With /’- alkylidenephosphoranes

We now wish to report a new simple method for the synthesis of indoles which is based on the intramolecular reaction of amide with alkylidenephosphoranes—(scheme 2)... 

The reaction of the phosphonium salts 28, generated from the -halogencarboxylic esters 26, with sodium ethoxide in DMF or sodium hydride in DMSO yields the phosphoranes 29 which, on treatment with aldehydes 30, are converted into (Z)-alkenoic esters 31 49,51 53). To synthesize As-unsaturated acids and higher homologous acids of type 31 (m 11) Bergelson et al. 49,54) olefinated ethyl co-formyl-alkanoates 34, obtained from co-iodoalkanoic esters 32, with alkylidenephosphoranes 35 to the ethyl esters 31 (Scheme 7). 

By this method (Z)-monounsaturated fatty acids and esters could be obtained with an ( )-isomer content of less than 10% this stereoselectivity being however inferior to that of the commonly used acetylenic approach 55,56). However, the salt-free techniques used today in Wittig reactions allow (Z)-alkenoic acids to be synthesized with less than 2% of the ( )-isomers. Thus, Bestmann et al. prepared methyl and ethyl esters of (Z)-4,5,6,7,8,9,ll- and 13-alkenoic acids of different chain lengths 35,57 62), which served as intermediates in the synthesis of insect pheromones, both by reaction of co-alkoxycarbonyl-substituted alkyl-triphenyl-phosphonium salts with simple alkanals and of co-formylalkanoic esters with alkylidenephosphoranes. As the starting material for the synthesis of -substituted alkyl-phosphonium salts co-chloro- and -bromocarboxylic esters were used. The corresponding -substituted aldehydes can usually be obtained by ozone cleavage of suitable olefin derivatives or by oxidation of alkohols 57,58). 

Dialkylboron-substituted phosphonium ylides have been prepared by reaction of dialkylchloroboranes with alkylidenephosphoranes (equation 50). The reaction of phosphonium ylides with alkyldichloro-boranes leads to the formation of boron-bridged 1,3-bisylides (equation 51). ... 

The olefination of cyclopropanone hemiacetales with alkylidenephosphoranes has also been published 121) but the yields are rather low. 

Benzotrithiins (349) are accessible by the reaction of benzopentathiepin (347) with alkylidenephosphoranes (Scheme 52) <91TL6345). Intramolecular nucleophilic addition in the dipolar intermediate (348) followed by extrusion of elemental sulfur accounts for the reaction course. Other nucleophiles, such as the anion derived from ethyl a-chloropropionate, also react with (347) in the same way <89H(29)2097). 

Quinquecovalent phosphoranes readily undergo ligand exchange on treatment with organolithium compounds. With alkyl-lithiums the resulting alkylphosphoranes give alkylidenephosphoranes, e.g. (2), by loss of benzene. 

P-(Chloro)alkylidenephosphoranes, reaction with hexafluoroacetone, 30 259 Chloroaminocyclotetraphosphazene, isomerization, 21 56... 

Since the publication of CHEC-II(1996), there have been very few examples related to the reactivity of substituents attached to ring carbon atoms. One case involves the reaction of 3-benzylidene-2,3-dihydro-2-methyl-l,2-benzothiazin-4-one 1,1-dioxide 163 with the alkylidenephosphorane derived from salt 164 forming the tricyclic-fused ring compound 165 (Scheme 20) <1996J(P1)2541>. This material 165 was oxidized with 2,3-dichloro-5,6-dicyano-l,4-benzoquinone (DDQ) affording the biphenyl 166. Ring-opened product 167 was produced from 165 upon exposure to />-toluene-sulfonic acid and heat. 

Quaternisation of triphenylphosphine with an alkyl halide gives a quaternary phosphonium halide (4) which under the influence of a strong base eliminates hydrogen halide to give an alkylidenephosphorane [(5), an ylide]. The latter reacts with an aldehyde or ketone to give first an intermediate betaine (6), which rearranges to the oxaphosphetane (7), which then under the reaction conditions eliminates triphenylphosphine oxide to form an alkene. 

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). 

Reacts with alkyltriphenylphosphonium salts to yield alkylidenephosphoranes (Wittig reagents (Section 19.11). 

Tertiary phosphines (especially triphenylphosphine) react with various compounds giving rise to the formation of alkylidenephosphoranes. " By the addition of carbenes and carbenoids, respectively, to tertiary phosphines especially, alkylidenephosphoranes are available which carry one or two halogen atoms at the a-carbon atom (equation 1). 

Alkylidenephosphoranes which carry a carbamoyl or thiocarbamoyl group in the a-position are formed from ylides and isocyanates or thioisocyanates (equation 79).im,i73 jf starting ylide has no activated a-H atom the reaction with thioisocyanates stops at the betaine intermediate (see equation 78) which can subsequently be alkylated and transformed into the corresponding substituted ylide with an external base. 

Besides protons a series of heteroligands in the a-position of phosphonium ylides can also be substituted, giving rise to the formation of new alkylidenephosphoranes. Halogen atoms have been substituted by carbon groups (with lithium organyls or acyl chlorides) or another halogen. Reaction of a-lithiated ylides (see equation 35) or ylide anions with electrophiles may be considered as substitution of an alkali metal substituent at the ylide carbon atom. 

In the reaction of OH-, NH-, SH- and CH-acidic compounds with phosphacumulene ylides the anion Nu of the initially formed phosphonium salt (c/. equation 101) is so nucleophilic, that addition of the anion to give a new alkylidenephosphorane is faster than cycloaddition of a second mole of starting ylide (equation 105). ° ... 

Carboxylic acids react with phenyliminovinylidenetriphenylphosphorane (equation 106) via the intermediates (1) with formation of the alkylidenephosphoranes (2), which, on heating, rearrange in an intramolecular acyl migration to ylides (3). By heating (2) in the presence of an alcohol the acyl ylides (4) and N-phenylurethanes are formed. - The reaction sequence allows the replacement of the OH group in carboxylic acids by the ylide function. 

The addition of acidic compounds to phosphacumulene ylides yielding substituted alkylidenephosphoranes is of particular interest in the reaction of those acidic molecules which carry, besides the Y— bond, a group capable of cyclization with the ylide function formed by addition. " ... 

Stepwise deprotonation of methylenebis(triorgano)phosphonium salts with bases yields carbodiphosphoranes via intermediate semi-ylide salts, which may also be accessible by alkylation or phosphinol-ation of corresponding alkylidenephosphoranes (equation 118). " It depends on the starting phosphonium salt and the base whether the intermediate ylide salts can be isolated or not. Suitable bases are sodium amide, alkali metal hydrides, alkylidenetrialkylphosphoranes, potassium and lithium orga-nyls. For the synthesis of hexaphenylcarbodiphosphorane improved methods have been reported by which this compound may be generate without isolation of the ylide salt and on a large scale. 

Alkylidenephosphoranes react with phenylselenyl bromide to yield selenophos-phoranes (59), which react normally with aldehydes. However, with ketones, the corresponding 2-phenylseleno-derivatives, e.g. (60), are formed. ... 

A method for the preparation of symmetrical alkenes by oxidation of resonance-stabilized alkylidenephosphoranes with hydroperoxides has been extended to the preparation of symmetrical carotenoids. Thus treatment of the triphenylphosphonium bromide (60) with hydrogen peroxide and sodium carbonate in aqueous propan-2-ol gave the C24 ester (61) in 33% yield. /S-Carotene. 

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