Corey/Chaykovsky cyclopropanation

Scheme 2.40 Enantioselective Corey-Chaykovsky cyclopropanation of enones with the use of chiral lanthanum(m) lithium(i)/sodium(i) tris(biphenoxide).

A diastereoselective synthesis of cyclopropanes combines an aryl acetonitrile, ArCH2CN, with an aldehyde, RCHO, to give 100% cis-product (116) as a racemic mixture of enantiomers. " The one-pot reaction shows yields of 45-93% covering a wide range of substrates Ar includes 3-pyridyl and 2-thiophenyl, and the aldehyde can be aromatic or aliphatic. The reaction sequence consists of a Knoevenagel condensation followed by a Corey/Chaykovsky cyclopropanation. 

The Corey-Chaykovsky reaction entails the reaction of a sulfur ylide, either dimethylsulfoxonium methylide (1, Corey s ylide, sometimes known as DMSY) or dimethylsulfonium methylide (2), with electrophile 3 such as carbonyl, olefin, imine, or thiocarbonyl, to offer 4 as the corresponding epoxide, cyclopropane, aziridine, or thiirane. ... 

Epoxidation of aldehydes and ketones is the most profound utility of the Corey-Chaykovsky reaction. As noted in section 1.1.1, for an a,P-unsaturated carbonyl compound, 1 adds preferentially to the olefin to provide the cyclopropane derivative. On the other hand, the more reactive 2 generally undergoes the methylene transfer to the carbonyl, giving rise to the corresponding epoxide. For instance, treatment of P-ionone (26) with 2, derived from trimethylsulfonium chloride and NaOH in the presence of a phase-transfer catalyst Et4BnNCl, gave rise to vinyl epoxide 27 exclusively. ... 

A weak base such as glycine added to [HMIMjPFg has also been reported to catalyze a Knoevenagel reaction of malononitrile and benzaldehyde 110). A KOH-treated [BMIMjPFg also provides a suitable medium for the Corey-Chaykovsky epoxidation of enones and cyclopropanation of aldehydes using trimethyl sulfonium iodide (///). 

The reaction of the Corey-Chaykovsky Reagent with enones is a 1,4-addition that is followed by ring closure to give a cyclopropane ... 

One of the steps in the highly stereoselective total synthesis of ( )-isovelleral involved the cyclopropanation of an a, 3-unsaturated ketone using dimethylsulfoxonium methylide. C.H. Heathcock and co-workers studied this transformation under various conditions and they found that THF at ambient temperature gave superior results to DMSO, which is the most common solvent for the Corey-Chaykovsky cyciopropanation. 

Related reactions Corey-Chaykovsky epoxidation and cyclopropanation ... 

Meyers and coworkers [327, 1494] have applied the Corey-Chaykovsky reaction to chiral bicyclic lactams 1.92. The face selectivity of the reaction of CH2=S(0)Me2 with this Michael acceptor depends upon the nature of the angular substituent R When R1 = H, the cyclopropane is introduced selectively on the exo... 

Substituted (2/J,3/J)-ethyl azmdine-2-carboxylates are synthesized from imines and ethyl diazoacetate. The catalyst system is composed from (PhOlsB and (Sl-VAPOL." Asymmetric cyclopropanation of electron-deficient aUcenes can be carried out with a Co(II) porphyrinate in which chiral substituents are set in two disjunct mero-positions. The presence of 129 or 130 renders the Corey-Chaykovsky method for cyclopiopana-tion of conjugated aldehydes asymmetric. Thus it is easy to access (15,2/J)-2-formylcyclo-propyl ketones from enals and acymethylsulfonium ylides. ... 

Corey-Chaykovsky epoxidation—additive oxidation Cyclopropanation [(1 + 2) + (1 + 2)]... 

The Corey-Chaykovsky reaction will be used to cyclopropanate your chalcone from Experiment 61. The reaction involves the reaction of trimethylsulfoxonium iodide and potassium fcrf-butoxide in anhydrous dimethylsulfoxide (DMSO). The reaction is stirred at room temperature for 1 hr. For example, frans-chalcone (1,3-diphenyl-2-propen-l-one) produces an 88% yield of the cyclopropanated product. You will analyze your product by NMR and infrared spectroscopy. 

Other modifications or variations of the Wittig reaction exist. Some are more analogous than others. For example, sulfur ylides have also been investigated and the Corey-Chaykovsky reaction employs their use. However, olefmation is not the outcome of this reaction sequence. The nucleophilic addition of ylide 112 to the carbonyl compound 30 gives rise to the corresponding epoxides 113. Furthermore, reaction with imines produces aziridines and cyclopropanes are formed with a,[3-unsaturated carbonyl systems. 

For example, the first chiral phosphine-catalyzed [3+2] cycloaddition has been reported in 1997 by Zhang s group [95] (Schane 6.33A), and a variety of different chiral phosphine catalysts and apphcations thereof have been reported over the last years [94], Besides monofunctional catalysts, also bifunctional phosphines like the amino add-derived 197 have been successfully designed and apphed for challenging reactions recently [96], and this additional noncova-lent coordination site turned out to be highly beneficial to obtain good selectivities in these transformations. Chiral sulfides have emerged as powerful catalysts to facihtate catalytic stereoselective Corey-Chaykovsky-type epoxida-tion, cyclopropanation, or aziridination reactions (for an early example in this field, see Scheme 6.33C) [97,98],... 

In Corey and Chaykovsky s initial investigation, a cyclic ylide 79 was observed from the reaction of ethyl cinnamate with ylide 1 in addition to 32% of cyclopropane 53. In a similar fashion, an intermolecular cycloaddition between 2-acyl-3,3-bis(methylthio)acrylnitrile 80 and 1 furnished 1-methylthiabenzene 1-oxide 81. Similar cases are found in transformations of ynone 82 to 1-arylthiabenzene 1-oxide 83 and N-cyanoimidate 84 to adduct ylide 85, which was subsequently transformed to 1-methyl-lX -4-thiazin-l-oxide 86. ... 

Treatment of (R)-carvone with racemic lithiated 2b gave a mixture of the diastereomeric 1,2-adducts 80 at -78 °C and the diastereomeric cyclopropanes 81a,b, and the double addition product 82 as a single diastereoisomer at room temperature. The diastereoselectivity in the case of 81 was similar to that obtained when (5)-2b was employed. Compound 81 has been prepared as a single diastereoisomer by Corey and Chaykovsky.60... 

Scheme 9.57. A representation of the reaction between dimethylsnlfoxoninm methylide [(CH3)2S (0)CH2 ] and the naturally occurring terpenone (Chapter 11), R-(-)-5-isopropenyl-2-methylcyclohex-2-en-l-one [R-(-)-carvone] to produce the corresponding cyclopropane. (See Corey, E. J. Chaykovsky, M. /. Am. Chem. Soc., 1962,84 3782.)...

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