted chiral spiroketals derived from -menthone gave 00% equatorial attack and formation of a single one of the four possible diastereoisomers (Scheme 9) 3, 4 -pjjjg methodology, followed by protection of the hydroxy group (X = OTHP, (XIPh.i) and alkaline removal of the chiral auxiliary was used for the synthesis of several natural products. ... 

Compared to iron(III), copper(ll), and especially manganese(III) and cerium(IV) other metals have found less application for the oxidative generation of radicals [1]. An exception is cobalt(III)-mediated radical reactions, based on the pioneering work of Iqbal et ah, which was recently reviewed [20] (see also Volume 1, Chapter 1.8). Some examples of oxidative couplings of silyl enol ethers 44 in the presence of silver(I) oxide were developed [21]. However, there is no advantage over copper(II)-mediated radical reactions, since the reagent is more expensive and the 1,4-diketones 45 are isolated in only moderate yield (Scheme 15). 

Scheme 15. Silver(l)-mediated oxidative coupling of silyl enol ethers 44...

Cross-coupling of silyl enol ethers and allylic silanes. The formation of y,S-unsaturated carbonyl compounds involves one-electron oxidation. 

Silyl enol ethers as electron-rich olefins are susceptible to one-electron oxidation by metallic oxidants [121-123]. The chemoselectivity in the oxidative transformations is controlled by the redox potentials of the reactants. VO(OEt)Cl2 induces chemose-lective homo- or cross-coupling of silyl enol ethers as shown in Scheme 2.58 to give the 1,4-diketones via regioselective carbon-carbon bond formation [124]. The more highly substituted the silyl enol ethers 68 are, the more readily they are oxidized. The silyl ketene acetals 73 are also readily oxidized and undergo cross-coupling with silyl enol ethers 69 to give the y-keto esters 74 (Scheme 2.59). 

T. Hayashi, Y. Katsuro, and M. Kumada, Tetrahedron Lett., 1980, 3915 Ni-catalysed coupling of silyl enol ether and Grignard reagent. 

In Xia s light-mediated coupling of silyl enol ethers to 1 (Scheme 11.28), the absenee of the nucleophile led to the formation of the metho - (27a) and hydrojgr-substituted intermediates (27b) in yields of 43% and 57% respectively in a similar fashion to that proposed by Klussmann for the copper-mediated CDC reaction, i.e., off-cycle equilibria that trap the reactive intermediate. The use of wet methanol gave complete conversion to the hemiaminal. The authors proposed that formation of these products prevented further irreversible oxidation to the corresponding amide 84. Instead, 27a and 27b are in equilibrium with the iminium ion and this competes with the irreversible carbon-carbon bond-forming reaction to give 27e upon addition of the nucleophile. 

SCHEME 11 Coupling of silyl enol ether via radical cations. 

Ryter, K. and Livinghouse, T, Dichloro(2,2,2-trifluoroethoxy)oxovanadium(V). A remarkably effective reagent for promoting one-electron oxidative cycHzation and unsymmetrical coupling of silyl enol ethers, /. Am. Chem. Soc., 120, 2658, 1998. 

Cyclic and acyclic silyl enol ethers can be nitrated with tetranitromethane to give a-nitro ketones in 64-96% yield (Eqs. 2.42 and 2.43).84 The mechanism involves the electron transfer from the silyl enol ether to tetranitromethane. A fast homolytic coupling of the resultant cation radical of silyl enol ether with N02 leads to a-nitro ketones. Tetranitromethane is a neutral reagent it is commercially available or readily prepared.85... 

Schafer reported that the electrochemical oxidation of silyl enol ethers results in the homo-coupling products. 1,4-diketones (Scheme 25) [59], A mechanism involving the dimerization of initially formed cation radical species seems to be reasonable. Another possible mechanism involves the decomposition of the cation radical by Si-O bond cleavage to give the radical species which dimerizes to form the 1,4-diketone. In the case of the anodic oxidation of allylsilanes and benzylsilanes, the radical intermediate is immediately oxidized to give the cationic species, because oxidation potentials of allyl radicals and benzyl radicals are relatively low. But in the case of a-oxoalkyl radicals, the oxidation to the cationic species seems to be retarded. Presumably, the oxidation potential of such radicals becomes more positive because of the electron-withdrawing effect of the carbonyl group. Therefore, the dimerization seems to take place preferentially. 

Tin enolates of ketones can be generated by the reaction of the enol acetate 733 with tributyltin methoxide[601] and they react with alkenyl halides via transmetallation to give 734. This reaction offers a useful method for the introduction of an aryl or alkenyl group at the o-carbon of ketones[602]. Tin enolates are also generated by the reaction of silyl enol ethers with tributyltin fluoride and used for coupling with halides[603]. 

