Methylene triphenylphosphoran

Freshly distilled cyclohexanone, 10.8 g (0.11 mole), is added toO. 10mole of methylene-triphenylphosphorane, and the reaction mixture is stirred at room temperature for 30 minutes followed immediately by distillation under reduced pressure to give about 8 g (85%) of methylenecyclohexane, bp 42" (105 mm), which is collected in a cold trap. 

The aldehyde function at C-85 in 25 is unmasked by oxidative hydrolysis of the thioacetal group (I2, NaHCOs) (98 % yield), and the resulting aldehyde 26 is coupled to Z-iodoolefin 10 by a NiCh/CrCH-mediated process to afford a ca. 3 2 mixture of diaste-reoisomeric allylic alcohols 27, epimeric at C-85 (90 % yield). The low stereoselectivity of this coupling reaction is, of course, inconsequential, since the next operation involves oxidation [pyridinium dichromate (PDC)] to the corresponding enone and. olefination with methylene triphenylphosphorane to furnish the desired diene system (70-75% overall yield from dithioacetal 9). Deprotection of the C-77 primary hydroxyl group by mild acid hydrolysis (PPTS, MeOH-ClHhCh), followed by Swem oxidation, then leads to the C77-C115 aldehyde 28 in excellent overall yield. 

The Wittig reaction, or its phosphonate modification, can be a very useful reaction in the synthesis of anomerically functionalized precursors to C-nucleosides, particularly when the ring-closure reaction leads to five-membered, anhydro derivatives, and occurs with a high degree of stereocontrol. Zhdanov and coworkers,130 showed that the following five-membered, Wittig products (179-182) were formed from various free sugars and (p-methoxybenzoyl)- and (acetyl-methylene)-triphenylphosphoranes. 

As far as the stereochemistry concerns, when the cyclization occurs through a Michael reaction, the thermodynamic product is generally obtained, but some exceptions have been observed such as that of A-acetyl glucosamine protected as 4,6-benzylidene, the reaction of which with [(ethoxycarbonyl)methylene]triphenylphosphorane afforded the ot-C-glycosyl compound stereoselectively.28... 

M. Nomura, K. Endo, S. Shuto, and A. Matsuda, Nucleosides and nucleotides. 191. Ring expansion reaction of l-[2,3,5-tri-0-TBS-4 alpha-formyl-beta-D-ri o-pentofuranosyl] uracil by treating with (methylene)triphenylphosphorane to give a new nucleoside containing dihydrooxepine ring at the sugar moiety, Tetrahedron, 55 (1999) 14847-14854. 

Total synthesis of racemic limonene by Diels-Alder reaction of isoprene with methyl vinyl ketone and subsequent Wittig reaction of the resulting ketone with methylene triphenylphosphorane... 

Bestmann and Seng (5) reported that the reaction of methylene triphenylphosphorane with crotonic ester gave a cyclopropane derivative. We found that the less active carbomethoxymethylene triphenylphosphorane did not react with crotonic ester at all. 

Quinuclidine aldehydes are important synthetic intermediates. All three monoformylquinuclidines are known 2- and 3-formylquinucli-dines (75 and 76) were prepared 139,140 by reduction of JV-methyl-quinuclidinecarboxanilides with calculated amounts of LiAlH4 or by reduction of ethyl quinuclidinecarboxylates with NaAlH4. 4-Formyl-quinuclidine (77) was made by oxidation of quinuclidyl-4-carbinol (78) with potassium dichromate.87 3-Formylquinuclidine (76) was also synthesized from quinuclidin-3-one (2) by reaction with methoxy-methylene triphenylphosphorane and hydrolysis of the 3-methoxy-methylenequinuclidine (79) with hydrochloric acid.141... 

ALLYL ALCOHOLS Benzeneselenenyl halides. Methylene triphenylphosphorane. Sodium naphthalenide. 

Reaction of 3-formyl-4//-pyrido[l,2-a]pyrimidin-4-ones 409 with [(ethoxycarbonyl)methylene]triphenylphosphorane in a Wittig reaction in dimethylformamide at ambient temperature for 10 hours gave 3-trans-acrylates 410 (92JHC559). The 3-formyl group of 3,9-diformyl-l,6,7,8,-tetrahydro and 3-formyl-9-phenylhydrazono-6,7,8,9-tetrahydro-4//-pyr-ido[l,2-a]pyrimidines was transformed to a trans-acrylate side chain in a Wittig reaction with [(ethoxycarbonyl)methylene]triphenylphosphorane in dimethyl sulfoxide at room temperature for 24 hours (84JMC1253). 

In a paper edited in 1953, concerned with the preparation of the stereoisomeric forms of pentaphenylphosphorus, Wittig and GeiBler described the reaction of methylene-triphenylphosphorane 1 and benzophenone 2, forming 1,1-diphenylethylene 3 and triphenylphosphine oxide 4 (Scheme 1). Soon afterwards, it could be demonstrated that alkylidenephosphoranes (phosphine alkylenes, phosphorus ylides) generally react with carbonyl compounds such as aldehydes and ketones to give alkenes with the formation of phosphine oxide 1,2). 

