Cyclohexanone methylide

Another difference between dimethylsulfonium methylide and dimethylsulfoxonium methylide concerns the stereoselectivity in formation of epoxides from cyclohexanones. Dimethylsulfonium methylide usually adds from the axial direction whereas dimethylsulfoxonium methylide favors the equatorial direction. This result may also be due to reversibility of addition in the case of the sulfoxonium methylide.92 The product from the sulfonium ylide is the result the kinetic preference for axial addition by small nucleophiles (see Part A, Section 2.4.1.2). In the case of reversible addition of the sulfoxonium ylide, product structure is determined by the rate of displacement and this may be faster for the more stable epoxide. 

Methylenecyclohexane oxide has been prepared by the oxidation of methylenecyclohexane with benzonitrile-hydrogen peroxide or with peracetic acid by treatment of 1-chlorocyclo-hexylmethanol with aqueous potassium hydroxide and by the reaction of dimethylsulfonium methylide with cyclohexanone. This reaction illustrates a general method for the conversion of ketones and aldehydes into oxiranes using the methylene-transfer reagent dimethyloxosulfonium methylide. The yields of oxiranes are usually high, and the crude products, in most cases, are of sufficient purity to be used in subsequent reactions (e.g., rearrangement to aldehydes) without further purification. 

The intermediacy of such oxaspiropentanes has been proposed in the addition of diazomethane to ketonesi0) and in the reaction of dimethyloxosulfonium methylide with a-haloketones55). In contrast to phosphorous ylides, sulfur ylides usually condense with carbonyl compounds to yield epoxides, thus reaction of the N,N-dimethylaminophenyloxosulfonium cyclopropylide 99 with cyclohexanone produced the dispiroepoxide 100 which rearranged to the spiro [3.5] nonan-l-one 101 upon isolation by gas chromatography, Eq. (29) S6). 

Figure 9.4 shows stereogenic epoxide formations with S ylides and a ketone. The substrate is a conformationally fixed—because it represents a trans-decalin—cyclohexanone. Both the dimethylsulfoxonium methylide and the dimethylsulfonium methylide convert this cyclohexanone into an epoxide diastereoselectively. As Figure 9.4 shows, the observed diastereoselectivities are complementary. The sulfoxonium methylide attacks the carbonyl carbon equatorially, whereas the attack by the sulfonium ylide takes place axially. 

The intermediacy of oxaspiropentanes was first proposed in some reactions i.e. the addition of diazomethane to cyclohexanone the reaction of dimethyloxosulphonium methylide with a-haloketones and the reaction of iV,iV-dimethylaminophenyloxo-sulphonium cyclopropylide with ketones . The parent oxaspiropentane (115) has been obtained from the p-nitroperbenzoic acid oxidation of a methylene chloride solution of methylenecyclopropane (69) at - 10°C (equation 82). ... 

It is known that dimethylsulfonium methylid (610) generally adds irreversibly to ketones and aldehydes. On the other hand, dimethylsulfoxonium methylid (612) adds reversibly to a carbonyl. This difference is reflected in their reactivity with cyclic ketones such as A-tert-huiyl cyclohexanone (617). Dimethylsulfonium methylid (610) reacted with 617 to give the oxirane with an axial exocyclic C—C bond (618), which is less stable than the product with an axial C—O bond (619).535 when 612 reacted with 617, however, the oxirane with the more stable equatorial exocyclic C—C bond (619) was formed.336 This is attributed to the reversibility of the addition of 612 to the ketone leading to the more stable oxirane, whereas 610 generated the intermediate salt irreversibly in what is essentially a kinetic process. 

Scheme 9.55. A representation of the reaction of 4-(l,l-dimethylethyl)cyclohexanone (4-f-butylcyclohexanone), with dimethylsulfonium methylide [(CH3)2S CH2 ]. Addition occurs primarily (ca. 80 20) from the axial direction and elimination of dimethyl sulfide [( 113)28] leads to the corresponding epoxide (oxirane).

In contrast, dimethylsulfoxonium methylide [(CH3)2S" (0)CH2 ] reacts with a,P-unsaturated ketones such as R-(-)-5-isopropenyl-2-methylcyclohex-2-en-l-one [R-(-)-carvone] to produce the cyclopropane product of conjugate addition (Scheme 9.57), 4-isopropenyl-l-methylbicyclo[4.1.0]heptan-2-one, and addition to 4-t-butyl-cyclohexanone produces the product resulting from equatorial attack (exclusively) (Scheme 9.58). 

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