Ketenes, cycloadditions with imines

During the study of the reaction of ketene 65 with imines 66 in sulfur dioxide, substituted thiazolidin-4-one 1,1-dioxides (67) are formed [Eq. (20)], rather than the expected azetidinones.80 This cycloaddition was initially suggested to proceed through a 1,4-dipolar species 68s 8 whereas later, a (3 + 2)-cycloaddition, via a 1,3-dipolar intermediate 69, was demonstrated to support the results better.85 This ketene-sulfur dioxide adduct 69 reacts... 

Borer and Balogh [30] used the chiral ketene precursor 33 in the asymmetric [2-h2] cycloaddition with imine 34 derived from cinnamaldehyde. After detachment from the chiral auxiliary under acidic conditions, the cw-P-lactam 35 was obtained in 52% overall yield and 70% ee (Scheme 10.8). 

Ketenes react with imines via [2+2]-cycloaddition to produce P-lactams.278 An example is the reaction of the acid chloride of phenylacetic acid with Proton Sponge to give ketene 340, which reacted with the tosyl imine shown and a quinuclidine catalyst to give a 65% yield of P-lactam 341, in 96% ee.229 A-Substituted isocyanates also undergo thermal [2+2]-cycloaddition reactions with alkenes, generating P-lactams.280... 

G(d,p) level the reaction of ketene (125) with imines (126a,b) in the presence of BF3 (Scheme 32). These authors found that the most likely mechanism involves the coordination of the Lewis acid with the ketene to yield a stepwise mechanism, which is led by the endo and exo attacks to the formation of trans- and cis-cycloadducts (129a,b) via intermediates (127a,b) and (128a,b), respectively. A factor that complicates the efficiency of the reaction is the interaction between the Lewis acid and the imine, thus resulting in stable intermediates that make difficult the completion of the cycloaddition and the catalytic cycle. 

Cycloaddition. This ketene does not react with cyclopenfadiene or vinyl ethers, but it does undergo [2 + 2]cycloadditions with imines (equation I) and carbodiimides... 

Ketenes are another type of unsaturated molecules of high electron deficiency and structural strains therefore, they are very reactive for the [2+2] cycloaddition. The most common [2+2] cycloaddition involving ketenes are Staudinger [2+2] Cycloadditions to form fi-lactones, initially reported in 1911, and the dimerization of ketenes." Besides the easy cycloaddition with imine, as shown in the Staudinger [2+2] Cycloaddition, ketenes can also react with aldehydes to afford /3-lactones. It has been found that high diastereoselectivity can... 

The most prominent use of ketenes is for [2 + 2] cycloaddition with imine for the construction of /3-lactam skeleton. When the Y group in Scheme 1 is vinyl or aryl group, the deprotonation of the activated a-proton is highly facilitated. In this context, the carbonylation of some allylic derivatives, for example, allyl bromide, allyl acetate, allyl phenyl ether, allyl methyl carbonate, allyl phenyl sulfone, and allyl phosphate, documented to form TT-allylpalladium intermediates is examined. It is interesting to note that only phosphate undergoes the cycloaddition to produce /3-lactam. The characteristic dependency of the stereochemistry on the reaction conditions, being contrary to the results in the usual base-induced cycloaddition is also intriguing. Scheme 2 presents the... 

The interaction of acid chlorides (167 X = Cl) with imines in the presence of bases such as triethylamine may involve prior formation of a ketene followed by cycloaddition to the imine, but in many cases it is considered to involve interaction of the imine with the acid chloride to give an immonium ion (168). This is then cyclized by deprotonation under the influence of the base. Clearly, the distinction between these routes is a rather fine one and the mechanism involved in a particular case may well depend on the reactants and the timing of mixing. Particularly important acid chlorides are azidoacetyl chloride and phthalimidoacetyl chloride, which provide access to /3-lactams with a nitrogen substituent in the 3-position as found in the penicillins and cephalosporins. 