One of the reported syntheses of ( )-9-oxodec-2-enoic acid 392, the queen substance of the honey bee Apis mellifera, uses two ylide reactions 222). Starting from pimelic acid 385 the resonance-stabilized ylide 386 is prepared by alkylation of methylene-triphenylphosphorane 209 and the former hydrolyzed to 7-oxooctanoic acid 387. Reduction of the corresponding thiol ester 389 and olefination of the resulting aldehyde 390 with phosphorane 67 gives the ( )-2-unsaturated ester 391. The latter was hydrolyzed to pheromone 392 222) (Scheme 69). 

Using methylene-triphenylphosphorane 205, in many cases carbonyl functions have been converted into exomethylene groups in cyclic terpene chemistry. This technique was used, among others in the preparation of (+)-steviol methyl ether 244), dihydro-5,6-norcaryophyllene 245), ( )-nootkatone 246 (-)-phyllodadene 247), and (+)-e-cadinene 248). In the synthesis of the latter the trans-decalin derivative 462 was formed from the cis-decalone 461 the epimerization of which proceeded via the enol form during the methylenation 248 (Scheme 80). 

Coupling of glycolaldehyde with (p-methoxybenzoyl)methylene-triphenylphosphorane produced7 8 an unexpected product having electronic and infrared spectra similar to those of p-methoxyaceto-phenone. This compound was readily converted into the furan derivative 199b and may, therefore, be the cyclopropane derivative... 

The Wittig olefination of 1,5-oxazocine 416 with [(methoxy)methylene]triphenylphosphorane led to the formation of the enol ether 431a (88% yield) as an inseparable mixture of E and Z isomers (2.5 1 ratio). Instead, when the reaction was carried out using methyltriphenylphosphorane as Wittig reagent, the as 3,5-disubstituted diastereoisomer 431b was exclusively formed in 85% yield (Scheme 84) <1998JOC3492>. 

As shown in Scheme 11.87, aldehyde 431 was transformed into sUylenol ether 432, which was treated with methylene triphenylphosphorane to give the expected cyclopentenone. Reduction of the keto group and protection of the resulting alcohol gave 433. As in Chiara s synthesis, epoxidation and opening of the latter with sodium azide completed the synthesis of 6-epi-trehazoline 434. 

Miscellaneous. Some rearrangements in steroids that are initiated by methylene-triphenylphosphorane have been reported. Thus 17 -acetyl-A -oestren-17/S-ol gave (33) with a limited amount of ylide. The desired isopropenyl compound could be obtained by protecting the 17/S-hydroxy-group as the silyl ether. 

Bochmann and co-workers report the coordination chemistry of a family of chelating iminophosphorane ligands. The iminophosphoranes (134), (135) and (136) form a variety of complexes with first row transition metals (137)-(140). The a-keto ylide, [(2-thiazoylcarbonyl)methylene]triphenylphosphorane... 

Treatment of 2-bromoacetylthiazole (142) with tripenylphosphine affords the phosphonium salt which on treatment with aqueous sodium hydroxyde gives the stabilized [(2-thiazolyl-carbonyl)methylene]triphenylphosphorane (143) (Scheme 35) <9lTL3247, 94ja3324>. This compound... 

To continue the synthesis (Figure 2.52), (-)-ketone E was treated with methylene triphenylphosphorane to give F. Deprotection followed by oxidation of F afforded the naturally occurring (+)-mispyric acid (59), whose absolute configuration was determined as 25,45. Similarly, the other diastereomer G obtained by optical resolution afforded unnatural (2R,4R)-(—)-59. ... 

Methylenemagnesium bromide (iodide), CH2(MgX)2 [1, 678, before Methylene-triphenylphosphorane]. Prepared1 by reaction of magnesium amalgam with one of the following halides methylene bromide, CH2Br2, mol. wt. 173.86, b.p. 98.2° methylene iodide, CH2I2, mol. wt. 267.85,b.p. 180°. Supplier of both Eastman. 

Synthesis from o-arabinose (35, 55 )-Quinuclidine-3,5-diol (2) has been synthesized from D-arabinose by conversion to the furanoside 21 in 59% overall yield (Schemes 4) Oxidation of the C-3 hydroxyl group with pyridinium chlorochromate followed by treatment with [(methoxycarbonyl)methylene]triphenylphosphorane and subsequent hydrogenation gave the corresponding ester, which upon reduction, mesylation and nucleophilic displacement of the mesylate group by azide ion afforded the branched azi-doethyl lyxofuranoside 22. Two pathways were used to convert 22 into 2. Acid hydrolysis of... 

Alkylation of [(methoxycarbonyl)methylene]triphenylphosphorane An alkyl halide (0.2 mole) is added to a boiling solution of [(methoxycarbonyl)methylidene]triphenylphos-phorane (0.4 mole) in anhydrous ethyl acetate, and the mixture is boiled under reflux for 2 h. The precipitated [(methoxycarbonyl)methyl]triphenylphosphonium halide is filtered off (yield 80-95%) and the filtrate is evaporated. The residue consists of the alkylated ylide it is often obtained as an oil, but this generally crystallizes when rubbed and can be recrystallized from ethyl acetate. 

The 3-pyrrolines (59) were formed on refluxing the aziridine (58) with the stable ylides PhgP CHR (R = CN or COgMe) in toluene. Methylene-triphenylphosphorane with benzoyl isocyanate gave a compound that has been assigned structure (60). ... 

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