Dipolarophiles, in 1,3-dipolar cycloaddition

Benzocyclobutene, when generated by oxidation of its iron tricarbonyl complex, can function as the dipolarophile in 1,3-dipolar cycloaddition reactions with arylnitrile oxides (Scheme 113).177 Unfortunately the synthetic versatility of this type of process is limited because of the unreactivity of other 1,3-dipolar species such as phenyl azide, benzonitrile N-phenylimide, and a-(p-tolyl)benzylidenamine N-oxide.177... 

The carbon-nitrogen triple bond of aryl thiocyanates acts as a dipolarophile in 1,3-dipolar cycloadditions. Reactions with nitrile oxides yield 5-arylthio-1,2,4-oxadiazoles 227 (X = O Y = S). Aryl selenocyanates behave similarly forming 5-arylseleno-l,2,4-oxadiazoles 227 (X = 0 Y = Se). Reactions of 5-aryl-... 

The use of nitriles as dipolarophiles in 1,3-dipolar cycloaddition reactions is scarce because of their relative inertness in such reactions. Indeed, nitriles with electron-donor substituents do not react with nitrones even under harsh conditions. Hence, an additional activation of the reactants is required. This can be achieved, either by activating the nitrile (dipolarophile) or the nitrone (dipole), or both of them. For example, the reaction of electron-difficient nitriles such as... 

Numerous reactions of acetylenic esters are reported in the literature, and many of these lead to heterocyclic compounds. Acetylenic esters undergo very facile addition reactions with several nucleophiles and also they participate as dipolarophiles in 1,3-dipolar cycloadditions, and as... 

Dipolar Cycloaddition Reactions. Dehydroamino acid derivatives behave as dipolarophiles in 1,3-dipolar cycloaddition reactions that leads to a variety of interesting compounds. For example, 1,3-dipolar cycloaddition of diazomethane to dehydroamino acid esters 475 and 481 gives the corresponding pyrazolines 476 and... 

Alkynic esters participate as dipolarophiles in 1,3-dipolar cycloadditions and as dienophiles in Diels-Alder additions. They participate in [2+2] cycloadditions with alkenes, and they also undergo facile addition reactions with several nucleophiles to give (5,5)-fused heterocyclic ring systems (76AHC(19)279). 

Interestingly, phosphirenes can act as dipolarophiles in 1,3-dipolar cycloaddition reactions. The mesoionic dithio-liumolate yields a 4//-l,4-thiaphosphinine with 1,2,3-triphenylphosphirene via the primary cycloadduct (Equation 20) <1995H(40)311>. 

Dipoles react with alkenes and alkynes (dipolarophiles) in 1,3-dipolar cycloadditions (a.k.a. [3 + 2] cycloadditions) to give five-membered heterocycles. Many agrochemicals and pharmaceuticals contain five-membered heterocycles, and the dipolar cycloaddition is an important synthetic route to these compounds. 

Knoevenagel products are highly reactive compounds because of their low energy LUMO. They can act as dienophiles in the normal Diels-Alder reaction, as heterodienes in the hetero Diels-Alder reaction with inverse electron demand,- as dipolarophiles in 1,3-dipolar cycloadditions, as enophiles in the ene reaction and as acceptors for the addition of allylsilanes. Sigmatropic rearrangements and photochemical reactions have been described. 

Menthol [(—)-l] has been used as a chiral ligand for aluminum in Lewis acid catalyzed Diels-Alder reactions with surprising success2 (Section D.l.6.1.1.1.2.2.1). The major part of its application is as a chiral auxiliary, by the formation of esters or ethers. Esters with carboxylic acids may be formed by any convenient esterification technique. Esters with saturated carboxylic acids have been used for the formation of enolates by deprotonation and subsequent addition or alkylation reactions (Sections D.l.1.1.3.1. and D.l.5.2.3.), and with unsaturated acids as chiral dienes or dienophiles in Diels-Alder reactions (Section D. 1.6.1.1.1.), as chiral dipolarophiles in 1,3-dipolar cycloadditions (Section D.l.6.1.2.1.), as chiral partners in /(-lactam formation by [2 + 2] cycloaddition with chlorosulfonyl isocyanate (SectionD.l.6.1.3.), as sources for chiral alkenes in cyclopropanations (Section D.l.6.1.5.). and in the synthesis of chiral allenes (Section B.I.). Several esters have also been prepared by indirect techniques, e.g.,... 

A study of the ability of tetrazolo[l,5-a]pyridines to act as dipolarophiles in 1,3-dipolar cycloadditions showed that the presence of a nitro group in the pyridine moiety is necessary for transformations with diazopropane <89H(28)259>. When 6-nitrotetrazolo[l,5-a]pyridine (38) was treated with this reagent, both double bonds C-5—C-6 and C-7—C-8 reacted and the bis-cycloadduct (39) was formed which easily underwent nitrogen elimination to give the product (40) (Scheme 6). 

One of the most powerful derivatization techniques of Pi position was presented in 2003 by Makaritis et al. They prepared phosphinic pseudodipeptide precursors bearing a propargyl group in their Pi side chain (42) and saw that these molecules can serve as excellent dipolarophiles in 1,3-dipolar cycloadditions with in situ-prepared nitrile oxides (Scheme 21) [74], This approach can be easily applied in both solid phase and solution s5mtheses, and has been successfully used in the discovery of selective inhibitors of several Zn-metalloproteases [38, 84, 92, 103, 104]. 

It was demonstrated that the reaction proceeds without racemisation of the stereogenic phosphorus atom and with total selectivity towards the ( )-alke-nylphosphine oxide. Unexpectedly, it was also possible to dimerise phosphine oxide 109 (with R = Me) with 5% of 112b to obtain the corresponding optically pure ( )-diphosphine oxide in 85% yield. The crystal structure of this compound has been determined by X-ray diffraction and has been used as dipolarophile in 1,3-dipolar cycloadditions with nitrones, yielding several optically pure diphosphine oxides. Similar homometathesis reactions have been investigated in more detail by Grela, Pietrusiewicz, Butenschon and co-workers with other (racemic) substrates such as 109 and different catalysts. Gouverneur and co-workers studied a similar dimerisation of... 

Shen T, Wang T, Qin C, Jiao N (2013) Silver-catalyzed nitrogenation of alkynes a direct approach to nitriles through C=C bond cleavage. Angew Chem Int Ed 52(26) 6677-6680 Kadaba PK (1990) TriazoUnes XX. Vinyl azides as dipolarophiles in 1,3-dipolar cycloadditions intermolecular cycloaddition of hydrazoic acid and a-styryl azide to give a tetrazole. Synlett 6 349-351... 

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