Ketenes with alkenes

So special reactions are often used to make cyclobutanes. In the next chapter we shall see that thermal cycloadditions of alkenes with ketenes give four-membered rings, but the commonest method is photochemical cycloaddition. You are already aware that Diels-Alder reactions (chapter 17) occur easily when a diene 6 and a dienophile 7 are heated together and six-membered rings 8 are formed. Have you ever wondered why four-membered rings 9 are not formed instead Orbital symmetry allows cycloadditions involving six Ti-electrons but not those involving four 7r-electrons.2... 

Other isocyanates undergo [2 + 2] cycloaddition, but only with very electron rich alkenes. Thus phenyl isocyanate gives /3-lactams with ketene acetals and tetramethoxyethylene. With enamines, unstable /3-lactams are formed if the enamine has a /3-H atom, ring opened amides are produced 2 1 adducts are also found. Photochemical addition of cis- and traH5-stilbene to phenyl isocyanate has also been reported (72CC362). 

Scheeren et al. reported the first enantioselective metal-catalyzed 1,3-dipolar cycloaddition reaction of nitrones with alkenes in 1994 [26]. Their approach involved C,N-diphenylnitrone la and ketene acetals 2, in the presence of the amino acid-derived oxazaborolidinones 3 as the catalyst (Scheme 6.8). This type of boron catalyst has been used successfully for asymmetric Diels-Alder reactions [27, 28]. In this reaction the nitrone is activated, according to the inverse electron-demand, for a 1,3-dipolar cycloaddition with the electron-rich alkene. The reaction is thus controlled by the LUMO inone-HOMOaikene interaction. They found that coordination of the nitrone to the boron Lewis acid strongly accelerated the 1,3-dipolar cycloaddition reaction with ketene acetals. The reactions of la with 2a,b, catalyzed by 20 mol% of oxazaborolidinones such as 3a,b were carried out at -78 °C. In some reactions fair enantioselectivities were induced by the catalysts, thus, 4a was obtained with an optical purity of 74% ee, however, in a low yield. The reaction involving 2b gave the C-3, C-4-cis isomer 4b as the only diastereomer of the product with 62% ee. 

Dipolar cydoadditions are one of the most useful synthetic methods to make stereochemically defined five-membered heterocydes. Although a variety of dia-stereoselective 1,3-dipolar cydoadditions have been well developed, enantioselec-tive versions are still limited [29]. Nitrones are important 1,3-dipoles that have been the target of catalyzed enantioselective reactions [66]. Three different approaches to catalyzed enantioselective reactions have been taken (1) activation of electron-defident alkenes by a chiral Lewis acid [23-26, 32-34, 67], (2) activation of nitrones in the reaction with ketene acetals [30, 31], and (3) coordination of both nitrones and allylic alcohols on a chiral catalyst [20]. Among these approaches, the dipole/HOMO-controlled reactions of electron-deficient alkenes are especially promising because a variety of combinations between chiral Lewis acids and electron-deficient alkenes have been well investigated in the study of catalyzed enantioselective Diels-Alder reactions. Enantioselectivities in catalyzed nitrone cydoadditions sometimes exceed 90% ee, but the efficiency of catalytic loading remains insufficient. 

Attack on Unsaturated Carbon. The annual addition of phosphites to every variety of activated double bond continues. These include nitro-alkenes,9 a/S-unsaturated carboxylic acid derivatives,10 maleimides,11 fulvenes,12 and pyridinium salts.13 The reaction of diethyl phosphite with keten 0,N-, S,N, and Al,AT-acetals has been used to prepare the enamine phosphonates (19).14... 

The same ketene acetal, as well as telluro(thio)ketene acetals has been obtained with retention of configuration by subsequent treatment of ( )-l-bromo-l-seleno(or thio) alkenes with n-BuLi and diphenyl ditelluride, resulting from the preferential Br/Li exchange over chalcogeno exchange. ... 

Among the most commonly applied chiral moiety for nitrones (2) is the N-a-methylbenzyl substituent (Scheme 12.6) (18-25). The nitrones 8 with this substituent are available from 1 -phenethylamine, and the substituent has the advantage that it can be removed from the resulting isoxazolidine products 9 by hydrogeno-lysis. This type of 1,3-dipole has been applied in numerous 1,3-dipolar cycloadditions with alkenes such as styrenes (21,23), allyl alcohol (24), vinyl acetate (20), crotonates (22,25), and in a recent report with ketene acetals (26) for the synthesis of natural products. Reviewing these reactions shows that the a-methylbenzyl group... 

Carbonyl cyanide reacts readily with ketene and dialkylketenes to give the corresponding dicyano-/3-lactones (equation 109). This reaction seems entirely analogous to the addition of carbonyl cyanide with alkenes to give oxetanes, described in the preceding section (75MI51302). 

