Ketenimines 4+2 cycloaddition reactions

Thermal and photochemical cycloaddition reactions of 27r-electron species represent an important synthetic approach to four-membered rings. The reactions summarized in this section include 2 + 2 cycloaddition reactions of thioketones, thioketenes, isothiocyanates, sulfenes and iminosulfenes with alkenes, allenes, ketenes, ketenimines and alkynes. 

The cycloaddition reactions of ketenimines to thiocarbonyl groups to give both 1,2-(iminothietanes) and 1,4-adducts have been reviewed. The frontier molecular orbitals of the reactants are important for the addition that is classed as a ( 2 + 2a) process. Steric factors play a role and the rate of 1,2-addition to give 2-iminothietanes depends more on the substituents at the terminal carbon atom of the ketenimine than 1,4-addition to give a six-membered ring. The rate of 1,2-... 

Although no preparatively useful metal-catalyzed [3-F 2]-cycloaddition reactions involving ketenes have been developed due to the pronounced [2-F2]-cycloaddition reactivity of this substrate vide supra), ketene derivatives, e.g. ketenimines, are much less prone to undergo [2 + 2] cycloadditions, so that [3-1-2] cycloaddition can successfully compete. However, instead of the primarily expected 2,4-bis(methylene)pyrrolidines or a-methylene-d -pyrrolines, substituted pyrroles are formed whenever double-hond isomerization is possible. For example, such a reaction smoothly proceeds with the parent MCP (4) and iV-phenyldiphenylketenimine (19) which provides 2-(diphenylmethyl)-4-methyl-l-phenylpyrrole (20) in 96% yield. 

Reactions of triphenyl-2,2-bis(trifluoromethyI)vinylidenephosphorane, synthesized from a cyclic ylide-ketone adduct. 7 Cycloaddition reactions of triphenylphosphoranylideneketenc. 8 Synthesis of triphenylphosphoranylidene-ketenimines. 9... 

Acyl sulfenes, like all sulfenes, prefer to participate as 2it components of [2 + 2] or [4 + 2] cycloadditions (Chapter 5). Nonetheless, a range of [4 + 2] cycloaddition reactions of acyl sulfenes have been described46,47 (Scheme 8-XII), including their 4n- participation in dimerization reactions46-48 and reactions with imines,49 carbodiimides,50 ketenimines,51 1-azirines,52 vinyl ethers,53 and ketenes.47 The reactions often provide mixtures of [4 + 2] and [2 + 2] cycloadducts, and the observed course of the reaction usually depends on the reaction conditions. Consequently, many of the observed [4 + 2] cycloadditions of acyl sulfenes proceed by a stepwise, polar addition-cyclization reaction. 

Because of their predictable behavior and reactivity, thioacyl isocyanates comprise the bulk of this work, and extensive studies of their [4 -I- 2] reactions with olefins, enamines, enol ethers, thioacyl isocyanates, imines, carbodiimides, isocyanates, azirines, /3-enaminoke-tones, dianils, azines, hydrazones, imidazoline-4,5-diones, aryl cyanates, disubstituted cyanamides, aldehydes, ketones, ketenes, alkyl or aryl iminodithiocarbonates, and the carbon-carbon double bond of ketenimines have been detailed. In an extensive comparative study of the [4 + 2] cycloaddition reactions of thioacyl isocyanates, the heterocu-mulenes bearing strong electron-withdrawing substituents were found to be more stable and less prone to participate in cycloaddition reactions. Representative examples are summarized in Scheme 9-IV. 

Reactions of fluoroalkylketenimines which have been reported following these newly available synthetic approaches include hydrolysis and related additions of amines and alcohols, all of which occur at the olefinic bond. In contrast, the apparently similar addition of secondary phosphines occurs at the carbon-nitrogen double bond. These ketenimines appear to enter into cycloaddition reactions very readily with acetylenes they give quinolines, with nitrones they give oxindoles or oxadiazolidines (see p. 107), i > i and with isocyanides they yield iminoindolenines. These reactions are summarized in Scheme 54. 

A miscellany of papers dealing with the potency of the thioureido neighbouring group in nucleophilic substitution processes, the complexing ability of thioureas towards macrocyclic polyethers, and the cycloaddition reactions of thiocarbamoyl isothiocyanates (190) with ketens, ketenimines, imines, isocyanates, carbodi-imides, and isonitriles also deserve attention. 

The use of ketene equivalents in 4- -2-cycloaddition reactions for organic synthesis has been reviewed. " a-Carbonyl ketenes behave as dienes in Diels-Alder reactions with 4-aryl-2-methyl-2,3-dihydro-l,5-benzothiadiazepines to yield regiospecific cycloadducts. The reactions of diphenylketene with cyclic ( -cw)-l,3-dienes such as cyclopentadiene and cyclohexadiene initially yield the Diels-Alder adducts, which are converted into the Staudinger cyclobutanones by [3,3]-sigmatropic rearrangementsl-Benzyl-l,3-diazabuta-l,3-dienes react with ketenes to produce the 4 - - 2-cycloadducts, substituted l-benzyl-4-(benzylidenimino)-4-phenylazetidin-2-ones, which rearrange into the more stable 5,6-dihydro-3//-pyrimidin-4-ones. The formal 4 - - 2-cycloaddition reaction of ketenimines has been used to synthesize benzoimidazo[l,2-Z ]isoquinolines. ... 

