Alkenes ketene cycloaddition

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. 

Scheme 6.8 gives some examples of ketene-alkene cycloadditions. In Entry 1, dimethylketene was generated by pyrolysis of the dimer, 2,2,4,4-tetramethylcyclobutane-l,3-dione and passed into a solution of the alkene maintained at 70° C. Entries 2 and 3 involve generation of chloromethylketene by dehydrohalo-genation of a-chloropropanoyl chloride. Entry 4 involves formation of dichloroketene. Entry 5 is an intramolecular addition, with the ketene being generated from a 2-pyridyl ester. Entries 6, 7, and 8 are other examples of intramolecular ketene additions. 

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],... 

A review of the mechanism of thermal 2 + 2-cycloadditions of activated alkenes to allenes and ketenes has been published. " Stereoselective intramolecular 2 + 2-cycloadditions of alkene-keteniminium salts (19) derived from L-glutamic salts yield... 

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... 

The stereochemistry with respect to the ketene iminium salt in cases of monosubstituted or unsymmetrically disubstituted derivatives in cycloadditions to alkenes show differences from the ketene counterpart. In contrast to ketene cycloadditions of monosubstituted ketenes with alkenes where the substituent in the bicyclic derivative ends up in the endo position, the cycloaddition of two monosubstituted ketene iminium salts with cyclopentene and cyclohexenc gives the e.wp-substituted derivatives 4.6... 

Intramolecular [2n + 27r] cycloadditions leading to cyclobutanes formally belong to valence isomerizations. Alkene/alkcne, ketene/alkene, and allene/alkene cycloadditions have received detailed attention. These rearrangements provide powerful methods for the synthetic arsenal. An example is the facile synthesis of bieyelo[3.2.0]heptenones 3 by intramolecular ketene/alkene cycloaddition after electrocyclic ring opening of cyclobutenoncs l.89... 

Two possible [2+2] cycloadditions can be envisaged for the synthesis of (3-lactams (Scheme 1). Interestingly, the same fragmentations have been observed in the mass spectra of these compounds [10, 11], One possibility consists of the [2+2] cycloaddition between ketenes (2) and imines (3) to yield (3-lactams (1). This reaction has been explored experimentally and it is also known as the Staudinger reaction between ketenes and imines [12-15]. In an alternative approach, the [2+2] cycloaddition between alkenes (5) and isocyanates (4) leads to (3-lactams (1). This reaction has been less extensively used, but it has proven to be useful in the chemical synthesis of interesting compounds [16-19]. 

Irradiation of carbene complexes in CO atmosphere generates the ketene 305 and its [2+2] cycloaddition to alkene gives the cyclobutanone 306 [93], Total synthesis of (+)-cerulenin (310) has been carried out by the formation of cyclobutanone 309 by cycloaddition of 307 to the double bond of 308 as the key reaction without attacking the triple bond. Then cyclobutanone 309 was converted to (+)-cerulenin (310) via regioselective Bayer-Villiger reaction of 309, and side-chain elongation using n-methallylnickel bromide, epoxidation and hydrolysis [94],... 

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... 

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. 

This chapter reviews thermal [2 + 2] cycloadditions of alkenes to form cyclobutanes, extending the coverage provided by earlier summaries of the literature.It docs not deal with [2 + 2] cycloadditions that are achieved photochemically, or that utilize allenes, arynes or ketenes, or that are deliberately catalyzed, or that result in heterocyclic four-membered rings, even though these other varieties of [2 + 2] cycloaddition reactions are important and of substantial interest. 

The ketene-alkene cycloaddition gives cyclobutanones in a thermal reaction. Most ketenes are not kinetically stable, so they are usually generated in situ, either by E2 elimination of HC1 from an acyl chloride or by a Wolff rearrangement of an a-diazoketone (see Chapter 2). 

Three classes of [2 + 2] cycloadditions do proceed under thermal conditions. Ketenes (R2C=C=0) undergo concerted cycloadditions to alkenes under thermal conditions because the ketene can react antarafacially with an alkene that reacts suprafacially. The two termini of the C=C tt bond of the ketene react from op-... 

The formation of a cyclobutanone almost always indicates a ketene-alkene [2 + 2] cycloaddition. 

Like ketenes, allenes generally undergo [2 + 2] cycloadditions with alkenes affording methylene cyclobutanes . In reactions with 1,3-butadienes, both Diels-Alda- adducts and [2 -F 2] cycloadducts are formed. Cyclopentadiene, however, has been reported to react with several allenes to give exclusively Diels-Alder adducts. From the sevraal possible mechanisms by which [2 -F 2] cycloaddition reactions of allenes could occur,... 

Keteniminium salts arc an attractive alternative to ketenes for cycloaddition with alkenes to give cyclobutanones31-32. Keteniminium salts do not dimerize and are more electrophilic than ketenes. They can be easily prepared by treatment of a dialkyl amide with 2,4,6-trimethylpyri-dine (collidine) and triflic anhydride in an inert solvent or from an a-haloenamine and a Lewis acid. The cycloadditions of keteniminium salts with alkenes are stepwise, not concerted, so that products from syn addition to the alkene are not always obtained stereoselectively. Of greater concern is the fact that the major product from alkenes which can form a tertiary carbocation is the Kriedel-Crafts product. The cycloaddition procedure is therefore limited to mono- and 1,2-disubstituted alkenes. 

Three classes of [2 -t- 2] cycloadditions do proceed under thermal conditions. Ketenes (R2C=C=0) undergo concerted cycloadditions to alkenes under thermal conditions because the ketene can react antarafacially with an alkene that reacts suprafacially. The two termini of the C=C tt bond of the ketene react from opposite faces of the tt bond, creating positive overlap between the orbitals at both termini of the two tt systems. The antarafacial nature of the ketene does not have any stereochemical consequences, as there is no cis-trans relationship in the ketene to preserve in the product. The alkene component of the [2 -I- 2] cycloaddition with ketenes, however, reacts suprafacially, and its stereochemistry is preserved in the product. 

The intramolecular ketene-alkene cycloaddition has also been used to prepare highly substituted phenols. As originally formulated, a cyclobutenone such as 342 was converted to a phenol derivative (346). When 342 was heated in benzene, ketene 343 was formed. When done in the presence of an alkyne,281 an in situ [2+21-cycloaddition led to a new cyclobutenone (344) but under the reaction conditions, a four-electron electro-cyclic cleavage reaction occurred to give 345. This compound also reacted, via a six-electron electrocyclic... 

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