Cycloadditions of ketenes

Cyclobutanes can also be formed by noncerted reactions involving dipolar intermediates. Enamines react with certain electron-deficient alkenes to give cy- 

Dipolar intermediates are also involved in cycloaddition of tetracyanoethylene and enol ethers. Again, the two addends are substituted so that separation of charge is energetically acceptable. This reaction strongly favors retention of the vinyl ether 

Photochemical cycloadditions provide a method that is often complementary to thermal cycloadditions with regard to the types of compounds that can be prepared. The theoretical basis for this complementary relationship between the thermal and photochemical modes of reaction lies in orbital-symmetry relationships and was discussed in detail in Part A, Chapter 10. 

Intermolecular addition of alkenes can be carried out by photosensitization with mercury or directly with short-wavelength sources. Relatively little preparative use has been made of simple alkenes, however. Dienes can be photosensitized using such materials as benzophenone, butane-2,3-dione, and acetophenone. Under these conditions, preparatively useful yields of stereoisomeric mixtures of dimers are obtained. Usually, some 4 + 2 adduct accompanies the dominant 2 + 2 adduct. 

The photodimerizations of substituted styrenes were among the earliest photochemical reactions to be studied. These compounds give good yields of dimers 

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Simple olefins do not usually add well to ketenes except to ketoketenes and halogenated ketenes. Mild Lewis acids as well as bases often increase the rate of the cyclo addition. The cycloaddition of ketenes to acetylenes yields cyclobutenones. The cycloaddition of ketenes to aldehydes and ketones yields oxetanones. The reaction can also be base-cataly2ed if the reactant contains electron-poor carbonyl bonds. Optically active bases lead to chiral lactones (41—43). The dimerization of the ketene itself is the main competing reaction. This process precludes the parent compound ketene from many [2 + 2] cyclo additions. Intramolecular cycloaddition reactions of ketenes are known and have been reviewed (7). 

Photochemical [2 + 2] cycloaddition of ketene and (trifluoromethyl)tria-zinone 25 gave 26 (88CPB3354). The role of the CF3 group in the activation of the imine function of 25 was investigated (Scheme 7),... 

Like the similar cycloaddition of ketenes to alkenes (15-61), most of these reactions probably take place by the di-ionic mechanism c (p. 1078). P-Lactams have also been prepared in the opposite manner by the addition of enamines to isocyanates ... 

Staudinger observed that the cycloaddition of ketenes with 1,3-dienes afforded cyclobutanones from a formal [2+2] cycloaddition [52] prior to the discovery of the Diels-Alder reaction. The 2+2 cycloadditions were classified into the symmetry-allowed 2+2 cycloaddition reactions [6, 7], It was quite momentous when Machiguchi and Yamabe reported that [4+2] cycloadducts are initial products in the reactions of diphenylketene with cyclic dienes such as cyclopentadiene (Scheme 11) [53, 54], The cyclobutanones arise by a [3, 3]-sigmatropic (Claisen) rearrangement of the initial products. 

Berlin JM, Eu GC (2008) Enantioselective nucleophilic catalysis the synthesis of Aza-P-lactams through [2 -I- 2] cycloadditions of ketenes with azo compounds. Angew Chem Int Ed 120 7156-7158... 

Dochnahl M, Fu GC (2009) Catalytic asymmetric cycloaddition of ketenes and nitroso compounds enantioselective synthesis of a-hydroxycarboxylic acid derivatives. Angew Chem Int Ed 48 2391-2393... 

The existence of ketenes was established over a hundred years ago, and, in recent years, asymmetric synthesis based on [2 + 2] cycloadditions of ketenes with carbonyl compounds to form chiral p-lactones has been achieved with high yields and high stereoselectivities. In 1994, Miyano et al. reported the use of Ca-symmetric bis(sulfonamides) as ligands of trialkylaluminum complexes to promote the asymmetric [2 + 2] cycloaddition of ketenes with aldehydes. The corresponding oxetanones were obtained in good yields and enantioselectivities... 

Scheme 10.15 [2 + 2] Cycloadditions of ketene with aldehydes catalysed by bis...

Cycloadditions of ketenes and alkenes have synthetic utility for the preparation of cyclobutanones.163 The stereoselectivity of ketene-alkene cycloaddition can be analyzed in terms of the Woodward-Hoffmann rules.164 To be an allowed process, the [2ir + 2-tt] cycloaddition must be suprafacial in one component and antarafacial in the other. An alternative description of the TS is a 2irs + (2tts + 2tts) addition.165 Figure 6.13 illustrates these combinations. Note that both representations predict formation of the d.v-substituted cyclobutanone. 

