Ketones methylene transfer

Synthesis of terminal olefine from ketones or esters via a Ti methylene transfer reagent. 

Although steroidal spiro oxiranes are difficult to obtain stereochemically pure by peracid epoxidations of exocyclic methylenes,the recently developed methylene transfer reagents, dimethylsulfonium methylide and di-methylsulfoxonium methylide in tetrahydrofuran, proved useful in the stereoselective transformation of steroid ketones to a- and -oxiranes, (87) and (88), respectively. ... 

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. ... 

Due to the high reactivity of sulfonium ylide 2 for a,P-unsaturated ketone substrates, it normally undergoes methylene transfer to the carbonyl to give the corresponding epoxides. However, cyclopropanation did take place when 1,1-diphenylethylene and ethyl cinnamate were treated with 2 to furnish cyclopropanes 53 and 54, respectively. 

Racemic 5-methyl-5 -(sodiomethyl)-A-(4-methylphenylsulfonyl)sulfoximine reacts with ketones to give an initial methylene transfer which produces an intermediate epoxide that is ring expanded to the oxctanc56. Application to 4-rerf-butylcyclohexanonc affords a single oxetane in 69% yield. While only achiral alkylidcne transfer reagents were utilized, in principle this reaction is amenable to the asymmetric synthesis of oxetanes. 

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. 

Dimethylsulfoxonium methylide (DMSY, also referred to as Corey s reagent) is a convenient methylene transfer reagent. It appears to be the most used sulfur ylide and a Tetrahedron Report [455] covers most of its chemistry (345 references). In contrast to dimethylsulfonium methylide, which must be used as soon as it is formed, DMSY is much more stable and can be stored for several days at room temperature. It is the reagent of choice in many instances. However, with a,(3-unsaturated ketones the two reagents react in different ways, as shown for cyclohexenone. 

METHYLENE KETONES AND ALDEHYDES BY SIMPLE, DIRECT METHYLENE TRANSFER 2-METHYLENE-1-OXO-l, 2,3,4-TETRAHYDRONAPHTHALENE... 

The procedure described herein demonstrates a general synthetic method to form a-methylene ketones by direct methylene transfer. A number of methods have been previously described and reviewed.2 3 The advantages of direct methylene transfer for the formation of a-methylene ketones are the aprotic, nearly neutral conditions utilized. Although the reaction is not regiospecific, it is highly sensitive to steric hindrance, and transfer occurs at the less hindered site of unsymmetrical ketones. The reaction has been applied to cyclic and acyclic ketones4 and extended to the synthesis of vinyl ketones3 and a-methylenealdehydes. It is not applicable to y- or 8-lactones, or strained cyclic ketones such as norcamphor or cyclobutanone. With cyclohexanone, cyclopentanone, or aldehydes as substrates, pre-formation of the iminium intermediate... 

METHYLENE KETONES BY SIMPLE, DIRECT METHYLENE TRANSFER 89... 

Usually reaction (25) is not applicable to ketones (193), although a ketone function in a steroid was replaced by methylene group with use of the Simmons-Smith reagent in the presence of excess zinc-copper couple (517). The reaction of bis(chloromethyl)zinc with benzophenone gives dioxoranes in a poor yield (546). The Simmons-Smith reagent undergoes the methylene transfer to the C=C bond of a,)3-unsaturated... 

Gras JL (1990) Methylene Ketones and Aldehydes by Simple, Direct Methylene Transfer 2-Methylene-l-oxo-l,2,3,4-tetrahydronaphthalene. In Organic Synthesis, Coll VII., p. 332. Wiley, New York, Chichester, Brisbane, Toronto, Singapore... 

Like S,S-Dimethyl-N-(p-toluenesulfonyl)sulfoximine and (dimethylamino)dimethyloxosulfonium tetrafluoroborate, the 7Y-tosylsulfilimine (1) reacts as a methylene transfer reagent, converting aldehydes and ketones to epoxides (eq 3). Thus (1) is heated at 80-90 °C for 0.5 h in DMSO in the presence of Sodium Hydride, and the resulting anion is allowed to react with carbonyl compounds to give 1-mono- and 1,1-disubstituted oxiranes in 46-56% yields. ... 

The methylene transfer reaction from ylides to ketones has been developed as a convenient synthetic method for obtaining oxiranes [24]. However, the experimental procedure is complex. For example, a THF solution of dimethylsulfonium-methylide (61) is obtained by treatment of trimethylsulfonium iodide (60) with BuLi in THF at 0°C, and after addition of the ketone the mixture is heated at 50-55 °C under nitrogen to yield the oxirane. Throughout the reaction and separation of the product, the organic solvent is essential [25]. 

This methylene transfer reaction can also be accomplished without using solvent, and the reaction product isolated from the reaction mixture by distillation. For example, a mixture of propiophenone (62a) (0.5 g), 60 (0.9 g) and powdered Bu/OK (0.5 g) was heated at 60 °C for 1 h in a flask, and then the reaction mixture was distilled using a Kugelrohr apparatus at 150°C under 18 mmHg, to give 63a (0.4 g, 75% yield). By a similar procedure, 63b-j were prepared from the corresponding ketones (62b-f), and the products were isolated by distillation to give the yields shown in Table 15-16 [25]. 

Methylene transfer from isopropylidenetriphenyl-l -phosphane to a,/i-unsaturated esters allows the preparation of gew-dimethyl-substituted cyclopropyl ketones, e.g. The ketones... 

Reactions. In a reaction reminiscent of methylene transfer with dimethyloxo-sulfonium methylide, EDSA reacts with ,/)-unsaturatcd aldehydes and ketones in aprotic solvents to give cyclopropanes in 65-90% yield.1 EDSA reacts with ,/3-unsaturated esters to give esters of acyclic polybasic acids.2... 

The differing behavior appears to be due to ease of enolization of the starting ketone. a,/3-Unsaturated ketones that do not enolize readily react normally those that enolize readily form an enolate complex with the reagent which prevents methylene transfer.5 (See also 2, 371-372.)... 

The nucleophilic methylene transfer reaction can be realized with substances other than aldehydes and ketones. Thus the reaction of benzalaniline (7) with either (3) or (ft) gives the nziridine (8) in 86% yield,... 

Trimethylsulfonium iodide undergoes ylid formation by reaction with 50% aqueous sodium hydroxide in the presence of catalytic tetrabutylammonium iodide [16]. The ylid thus formed reacts with aldehydes and ketones to form the corresponding epoxides (Eq. 14.7). The yields with aldehydes are considerably better than those with ketones. The fact that the reaction is slow (48 hours) may be due to the iodide of the catalyst. On the other hand, lauryldimethylsulfonium chloride undergoes reaction with ketones and aldehydes to yield epoxides under alkaline phase transfer conditions considerably more rapidly (6—10 hours). The enhanced rate of this methylene transfer reaction is probably due to the greater organic solubility of the lauryldimethylsulfonium cation [17]. Catalyst poisoning is observed with lauryldimethylsulfonium iodide. Similar reactions have been conducted under ion pair extraction conditions [18]. 

Likewise, trimethylsulfoxonium iodide undergoes ylid formation by reaction with 50% aqueous sodium hydroxide under phase transfer conditions. This ylid reacts with benzaldehyde to give styrene oxide, the expected product of methylene transfer in 20—30% yield (Eq. 14.8). The ylid, however, adds to o ,i3-unsaturated ketones to con-... 

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