Michael silyl enol ethers

Hydrazoic acid can be added to certain Michael-type substrates (Z is as defined on p. 975) to give 3-azido compounds. The reaction apparently fails if R is phenyl. Ammonia also adds to enol ethers CH2=CHOR to give CH3—CH(OR)N3, and to silyl enol ethers, but it does not add to ordinary alkenes unless a Lewis acid catalyst, such as TiCU, is used, in which case good yields of azide can be obtained. Ammonia can also be added indirectly to ordinary alkenes by azidomercuration, followed by demercuration, analogous to the similar procedures mentioned in... 

Methyl 1-phenylthiovinyl ketones can also be used as enones in kinetically controlled Robinson annulation reactions, as illustrated by Entry 6. Entry 7 shows a annulation using silyl enol ether as the enolate equivalent. These reactions are called Mukaiyama-Michael reactions (see Section 2.6.3). 

Conditions for effecting conjugate addition of neutral enolate equivalents such as silyl enol ethers in the presence of Lewis acids have been developed and are called Mukaiyama-Michael reactions. Trimethylsilyl enol ethers can be caused to react with electrophilic alkenes by use of TiCl4. These reactions proceed rapidly even at -78° C.308... 

Initial stereochemical studies suggested that the Mukaiyama-Michael reaction proceeds through an open TS, since there was a tendency to favor anti diastereoselec-tivity, regardless of the silyl enol ether configuration.312... 

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... 

Under classical Mukaiyama conditions, silyl enol ether 2-372 and the Michael acceptors 2-373 and 2-374 underwent a twofold 1,4-addition to form an enolate in which an ideal set-up exists for an intramolecular aldol reaction. This led to 2-375 with the desired structural core of 2-376 in an overall yield of 42%. 

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. 

Michael addition of various a,fi-unsaturated carbonyl compounds to silyl enol ether catalyzed by Ti-beta and TS-1... 

The utilization of copper complexes (47) based on bisisoxazolines allows various silyl enol ethers to be added to aldehydes and ketones which possess an adjacent heteroatom e.g. pyruvate esters. An example is shown is Scheme 43[126]. C2-Symmetric Cu(II) complexes have also been used as chiral Lewis acids for the catalysis of enantioselective Michael additions of silylketene acetals to alkylidene malonates[127]. 

Michael reactions of silyl enol ethers.1 2 3 The silyl enol ether of 1-acetylcy-clohexene (1) undergoes two consecutive Michael reactions with an a,p-enone or -enal in the presence of this Lewis acid to form 1-decalones. 

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

The asymmetric allylic C-H activation of cyclic and acyclic silyl enol ethers furnishes 1,5-dicarbonyl compounds and represents a surrogate of the Michael reaction [136]. When sufficient size discrimination is possible the C-H insertion is highly diastereoselective, as in the case of acyclic silyl enol ether 193 (Eq. 22). Reaction of aryldia-zoacetate 192 with 193 catalyzed by Rh2(S-DOSP)4 gives the C-H insertion product 194 (>90% de) in 84% enantiomeric excess. A second example is the reaction of the silyl enol ether 195 with 192 to form 196, a product that could not be formed from the usual Michael addition because the necessary enone would be in its tautomeric naphthol form (Eq. 23). 

Michael adducts can also be obtained with this catalyst from the reaction of a,fi-unsuturaied ketones with silyl enol ethers. 

CsF in the presence ol tetraalkoxysilanes also effects Michael addition of ketones lo a,/ -unsaturaied ketones, esters, and nitriles. Presumably the enolate is generated and is converted by Si(OR)a into the silyl enol ether, which reacts in situ.2 Examples ... 

Michael reaction. In the presence of (C6H5)3CC104, silyl enol ethers undergo Michael addition to a,p-enones. The adducts can be isolated or rearranged to 1,5-diketones by base. The intermediates cannot be isolated from reactions catalyzed by TiCl4 or CsF. 

Michael-aldol reactions.1 In the presence of (C6H5)3CC104, the conjugate adducts of silyl enol ethers to enones can undergo aldol reactions to provide y-acy 1-8-hydroxy ketones. 

Use of the preformed Z-silyl enol ether 18 results in quite substantial anti/syn selectivity (19 20 up to 20 1), with enantiomeric purity of the anti adducts reaching 99%. The chiral PT-catalyst 12 (Schemes 4.6 and 4.7) proved just as efficient in the conjugate addition of the N-benzhydrylidene glycine tert-butyl ester (22, Scheme 4.8) to acrylonitrile, affording the Michael adduct 23 in 85% yield and 91% ee [10]. This primary product was converted in three steps to L-ornithine [10]. The O-allylated cinchonidine derivative 21 was used in the conjugate addition of 22 to methyl acrylate, ethyl vinyl ketone, and cydohexenone (Scheme 4.8) [12]. The Michael-adducts 24-26 were obtained with high enantiomeric excess and, for cydohexenone as acceptor, with a remarkable (25 1) ratio of diastereomers (26, Scheme 4.8). In the last examples solid (base)-liquid (reactants) phase-transfer was applied. 

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... 

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>. 

The use of simple silyl enol ethers for the asymmetric organocatalyzed Mukaiyama-Michael addition was recently reported. For reference, see W. Wang, H. Li, J. Wang, Org. Lett. 

The best catalyst for this transformation was AgSbFg (10 mol%), and (3-ketoesters, malonates, and silyl enol ethers have been used for the nucleophilic addition on the pyridinium intermediate DD. The dihydroisoquinolines 48 have been further used in several reactions in order to assemble the framework of various alkaloids. One example is given in the formation of dihydroisoquinoline 49, bearing a pendent a, 3-unsaturated ketone. Compound 49 can rearrange to the tetracycle 50 (related to the core structure of karachine, Scheme 5.23), using TMSOTf, via a tandem Michael addition-Mannich reaction process (intermediates EE and FF). 

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. 

Disilylation of enones.1 In the presence of Pd[P(C6H5),]4, this disilane undergoes 1,4-addition to a,p-enones to give -y-(phenyldichlorosilyl) silyl enol ethers, which can be converted into lithium enolates by exchange with methyllithium. The reaction can provide 3-hydroxy ketones. The Michael addition is enantioselective when catalyzed by Cl2Pd[( + )-BINAP] (12, 53-57). 

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