Dimerization of Silyl Enol Ethers or of Lithium Enolates 3/O-De-trimethylsilyM / C-coupling... 

Coupling with silyl enol ethers. Alkenes can be prepared by coupling of Grignard reagents with silyl enol elbers. Nickel aectylacetonate is the most active... 

Since silyl enol ethers have a silyl group ji to the jr-system, anodic oxidation of silyl enol ethers takes place easily. In fact, anodic oxidation of silyl enol ethers proceeds smoothly to provide the homo-coupling products, 1,4-diketones (equations 37 and 38)42. This dimerization of the initially generated cation radical intermediate is more likely than the reaction of acyl cations formed by two electron oxidation of unreacted silyl enol ethers in these anodic reactions. 

This vanadium method enables the cross-coupling only in combinations of silyl enol ethers having a large difference in reactivity toward radicals and in their reducing ability. To accomplish the crosscoupling reaction of two carbonyl compounds, we tried the reaction of silyl enol ethers and a-stannyl esters based on the following consideration. a-Stannyl esters (keto form) are known to be in equilibrium with the enol form such as stannyl enol ethers, but the equilibrium is mostly shifted toward the keto form. When a mixture of an a-stannyl ester such as 45 and a silyl enol ether is oxidized, it is very likely that the stannyl enol ether will be oxidized preferentially to the silyl enol ether. The cation radical of 45 apparently cleaves immediately giving an a-keto radical, which reacts with the silyl enol ether selectively because of the low concentration of the stannyl enol... 

One case has been reported where simple photolysis of a crude silyl enol ether has generated the a-hydroxy derivative (66 to 67). This was considered to arise through coupling of the enol ether with... 

Coupling with Silyl Enol Ethers and Silyl Ketene Acetals. Silyl enol ethers can couple to the bromooxazinone to give both the syn and anti diastereomers. - The reaction can proceed via the Sn 1 mechanism discussed above or by a Lewis acid assisted Sn2 displacement of the bromide. The reaction conditions can be manipulated to favor the SnI (stronger Lewis acids, more polar solvents) or Sn2 path (weaker Lewis acids, less polar solvents) (eq 12 and eq 13). ... 

Aldol-type condensation of silyl enol ethers with acetals under the influence of la is rather familiar. Unlike the Mukaiyama aldol reaction, 1-5 mol % loading of la is enough to complete the coupling reaction under mild conditions [20]. This transformation is applicable to the synthesis of a wide variety of / -alkoxy carbonyl substrates and has three characteristic features ... 

Conversion of silyl enol ethers of ketones to a,p-unsaturated ketones or coupling to 1,4-diketones by means of Ag20 or Pd(ll) for a one pot conversion of ketones, aldehydes or alcohols to a,0-unsaturated ketones (aldehydes) with iodoxybenzoic add see Nicolaou. 

Nucleophilic displacement of chlorine, in a stepwise manner, from cyanuric chloride leads to triazines with heteroatom substituents (see Section 6.12.5.2.4) in symmetrical or unsymmetrical substitution patterns. New reactions for introduction of carbon nucleophiles are useful for the preparation of unsymmetrical 2,4,6-trisubstituted 1,3,5-triazines. The reaction of silyl enol ethers with cyanuric chloride replaces only one of the chlorine atoms and the remaining chlorines can be subjected to further nucleophilic substitution, but the ketone produced from the silyl enol ether reaction may need protection or transformation first. Palladium-catalyzed cross-coupling of 2-substituted 4,6-dichloro-l,3,5-triazine with phenylboronic acid gives 2,4-diaryl-6-substituted 1,3,5-triazines <93S33>. Cyanuric fluoride can be used in a similar manner to cyanuric chloride but has the added advantage of the reactions with aromatic amines, which react as carbon nucleophiles. New 2,4,6-trisubstituted 1,3,5-triazines are therefore available with aryl or heteroaryl and fluoro substituents (see Section 6.12.5.2.4). 

Enoxysilacyclobutanes. These compounds can be prepared by Wurtz coupling of 3-chloropropyltrichlorosiIane with Mg in ether. Introduction of one alkyl group is accomplished by reaction with an organolithium reagent, and the silyl chloride can then be used for the formation of silyl enol ethers. Such 0-silyl ketene acetals are extremely reactive in aldol condensations with aldehydes without catalysts. The reaction is syn-selective. An asymmetric version uses silyl ketene acetals bearing a chiral Si-alkoxy (e.g., 8-phenylmenthoxy) group instead of an alkyl substituent. 

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