Cycloaddition of ketenimines

Some examples dealing with the [4 + 2] cycloaddition of ketenimines have been recorded (Scheme 58). Thus, thioketones and ynamines reacted with N-aryl ketenimines 257 through the carbon—nitrogen and the conjugated aromatic carbon—carbon double bonds to yield benzothiazine derivatives 258 (80JOC3766 82JOC3998) and substituted quinolines 259 (73JA5417), respectively. Simple ketenimines 261 were formed by reaction... 

Ab initio calculations indicate that in the gas phase the reaction of ketene inline and formaldehyde is concerted but asynchronous whereas in dichloromethane it is a two-step zwitterionic reaction.38 The 2 + 2-cycloadditions of keteniminium triflates with imines yields 2-azetidiniminium salts with cis stereoselectivity.39 The intramolecular 2 + 2-cycloaddition of ketenimines with imines (24) provides a novel synthesis of azeto[2,l-Z>]quinazolines (25) (Scheme 9).40... 

Thermal cycloadditions of ketenimines to cait>onyl compounds requires activation of the 0=0 bond. The highly electrophilic bis(trifluoromethyl) ketone reacts at high temperature with diphenyl-N-to-lylketenimine (equation 73). Lanthanide shift reagents such as tris(6,6,7,7,8,8,8-heptafIuoro-2,2-di-methyl-3,S-octanedionato)-europium or -ytterbium [Eu(fod)3 or Yt(fod)a] are efficient catalysts for the cycloaddition of ketenimines with aldehydes (equation 74). The use of chiral catalysts such as tris[3-(heptafluoropropylhydroxymethylene)-(+)-camphorato)-europium or -ytterbium [Eu(hfc)3 or Yt(hfc)3] has been found to generate only moderate enantiomeric excesses (20-40%). ... 

The synthesis of imino-penam and -cephem derivatives has also been investigated using the [2 + 2] cycloaddition of ketenimines to Schiff bases as the key-step [24]. N-(aryl) and N-(alkyl)ketenimines are not electrophilic enough to react with Schiff bases. On the other hand, iV-(tosyl)ketenimines 25 were susceptible to nucleophilic attack by imines (Scheme 9). They were readily generated in situ from the corresponding sulphimides 23. The a-bromo-iminium bromide intermediates 24 reacted with Schiff bases and triethylamine to give JV-(tosyl)azetidin-2-imines 26. 

AMI studies of the 2 - - 2-cycloaddition of ketenimines with imines show that the reaction involves a stepwise mechanism via an intermediate and two transition states. A computational investigation of the thermal 2 - - 2-cycloaddition between imines and ketiminium cations finds that the reaction takes place via a stepwise mechanism.The reaction of benzyne with Schiff bases, diimines, yields l,4-bis(2-substituted acridin-10-yl)benzene via an initial double 2 - - 2-cycloaddition. 

However, the cycloaddition of ketenimines to azomethines is also catalyzed by zinc chloride and yields of 14-57 % of the [2+2] cycloadducts are obtained. ... 

DeKorver, K. A., Hsung, R. R, Song, W. Z., Wang, X. N., Walton, M. C. (2012). An intramolecular 2-1-2 cycloaddition of ketenimines yia palladium-catalyzed rearrangements of N-allyl-ynamides. Organic Letters, 14, 3214-3217. 

A cascade reaction involving 1,3-dipolar cycloaddition of ketenimine was reported by Li et al. [69], The transformation combines a CuAAC reaction, a Lewis add-catalyzed 6-endo cyclization of Af -(2-alkynylbenzylidene)hydrazide, a [2+3] cycloaddition, and an aromatization in a single step to afford 2-amino-//-pyrazolo[5,l-a] isoquinolines 102 in good to excellent yields (Schane 5.66). The copper-catalyzed three-component reaction of sulfonyl azides, alkynes, and nitrones also involves 1,3-dipolar cycloaddition between ketenimine and nitrone (Scheme 5.67) [70]. The nitrone substrates in this transformation could be generated in situ from benzalde-hydes and hydroxylamines. 

