And dimethylsulfonium methylid

Aldehydes and ketones can be converted to epoxides in good yields with the sulfur ylids dimethyloxosulfonium methylid (60) and dimethylsulfonium methylid (61). For most purposes, 60 is the reagent of choice, because 61 is much less... 

Dialkylamino-2,3-dihydrothieno[2,3-6]thiophenes are assumed intermediates as in Scheme 4. Such thiophenes are also formed in the reaction between thione (85) and dimethylsulfonium methylide (Scheme 5). ... 

Corey, E. J., Chaykovsky, M. Dimethyloxosulfonium methylide and dimethylsulfonium methylide. Formation and application to organic synthesis. J. Am. Chem. Soc. 1965, 87,1353-1364. 

Construction of the suitably substituted geranic acid for making the furan ring has been effected too. For example, Poulter et al. have prepared the substituted geranate 865 by reaction of 4-methyl-3-pentenylcopper with the acetylenic ester 866. The ester 865 then underwent cyclization in the presence of acid to the lactone 867, related to scobinolide (161), and the action of acid on the lactol produced from 867 with diisobutylaluminum hydride gave perillene (849). The lactone 867 has also been prepared by a slightly different method the C9 alcohol 868 was made (in poor yield) from isobutenol and prenyl chloride with butyllithium. The extra carbon atom was introduced by the action of sodium cyanide on the epoxide of 868, and hydrolysis of the cyano group followed by dehydration yielded the lactone 867. The dimethylthioacetal of 867 has been used to synthesize perillene (849). This thioacetal was made from the suitably substituted ketene thioacetal 869 and dimethylsulfonium methylide. Thus the ketene thioacetal 870 (readily prepared from acetone, carbon disulfide, and sodium amylate, followed by methylation °) can be prenylated with lithium... 

The salt is prepared by quaternization of (-)-ephedrine with methyl bromide. Asymmetric oxirane synthesis. Japanese chemists have reported asymmetric synthesis of 2-phenyloxirane from benzaldehyde and dimethylsulfonium methylide generated from tiimethylsulfonium iodide in 50% NaOH with the chiral phase-transfer catalyst (-)-N,N-dimethylephedrinium bromide (1). 

Ylides derived from sulfur rank next in importance to those derived from phosphorus in synthetic utility. The first widely used sulfur ylides were dimethyloxo-sulfonium methylide (4) and dimethylsulfonium methylide (5). The preparations of these compounds are outlined below ... 

Bravo et al. studied the reaction of various ylides with monooximes of biacetyl and benzil. Dimethylsulfonium methylide and triphenylarsonium methylide gave 2-isoxazolin-5-ol and isoxazoles, with the former being the major product. Triphenylphosphonium methylide and dimethyloxosulfonium methylide gave open-chain products (Scheme 135) (70TL3223, 72G395). The cycloaddition of benzonitrile oxide to enolic compounds produced 5-ethers which could be cleaved or dehydrated (Scheme 136) (70CJC467, 72NKK1452). 

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. ... 

In the initial report by Corey and Chaykovsky, dimethylsulfonium methylide (2) reacted smoothly with benzalaniline to provide an entry to 1,2-diphenylaziridine 67. Franzen and Driesen reported the same reaction with 81% yield for 67. In another example, benzylidene-phenylamine reacted with 2 to produce l-(p-methoxyphenyl)-2-phenylaziridine in 71% yield. The same reaction was also carried out using phase-transfer catalysis conditions.Thus aziridine 68 could be generated consistently in good yield (80-94%). Recently, more complex sulfur ylides have been employed to make more functionalized aziridines, as depicted by the reaction between A -sulfonylimine 69 with diphenylsulfonium 3-(trimethylsilyl)propargylide (70) to afford aziridine 71, along with desilylated aziridine 72. ... 

Recently, in connection with the use of sulfur ylides in polymerization, Kondo and his coworkers [64] attempted to use diphenylsulfonium bis(methoxycarbo-nyl)methylide (DPSY) (Schemes 27, 29) methylphen-ylsulfonium bis-(methoxycarbonyl)methylide (MPSY) (Scheme 30) and dimethylsulfonium bis (methoxycar-bonyl) methylide (DMSY) (Scheme 31) as photoinitiators for the polymerization of MMA and styrene. They concluded that DPSY and MPSY are effective photoini-... 

In the third sequence, the diastereomer with a /i-epoxide at the C2-C3 site was targeted (compound 1, Scheme 6). As we have seen, intermediate 11 is not a viable starting substrate to achieve this objective because it rests comfortably in a conformation that enforces a peripheral attack by an oxidant to give the undesired C2-C3 epoxide (Scheme 4). If, on the other hand, the exocyclic methylene at C-5 was to be introduced before the oxidation reaction, then given the known preference for an s-trans diene conformation, conformer 18a (Scheme 6) would be more populated at equilibrium. The A2 3 olefin diastereoface that is interior and hindered in the context of 18b is exterior and accessible in 18a. Subjection of intermediate 11 to the established three-step olefination sequence gives intermediate 18 in 54% overall yield. On the basis of the rationale put forth above, 18 should exist mainly in conformation 18a. Selective epoxidation of the C2-C3 enone double bond with potassium tm-butylperoxide furnishes a 4 1 mixture of diastereomeric epoxides favoring the desired isomer 19 19 arises from a peripheral attack on the enone double bond by er/-butylper-oxide, and it is easily purified by crystallization. A second peripheral attack on the ketone function of 19 by dimethylsulfonium methylide gives intermediate 20 exclusively, in a yield of 69%. 

