Lactones cycloaddition

Silylketenes are more stable than the parent ketenes and have been used in cycloaddition reactions, particularly with aldehydes to form p-lactones. Cycloaddition of a ketene with an aldehyde normally requires a Lewis acid catalyst, such as AICI3, BF3-OEt2 or ZnCl2 and under such conditions good yields of the P-lactone products can be obtained. For example, cycloaddition of the aldehyde... 

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]. 

Cycloaddition of COj with the dimethyl-substituted methylenecyclopropane 75 proceeds smoothly above 100 °C under pressure, yielding the five-membered ring lactone 76. The regiocheraistry of this reaction is different from that of above-mentioned diphenyl-substituted methylenecyclopropanes 66 and 67[61], This allylic lactone 76 is another source of trimethylenemethane when it is treated with Pd(0) catalyst coordinated by dppe in refluxing toluene to generate 77, and its reaction with aldehydes or ketones affords the 3-methylenetetrahy-drofuran derivative 78 as expected for this intermediate. Also, the lactone 76 reacts with a, /3-unsaturated carbonyl compounds. The reaction of coumarin (79) with 76 to give the chroman-2-one derivative 80 is an example[62]. 

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). 

The highest priority ring disconnective T-goals for 272 are those which disconnect a cocyclic 5,5-fusion bond and offexendo bond pair. The internal ketene-olefin cycloaddition in tactical combination with the Baeyer-Villiger transform is well suited to the double disconnection of such a cyclopentane-y-lactone ring pair. 

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)... 

Dihydropyrans have been produced by the 1,3 cycloaddition of methyl vinyl ketone (77) or acrolein (29-J7) with enamines (see Section II.A.2). S-Lactones have been formed as a side product in the reaction of dimethyl ketene with enamines (77), and as the primary products in the reaction of excess ketene with enamines derived from ketones (75) (see Section II.A.4). 

Silylketenes in formation of (3-lactones and (3-lactams 98JCS(P1)2105. Syntheses of (3-lactams, (3-lactones, and 1,3- and 1,4-diazetidinediones by pho-tochemically induced cycloaddition reactions of chromium carbene complexes with imines, aldehydes, and azo compounds 97T4105. 

The isomeric 4-iodopyrazole-5-carboxylic acid is cyclocondensed in a similar way. Introduction of the additional methyl group into the ring has no effect on the direction of cycloaddition 4-iodo-l,3-dimethylpyrazole-5-carboxylic acid forms only 5-lactones (Scheme 118). 

Intramolecular cycloadditions of substrates with a cleavable tether have also been realized. Thus esters (37a-37d) provided the structurally interesting tricyclic lactones (38-43). It is interesting to note that the cyclododecenyl system (w = 7) proceeded at room temperature whereas all others required refluxing dioxane. In each case, the stereoselectivity with respect to the tether was excellent. As expected, the cyclohexenyl (n=l) and cycloheptenyl (n = 2) gave the syn adducts (38) and (39) almost exclusively. On the other hand, the cyclooctenyl (n = 3) and cyclododecenyl (n = 7) systems favored the anti adducts (41) and (42) instead. The formation of the endocyclic isomer (39, n=l) in the cyclohexenyl case can be explained by the isomerization of the initial adduct (44), which can not cyclize due to ring-strain, to the other 7t-allyl-Pd intermediate (45) which then ring-closes to (39) (Scheme 2.13) [20]. While the yields may not be spectacular, it is still remarkable that these reactions proceeded as well as they did since the substrates do contain another allylic ester moiety which is known to undergo ionization in the presence of the same palladium catalyst. 

The absolute configuration of the cycloaddition products 54a,b was assigned by transformation to the lactones 66a,b with known configuration (Scheme 4.35)... 

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. 

Feringa-butenolide 114, in the presence of Dess-Martin periodinane reagent and 2,6-lutidine, gave the bis-ketone 115 which underwent intramolecular cycloaddition to afford endo-selectively the desired decalin-based lactone 116 (Equation 2.32) [114]. Double activation of butenolidic double bond strongly increases the reactivity of dienophile 115. 

The cycloaddition of glyoxylic acid with cyclopentadiene in water at pH 6 and 60 °C is slow and occurs with low yield and low diastereoselectivity [18] (Scheme 6.17). Proton (pH = 0.9) [18], copper salts [27] and Bi(OTf)3 [28] accelerate the reaction and increase the diastereoselectivity. The lactones 28 and 29 originate from endo and exo cycloadducts 27, respectively. The proposed rearrangement is depicted in Scheme 6.17 for the major endo adduct 30. A competitive ene reaction that originates 28 and 29 cannot be excluded [28]. 