SCHEME 5.66 Cu(I)/AgOTf-cocatalyzed cascade reaction involving 1,3-dipolar cycloaddition of ketenimine. 

The cycloaddition of nitrones with ketenes produced 5-isoxazolidinones as well as oxazolones, as shown in Scheme 162 (78H(9)457, 79JOC2961). In a similar fashion, nitrones also react with ketenimines to generate the 5-isoxazolidinone imines (75JHC175, 68JHC881). 

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... 

A reported example (12) of this ring system was prepared by Woemer et al. (71CB2789) by the cycloaddition of the ketenimine 11 to 3-phenyl-2//-... 

Diazetidinones are prepared by the thermal [2 + 2] cycloaddition of ketene with diazo compounds (Scheme 3) (83HC(42)443). Use of ketenimines instead of ketene furnished imino derivatives (67JHC155). 

The Paterno-Biichi reaction has been employed in the synthesis, often in high yield, of a large variety of substituted oxetanes. In addition to simple aliphatic and aromatic alkenes, cycloaddition of ketones to, for example, fumaronitrile,284 l,3-diacetylimidazolin-2-one288 [Eq. (73)], and allenes286 has been reported. Allenes yield both 1,5- and l,6-dioxaspiro[3.3]heptanes as well as the 2-alkylidene-oxetane this is illustrated for benzophenone and tetramethylallene in Eq. (74). Cycloaddition of ketones to ketenimines to form 2- and... 

In a manifestation of the reaction shown above, quinoline rings have also been formed by the cycloaddition of /V-arylketenimines 543 with 3,4-dihydro-2//-pyran 455 under high-pressure conditions (Scheme 100) <2001H(55)1971>. The reaction is proposed to proceed via the initial formation of 544 by attack of the enol ether on the protonated ketenimine subsequent electrophilic aromatic substitution gives 545. Protonation of the enamine to give 546 is followed by elimination to produce 547. Protection of the alcohol with 455 gives 548. 

Another possibility for the preparation of bicyclic systems such as III/47 from three-membered rings can be realized by a [2+2] cycloaddition of the cyclopropene, III/41, and an unsaturated molecule, III/46, such as alkene, alkyne, ketene, ketenimine, ketone, isocyanate, etc. A large number of examples of this reaction type have been reviewed recently [55]x). 

The spiro-triazoline (380) can be converted into both the ketenimine (381) and the cyclobutanimine (382) (74JOC63). Triazolines formed by cycloaddition of azides to norbor-nene lead to munerous interesting norbornane derivatives (of. 78bsf(2)48s). 5-Hydroxytriazo-lines (383) afford the ring-contracted amide (384) by thermal dehydration (67mi411oo). 

There are only few reports of [2 + 2] cycloadditions with ketenimines. " In most cases, reactions occur across the C=C bond. Only ynamines and polyfluorinated alkenes cycloadd to the C=N bond. 

Ketenimine complexes can serve as three-atom components in [3 + 2] cycloadditions. The reaction of the tungsten complex (378) with cyclohexyl isonitrile and phenyl isocyanate produces the heterocyclic carbene complex (379), which is the result of the in situ trapping of a ketenimine complex with the isocyanate. Complexes of the type (379) can be oxidatively cleaved to give the previously inaccessible 5-ethoxyhydantoins. [3 + 2] Cycloadditions of this type have also been carried out with aldehydes. 

Pd(PPh3>4]- or (PhO)3P/[Ni(COD)2]-catalyzed [3 + 2] cycloadditions of methylenecyclopropanes with ketenimines (66) lead selectively to pyrroles (67 equation 26), (68) and (69 (equation 27), or a-methylene-A -pynolines (70 equation 28) depending on the sutetituents of the imino group and the methylenecyclopropanes. Diphenylketene-N-methylimine reacts with (26) to give l-methylimino-3-methyl-5,5-diphenylcyclopent-2-ene in 38% yield. ... 

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-... 

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