Michael addition Of silyl enol ethers

Lewis acid-catalyzed Michael addition of silyl enol ether to a,P-unsaturated system. 

Michael reactions. This system promotes a Michael addition of silyl enol ethers to a,(3-unsaturated thiolesters, which are excellent Michael acceptors. Trityl salts are less effective, as are Lewis acids in combination with SnCl2. 

The blend SnC -ZnCli is an effective catalyst in the aldol reaction of silyl enol ethers with aldehydes (Eq. 87), acetals (Eq. 88), or ketones [122]. Product antilsyn ratios vary (32 69 to 89 11). The blend also catalyzes the Michael addition of silyl enol ethers with a,/3-unsaturated ketones (Eq. 89), yielding alkylation products (84-100 %) with anti selectivity antilsyn = 55 45 to 87 23). 

Tab. 8.27 Michael addition of silyl enol ethers and ketene silyl enol acetals...

In all instances, the Mukaiyama-Michael addition of silyl enol ethers is anti selective. For the most part, however, the selectivity is only modest. A... 

Na-, La-, and Re-exchanged zeolites have also been used as catalysts of the Michael reaction between silyl enol ethers and a, 6-unsaturated carbonyl compounds. This study, performed by Sasidharan et al. [87], focused mainly on the catalytic activity of titanium silicalite molecular sieves (TS-1 and TS-2). They found that TS-1 and TS-2 catalyze 1,4-Michael addition of silyl enol ethers and a,y5-unsatu-rated carbonyl compounds under anhydrous conditions. The zeolites tested as catalysts of this reaction, e. g. ReY, LaY, steamed zeolite Y, and cation-exchanged ZnZSM-5, were less active (or inactive). 

Asymmetric Michael Addition of Silyl Enol Ethers of Thiol Esters to Enones... 

The Yamamoto group developed tethered bis(8-quinolinolato)-Al complex 26-catalysed asymmetric Mukaiyama-Michael additions of silyl enol ethers to ot,p-unsaturated acyl phosphonates (Scheme 19.30). A range of tetra-substituted trimethylsilyl enol ethers reacted well and formed the adducts with all-carbon quaternary stereocentres in 80-99% enantiomeric excess. 

Scheme 19.30 A mmetric Mukaiyama-Michael additions of silyl enol ethers to a,p-unsaturated atyl phosphonate catalysed by bis(8-quinolinolato)-Al complex.

Diones are important intermediates in a number of syntheses of cyclopent-2-enones by aldol cyclization, and several routes to them have been published (see Review section). An attractive new approach involves the Michael addition of silyl enol ethers to nitro-olefins catalysed by Lewis acids, which leads directly to the 1,4-dione without isolation of nitroketone or related intermediates (Scheme 15). A feature of the method is that it is highly regiospecific in the selective formation of 1,4-diones with no double-bond migration in the silyl enol ether. 

The highly electrophilic cationic bis(8-quinolinolato)aluminum complex 407 enabled Yamamoto and coworkers to perform Mukaiyama-Michael additions of silyl enol ethers to crotonylphosphonates 406. The procedure was not only applicable to enol silanes derived from aryl methyl and alkyl methyl ketones (a-unsubstituted silicon enolates) but also to several cycfic a-disubstituted silyl enol ethers, as illustrated for the derivatives of a-methyl tetralone and indanone 405 in Scheme 5.105. Despite the steric demand of that substitution pattern, the reaction occurred in relatively high chemical yield with varying diastereoselectivity and excellent enantiomeric excess of the major diastereomer. The phosphonate residue was replaced in the course of the workup procedure to give the methyl esters 408. The protocol was extended inter alia to the silyl enol ether of 2,6,6-tetramethylcyclohexanone. The relative and absolute configuration of the products 408 was not elucidated [200]. 

Jung and coworkers reported AlBr3/Me3Al system as an effective mixed Lewis acid system for Diels-Alder reaction of sterically hindered dienophiles and dienes (Scheme 6.126) [150]. It was proposed that this reaction proceeds via Mukaiyama-Michael addition of silyl enol ether moiety to cyclohexenone followed by intramolecular Michael like process. 

A possible mechanism for the catalytic [2+2] cycloaddition reaction catalyzed by Tf2NH is depicted in Scheme 4.9. The Mukaiyama-type Michael addition of silyl enol ether to enoate catalyzed by silyl triflic imide aHbrds the corresponding silyl ketene acetal, and then it proceeds successively to the intramolecular silyl oxonium carbon to... 

