Dipolar intermediates

The TT-allylpalladium complexes 241 formed from the ally carbonates 240 bearing an anion-stabilizing EWG are converted into the Pd complexes of TMM (trimethylenemethane) as reactive, dipolar intermediates 242 by intramolecular deprotonation with the alkoxide anion, and undergo [3 + 2] cycloaddition to give five-membered ring compounds 244 by Michael addition to an electron-deficient double bond and subsequent intramolecular allylation of the generated carbanion 243. This cycloaddition proceeds under neutral conditions, yielding the functionalized methylenecyclopentanes 244[148], The syn-... 

Step 2 In a solvent such as water proton transfers convert the dipolar intermediate to the carbmolamme... 

The loss of one or two (or sometimes more) ring members from heterocyclics, concerted with or followed by formation of a new ring, is a highly versatile method for heterocyclic synthesis. Loss of N2, CO, CO2, S, SO, SO2, H2C=CH2, etc. is common. Diradical or dipolar intermediates are often encountered, and valence isomerization before the actual fragmentation is characteristic for some systems. 

In the investigation of a ring enlargement, discrimination was possible between the reaction paths via a 1,3-dipole (142) and a quaternary acyl product (143), precursors of different triazolidones. Exclusive formation of (144) from (141) and phenyl isocyanate decided in favor of the dipolar intermediate (142) (81JOC320). 

Two extreme mechanisms can be envisaged (Scheme 12), concerted [2 + 2] cycloaddition or the more generally accepted formation of a dipolar intermediate (164) which closes to a /3-lactam or which can interact with a second molecule of ketene to give 2 1 adducts (165) and (166) which are sometimes found as side products. In some cases 2 1 adducts result from reaction of the imine with ketene dimer. 

It is believed that a reactive ground-state species, the zwitterion A, is an intermediate and that it rearranges to the observed product. To test this mechanism, generation of species A by nonphotochemical means was undertaken. a-Haloketones, when treated with strong base, ionize to such dipolar intermediates. Thus, the bromoketone 6 is a potential precursor of intermediate A ... 

The acetoxy dienone (218) gives phenol (220). Here, an alternative primary photoreaction competes effectively with the dienone 1,5-bonding expulsion of the lOjS-acetoxy substituent and hydrogen uptake from the solvent (dioxane). In the case of the hydroxy analog (219) the two paths are balanced and products from both processes, phenol (220) and diketone (222), are isolated. In the formation of the spiro compound (222) rupture of the 1,10-bond in the dipolar intermediate (221) predominates over the normal electron transmission in aprotic solvents from the enolate moiety via the three-membered ring to the electron-deficient carbon. While in protic solvents and in 10-methyl compounds this process is inhibited by the protonation of the enolate system in the dipolar intermediate [cf. (202), (203)], proton elimination from the tertiary hydroxy group in (221) could reverse the efficiencies of the two oxygens as electron sources. 

The preferred formation of the tetrasubstituted isomer with the olefin without any bulky substituent at the electrophilic carbon atom is undoubtedly due to the preponderance of that conformation of the dipolar intermediate in which the substituent is syn to the morpholine group, as shown in (41). The situation is, however, reversed in case of the olefin with... 

It was, however, found 22) that when the pyrrolidine enamine of cyclohexanone was allowed to react with an excess of -nitrostyrene, a bis adduct (46), made up of one molecule of the enamine and two molecules of olefin, was obtained in addition to the monoadduct. That the bis adduct is not derived from the monoadduct was shown by the latter s failure to react with (9-nitrostyrene. Therefore, this adduct must be formed by the addition of the olefin to the dipolar intermediate (47), as shown in the following scheme. 

In the Wittig reaction, a phosphorus ylide, R2C—P(C6H03, also called a phosphoreme and sometimes written in the resonance form R2C=P(C6H5)3, adds to an aldehyde or ketone to yield a dipolar intermediate called a betaine. (An ylide—pronounced ill-id—is a neutral, dipolar compound with adjacent plus and minus charges. A betaine—pronounced bay-ta-een—is a neutral, dipolar compound with nonadjacent charges.)... 

In a similar reaction, but with reversed polarities in the starting materials 3-nitrobenzofuran adds to l-phenyl-2-pyrrolidinoacetylene to afford a mixture of three components, one being 5-nitro-3-phenyl-2-pyrrolidino-l-benzoxepin (3, 27 %).183 In the first step of this reaction, a bond between C2 of the furan and the carbon atom in the a-position to the phenyl group is formed to produce a dipolar intermediate that can react in different directions. 

The addition of dimethyl acetylenedicarboxylate to 5-/er/-butyl-Ar,Ar,Ar, Ar -tetramethyl-2-aza-pentalene-1,3-diamine (20) is frontier orbital rather than charge controlled, and results initially in attack at the 3a-position to give, via a dipolar intermediate, tricycle 21, which undergoes valence isomerization to the cyclopent[c]azepine 22.107... 

Phenylsulphine prepared in situ from phenylmethanesulphinyl chloride and triethyl-amine reacted with 1 -morpholinocyclohexene to form the addition product 169 having the enamine structure218. A similar experiment with phenylsulphine and 2-pyrrolidinocyclo-hexene gave only 2-phenylmethanesulphinyl cyclohexanone 170. The latter is most probably formed by hydrolysis of the corresponding enamine sulphoxide upon isolation. The reaction of sulphines with enamines is apparently a stepwise process involving the transient formation of the dipolar intermediate 171 which is stabilized by proton transfer, giving the enamine sulphoxide. 

Still other proposed mechanisms involve diradicals or dipolar intermediates. OS IV, 895. 

