Ketene-diene cycloaddition

The formation of polysubstituted cycloheptadienones depicted in Eq. (5.334) constitutes the first example of an acid-induced ketene-diene cycloaddition.908... 

Neooctams, such as the unsubstituted parent compound (191), are easily obtained in cycloadditions. Isocyanates [125,126], sulphonyl isocyanates (43) [29,127] and especially chlorosulphonyl isocyanate (189) [128] react with alkenes to form variously-substituted j3-lactams [129—135]. Synthesis of compound (191) is an example of this reaction which has been discussed in detail [52]. The same compound (192) can be obtained in the photolytic rearrangement of the pyrazolone (194) [136]. Compound (196) is neooctam-5,7-diene, obtained from the azocine (195) and hydrogen bromide [137]. Lactam (196)is a partly saturated form of (199). The latter is an unstable neooctam derivative, formed in an intramolecular ketene-imine cycloaddition reaction (see (198))... 

The full paper on the stereoselectivity and stereospecificity in electron-deficient diene cycloadditions, the preliminary results on which were reported extensively last year, has now appeared. As compared with other ketenes, t-butylcyanoketene is extraordinarily reactive towards norbornene, and only one cyclobutanone, the exoadduct (193), is obtained. Reaction of 4,4-dimethylcyclobutenone with cyclo-pentadiene under boron trifluoride etherate catalysis produces the exo-adduct (194). ... 

In the presence of a double bond at a suitable position, the CO insertion is followed by alkene insertion. In the intramolecular reaction of 552, different products, 553 and 554, are obtained by the use of diflerent catalytic spe-cies[408,409]. Pd(dba)2 in the absence of Ph,P affords 554. PdCl2(Ph3P)3 affords the spiro p-keto ester 553. The carbonylation of o-methallylbenzyl chloride (555) produced the benzoannulated enol lactone 556 by CO, alkene. and CO insertions. In addition, the cyclobutanone derivative 558 was obtained as a byproduct via the cycloaddition of the ketene intermediate 557[4I0]. Another type of intramolecular enone formation is used for the formation of the heterocyclic compounds 559[4l I]. The carbonylation of the I-iodo-1,4-diene 560 produces the cyclopentenone 561 by CO. alkene. and CO insertions[409,4l2]. 

A key transformation in Corey s prostaglandin synthesis is a Diels-Alder reaction between a 5-(alkoxymethyl)-l,3-cyclopenta-diene and a ketene equivalent such as 2-chloroacrylonitrile (16). As we have already witnessed in Scheme 3, it is possible to bring about a smooth [4+2] cycloaddition reaction between 5-substituted cyclopentadiene 15 and 2-chloroacrylonitrile (16) to give racemic 14 as a mixture of epimeric chloronitriles. Under these conditions, the diastereomeric chloronitriles are both produced in racemic form because one enantiotopic face of dienophile 16 will participate in a Diels-Alder reaction with the same facility as the other enantiotopic face. In subsequent work, Corey s group demonstrated that racemic hydroxy acid 11, derived in three steps from racemic 14 (see Scheme 3), could be resolved in a classical fashion with (+)-ephe-... 

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. 

The synthetic utility of the D-A reaction can be expanded by the use of dienophiles that contain masked functionality and are the synthetic equivalents of unreactive or inaccessible compounds. (See Section 13.1.2 for a more complete discussion of the concept of synthetic equivalents.) For example, a-chloroacrylonitrile shows satisfactory reactivity as a dienophile. The a-chloronitrile functionality in the adduct can be hydrolyzed to a carbonyl group. Thus, a-chloroacrylonitrile can function as the equivalent of ketene, CH2=C=0,63 which is not a suitable dienophile because it has a tendency to react with dienes by [2 + 2] cycloaddition, rather than the desired [4 + 2] fashion. 

As discussed in Section 10.4 of Part A, concerted suprafacial [2tt + 2tt] cycloadditions are forbidden by orbital symmetry rules. Two types of [2 + 2] cycloadditions are of synthetic value addition reactions of ketenes and photochemical additions. The latter group includes reactions of alkenes, dienes, enones, and carbonyl compounds, and these additions are discussed in the sections that follow. 

Nitroethene undergoes rapid cycloaddition to 1,3-dienes the subsequent Nef reaction gives cyclohexenones, which are formally produced by the Diels-Alder reaction of ketene with... 