Nitroalkenes are also reactive Michael acceptors under Lewis acid-catalyzed conditions. Titanium tetrachloride or stannic tetrachloride can induce addition of silyl enol ethers. The initial adduct is trapped in a cyclic form by trimethylsilylation.316 Hydrolysis of this intermediate regenerates the carbonyl group and also converts the ad-nitro group to a carbonyl.317... 

The use of oxygen-containing dienophiles such as enol ethers, silyl enol ethers, or ketene acetals has received considerable attention. Yoshikoshi and coworkers have developed the simple addition of silyl enol ethers to nitroalkenes. Many Lewis acids are effective in promoting the reaction, and the products are converted into 1,4-dicarbonyl compounds after hydrolysis of the adducts (see Section 4.1.3 Michael addition).156 The trimethylsilyl enol ether of cyclohexanone reacts with nitrostyrenes in the presence of titanium dichloride diisopropoxide [Ti(Oi-Pr)2Cl2], as shown in Eq. 8.99.157 Endo approach (with respect to the carbocyclic ring) is favored in the presence of Ti(Oi-Pr)2Cl2. Titanium tetrachloride affords the nitronates nonselectively. 

Among the best specific enol equivalents for Michael addition are silyl enol ethers that are rather beyond the scope of this book but are treated in detail in Strategy and Control. So the silyl enol ether 54 of the ester 53 adds to the enone 55 with Lewis acid catalysis to give a reasonable yield of the ketoester 56 considering that two quaternary centres are joined together.6... 

The Lewis acid-catalyzed conjugate addition of silyl enol ethers to a,y3-unsaturated carbonyl derivatives, the Mukaiyaraa Michael reaction, is known to be a mild, versatile method for carbon-cabon bond formation. Although the development of catalytic asymmetric variants of this process provides access to optically active 1,5-dicarbonyl synthons, few such applications have yet been reported [108], Mukiyama demonstrated asymmetric catalysis with BINOL-Ti oxide prepared from (/-Pr0)2Ti=0 and BINOL and obtained a 1,4-adduct in high % ee (Sch. 43) [109]. The enantioselectiv-ity was highly dependent on the ester substituent of the silyl enol ether employed. Thus the reaction of cyclopentenone with the sterically hindered silyl enol ether derived from 5-diphenylmethyl ethanethioate proceeds highly enantioselectively. Sco-lastico also reported that reactions promoted by TADDOL-derived titanium complexes gave the syn product exclusively, although with only moderate enantioselectiv-ity (Sch. 44) [110]. 

The Mukaiyama-Michael addition of silyl enolates to a, -unsaturated thioesters is promoted by an SbCl5-Sn(OTf)2 binary catalyst to afford d-keto thioesters with high anti selectivity (Scheme 14.23) [60]. The successive treatment of lactones with a ketene silyl acetal and silyl nucleophiles in the presence of an SbCl5-Me3SiCl-Snl2 ternary catalyst yields a-mono- and a/ -disubstituted cyclic ethers (Scheme 14.24) [61]. SbFs promotes the condensation of a,y5-unsaturated aldehydes and ketones with a-diazo-carbonyl compounds to give cyclopropane derivatives in high isomeric purity [62]. 

In some instances, particularly when a dependence of the stereochemistry on the double-bond geometry of either the acceptor or donor is observed, it appears likely that the stereochemistry-determining step is the initial conjugate addition. The stereochemical consequences of Lewis-acid-mediated additions of silyl enol ethers (116) and allylsilanes (117,118) have frequently been rationalized by open-extended transition states. Similar pathways seem likely with the Mukaiyama-Michael addition (vide infra) (77,79). 

In 1974,Mukaiyama and co-workers reported the first examples of Lewis acid-catalyzed Michael reactions between silyl enolates and a,p-unsaturated carbonyl compounds [33]. Evans and co-workers developed a catalytic asymmetric Michael reaction of silyl enol ethers of thiol esters to alkylidene malonates. For example, the reaction of alkylidene malonate 23 with 2.2 equiv of silyl enol ether 22 was carried out in the presence of 10 mol % of catalyst 25 and 2 equiv of hexa-fluoro-2-propanol (HFIP) in PhMe/CH2Cl2 (3 1) at -78 °C to give the expected adduct 24 in 93% ee (Scheme 5) [34]. Borane complex-catalyzed asymmetric Michael addition has also been reported [35]. 