Only c/s-disubstituted and trisubstituted alkenes yield l,4-dioxan-2-ones by way of a cycloaddition reaction when oxidised by dimethyl a-peroxy lactone. An open 1,6-dipolar intermediate is postulated, involving steieoelectronic control <96JA4778>. 

Olefination Reactions Involving Phosphonium Ylides. The synthetic potential of phosphonium ylides was developed initially by G. Wittig and his associates at the University of Heidelberg. The reaction of a phosphonium ylide with an aldehyde or ketone introduces a carbon-carbon double bond in place of the carbonyl bond. The mechanism originally proposed involves an addition of the nucleophilic ylide carbon to the carbonyl group to form a dipolar intermediate (a betaine), followed by elimination of a phosphine oxide. The elimination is presumed to occur after formation of a four-membered oxaphosphetane intermediate. An alternative mechanism proposes direct formation of the oxaphosphetane by a cycloaddition reaction.236 There have been several computational studies that find the oxaphosphetane structure to be an intermediate.237 Oxaphosphetane intermediates have been observed by NMR studies at low temperature.238 Betaine intermediates have been observed only under special conditions that retard the cyclization and elimination steps.239... 

The stereochemistry of these reactions depends on the lifetime of the dipolar intermediate, which, in turn, is influenced by the polarity of the solvent. In the reactions of enol ethers with tetracyanoethylene, the stereochemistry of the enol ether is retained in nonpolar solvents. In polar solvents, cycloaddition is nonstereospecific, as a result of a longer lifetime for the zwitterionic intermediate.177... 

The thermolysis of the adduct in Step D generates a diradical (or the corresponding dipolar intermediate), which then closes to the desired carbon skeleton. 

In the reaction with acetylenic compounds (PhC==CH or EtOC==CH), (E)-3 afforded 1 1 stereoisomeric products, indicating that the reaction proceeds stepwise via a diradical or dipolar intermediate.72... 

It is more likely that the dipolar intermediate (102) collapses to the product (99) before rearrangement can occur and thus gives rise to a product identical to that expected to be derived in a concerted process. The same type of products have been obtained with a number of other arynes 136,137). 

This result suggests that the 1,4-dipolar intermediate (133) is involved in this last reaction, and in accord with this is the formation of a 1 1 1 adduct of tetrachlorobenzyne, acetone and butan-2,3-dione, which has been shown to have the structure (134) 168>. 

With l,3>5-cycloheptatriene 2 can be trapped to yield four isomeric [2+2] adducts and the exo/endo isomeric [6+2] compound 16. Heating this mixture to 110°C leads to the complete transformation of the silacyclobutanes into 16 via a dipolar intermediate. The attempted synthesis of the diphenyl derivative of the [2+2] products leads to the stereospecific formation of endo-Yl which could be characterized by X-ray diffraction analysis [4]. 

The question as to whether enol ether 72, the insertion product derived from diethyl diazomalonate and 1-methoxycyclohexene, has a similar origin or arises from a dipolar intermediate of type 102, has already been discussed (Sect. 2.3.1). Interestingly enough, only one formal C/H insertion product was reported in that case, rather than three as in the reaction with 1-methylcyclohexene. 

The cycloadditions in entries 1-3 are still believed to occur via a diradical stepwise pathway, as confirmed by obtaining a thermodynamic 78 22 trans/cis mixture of dispirooctanes 536 from frans-dicyanoethylene (533) (entry 3) [13b, 143], The cycloaddition to tetracyanoethylene (131) in the absence of oxygen gives only low yields of the [2 + 2] adduct, due to the simultaneous formation of products 542 and 543 (Scheme 74) [13b]. Still, the formation of the cyclobutanes 537 and 542 is noteworthy, since the reactions of TCNE with phenyl substituted MCPs exclusively afford methylenecyclopentane derivatives [37,144], The reaction is thought to occur via dipolar intermediates 539-541 formed after an initial SET process (Scheme 74) [13b]. The occurrence of intermediates 540 and 541 has been confirmed by trapping experiments [13b]. 

The only successful [2 + 2] cycloaddition reported so far involving an MCP derivative and a carbon-heteroatom double bond is the reaction of BCP (3) with chlorosulfonylisocyanate (CSI) (594) [13b, 143], CSI is a typical [2 + 2] cycloaddend with most alkenes, but has been demonstrated to be also involved in stepwise cycloadditions via polar intermediates [157], The reaction of BCP and CSI gives the [2 + 2] cycloadduct 596 only as a minor product, besides the major [3 + 2] adduct 599 (Scheme 83) [13b, 143], Therefore, it has been reasonably suggested that both products derive from a common dipolar intermediate 595, formed by nucleophilic attack of BCP on the electron-deficient carbon of CSI (Scheme 83) [13b]. 

Indene, however, does give four-membered ring adducts with PTAD,69 and phthalazine-t,4-dione.70 The reaction with PTAD proceeds stepwise via the dipolar intermediate 43, which was trapped in the presence of water to give 44, under conditions in which the 1,2-diazetidine (45) was not opened by water to 44 (Scheme 5).69 Hydrolytic cleavage of the triazole ring in 45 using potassium rm-butoxide in wet dimethyl sulfoxide, followed by... 

A 1,2-diazetidine has been proposed as an intermediate in the reaction of pyridazine-3,6-dione (12) with styrene.87 The observed product was thought to arise from addition of water to the 1,2-diazetidine, although the alternative more likely explanation involving a dipolar intermediate (cf. Scheme 5) was apparently not considered. In the photochemical reaction of styrene with DEAZD, a 1,2-diazetidine structure was tentatively assigned to a minor product.88 Attempted photochemical [2 + 2] cycloaddition of DEAZD to other olefins failed to give any 1,2-diazetidines.88... 

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