Shao reported the microwave-assisted hetero-Diels-Alder cycloaddition reaction of a series of acetylenic pyrimidines to introduce a fused lactone/lactam ring, with no degradation of either reactants or products typical for the harsh thermal conditions (150-190°C, 15-144h) [131]. In contrast to the results reported when conventional heating was applied, the Diels-Alder cycloaddition under microwave irradiation gave a high yield of the desired fused lactones or lactams [132]. This reaction provided a practical and general method for the preparation of fused bicyclic pyridines 205 (Scheme 74). 

The dimerization of the parent ketene gives the P-lactone. One molecule of ketene reacts across the C=C bond as a donor and the other molecule reacts across the C=0 bond as an acceptor. This is similar to the concerted [2+2] cycloaddition reaction between bis(trifluoromethyl)ketene and ethyl vinyl ether to afford the oxetane (Scheme 26) [127], A lone pair on the carbonyl oxygen in the ketene molecule as a donor activates the C=C bond as the alkoxy group in vinyl ether. 

Only c/s-disubstituted and trisubstituted alkenes yield l,4-dioxan-2-ones by way of a cycloaddition reaction when oxidised by dimethyl a-peroxy lactone. An open 1,6-dipolar intermediate is postulated, involving steieoelectronic control <96JA4778>. 

The lactone ring in (9) is now a serious problem. If it were a symmetrical ring - say an anhydride (10) -we could make it easily by a 2 + 2 cycloaddition, as it would be symmetrical. 

Wilson JE, Fu GC (2004) Asymmetric synthesis of highly substituted P-lactones by nucleophile-catalyzed [2 -t 2] cycloadditions of disubstituted ketenes with aldehydes. Angew Chem Int Ed 43 6358-6360... 

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... 

The highly ordered cyclic TS of the D-A reaction permits design of diastereo-or enantioselective reactions. (See Section 2.4 of Part A to review the principles of diastereoselectivity and enantioselectivity.) One way to achieve this is to install a chiral auxiliary.80 The cycloaddition proceeds to give two diastereomeric products that can be separated and purified. Because of the lower temperature required and the greater stereoselectivity observed in Lewis acid-catalyzed reactions, the best diastereoselectivity is observed in catalyzed reactions. Several chiral auxiliaries that are capable of high levels of diastereoselectivity have been developed. Chiral esters and amides of acrylic acid are particularly useful because the auxiliary can be recovered by hydrolysis of the purified adduct to give the enantiomerically pure carboxylic acid. Early examples involved acryloyl esters of chiral alcohols, including lactates and mandelates. Esters of the lactone of 2,4-dihydroxy-3,3-dimethylbutanoic acid (pantolactone) have also proven useful. 

The domino process can be catalyzed by a Cu-complex with (S.S)-tBu-bis(oxazo-line) to give 2-616 with excellent enantioselectivity (97-98% ee) [320b,c]. The use of 5 A molecular sieves turned out to be obligatory. Wada and coworkers also reported on a related transetherification/l,3-dipolar cycloaddition procedure to give access to trans-fused bicyclic y-lactones [321]. 

One of the best methods to synthesize cyclopentenone derivatives is the Pauson-Khand procedure. However, Shindo s group have recently developed a domino process consisting of a [2+2] cycloaddition of a ketone with anynolate, followed by a Dieckmann condensation to give a 3-lactone as 4-190 which is decarboxylated under reflux in toluene in the presence of silica gel to afford cyclopentenones [64a]. Thus, the reaction of 4-188 and 4-189 led to 4-190, which on heating furnished the linear cucumin 4-191 (Scheme 4.41). This natural product has been isolated from the mycelial cultures of the agaric Macrocystidia cucumis [65, 66]. The domino procedure described was also used to synthesize dihydrojasmone and a-cuparenone. Moreover, the [2+2] cycloaddition can be combined with a Michael reaction [64b]. 

Intramolecular [4+2] cycloaddition of E,E- or L.Z-nitrodienes gives tranr-nitronates or ci.v-nitronates, respectively, with high stereoselectivity (Eq. 8.96).153 These products have been converted into y-lactones by the Nef reaction. 

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