Michael Reactions. The Michael reactions of silyl enol ethers or ketene silyl acetals with a,/3-unsaturated carbonyl compounds are catalyzed by Sc(OTf)3 to give the corresponding 1,5-dicarbonyl compounds in high yields after acid work-up (eq 5). When the crude adducts were worked up without acid, the synthetically valuable silyl enol ethers could be isolated. The catalyst can be recovered almost quantitatively and reused. Sc(OTf)3 also catalyzes 1,4-addition of PhMe2Si-ZnMe2Li to enones in the presence of 3 mol % of Me2Cu(CN)Li2. ... 

This reaction was first reported by Mukaiyama et al. in 1974. It is a Lewis acid-catalyzed Michael conjugate addition of silyl enol ether to o ,/3-unsaturated compounds. Therefore, it is generally referred to as the Mukaiyama-Michael reaction. Because this reaction is essentially a conjugate addition, it is also known as the Mukaiyama-Michael addition or Mukaiyama-Michael conjugate addition. This reaction is a mechanistic complement for the base-catalyzed Michael addition, j and often occurs at much milder conditions and affords superior regioselectivity. s Besides silyl enol ether, silyl ketene acetals are also suitable nucleophiles in this reaction.For the hindered ketene silyl acetals, the Lewis acid actually mediates the electron transfer from the nucleophiles to o ,/3-unsaturated carbonyl molecules.On the other hand, the Q ,j8-unsaturated compounds, such as 3-crotonoyl-2-oxazolidinone, alkylidene malonates, and a-acyl-a,/3-unsaturated phosphonates are often applied as the Michael acceptors. It has been found that the enantioselectivity is very sensitive to the reactant structures —for example, Q -acyl-Q ,j8-unsaturated phosphonates especially prefers the unique syn- vs anft-diastereoselectivity in this reaction. In addition,... 

A full report of the Michael reaction of silyl enol ethers with a/S-unsaturated ketones is noted a convenient method for the preparation of S-keto-esters entails titanium(iv)-promoted Michael-type additions of o-silylated keten acetals with ajS-unsaturated carbonyl compounds. ... 

The conditions used for the Mukaiyama-aldol type reactions employing InCh (see Section 8.2) were found by Loh et al. to be useful in Michael-type additions of silyl enol ethers to a,P-unsaturated carbonyl compounds [49] (Figure 8.25). 

Conjugate addition of allylsilanes to enones results in regiospe-cific introduction of the allyl group (eq 34). The reaction can be intramolecular (eq 35). TiCU or SnCU activates nitro alkenes for Michael addition with silyl enol ethers or ketene silyl acetals. The silyl nitronate product is hydrolyzed to a 1,4-diketone or -y-keto ester (eq 36). ... 

As an extension of this highly enantioselective Michael addition of silyl nitronates with a, p-unsaturated aldehydes, the reactions with cyclic a,p-unsaturated ketones as a Michael acceptor were also tested (Scheme 9.15). Cyclohexenone and cyclohepte-none were employed as a useful Michael acceptor with various silyl nitronates in the presence of catalyst (R,R)-6c, and gave the corresponding enol silyl ethers 28 with excellent stereoselectivities [30]. 

Highly enantioselective Michael addition of silyl nitronates (105) to cyclic o /3-unsaturated ketones (106 n = 0-2) has been accomplished by the utilization of N-spiro C2-symmetric chiral quaternary ammonium bifluoride (108) as an organocatalyst, offering a new route to the enol silyl ethers of scalemic y-nitro ketones (107 70-90% ee).156... 

Table 4.2 Asymmetric Michael addition of silyl nitronate 16 to a,/ -unsaturated aldehydes and cyclohexenone catalyzed by chiral quaternary ammonium bifluorides (/ ,/ )-15. Isolation of optically active enol silyl ethers 20 and 21.

Michael addition to a., -enoates- Aluminum ion-exchanged montmorillonite (Al-Mont1) is a very effective catalyst for Michael addition of silyl ketene acetals or silyl enol ethers to a,(3-enoates. In fact this heterogeneous catalyst is more effective than Lewis acids, which are generally required in a stoichiometric amount. It also facilitates Michael addition to a,p-enones.2 Examples ... 

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