Fig. 5. Regioisomeric pathways in the [2 + 2] cycloaddition of ketenes to alky-lidenecyclopropanes...

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],... 

Cycloaddition of ketene and imine to form 3-lactam. Other coupling partners for ketene also include olefin to give cyclobutanone and carbonyl to give 13-lactone. 

Fields cf oZ. have pointed out that the differences observed between the rate of cycloaddition of ketene acetal with the acridizinium ion and that of various acridizinium benzologs qualitatively parallels those which are encountered when the rate of cycloaddition of maleic anhydride with... 

Cycloaddition of ketenes to Cjq is expected to be difficult due to their electrophilic character. Nevertheless, the reaction of Cjq vhth some aryloxy- and alkoxy-ketenes led to the successful characterization of cycloaddition-products [356]. The reaction proceeds via a formal [2-1-2] cycloaddition, followed by enolization and acylation. Products 320 are stable and can be obtained in moderate yields (Scheme 4.64). 

Four-membered ring adducts from 2n + 2n cycloaddition of keten-imines to sulfur dioxide. Isolation of l,2-thiazetidin-3-one 1-oxides. jS-Sultames. Simple method for synthesis of substituted 1,2-thia-zetidin 1,1-dioxide. ... 

The [4-I-2] cycloaddition of ketenes 628 with 1,3-diazabutadienes 629 is now a well-established route to 5,6-dihydro-4-pyrimidinones 630 and, when a leaving group is present, 4-pyrimidinones 631 <1997X13841, 1998H(47)933, 2001 H(55>2283, 2002ARK(vii)106, 2002J(P1)774>. 

Acid-catalyzed ring expansions of related 6-5-4 tricyclic systems are also known. For example, the acetal (257), formed by cycloaddition of keten acetal and 3-ethoxyisoindolone, in hydrochloric acid rearranges to the 2-benzazepine-l,5-dione (258) (75JA7288). 

Ketene acetals and thioacetals can be used as ketene equivalents in cyclobutanone synthesis in situations where ketene to alkene cycloadditions are inefficient such as in the case of electron-deficient alkenes.14 Although thermal cycloadditions of ketene acetals and thioacetals with electron-deficient alkenes have been observed (see Section 1,3.2.1.), such cycloadditions proceed more efficiently and under milder conditions with metal catalysts. Efficient cycloadditions between ketene dimethyl acetal and alkenes substituted by a single electron-withdrawing group have been reported.15... 

The use of chiral catalysts can result in asymmetric induction in [2 + 2] cycloadditions. The cycloaddition of ketene dimethyl thioacetal (44) with various enamides (43) in the presence of a chiral titanium(IV) catalyst, generated in situ, gives good yields of cyclobutanes 45 with high enantioselectivity.18... 

Examples of cycloadditions of ketenes to alkcncs, cycloalkcnes, and strained alkenes are given in Tables 1-3, respectively. 

Table 4. Cycloaddition of Ketenes to Conjugated Acyclic Alkenes...

Table 5. Cycloaddition of Ketenes to Endocyclic Conjugated Cycloalkenes ...

Table 6. Cycloaddition of Ketenes to Enol Ethers, Sulfides and Enamines3...

For reviews of cycloadditions of ketenes, see Ghosez O Donnell. Ref. 926 Brady Synthesis 1971, 415-422 Luknitskii Vovsi Russ. Chem. Rev. 1969,38, 487-494 Ulrich Cycloaddition Reactions of Heterocumulenes, Academic Press New York, 1967, pp. 38-121 Holder /. Chem. Educ. 1976, 53, 81-85. For a review of intramolecular cycload-dilions of ketenes to alkenes, see Snider Chem. Rev. 1988, 88, 793-811. 

On the other hand, molecular orbital calculations predict that the cycloaddition of ketenes to olefins docs not take place by a [,2, +, 2.) mechanism Wang Houk J. Am. Chem. Soc. 1990, 112. 1754 Bemardi Bottoni Robb Venturini J. Am. Chem. Soc. 1990,112, 2106 Valenti Peric s Moyano J. Org. Chem. 1990, 55, 3582. 

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