Ketenes cycloadducts derived from

Cycloaddition Reactions Across C—C Multiple Bonds. Cycloadducts derived from carbodiimides and olefins or allenes are not known. However, the [2+2] cycloaddition of ketenes, R2C=C=0, to carbodiimides affords 4-imino-2-azetidinones (/3-lactames) 239 in high yield. Aliphatic carbodiimides show higher reactivity in comparison to aromatic carbodiimides, and the reaction proceeds across the aliphatic C=N bond in N-alkyl-N -arylcarbodiimides. The cycloadducts obtained in this reaction are listed in Table 2.3. 

Table 2.3 Cycloadducts derived from Ketenes and Carbodiimides...

Table 3. 15 Some cycloadducts derived from ketenes and carbodiimides...

Table 43 [2+2] Cycloadducts derived from ketenes and olefins...

When the [2+2] cycloadducts derived from ketenes and vinyl ethers are treated with basic or neutral AI2O3, the cyclobutenones 203 are obtained in high yields ". Heating of 203 affords the naphthalene derivatives 205 in quantitative yields via the vinyl ketene intermediate 204 " . 

In the catalyzed thermal reaction of alkylarylketenes with cyclopentadiene [4+2] cycloadducts are obtained (see Section 4.1.4.2). In this reaction, the ketene undergoes the reaction across its C=0 bond initially, but the isolated cycloadducts derive from addition across the C=C bond. In contrast, olates, such 6-oxo-3,6-dihydro-l-pyrimidinium-4-olates 377, react with dimethyl- and diphenylketene across the C=0 bonds to give the stable... 

Benzonitrile reacts similarly with a-oxoketenes to give the [4-f2] cycloadducts Linear and cyclic azomethines also form 1 2 cycloadducts with ketenes. The initially formed ionic 1 1 adduct reacts with another equivalent of the ketene to give the [4-1-2] cycloadduct. The total reaction is a [2- -2- -2] cycloaddition reaction. The [2-F2-F2] cycloadducts derived from azomethines and ketenes are listed in Table 4.12. In the reaction of ketene or diketene with heterocyclic compounds the so-called Wollenberg compounds are obtained. For example, from quinoline and ketene the tricyclic compound 410 is obtained (see Table 4.12). 

In the reaction of some 1,3-diazabutadienes with diphenylketene, [4+2] cycloadducts are also obtained (for [2+2] cycloadducts, see Section 4.1.4). The [4+2] cycloadducts derived from 1,3-diazabutadienes and diphenylketene 414 are listed in Table 4.14. Ab initio and density functional studies found that the vinylic C=C and the carbonyl C=0 group of the ketenes are found to participate in this concerted asynchronous [4+2] cycloaddition... 

A study of ketene A, O-acetals has shown that such compounds derived from lactam acetals may be used in the preparation of larger heterocyclic systems via reaction with a 1,3-dipolar species, the initial cycloadducts stabilizing their structures by aromatization. Pyrrolo[2,3-i/]-l,2,3-triazole derivatives, however, do not undergo such elimination reactions and stable cycloadducts may be obtained. Thus, the lactam acetals (133) give the ketene A,0-acetals (134), which on reaction with p-nitrophenyl azide yield substituted pyrrolo[2,3-d]-l,2,3-triazole derivatives (135) <86CB359l>. 

For example, photocyclization61,78 of compound 49, derived from the phenyl complex la by addition of cyclopentadiene, was shown to afford the 1,2-dioxy naphthalene 50 (Scheme 18).79 Thus, the regiochemistry of this type of ring annulation is complementary to that of the Dotz reaction, which yields 1,4-dioxy compounds. Photocyclization of aminocarbene complex 5180 involves insertion of carbon monoxide and leads to production of an 2-amino-l-oxy naphthalene derivative 52. Regio isomers, e.g., l-amino-2-oxy compounds 54, can be generated thermally by intermediate formation of a ketene imine 53 by addition of an isocyanide to compound 49 79,81,82 (Amino)alkynylcarbene complexes also give [4+2] cycloadducts, but they prove to be much less reactive than the corresponding alkoxycar-bene compounds (Scheme 18).42,83... 

The first 2-azetidinone O-lactam) was obtained by Staudinger from the reaction of diphenylketene with benzylideneaniline (equation 13). Most of the -lactams prepared by this method have been made from imines derived from aromatic carbonyl compounds and ketoketenes. - The reaction of ketene itself with imines has been recently reinvestigated. Good yields of 3-lactams are obtained when a stream of ketene gas is passed through Ae imine in the absence of solvent (equations 14 and IS). No [4 + 2] cycloadduct is formed with N-cinnamylideneaniline. 

Imines derived from glyoxylic acid derivatives successfully lead to 3-lactams which are potential precursors of various antibiotics (equation 29). Conjugated imines have also been used in this context they give exclusively [2 -i- 2] cycloadducts with azido-, phthalimido-, phenoxy- and vinyl-ketene precursors (equations 30 and 31). However, [4 -i- 2] adducts are the only observed products with haloketene precursors (equation 32). - ... 

The reactions of ketene acetals with Schiff bases derived from (S)-valine esters 1.59 (R = /-Pr) under TiCl4 catalysis are highly selective, but the chiral auxiliary has not been removed [264], Engler and coworkers [1532] performed the asymmetric [2+2]-cycloaddition of 2-methoxy-l,4-benzoquinone with 1-arylpro-penes substituted by electron-donating groups. These reactions occur at -78°C when catalyzed by chiral titanium complexes derived from 2.50 (R = Me, Ar = R = Ph). Cycloadducts are obtained with a good selectivity (Figure 9.6). 