Density functional and semiempirical AMI molecular orbital calculations have been used to investigate substituent effects on site selectivity in heterocumulene-hetero-diene4 + 2-cycloadditions between ketene imines and acroleins.The new and novel heterocumulenes a, /3-unsaturated thioaldehyde S -oxides (97) behave as both diene... 

CH2=C=0.23 Ketene is not a suitable dienophile because it has a tendency to react with dienes by [2 + 2] cycloaddition, rather than in the desired [4 + 2] fashion. 

The Cj - and 54-symmetric tetraesters of tricyclo[3.3.0.0 ]octane (430 and 431) have been prepared by oxidation of diene 429 To access the parent hydrocarbon (435), acid chloride 432 was transformed to the derived ketene which undergoes intramolecular [2+2] cycloaddition The resulting cyclobutanone (433) serves as precursor to perester 434 whose thermal decomposition proceeds with chain transfer in competition with cleavage The unique arrangement of the carbon atoms in 435 is such that the smallest rings are all five-membered. The highly symmetric structure may be viewed as a constrained cisoid bicyclo[3.3.0]octane (as well as the symbol of NATO). 

Triazines are generally more reactive in [2 + 4] cycloaddition in comparison with 1,2,3-tria-zines. The wide variety of dienophiles can be employed enamines, enaminones, vinyl silyl ethers, vinyl thioethers, cyclic ketene jV,O-acetals, /V-phenylmaleimide, 6-dimethylaminopentafulvene, 2-alkylidene-imidazolidines (cychc ketene aminals), cyclic vinyl ethers, arynes, benzocyclopropene, acetylenes, and alkenes like ethylene, (Z)-but-2-ene, cyclopentene, cyclooctene and bicyclo[2.2.1]hept-2-ene, hexa-1,5-diene, cycloocta-1,5-diene, diallyl ether, cyclododeca-l,5,9-triene,... 

Synthesis of the dibenzofuran (27) by irradiation of grisa-3, 5 -diene-2, 3 -dione (28) is believed to involve electrocyclic ring opening followed by intramolecular cycloaddition to the ketene and elimination of carbon dioxide, as shown in Scheme 2.24 Analogous photocyclizations are responsible for the photochromism exhibited by heterocyclic fulgides such as ( )-a-3-furyl-ethy idene(isopropylidene)succinic anhydride (29), which on irradiation... 

A new protocol for the stereoselective synthesis of (i-lactams [213] has been reported to be performed by a conrotatory ring closure of l-halo-3-aza-4-alkyl-l, 3-dienes, previously prepared by Staudinger methodology, (for the synthesis and chemistry of /V-silyl imines see [214] for [2+2] cycloaddition of /V-silyl imines and ketenes see [215]) in refluxing toluene (Scheme 96). 

In accord with their unusually high reactivity, cyclopropanones may undergo various types of cycloaddition reactions. In addition to Diels-Alder type addition with conjugated dienes (4+3- 7 cycloadditions), substituted cyclopropanones also react with aldehydes forming dioxo-lanes (3 +2->-5), and with ketenes yielding (3-lactones (2 +2- 4).118>... 

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... 

Others are not so obvious. Cyclobutanone 22 might come from diphenylketene and the diene 21 (disconnection 22a) or from ketene itself and the diene 23 (disconnection 22b). No doubt both dienes could be made but the regioselectivity of both cycloadditions looks in doubt. 

Chiral dienes have proved to be less popular in asymmetric Diels-Alder reactions than their chiral dienophile counterparts. This is primarily a result of the problem of designing a molecule that incorporates a chiral moiety, such as the formation of a chiral isoprenyl ether or vinyl ketene acetal.187-190 In addition, diastereoselectivities often are not high,54 191-199 as illustrated by the cycloaddition of the chiral butadiene 5 with acrolein (Scheme 26.4). Improved stereoselection is observed through the use of double asymmetric induction, although this is a somewhat wasteful protocol.35,54 177 200... 

The 4-vinyloxetan-2-ones generated in a Pd-catalysed [2+2] cycloaddition between ketene and a,P-unsaturated carbonyl compounds undergo a spontaneous allylic rearrangment. A zwitterionic intermediate is proposed that cyclises to a 3,6-dihydro-2//-pyran-2-one, but which may alternatively decarboxylate to a diene <02T5215>. 

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