Ketenes Michael addition

High enantioselectivities may be reached using the kinetic controlled Michael addition of achiral tin enolates, prepared in situ, to a,/i-unsaturated carbonyl compounds catalyzed by a chiral amine. The presence of trimethylsilyl trifluoromethanesulfonate as an activator is required in these reactions236. Some typical results, using stoichiometric amounts of chiral amine and various enolates are given below. In the case of the l-(melhylthio)-l-[(trimethylsilyl)thio]ethene it is proposed that metal exchange between the tin(II) trifluoromethanesulfonate and the ketene acetal occurs prior to the 1,4-addition237,395. 

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. 

The controlled polymerization of (meth)acrylates was achieved by anionic polymerization. However, special bulky initiators and very low temperatures (- 78 °C) must be employed in order to avoid side reactions. An alternative procedure for achieving the same results by conducting the polymerization at room temperature was proposed by Webster and Sogah [84], The technique, called group transfer polymerization, involves a catalyzed silicon-mediated sequential Michael addition of a, /f-unsaluralcd esters using silyl ketene acetals as initiators. Nucleophilic (anionic) or Lewis acid catalysts are necessary for the polymerization. Nucleophilic catalysts activate the initiator and are usually employed for the polymerization of methacrylates, whereas Lewis acids activate the monomer and are more suitable for the polymerization of acrylates [85,86]. 

Michael addition in the absence of any catalytic agent has been reported for dialkyl and diaryl phosphites and thiophosphites with a-cyanoacrylate esters and a-cyanoacrylic acid.444 Yields of the conjugate addition products were moderate to good. The regiochemistry of this process is the opposite of that previously reported for similar additions to ketene acetals, the latter presumably proceeding by initial protonation of the distal olefinic carbon site.445... 

In contrast to these transformations, Michael additions of simple enolates to acceptor-substituted dienes often yield mixtures of 1,4- and 1,6-addition products27-30. For example, a 70 30 mixture of 1,4- and 1,6-adducts was isolated from the reaction of the lithium enolate of methyl propionate with methyl sorbate30. This problem can be solved by using the corresponding silyl ketene acetal in the presence of clay montmorillonite as acidic promoter under these conditions, almost exclusive formation of the 1,4-addition product (syn/anti mixture) was observed (equation ll)30. Highly regioselective 1,4-additions... 

Group-transfer polymerizations make use of a silicon-mediated Michael addition reaction. They allow the synthesis of isolatable, well-characterized living polymers whose reactive end groups can be converted into other functional groups. It allows the polymerization of alpha, beta-unsaturated esters, ketones, amides, or nitriles through the use of silyl ketenes in the presence of suitable nucleophilic catalysts such as soluble Lewis acids, fluorides, cyanides, azides, and bifluorides, HF. ... 

In contrast, phosphine oxides were later applied in Michael additions of silyl ketene acetals to cycHc and acychc a,P-unsaturated ketones promoted by 59a as scavengers of any catalytically active Me3Si species formed during the reaction (Scheme 5.80) [151]. Further, this methodology now allows the realization of an... 

Mukaiyama-Michael addition of a chiral ketene acetal to nonprochiral vinyl ketones gives products of 72-75% ee.145 A chirally modified glycine derivative (Schiff-base) adds to vinylic phosphorus compounds to yield, after hydrolysis, products with 54-85% ee.146 Another chiral glycine equivalent was used for the preparation of homochiral proline derivatives via diastereoselective addition to a,3-unsatu-rated aldehydes and ketones.147-148... 

Keywords ketene silyl enol edier, ,/(-unsaturated ketone, Michael addition, indium trichloride, 1,5-dicarbonyl compound... 

In 2008 Yang and coworkers have reported an efficient synthesis of substituted a-alkilidene-fi-lactams via aNaOH- promoted intramolecular aza-Michael addition of a-carbamoyl, a-(l-chlorovinyl) ketene-S,S-acetals and subsequent nucleophilic vinylic substitution reaction in alcoholic media (Scheme 90), [198]. 

Michael additions. Michael addition of nitroalkanes to vinyl sulfoxides (equation 1) and to ketene diethyl dithioacetal S-monooxide (equation II) proceeds in high yield when DBU is used as base. The adducts can be converted into a,/J-enals.1... 