In the [3+2] cycloaddition reaction with ketenimines two isomeric adducts 12 and 13 are formed by reaction across either the C=C or the C=N bond of the ketenimines . 

The substituent R determines the reactivity of the isocyanate. Aromatic isocyanates react faster than aliphatic isocyanates, and carbonyl and sulfonyl isocyanates are considerably more reactive than the former. Isocyanate groups attached to oxygen or nitrogen are not stable in their monomeric forms. In cycloaddition reactions, isocyanates react preferentially across their C=N bonds, but additions across the C=0 bonds are also encountered. In this respect, isocyanates resemble ketenes (see Chapter 4, Section 4.1.). Suitable substrates for cycloaddition reactions are carbon multiple bonds (acetylenes, olefins, ketenes, etc.), C=N bond-containing compounds (imines, amidines, ketenimines, azines, carbodiimldes, etc.), C=0 bonds and C=S bond-containing substrates and phosphorus multiple-bond-containing substrates. Cycloaddition reactions of isocyanates across multiple metal bonds are also known. 

When C=N groups are part of a heterocumulene system, as in ketenimines and carbodi-imides, they readily undergo [2+2] cycloaddition reactions with isocyanates. For example, C,C-diphenyl-A -p-tolylketenimine 138 reacts with phenyl isocyanate to give the four-membered ring cycloadduct 139 in 83 % yield. The cycloaddition proceeds exclusively across the C=C bond of the ketene imine. ... 

In ketenimines, the cumulative double bond system absorbs in the infrared region at 2000-2050 cm . In cycloaddition reactions, ketenimines are less reactive than ketenes, and A-arylketenimines react faster than A-alkylketenimines. These reactions most likely proceed via a linear ionic intermediate, which can cyclize to give four-membered ring or six-membered ring cycloadducts, or react with a second mole of ketenimine to give a [2-I-2-I-2] cycloadduct. 

Generally, ketenimines undergo inter- and intramolecular [2-1-2] cycloaddition reactions across their C=C bonds. In [4+2] cycloaddition reactions, ketenimines can participate as dienophiles via their C=C or C=N bonds or they react as azadienes. The [3+2] cycloaddition reactions are also known but they are less prominent. Also, many electrocyclization reactions are reported. 

The ketenimines 11 react with methylsulfonyl nitrene via a [2+1] cycloaddition reaction to give the diaziridines 12 . 

Across carbon-carbon multiple bonds The [2+2] cycloaddition reaction of ketenimines to acetylenic compounds affords 2-azetines and six-membered ring 2-iminotetrahydropyridine derivatives. For example, reaction of 1-diethylamino-l-propyne with iV-methyldiphenylketenimine in acetonitrile for seven days gives an equimolar mixture of the [2+2] cycloadduct 13 and the [2+2+2] cycloadduct 14... 

Keteniminium salts undergo [2-1-2] cycloaddition reactions with unreactive olefins, such as ethylene, cyclopentene, cyclohexene and styrol to give cyclobutane ammonium salts 23, which are readily hydrolyzed to give cyclobutanones 24. Likewise, reaction with acetylene derivatives affords cyclobutenylidene ammonium salts 25, which are also readily hydrolyzed to give the cyclobutenones 26. Some of the [2-1-2] cycloadducts obtained from keteniminium salts and olefines are shown in Table 4.17. The keteniminium salts are easily synthesized from suitable dimethylamides and phosgene, or trifluoromethanesulfonic acid anhydride. The reaction of the amide with phosgene generates a chloro compound 21, which is in equilibrium with the ketenimine salt 22. 

The [2+2] cycloaddition reaction between ketenimines and aldehydes is also catalyzed by Y+ and Eu+ shift reagents Heating of the respective iminooxetanes in the presence of the same catalysts causes formation of the isomeric -lactams Also, duroquinone reacts photochemically with Ph2C=C=NPh to give the isomeric imino... 

An intramolecular cycloaddition reaction involving a ketenimine with two different substituents on its sp carbon terminus 42 affords a mixture of mainly m-azeto[2,lb]-quinazoline 43 and the trans- isomer 44 in total yields of 29-84... 

Likewise, the imino(acylimino)ketenimines 51, generated in situ, undergo an intramolecular cycloaddition reaction to give 52. ... 

Azeto[l,2]imidazoles 56 are also obtained in low yields by a formal intramolecular [2+2] cycloaddition reaction of the imino ketenimines 55/ ... 

An intramolecular ketenimin-ketenimine [2+2] cycloaddition reaction has also been observed. The bis-ketenimine 57 was generated in situ by the aza-Wittig reaction and intramolecular cyclization afforded azeto[2,l-b]quinazolines 58 in moderate to good yields." ... 

Across N=N bonds Another pronounced [2+2] cycloaddition reaction of ketenimines is their addition to the N=N bond in cis-azomethines to give the imino-l,2-diazetidines 62 and 63. This reaction is conducted with UV irradiation to convert the unreactive trans-azobenzenes into the reactive cis-cis compounds. Asymmetrically substituted azobenzenes afford mixtures of the two regio isomers. Electron donating substituents on the azobenzenes increase the rate of addition. Some of the [2+2] cycloadducts obtained in the reaction of ketenimines with azo compounds are listed in Table 4.22. 

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