Ketene-allene cycloaddition

Lately a third type of transition state has been favored for [2 + 2] cycloadditions forming carbocyclic and heterocyclic four-membered rings. The experimental data on the addition of diarylketenes to arylethylenes are well accommodated by the [ 2s + 2s + 2s] process proposed by Baldwin (70JA4874). The steric effects on the cycloaddition of allenes to ketenes also favor this mechanism (76JA7698). 

Ketene is also a suitable partner for [2 + 2]-cycloaddition with allenes. Diphenylke-tene and dimethylketene react readily with tetramethylallene at room temperature to give 2-isopropylidenecyclobutanones in good yields [49]. 

Another reactive ketene which undergoes efficient cycloaddition with allenes is tert-butyl-cyanoketene (TBCK). Again mixtures of isomeric cycloadducts are obtained when unsymmet-rically substituted or 1,3-disubstituted allenes are employed.10-12... 

An ab initio study of the 2 + 2-cycloadditions of allene to isocyanic acid and ketene to vinylimine found the reactions to be concerted and mostly asynchronous.28,29 The diastereoselective 2 + 2-cycloaddition of dichloroketene with a chiral enol ether (26) produced the cyclobutanone (27), which leads to a key intermediate (28) in (g) the total synthesis of the natural alkaloid (-)-Swainsonine (29) (Scheme 8).30 The... 

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,... 

Reactions of Ketenes, Allenes and Carbenes which Appear to be Forbidden. Some [2 + 2] cycloadditions only appear to be forbidden. One of these is the cycloaddition of ketenes to alkenes. These reactions have some of the characteristics of pericyclic cycloadditions, such as being stereo-specifically syn with respect to the double bond geometry, and hence suprafacial at least on the one component, as in the reactions of the stereoisomeric cyclooctenes 6.144 giving the diastereoisomeric cyclobutanones 6.145.720 However, stereospecificity is not always complete, and many ketene cycloadditions take place only when there is a strong donor substituent on the alkene. An ionic stepwise pathway by way of an intermediate zwitterion is therefore entirely reasonable in accounting for many ketene cycloadditions. 

Cycloaddition to allenes. The thermal cycloaddition of dimethylketene to allenes is regiospecific the central carbon of the allene is joined in all cases to the carbon of the carbonyl group of the ketene. The products are conjugated methylene- or alkylidenecyclobutanones. 

Computational studies have compared substituent effects on the stability of ketenes, allenes, diazomethanes, diazirines, and cyclopropenes. Ketenes belong to the first generation of reactive intermediates along with carbocations, carbanions, radicals, and carbenes, and are intensively studied members of the cumulene family, with many useful synthetic applications. Ketenes were first recognized in 1905, when diphenylketene, a stable and isolable example, was obtained from the dehalogenation of the a-bromodiphenylacetyl bromide (Scheme 7.37). The most characteristic reaction of ketene is cycloaddition, as in the formation of p-laclams. 

Cycloaddition Reactions.— The theoretical predictions of Woodward and Hoffmann to the effect that [2 + 2] cycloadditions of allenes (and ketens)... 

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)... 

The thermal [2 + 2] cycloaddition is limited to certain activated alkenes. For instance tetrafluoroethylene, tetrachloroethylene, allenes e.g. 17, ketenes and ena-mines can form cyclic dimers or react with other alkenes ... 

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. 

Other examples are given in Table 12.3. The cycloaddition reactions take place even at 0 °C. A regioisomeric mixture was obtained from 1,1-dimethylallene [50]. As for the mechanism of the allene-ketene [2 + 2]-cycloaddition, it is not clear whether the reaction proceeds via a concerted process (ketene antrafacial) or a two-step process. 

Although an intramolecular thermal [2 + 2] allene-ketene cycloaddition reaction was reported, the regioselectivity was moderate [55]. 

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... 

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. 

