Anhydrides with phosphoranes

Oxidation of 754 under Swem conditions provides aldehyde 760. Wittig reaction of 760 with phosphoranes yield Z-olefins 761 [166] phosphonates yield the. E-olefin 762 (Scheme 110) [102]. Reduction of 762 in acetic anhydride gives N-acetyl-protected diol 763, which is identical to one of the degradation products of the polyene macrolide lienomycin. 

Reaction of perthiophosphonic anhydrides (64) with amines leads first to (105) and then, by further attack, to (106). With ammonia itself the second addition proceeds at the same phosphorus atom as the initial attack, giving (107) and (108). The anhydride (64) is also reported to react with 1,3-dioIs to give cyclic phosphonyl disulphides (109). Thermal decomposition of phenylphosphinic anhydride (110) may lead to the formation of PhP since in the presence of benzil the formation of the phosphorane (111) was observed. ... 

In acetic acid, or aqueous acetone with subsequent treatment with acetic anhydride, the esters (196 R=4-Me0 or 4-MeS) give rise to the expected esters(197) or (198). For the 4-chlorophenyl derivative, a mixture of the unexpected products (199, 200 Ar=4-chlorophenyl) was obtained. The unsubstituted compound (196 R=H) gave only (199) in aqueous acetone, but (200) in acetic acid. The postulated mechanism tor such a rearrangement centres around pseudophosphonium and-or phosphorane... 

Since the electrophilic character of carbonyl groups in acid halides is more pronounced than in carboxylic anhydrides, the former are better suited for aza-Wittig reactions. Zbiral et al. studied the reaction of imino-phosphoranes with acid halides and obtained imidoyl halides (69LA29 72PS35). A -alkyl and A -aryl iminophosphoranes can be set to use in this reaction (72PS35). 

Alkylidene derivatives of phthalic thioanhydride are formed as shown in Scheme 160. Reaction of phthalic thioanhydride with hot triethyl phosphite produces trafts-S -bithioph-thalide (457), probably via the carbene and phosphorane (Scheme 161) (72AHC(14)331>. Support for this mechanism stems from the fact that brief treatment of phthalic thioanhydride with triethyl phosphite in the presence of phthalic anhydride gives (458) in the presence of benzaldehyde the same reaction leads to the benzylidene derivative (456). An alternative mechanism has also been suggested, in which the penultimate step is the formation of an epoxide, which is deoxygenated to yield the product (72AHC(14)331>. 

A one-pot synthesis of alkyl perfluoroalkyl ketones has been developed. Phosphoranes, generated in situ, are acylated with a perfluoroacyl anhydride, and the resulting phosphonium salts are hydrolyzed with alkali [48] (equation 48) Hydrolysis of a carbon-sulfur bond in 2-chloro-2,4,4-trifluoro-1,3-dithietane-S-trioxide, which can be obtained from 2,2,4,4-tetrachloro-l,3-dithietane by fluor-ination with antimony trifluonde followed by selective oxidauons, opens the ring to produce 2-chloro-l,l,2-trifluorodimethyl sulfone [49] (equation 49)... 

Experiments with aspartic acid have shown that only a-aspartic acid dipeptides are formed [123], which is consistent with the transformation of the substrate into a pentacoordinated phosphorane mixed anhydride 17 [24] containing a five-membered ring through a self-activation process. 

Phosphoranes and phosphonate derived carbanions are also known to react with carbonyl compounds other than aldehydes and ketones, in reactions often referred to as non-classical Wittig reactions.35 Wittig olefination products can be obtained from the reaction of esters, anhydrides and some amides and imides with a range of stabilized and reactive phosphoranes. The reaction of stabilized and semi-stabilized phosphoranes with esters gives alkenes (Scheme 7). However, non-stabilized phosphoranes, such as methylenetriphenylphosphorane, tend to give P-keto phosphoranes on reaction with esters (Scheme 7)—the careful choice of the reaction conditions can also permit the preparation of the alkene in these reactions. 

Methylene(oxo)phosphoranes are formally anhydrides of phosphinic acids a recent review 14) has summarized the existing knowledge on methods of generation of the species and their reactivity. Two cases (14 and 15) are known of compounds with sufficient stability to allow isolation, but as in the case of other metaanhydride substances, they are usually far too reactive to allow observation or isolation. 