Michael addition.1 This ketene silyl acetal undergoes Michael addition to a,fl-enones in acetonitrile in the absence of a Lewis acid to afford the corresponding O-silylated Michael adduct in high yield. These O-silyl enolates undergo site-specific electrophilic substitution. This sequence was used for vicinal dialkylation of cyclohexanone (equation I) and of cyclopentanone. It is particularly useful for synthesis of methyl jasmonate and related compounds from cyclopentenone. 

MICHAEL ADDITIONS Alumina. Aluminum chloride. Cesium fluoride-Silicon(lV) cthoxidc. 1,4-Diazabicyclo[2.2.2]octanc. l,8-Diazabicyclo[5.4.0]-7-undecene. Ketene r-butyldimethylsilyl methyl acetal. Lithium acetylides. (S)-( + )-2-Mcthoxymethylpyrrolidine. Methyl lithiodithioacetate. Methyl (phcnylsulfinyl)acetate. Methyl 2-trimcthylsilylacrylate. Nickel carbonyl. Organocopper reagents. 8-Phenylmcnthol. Phenyl 2-(trimethylsilyl)ethynyl sulfone. Tetra-n-butylammonium fluoride. Tiianium(IV) chloride. 3-Triisopropylsilylpropynyllithiuni. Zirconium(IV) n-propoxiilc... 

Recently, Mukaiyama and co-workers prepared cinchona alkaloid-derived chiral quaternary ammonium phenoxide-phenol complex 23 and used it as an efficient organocatalyst for the tandem Michael addition and lactonization between oc,f-unsaturated ketones and a ketene silyl acetal 24 derived from phenyl isobutyrate. This approach permits the highly enantioselective synthesis of a series of 3,4-dihydropyran-2-ones (25), as shown in Scheme 4.11 [17]. 

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 ... 

Michael additions of ketene alkyl silylacetals. In the presence of TiCl, (1 equiv.) these acetals undergo Michael addition to ethyl propiolate via a titanate intermediate. 

Roush WR, Hall SE (1981) Studies on the total synthesis of chlorothricol-ide stereochemical aspects of the intramolecular Diels-Alder reactions of methyl undeca-2,8,10-trienoates. J Am Chem Soc 103 5200-5211 Rudler H, Denise B, Xu Y, Parlier A, Vaissermann J (2005) Bis(trimethylsilyl)-ketene acetals as C,0-dinucleophiles one-pot formation of polycyclic y-and 8-lactones from pyridines and pyrazines. Eur J Org Chem 3724-2744 Sekino E, Kumamoto T, Tanaka T, Ikeda T, Ishikawa T (2004) Concise synthesis of anti-HIV-1 Active (+)-inophyllum B and (+)-calanolide A by application of (-)-quinine-catalyzed intramolecular oxo-michael addition. J Org Chem 69 2760-2767... 

Michael addition of ketene sUyl acetals. TASF catalyzes the conjugate addition of ketene silyl acetals to enones in THF at room temperature. A similar addition can be effected without a catalyst in a polar solvent, acetonitrile at 55° (ref. 2) or CH,NO, at 25°, in the case of some less hindered ketene silyl acetals. The addition shows no dia-stcreoselection. The adducts can be alkylated to provide 2,3-disubstitutcd cycloalkanoncs as a 1 1 mixture of two diastereomers (both probably Irons). 

Although the Michael addition of metal ynolates to a,/ -unsaturated carbonyl compounds is expected to give six-membered cycloadducts, 1,2-addition to carbonyl groups usually precedes 1,4-addition. The cycloaddition of the lithium-aluminum ate complex of silyl-substimted ynolate 112 with ethyl benzylideneacetoacetate (113), which is doubly activated by the ester and keto functions, gives the y-lactone 114 via a [4 4- 2] type cycloaddition (equation 46). Diethyl benzylidenemalonate (115) affords the uncyclized ketene 116 by reaction with 112 (equation 47). This could be taken as evidence for a stepwise mechanism for equation 46. ... 

Monomer addition, which is catalyzed by anions like HF , F , CN or selected Lewis acids, proceeds by Michael addition in which the silyl group is transferred to the new monomer unit to renew the terminal silyl ketene acetal. (A Michael reaction, in general, is the addition of an enolate to an a,/9-unsaturated carbonyl compound.)... 

Isoxazolidin-5-ones 549 can be prepared by 1,3-dipolar cycloaddition of nitrones and ketenes or ynolates or, alternatively, by cyclization of 3-(hydroxyamino)propanoates 550 in turn obtained by addition of ketene acetals to nitrones or by Michael addition of hydroxylamine derivatives to a,/3-unsaturated esters (Scheme 132). 

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