The sense of asymmetric induction could be tuned in two ways firstly through the chirality of the sufinyl group, and secondly through the use of dimethylox-osulfonium methylide (n = 1) or of dimethylsulfonium methylide (n = 0), which was found to provide aziridines with opposite diastereoselectivity. This was interpreted by assuming the process to be under thermodynamic control in the former... 

Whereas phosphonium ylides normally react with carbonyl compounds to give alkenes, dimethylsulfonium methylide and dimethylsulfoxonium methylide yield epoxides. Instead of a four-center elimination, the adducts from the sulfur ylides undergo intramolecular displacement of the sulfur substituent by oxygen. In this reaction, the sulfur substituent serves both to promote anion formation and as the leaving group. 

Dimethylsulfonium methylide is both more reactive and less stable than dimethylsulfoxonium methylide, so it is generated and used at a lower temperature. A sharp distinction between the two ylides emerges in their reactions with a, ( -unsaturated carbonyl compounds. Dimethylsulfonium methylide yields epoxides, whereas dimethylsulfoxonium methylide reacts by conjugate addition and gives cyclopropanes (compare Entries 5 and 6 in Scheme 2.21). It appears that the reason for the difference lies in the relative rates of the two reactions available to the betaine intermediate (a) reversal to starting materials, or (b) intramolecular nucleophilic displacement.284 Presumably both reagents react most rapidly at the carbonyl group. In the case of dimethylsulfonium methylide the intramolecular displacement step is faster than the reverse of the addition, and epoxide formation takes place. 

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. 

Examples of the use of dimethylsulfonium methylide and dimethylsulfoxonium methylide are listed in Scheme 2.21. Entries 1 to 5 are conversions of carbonyl compounds to epoxides. Entry 6 is an example of cyclopropanation with dimethyl sulfoxonium methylide. Entry 7 compares the stereochemistry of addition of dimethylsulfonium methylide to dimethylsulfoxonium methylide for nornborn-5-en-2-one. The product in Entry 8 was used in a synthesis of a-tocopherol (vitamin E). 

Dimethylsulfonium methylide reacts with reactive alkylating reagents such as allylic and benzylic bromides to give terminal alkenes. A similar reaction occurs with primary alkyl bromides in the presence of Lil. The reaction probably involves alkylation of the ylide, followed by elimination.289... 

The synthesis of S. J. Danishefsky s group is outlined in Scheme 13.55. The starting material is a protected derivative of the Wieland-Miescher ketone. The oxetane ring is formed early in this synthesis. An epoxide is formed using dimethylsulfonium methylide (Step A-3) and opened to an allylic alcohol in Step A-4. The double bond... 

Diphenylcyclopropane has been prepared in 24% yield by the Simmons-Smith reaction,2 in 78% yield by treatment of 3,3-diphenylpropyltrimethylammonium iodide with sodium or potassium amide,3 in 61% yield by reaction of 1,1-diphenyl-ethylene with dimethylsulfonium methylide,4 and in unspecified yields from 1,1-diphenylethylene by reaction with diazomethane followed by pyrolysis of the resulting pyrazoline or by reaction with ethyl diazoacetate followed by distillation of the corresponding acid over calcium oxide.5... 

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. 

Disubstituted furans have been obtained from ketones using the reaction sequence shown in Scheme 24 (73JA250). The ketone is converted to the thioenol ether (117) which on reaction with dimethylsulfonium methylide yields the oxirane (118). Rearrangement leads to the dihydrofuran and thence to the 3,4-disubstituted furan (119). The terpenoid furans perillene (122) and dendrolasin (123) have been synthesized by treatment of the n-butylthiomethylene derivatives of the ketones (120) and (121) respectively with dimethylsulfonium methylide (Scheme 25). 

Disubstituted furans (130) can be obtained by treatment of j8-alkoxy- and j8-arylthio-a,j8-unsaturated ketones, for example 3-methoxy-l-phenyI-2-buten-l-one (128) or 3-ethylthio-l-phenyl-2-buten-l-one (129), with dimethylsulfonium methylide (79JHC815, 69TL679). The possible reaction pathway (Scheme 27) shows the initially formed epoxides as rearranging by ring opening at the tertiary epoxide carbon atom. 

Dimethylsulfonium methylide reacts smoothly with o- and p-hydroxybenzylidene ketones (208), giving 2-(o-hydroxyphenyl)- and 2-(p-hydroxyphenyl)-2,5-dihydrofurans (209). It is thought likely that the intermediate epoxide is converted to a quinone methide in which the alkoxide group is in a favourable position to add, thereby allowing ring closure to the dihydrofuran ring (Scheme 54) (79CC438). 

However, their potentialities as synthetic intermediates were shown much later by the work of Corey and Chaykovsky [201,202] on the preparations and methylene transfer reactions of dimethylsulfonium methylide (1) and dimethylsulfoxonium methylides (2). 

The reaction of a-oxoketene dithioacetals with dimethylsulfonium methylide led to another general route to furans and butenolides [454], according to the accompanying scheme. 

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