Alkylidenephosphoranes

A variety of 1-azirines are available (40-90%) from the thermally induced extrusion (>100 °C) of triphenylphosphine oxide from oxazaphospholines (388) (or their acyclic betaine equivalents), which are accessible through 1,3-dipolar cycloaddition of nitrile oxides (389) to alkylidenephosphoranes (390) (66AG(E)1039). Frequently, the isomeric ketenimines (391) are isolated as by-products. The presence of electron withdrawing functionality in either or both of the addition components can influence the course of the reaction. For example, addition of benzonitrile oxide to the phosphorane ester (390 = C02Et) at... 

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. 

A particularly interesting reaction is the C-formylation[2] of alkylidenephosphoranes by A-formylimidazole to give a-formyl derivatives (C6H5)3P=C(R)CHO which can be further transformed into a,/ -unsaturated aldehydes by Wittig reaction, or hydrolyzed to produce aldehydes RCH2-CHO. 

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. 

The P=C bond of ), a -phosphoranes is also accessible to a 1,3-dipolar cycloaddition reaction. The formation of 97 (Scheme 8.23), of 3,5-dihydro-1,2,4-diazaphosphole sulfide 132 from an amino(methylene)thioxophosphorane (190) and of phosphirane imine 133 from an amino(imino)alkylidenephosphorane (191) (Scheme 8.29) illustrate the chemical behavior of phosphaalkenes containing a A, a -phosphoms atom. 

The alkylidenephosphoranes are among the most powerful bases known, and the displacement of a coordinated ligand is a useful method for the preparation of transition metal ylide complexes. 

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. 

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)... 

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). 

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). 

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

The Wittig reaction proceeds more rapidly in dimethyl sulfoxide than in other customary solvents due to the enhanced deprotonation of the phosphonium salts to alkylidenephosphoranes [327]. Even camphor, a rather unreactive ketone, undergoes the Wittig reaction easily in base/CH3SOCH3 systems [327]. 

Halogens (mainly chlorine) at position 4 of quinazolines 12 can be displaced by a variety of carbon nucleophiles, c.g. carbon nucleophiles derived from active methylene compounds, ketone enolates, aromatic aldehydes, organolithium reagents, alkylidenephosphorane, dimethyloxosulfonium methylide, alkynes, and cyanide. ... 

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 containing the bis(aiyl/alkylsulfonyl)methylene functionality may be obtained from aryli onium ylides and triphenylphosphine, a carbene mechanism presumably being involved. ... 

The generation of an ylide from a phosphine oxide and an alkyne is of interest because it represents the reversal of the known intramolecular Wittig reaction of acylated alkylidenephosphoranes. ... 

Acyl ylides add to N—N double bonds of azo compounds giving rise to the formation of l-A/-sub-stituted alkylidenephosphoranes (e.g. equation 29). ° It should be mentioned that l-/V-substituted ylides, which carry only hydrogen or alkyl groups at the nitrogen, are unknown. ... 

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). ... 

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. 

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