Allene ketene cycloadditions are of greater synthetic utility than cither mixed allene dimerization or mixed ketene dimerization. In this class of reaction the ketene is the more reactive species and homodimerization of ketene can be minimized by use of excess allene. Such cycloadditions always result in 2-alkylidenecyclobutanones with the sp carbons of both moieties forming the initial bond. In substituted allenes and ketenes, mixtures of stereoisomers of 2-alkylidenecyclobutanones are obtained with very little stereoselectivity, the stereoisomers arise from cisUrcins isomerism in the cyclobutane ring and EjZ isomerism of the exocyclic double bond. In unsymmetrically substituted allenes some regiochemical preference for ketene cycloaddition is observed. Examples of dimethylketene allene cycloadditions are summarized in Table 1,2... 

Virtually all reactions involving cyclobutane formation via cycloaddition of a cumulene to another C —C double-bond system involves excitation of this latter moiety, e.g. an enone or a quinone, and not of the allene or ketene itself.1 Earlier examples of such reactions have been discussed in Houben-Weyl, Vol. 4/5 b, pp 926 931. 

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... 

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. 

We have not given you much evidence to decide why it is that some thermal [2 + 2] cycloadditions occur but not others. What is special about fluoroalkenes, allenes, and ketenes in these reactions One possibility is that Mobius rather than the Hiickel transition states are involved, but the Mobius transition states are expected to suffer from steric hindrance (Section 21-10B). It is also possible that [2 + 2] cycloadditions, unlike the Diels-Alder additions, proceed by stepwise mechanisms. This possibility is strongly supported by the fact that these reactions generally are not stereospecific. Thus with tetrafluoroethene and trans,trans-2,5-bexadiene two products are formed, which differ in that the 1-propenyl group is trans to the methyl group in one adduct, 45, and cis in the other, 46 ... 

The formation of four-membered rings through 2 + 2 cycloaddition is a well-established reaction and the most generally effective synthetic approach to cyclobutanes. Most olefins cannot be induced to undergo this reaction thermally, a finding that is readily rationalized by the forbidden nature of the 2s + 2s addition and the steric difficulties associated with the allowed 2s + 2a pathway. There are nevertheless exceptions. Olefins substituted by two or more fluorine atoms undergo thermal 2 + 2 additions under relatively mild conditions,16 as do ketenes and allenes. 

Dobrowolski and co-workers reported calculations of the thermodynamic stability of the products derived from cycloaddition of vinylimine and ketene and of isocyanic acid and allene using MP2, density functional theory (DFT) (B3PW91), and Hartree-Fock (HF) methods with the 6-311+- -G basis set. Fourteen different structures were calculated for these cycloaddition reactions and the values of the free Gibbs energy showed that only 4- and 3-methylene-/3-lactams could be formed in considerable amount. 

Anhydro-5-hydroxyoxazolium hydroxides lacking substituents at C(4) dimerize spontaneously by a process in which one molecule acts as an electrophile and the other as a nucleophile (Scheme 21). This accounts for the fact that dimeric products of this type are obtained by the action of dicyclohexylcarbodiimide on acylamino acids of the general formula R1C0NR2CH2C02H. Substituents at position 4 stabilize the mesoionic system the first compounds to be prepared were the acetyl derivatives (220) (B-49MI41800) and (221) (58Cl(L)46l) and much of the more recent work has been carried out with the relatively stable methyldiphenyl compound (222). This miinchnone decomposes above 115 °C to yield the allene (225) with loss of carbon dioxide. The mechanism proposed for this remarkable reaction (Scheme 22) involves valence isomerization to the ketene (223), which undergoes a 1,3-dipolar cycloaddition with the miinchnone. The product loses carbon dioxide to form a new betaine (224), which collapses to the allene as shown. 

Allene and ketene, though isoelectronic, have quite different photoelectron spectra and electronic structures 4> that they undergo (2 + 2) cycloadditions with olefins by quite distinct mechanisms 6-8> is not altogether surprising. 

Related to ketene cycloadditions are the group of cycloadditions with vinyl cation intermediates. The reaction between 2-butyne 6.120 and chlorine giving the dichlorocyclobutene 6.122 is the Smirnov-Zamkow reaction, and there is a similar reaction between allene 6.123 and hydrogen chloride giving the... 

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. 

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