Methylenation Methylenetriphenylphosphorane

The base catalyzed rearrangement of a monotosylated 1,2-diol on alumina, followed by immediate condensation of the sensitive ketone with methylenetriphenylphosphorane, gave the exo-methylene compound below (G. Btlchi, 1966B). 

The aldehyde group of laevulinic aldehyde reacted preferentially with the ester phosphorane (38), while the 2-acetyl groups of the benzofurans (39) were selectively methylenated with methylenetriphenylphosphorane. The aldehyde group was protected as the dimethylacetal in the synthesis of the steroidal a-methylene-aldehyde (40). 

Ketones. Treatment of the diketone (26) with methylenetriphenylphosphorane gave a high yield of 1,6-dimethylenecyclodecane.29 Diphenylcyclobutenedione reacts with ylides, e.g. (27), to yield substituted 4-methylene derivatives.30... 

Reaction of the ketones (93) with excess methylenetriphenylphosphorane gave, not only the expected methylene compounds, but also the diene (94) formed by elimina-... 

Another system, which is also allowed by IUPAC and is sometimes very convenient (but which should be avoided when official names are established by IUPAC and cited in Chemical Abstracts), is the so-called a -nomenclature, in which the term phospha indicates replacement of carbon by phosphorus, e.g. phosphacyclohexane = phosphorinane, and phosphabenzene = A3- phosphorin. Five-coordinate phosphorus compounds are called phos-phoranes. However, this name is also used for phosphorus ylides with a four-coordinate phosphorus and a more or less polar R3f—CX moiety or a d -p R3P=CX double bond, e.g. methylenetriphenylphosphorane = triphenylphosphorus methylene ylide or tri-phenylphosphonium methyl ylide, Ph3P=CH2 = Ph3P—CH2. 

Mcthy lene-y-butyrolactones, 136 0-Methylene cyclic ethers, 270 6-Methylene-3-ketoA -steroids, 193 3-Methyleneoxolanes, 136 Methylenetriphenylphosphorane, 338-339 Methyl enol ethers, 273-274, 401 Methylenomycin B, 14, 162 14a-Methylestrone 3-methyl ester, 95 0-Methylhomoallyl alcohols, 143 Methylidenation, 182 Methyl jasmonate, 279, 301 Methylketcne methyl trimethylsilyl ketal, 340 Methyl lithiodithioacetate, 340 Methyl 5-lithiotetronates, 72, 73 Methyllithium-Tetramethylethylcnediamine,... 

M ETHYLENATION Dimethoxymethane. Dimethyl methylphosphonate. Methylene bromide-Zinc-Titanium(IV) chloride. Methylenetriphenylphosphorane. N-Methylphenylsulfonimidoylmethyllithium. Titanium(O). N,N,P-Trimethyl-P-phenylphosphinothioic amide. Trimethylsilylmethyllithium. 

Final W/ m g-methylenation with methylenetriphenylphosphorane gives 4 in excellent yield. 

Lactonization is not obligatory, as the byproduct formed in the reaction of 2-acetamido-2-deoxy-D-glucose with methoxycarbonyl-methylenetriphenylphosphorane was proved67 to have structure 134. This compound rapidly consumes one mole of periodate per mole, and shows signals at r 7.95 p.p.m. (doublet) and r 6.15 p.p.m. in its n.m.r. spectrum, corresponding to the a-methylenic and the ester group, respectively. Use of 2-acetamido-4,6-0-benzylidene-2-deoxy-D-arabino-hexose instead of the unprotected sugar does not prevent... 

Another example in the C-glycosylated, unsaturated hydrocarbon series is methyl 2-deoxy-3,4-0-isopropylidene-2-C-methylene-/3-D-erythro-pentopyranoside (213), obtained90 in 55% yield by the reaction of methyl 3,4-0-isopropylidene-/3-D-eryfhro-pentopyranosid-2-ulose (212) with methylenetriphenylphosphorane n-butyllithium was used as a proton acceptor. Subsequent reduction of 213 with 10% palladium-on-charcoal led to a 7 1 mixture of the 2-epimeric methyl 2-deoxy-2-C-methylpentopyranosides (214 and 215, respectively). In the n.m.r. spectrum of 214, the H-l resonance appeared as a doublet at r 5.62 p.p.m., exhibiting aJia coupling constant of 8 Hz, thus indicating H-2 to be axial and, therefore, the D con-... 

In 1973, Johnson reported the use of (N-methylphenylsulfonimidoyl)methyllithium (26) for addition to carbonyls, followed reductive elimination to produce the methylene derivative (28 Scheme 7). As with the Tebbe and Oshima procedures discussed in Sections 3. l.S and 3.1.6, this method can be applied to enones, ketones and, with comparatively diminished efficiency, aldehydes. The anion appears to be more nucleophillic than methylenetriphenylphosphorane, and there are several examples, detailed below, in which the Wittig reaction failed but the Johnson procedure succeeded. The addition and reductive cleavage can be combined into a single operation without isolation of the p-hydroxysulfoximine. ... 

The Peterson methodology has seen wide application in the synthesis of carbohydrates. The preparation of 3-C-methylene sugars (6) was demonstrated by Carey and coworkers, with the methylenation proceeding without elimination of the anomeric alkoxy group (equation 3). A more recent example of Peterson methylenation of a carbohydrate is the synthesis of a deoxyamino sugar (8) by Fraser-Reid (equation 4). In this case, the carbonyl failed to react with the methylenetriphenylphosphorane at room temperature, and forcing conditions resulted in decomposition. Application of the Oshima-Takai-Lom-bardo method also failed. The Peterson reagent added in excellent yield, and the elimination resulted in the formation of the desired methylene (8a) as well as the vinylsilane (8b). 

The basic nature of methylenetriphenylphosphorane caused D-homoannulation of 17a-acetyloestr-4-en-17/3-ol (294) before effecting a Wittig condensation the mixed 17-methylene-D-homoandrostanes (295) were formed. When the 17/3-OH group was protected by acetylation, an intramolecular Claisen condensation occurred in polar solvents under Wittig conditions, giving the spiro-lactone (296) and a... 

Methylenetriphenylphosphorane, 678 Methylene urethane, 677 Methyl 8,9-epoxyabietanoate, 616 l(S-Methylestrene-3-ketones, 249 Methyl ethers, 1130 cleavage, 1103... 

Many 6-poIyketones have been methylenated to give d-polyenes. Although the cyclohexadienone (23) with methylenetriphenylphosphorane gave the expected triene, the isomeric ketone (24) somewhat surprisingly failed to react. ... 

The Wittig reaction is a very elegant method of converting a carbonyl group into a C=C bond. It was first used by Wittig and Geissler999 who treated methylenetriphenylphosphorane (triphenylphosphine methylene) with benzophenone and obtained 1,1-diphenylethylene in 84% yield ... 

Tricyclic ketone 215 was converted by previously reported procedures to the ketoacid 218, which was treated with methylenetriphenylphosphorane to introduce the exocyclic methylene on the D ring (219) (Scheme 25). The ester was then converted to the aldehyde (220), treated with isopropenylmagnesium bromide to yield the allylic alcohol, subjected to Claisen rearrangement with methyl or thioacetate, and the resulting aldehyde converted to the tetramethyl allylic alcohol 208 by the previously described sequence (210 — 212, Scheme 24). The polyolefinic precursor to the serratene skeleton was obtained in overall yield of 3.1% from m-methoxycinnamic acid. 

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