Banik et al. [87,88] reported that when imines derived from condensed aromatic amines react with monosubstituted ketenes, only the corresponding rra 5-p-lactams are obtained. However, similar Staudinger reaction between A-phenylimines occurs under the same conditions—only the cw-cycloadducts are obtained with complete stereocontrol (Scheme 2.6). In addition, these rra 5-[3-lactams exhibited interesting anticancer activities [89,90]. 

Williams has demonstrated the use of 1-phenylsulfinyl-l-trimethylsilylethene (164) and phenyl vinyl sulfoxide as effective ketene equivalents for the Diels-Alder reaction [142,143], important as it is known that ketenes do not undergo satisfactory [4+2] cycloadditions. The initial cycloadduct (165), derived from the Diels-Alder reaction between 1-phenylsulfinyl-l-trimethylsilylethene (164) and cyclopentadiene, undergoes a facile sila-Pummerer rearrangement to give the thioacetal (166), which yields the product (167) upon hydrolysis (Scheme 5.55) [142]. 

The product-ion scan (the old, now-unaccepted term, still used by some, is daughter-ion scan) is the most common mode of MS/MS operation. That spectrum is useful in the structure elucidation of a specified analyte. Information obtained in this scan is similar to that derived from a normal mass spectrum, except that the spectrum contains only those product ions that are formed exclusively from a mass-selected precursor ion. To acquire this spectrum, the first mass analyzer is set to transmit only the precursor ion chosen, and the second mass spectrometer is scanned over a required miz range. As an example, the ketene radical cation reacts with neutral ketene to form a cycloadduct, the structure of which was delineated by mass-selecting the mIz of the adduct (at 84) and acquiring the product-ion scan (see Figure 4.3). 

Cycloadducts 88 (from glycals and isocyanates) undergo a two-stage oxidation (NaI04 followed by NaOCl) to provide i-lactams 89 and this chemistry has been used in clavam synthesis. Full details of synthesis of carbapenem precursors from aldono-1,5-lactones have also appeared. N-Aryl Schiff bases (derived from D-glyceraldehyde) undergo efficient [2+2] cycloaddition to ketenes (e.g. BnOCH=C=0) to afford P-lactams 90. This process, which has been carried out on 100-500 g scale, was shown to benefit greatly firom exposure to microwave radiation. ... 

Some of the [2+2] cycloadducts 21 derived from sulfenes and ketene acetals are listed in Table 2.3. 

Some [2+2] cycloadducts 101, derived from ketenes and acetylene derivatives, are listed in Table 4.2. 

Cycloadducts and linear adducts derived from ketenes and ketene 0,0, OJ, NJ and S,S -acetals are also known. However, four-membered ring [2+2] cycloadducts are only obtained in the reaction of diphenylketene with dialkylketene acetals. ... 

Ketenes are also easily generated using an anhydride derived from the corresponding carboxylic acid and A -[(chlorosulfinyl)oxy]methylene-Af-methyl methanaminium chloride 275. In the cycloaddition of diphenylketene, generated in this manner with l,3-diaza-l,3-butadiene, the [2-1-2] cycloadduct 276 is obtained... 

Vinyl ketenes derived from Fischer carbene complexes react with carbenoid reagents to give the [4+1] cycloadducts in high yields. For example, from the vinyl ketene 452 and Me3SiCH2N2, the cycloadduct 453 is obtained in 93 % yield... 

As for the C-C bond formation with fullerene, the pho-toinduced electron transfer with ketene silyl acetal (KSA) was reported. For example, KSA derived from ethyl acetates generated fullerene-acetates quantitatively upon photoirradiation in benzene (Scheme 4) [66]. Their reactivities to form Cgg-adducts are studied on the basis of the oxidation potentials of the KSA, indicating adduct formation via electron transfer with triplet excited Cgg. Furthermore, Danishefsky s diene, which is a vinylogue of KSA, formed [4 -I- 2] cycloadducts of Qg by the Diels-Alder reaction (Scheme 5)... 

Four-membered heterocycles are easily formed via [2-I-2] cycloaddition reac tions [65] These cycloaddmon reactions normally represent multistep processes with dipolar or biradical intermediates The fact that heterocumulenes, like isocyanates, react with electron-deficient C=X systems is well-known [116] Via this route, (1 lactones are formed on addition of ketene derivatives to hexafluoroacetone [117, 118] The presence of a trifluoromethyl group adjacent to the C=N bond in quinoxalines, 1,4-benzoxazin-2-ones, l,2,4-triazm-5-ones, and l,2,4-tnazin-3,5-diones accelerates [2-I-2] photocycloaddition processes with ketenes and allenes [106] to yield the corresponding azetidine derivatives Starting from olefins, fluonnaied oxetanes are formed thermally and photochemically [119, 120] The reaction of 5//-l,2-azaphospholes with fluonnated ketones leads to [2-i-2j cycloadducts [121] (equation 27)... 

Drawing from their success with catalytic [4 + 2] cycloaddition, Lectka group developed another highly enantioselective cycloaddition of o-quinone methide (o-QM) with silyl ketene acetals, using a chiral cinchona alkaloid derived ammonium, N-(3-nitrobenzyl)quinidinium fluoride Is, as a precatalyst. The free hydroxyl group of the cinchona alkaloid moiety was crucial to high optical induction. A variety of silyl ketene acetals had been screened to afford the cycloadducts 22 with good ee (72-90%) and excellent yield (84—91%) (Scheme 10.26) [35]. 

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