Abstract The photoinduced reactions of metal carbene complexes, particularly Group 6 Fischer carbenes, are comprehensively presented in this chapter with a complete listing of published examples. A majority of these processes involve CO insertion to produce species that have ketene-like reactivity. Cyclo addition reactions presented include reaction with imines to form /1-lactams, with alkenes to form cyclobutanones, with aldehydes to form /1-lactones, and with azoarenes to form diazetidinones. Photoinduced benzannulation processes are included. Reactions involving nucleophilic attack to form esters, amino acids, peptides, allenes, acylated arenes, and aza-Cope rearrangement products are detailed. A number of photoinduced reactions of carbenes do not involve CO insertion. These include reactions with sulfur ylides and sulfilimines, cyclopropanation, 1,3-dipolar cycloadditions, and acyl migrations. 

Cycloadditions give rise to four-membered rings. Thermal concerted [2+2] cycloadditions have to be antarafacial on one component and the geometrical and orbital constraints thus imposed ensure that this process is encountered only in special circumstances. Most thermal [2+2] cycloadditions of alkenes take place by a stepwise pathway involving diradical or zwitterionic intermediates [la]. Considerably fewer studies have been performed regarding the application of microwave irradiation in [2+2] cydoadditions than for other kinds of cydoaddition (vide supra). Such reactions have been commonly used to obtain /1-lactam derivatives by cycloaddition of ketenes with imines [18-20,117,118],... 

Condensation with imines to afford jS-lactams. These latter ones can also be obtained by cycloaddition of the same imines with the keten stemming from fluoroacetyl chloride. ... 

A number of cycloadditions of imines or imino compounds with a variety of alkenes, including allenes (88HCA1025), vinyl ethers (88TL547), methyl acrylate (86ZOR636), ketene acetals (87JOC365) and electrophilic alkenes (85T1953), afford functionalized azetidines. 

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... 

Gonzalez et al. [105] have further investigated the diastereoselective [2+2] cycloaddition reaction of unsymmetrical cyclic ketenes with imines for the synthesis of a variety of spiro-(3-lactams (Scheme 34). 

Chiral imines derived from D-(+)-glucose have allowed an asymmetric synthesis of p-lactams by the [2+2] cycloaddition with ketenes [85]. c/A-p-Lac tarns were formed with very high diastereoselectivity and the stereochemistry at the C-3 and the C-4 was established as 3S and 4R from the known absolute configuration of the sugar moiety (Scheme 24). 

The synthesis of 1,3-disubstituted-4-trichloromethyl azetidin-2-ones by the Staudinger cycloaddition of ketenes with imines derived from chloral has been described to occur with high stereoselectivity [91], The civ-isomer was obtained almost always as the major or the single product. 

Spiro-p-lactams have been synthesized via [2+2] cycloaddition of cyclic ketenes with imines [100]. Opposite trans or cis diastereoselectivity was obtained using different imines with electron-donating or electron-withdrawing (R1) substituents at the N-atom, (Scheme 33). 

Cycloaddition of a ketene complex with unsaturated bonds other than alkenes and alkynes is also possible. The ketene 312, formed from 311, adds to imine 313 to give the /1-lactam 314 under sunlight photolysis. The optically active /1-lactam 314 was prepared from the optically active carbene complex 311 with 99% ee, and converted to 315 [95]. Irradiation of carbene complex 316 generates ketene 317, which cyclizes to the o-hydroquinone derivative 318 [96],... 

Another common method for the synthesis of 2-azetidinones is the cycloaddition of imines with ketenes, which is known as the Staudinger reaction . Although commonly described as a [2 + 2]... 

As a Chiral Starting Material in p-Lactam Synthesis. Various p-lactams have been prepared via [2 + 2] cyclization of ket-enes with aryl or benzyl imines derived from the reagent. Thus the para-methoxyphenyl imine derived from condensation of the corresponding aniline and the reagent underwent [2 + 2] cycloadditions with various ketenes to afford p-lactams in moderate yields but with very high stereoselectivity (eq 14). ... 

While cycloadditions of imines with ketenes or their precursors often produce cis P-lactams, the corresponding reactions of keteniminium salts are trans stereoselective (equations 70 and 71). 0 222 It is not clear whether the trans stereoselectivity is kinetic or results from an equilibration of 2-azetidiniminium salts under the basic conditions used in both cycloaddition and hydrolysis steps. 

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