We have proceeded to apply the ring fragmentation approach to the generation of yet another type of previously unknown 3-coordinate phosphoryl derivative, where the methylene(oxo)phosphorane has an alkoxy substituent on phosphorus. Such structures (26-29) can be considered as anhydrides of monoalkyl alkylphosphonates. The precursors for these new species have the structures 22-25 (isomer mixtures) they are known compounds (72) from our previous work and are synthesized by the cycloaddition reaction of dihydrophosphinines with dimethyl acetylenedicarboxylate, as used in Scheme 4. 

Another synthesis of isoochracinic acid (27), utilises an interesting application of Wittig reaction. 3-Methoxyphthalic anhydride on reaction with carbobenzyl-oxymethylenetriphenyl phosphorane, followed by hydrogenation and demethylation furnishes 21. It may be noted that 3-methoxyphthallc anhydride can be readily obtained by aromatic lithiation of N,N-diethyl w-methoxy benzamide followed by treatment with COj (vide supra). 

The formation of acrylonitriles from the reaction of dihalogenomethylene-phosphoranes with aroyl cyanides has now been extended to include the use of aliphatic acyl cyanides, although the conditions need to be closely defined. Perfluoroisocyanates with diphenylmethylenetriphenylphosphorane give the expected keten-imines (28) or their rearrangement products (29). Formylation of both reactive and stable ylides has been achieved using the mixed anhydride of formic and acetic acids. ... 

Methylmaleinimide was prepared from citraconic anhydride and methylammonium acetate and after reaction with ethoxycarbonylmethylene(triphenyl)phosphorane (CMTP) gave ( )-5-ylidenepyrrol-2-(5//)-one (A) regio- and stereoselectively [160] (Scheme 39). 

An ingenious synthesis, albeit in low yield, of 1-oxo-1,2,3,4-tetrahydro-9-hydroxyanthracene has been achieved from a phosphoran and a ketene formed as an intermediate. The phosphoran with homophthalic anhydride (3.3mols.) and trimethylsilane (3mols.) upon themolysis in toluene at 150°C for 40 hours in a sealed tube gave the product in 23% yield (ref.24). 

Chromones.- Enamines have previously been converted into chromones and in another approach, the enamine (104) reacted with thionyl chloride to give the chromone (105 n=2) in moderate yield. The sulphinic acid was readily oxidized to the sulphonic acid (105 n=3) by 3-chloroperoxybenzoic acid.110 A convenient synthesis has been described of 2-methylchromene-4-thione in 57% yield from 4-(2-hydroxyphenyl)butane-1,3-dione.111 The t-amino-methylchromones (106) have been synthesized and shown to be central nervous system depressants. A new synthesis of 2-substituted chromones (including flavones) uses 2-acetoxyphenacyl bromide (107) which is converted into its phosphorane (108). Heating this with an alkanoyl or aroyl chloride or anhydride in pyridine gave good yields of the chromone (109).113... 

The reaction of triethyl phosphite with maleic anhydride has been re-investi-gated. The product is not the dimeric phosphorane (11), but the ylid (12). Reactions of alkyl or aryl diphenylphosphinites with 1-nitro-l-alkenes have been studied in detail. Radical ion-pairs are involved as shown by e.s.r. and P CIDNP experiments. Allene may be hydrophosphorylated in a radical-initiated process to give allyl- and isopropenyl-phosphonates. A phosphorane (14) has been observed during the reaction of ethyl diethylthiophosphinite (13) with methacrylic acid. ... 

Sodium amalgam-reduction of the salt (69) (obtained from the reaction of acyl-stabilized ylides with trifluoromethane sulphonic anhydride) provides a new synthesis of acetylenes (Scheme 11). A new synthesis of ethynyltriphenyl-phosphonium salts (70) is provided by the reaction of acylmethylenetriphenyl-phosphoranes with dibromotriphenylphosphorane and base. ... 

A general route to )8-alkylidene-butyrolactones, which are easily converted into the corresponding jS-alkylbutenolides and thence into 3-substituted furans, employs the phosphorane (64), synthesized from maleic anhydride and triphenylphosphine, in Wittig reactions with aldehydes followed by reduction of the ester group with sodium diethylaluminium hydride (Scheme 20). 

The diazo-ketone (43) forms the j -lactone (44) and 2-methylhexan-3,5-dione on refluxing in benzene, presumably through alkyl migration and cyclization of resulting hydroxyketen. Malonyl anhydrides (46) and ketens are formed from the deoxygenation of malonyl peroxides with triphenyl-phosphine, possibly via an intermediate phosphorane (45). 

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