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 limitations of the ketene method for generating cyclobutanoncs is the tendency for ketenes to dimerize as a major competing process. This can be overcome by using excess alkene and by control of reaction temperature in order to minimize dimerization. Another limitation of the ketene route is the inertness of electron-deficient alkcncs to undergo cycloaddition with ketenes. 

Unlike ketcnc cycloadditions, very few mechanistic studies have been carried out with ketene iminium salt cycloadditions. Differences in regiochemistry in the latter examples suggest that these reactions are not concerted and that a carbcne-type addition to the alkene leading to an intermediate such as 6 is responsible for these reactions.8... 

Ketene reacts with ketene iV,jV-acetals and iV,0-acetals to give 4-dialkylaminopyran-2-ones (64JOC2513). It is necessary that the acetal should contain an alkenic hydrogen atom. 

It has been long established that Lewis acid-catalysed [2+2] cycloaddition of ketenes and carbonyl compounds provides access to 2-oxetanones. In the development of this reaction prior to 1996, there has been a specific focus on controlling the stereochemistry of the /3-lactone product and cycloadditions have been achieved between trimethyl-silylketene and aldehydes with up to 90% stereoselectivity, as discussed in CHEC-II(1996) <1996CHEC-II(1)721>. CHEC(1984) and CHEC-II(1996) also discuss examples of the Lewis acid-catalyzed, nonphotolytic [2+2] cycloaddition of electron-rich alkenes with aldehydes or ketones <1984CHEC(7)363, 1996GHEC-II(1)721>. While this method can have some advantages over the photolytic reaction in terms of regioselectivity, no examples of this reaction have been reported in recent years. 

Cycloaddition to alkenes. This ketene adds regioselectively to alkenes, even tet-rasubstituted ones, with preservation of the stereochemistry of the alkene to afford 2-chloro-2-cyanocyclobutanones in good yield. 

For thermally induced [2 + 2] cycloadditions, the concerted mechanism is operative only in particular cases, such as in the reactions between an alkene or alkyne and a ketene. The ketene can be generated directly in the reaction mixture from the appropriate acid chloride with triethylamine. The cycloaddition reaction is stereospecific and occurs exclusively in a cis fashion. Although the intermolecular cycloaddition with ketene itself proceeds in poor yields due to the propensity of the unsubstituted ketene to undergo dimerization, it is quite an efficient reaction with ketenes containing electron-withdrawing substituents. Usually, a-chloro ketenes are employed as reagents formed in situ from the corresponding a-chloro acid chlorides. Typical examples are represented in the preparation of cycloadducts such as 378 and 379 (Scheme 2.127). The latter cycloadduct, prepared in modest yield (ca. 20%),... 

The carbonyl ir-bond has been found to add chemo- and regio-selectively across the alkenic ir-bond of ketenes. Thus diphenylketene readily reacts with benzoquinone to yield a stable [2 + 2] adduct (equation 1). With an excess of diphenylketene the bis-adduct is formed, which decomposes into tetraphe-nylquinodimethane and carbon dioxide (equation 2). With the less stable ketene, thermal [2 + 2] cycloadditions are observed with highly electrophilic carbonyl compounds (equation 3). With unactivated aldehydes and ketones, yields are much lower due to a faster oligomerization of the ketene reagent. However, in the presence of a Lewis acid catalyst, most aldehydes or ketones form P-lactones with ketene (equation 4). Cycloadditions with ketones usually require more active catalysts than with aldehydes. The catalyzed reaction of ketene with methyl vinyl ketone is chemoselective, yielding a 10 1 ratio of [2 + 2] versus [4 + 2] adducts (equation 5). In the absence of catalyst, methyl vinyl ketone reacts with ketene to give exclusively the [4 + 2] adduct. 

The addition of a C-2 (equation 1 R = H > alkyl, aryl > OMe NR2), C-3, or C-4 electron-donating substituent to a 1 -oxa-1,3-butadiene electronically decreases its rate of 4ir participation in a LUMOdiene-controlled Diels-Alder reaction (c/. Table 5). Nonetheless, a useful set of C-3 substituted l-oxa-l,3-buta-dienes have proven to be effective dienes ° and have been employed in the preparation of carbohydrates (Table 6). The productive use of such dienes may be attributed to the relative increased stability of the cisoid versus transoid diene conformation that in turn may be responsible for the Diels-Alder reactivity of the dienes. Clear demonstrations of the anticipated [4 + 2] cycloaddition rate deceleration of 1-oxa-1,3-butadienes bearing a C-4 electron-donating substituent have been detailed (Table 6 entry 4). >> "3 In selected instances, the addition of a strong electron-donating substituent (OR, NR2) to the C-4 position provides sufficient nucleophilic character to the 1-oxa-1,3-butadiene to permit the observation of [4 + 2] cycloaddition reactions with reactive, electrophilic alkenes including ketenes and sul-fenes, often in competition with [2 + 2] cycloaddition reactions. ... 

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