Methylenation dimethylsulfoxonium methylide

Addition of dimethylsulfoxonium methylide to the a-face of A -20-ketones, A -5a-H-ketones and A " -3-ketones results in the formation of the corresponding 16a,17a-methylene (1), la,2a-methylene-5a-H (2) and la,2a-methylene-A" steroids (3), respectively. Smooth reaction is also observed in the presence of 2-chloro and 2-bromo substituents in the A -5a-H-3-ketone series.Yields of 90% are obtained within a reaction period of 5 hr at room temperature. A A -3-keto system in (1) is not attacked under these conditions. 

Similar results are obtained by reaction of 6-chloropregna-4,6-diene-3,20-dione with dimethylsulfoxonium methylide. In this case a 2 1 mixture of 6a,7a-methylene and 6) ,7 -methylene adducts is obtained. 

Addition of dimethylsulfoxonium methylide has also been studied in the retro steroid (9, 10a) series. Results are somewhat different from observations in the normal series. Thus only the 6, 7)3-methylene adduct is obtained from a 4,6-dien-3-one while 6-chloro-9) ,10a-l,4,6-trien-3-ones undergo attack at the 6,7-double bond in preference to the 1,2-double bond resulting in the formation of 6a-chloro-6)5,7i5-methylene-A -3-ones. ... 

Spurred by these observations, we examined a relevant application of the method for nitrocyclopropane synthesis from nitroalkenes and dimethylsulfoxonium methylide (17), Equation 3. It had previously been employed for the synthesis of a 2,3-dideoxv-2,3-C-methylene-3-nitro-hexopyranoside, the first one of the small number of carhohvdrates containing the nitrocyclopropane structure thus far known (18). 

Trimethylsulfoxonium iodide (11) is of interest because treatment with sodium hydride or dimsyl sodium produces dimethylsulfoxonium methylide [5367-24-8] (12) (eq. 22), which is an excellent reagent for introducing a methylene group into a variety of structures (53) ... 

An unusual example involves the addition of a methylene group by the reaction with dimethylsulfoxonium methylide to give the fused cyclopropane (614) (68JCS(C)2302), whilst 2-styrylchromones behave as dienes and undergo cycloaddition to give fused chromanones <75ACH(84)319>. 

Thus a 1 1 mixture of 6a,7a- and 6/ ,7/ -methylene adducts is obtained from 17/S-hydroxyandrosta-4,6-dien-3-one (17) or its acetate and dimethylsulfoxonium methylide. 

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). 

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. 

A new approach for introducing a carbon side-chain at position 3 in the pyridazine ring is displacement of a methylthio group of quaternized py-ridazine with reactive methylene compounds to give 77 (79TL4837). Alternatively, a 3-chloropyridazine reacts with dimethylsulfoxonium methylide... 

During the total synthesis of (+)-phyllanthocin, A.B. Smith and co-workers installed the epoxide functionality chemo-and stereoselectively at the C7 carbonyl group of the intermediate diketone by using dimethylsulfoxonium-methylide in a 1 1 solvent mixture of DMSO-THF at 0 °C. The success of this chemoselective methylenation was attributed to the two a-alkoxy substituents, which render the C7 carbonyl group much more electrophilic than Cl 0. 

Dimethylsulfoxonium methylide. 14,152 15,147 16,146 17,126-127 18,148 19,139 Polyhomologation. The ylide provides the methylene unit in chain extension of triorganoboranes. Besides oxidative workup to generate alkanols, the replacement of the boron atom by a hydroxylated carbon on reaction with dichloromethyl methyl ether gives compounds with trident carbon chains. 

The synthesis of Drospirenone 41 (Scheme 1-15) [83] starts with the inexpensive androstenolone 66, which can be converted microbiologically (Colletotrichum lini) into the 7a,15a-dihydroxy derivative 67. A selective epimerization at C(7) proceeds by way of the acetal 68. Methylenation of the intermediate (C=C) bond appearing between C(15) and C(16) is successfully accomplished with the aid of dimethylsulfoxonium methylide to provide 71, and that of the (C=C) bond between C(6) and C(7) through a Simmons-Smith reaction. The conversion of 76 into 41 can be carried out in a one-pot procedure, with a Pd-catalyzed hydrogenation being followed by a Ru-catalyzed oxidation and a hydrochloric acid-induced dehydration. 

Deoxybenzoin added to a soln. of 1.1 equivalents phenylthiomethyllithium prepared from thioanisole and -butyllithium in the presence of triethylenediamine in tetrahydrofuran intermediate j -hydroxy sulfide (Y 88%) treated with a slight excess of trimethyloxonium fiuoroborate in methylene chloride until a homogeneous soln. indicates that most of the oxonium salt has been consumed, excess aq. 0.5 N NaOH added, and the 2-phase system efficiently stirred overnight -> 2-benzyl-2-phenyloxirane (Y 90%). Overall Y 79%. - Both dimethylsulfo-nium and dimethylsulfoxonium methylid (s. Synth. Meth. 17, 889) failed to perform this conversion. F. e. s. J. R. Shanklin et al., Am. Soc. 95, 3429 (1973). 

On the other hand, because TDM and dimethylsulfoxonium methylide 11 react with organoborane in a similar mechanism (formation of borate followed by 1,2-migration), organoborane-initiated copolymerization of TMD with 11 proceeded to give poly(TMSmethylidene-co-methylene), which is a partially TMS-substituted polymethylene [69]. Although the composition of TMSCH in the products was lower than that expected from the feed ratio of [TDM]/[11], oligomers with a relatively narrow MWD were obtained as shown in Scheme 47. 

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