Lactones cycloaddition reactions

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). 

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. 

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>. 

Intramolecular [4+2]-cycloaddition reactions, which involve base-induced isomerization of a propargyl ether to an allenyl ether, have been extensively studied. Treatment of 157 with a base caused an intramolecular Diels-Alder reaction of the intermediate allenyl ether to give tricyclic compounds 158 [131]. An asymmetric synthesis of benzofuran lactone 159 was achieved by an analogous procedure [132],... 

Diels-Alder reactions with furans constitute a major class of cycloaddition reactions, which have been used for the preparation of a variety of new compounds. Some examples will be given in this section. A one-pot stereoselective synthesis of tricyclic -y-lactones was achieved via Diels-Alder reactions of 2-methoxyfuran with masked o-benzoquinones, which are in turn available from the corresponding 2-methoxyphenols <99CC713>. 

Ketene dimerization is the principal synthetic route to 4-methylene-2-oxetanones. This reaction proceeds very satisfactorily for ketene and methylketene, but disubstituted ketenes dimerize only to cyclobutane-1,3-diones. The cycloaddition reaction of r-butylcyanoketene to ketene and to methylketene gives a-cyanoalkylidene-/3-lactones in about 40% yield in addition to the cyclobutane-1,3-dione dimer of f-butylcyanoketene. A mechanism has been proposed for the formation of both types of dimers from a common zwitterionic intermediate (equation 111), with the relative amount of each product determined by the configurational equilibrium of the intermediate (80JOC4483, 75JOC3417). 

Four-membered heterocycles are easily formed via [2+2] cycloaddition reac tions [63] These cycloaddition 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, p 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, l,4-benzoxazm-2-ones, l,2,4-tnazin-5-ones, and l,2,4-tnazm-3,5-diones accelerates [2+2] photocycloaddition processes with ketenes and allenes [106] to yield the corresponding azetidme derivatives Starting from olefins, fluonnated oxetanes are formed thermally and photochemically [119, 120] The reaction of 5//-1,2-azaphospholes with fluonnated ketones leads to [2+2] cycloadducts [121] (equation 27)... 

Intramolecular [2 + 2]cycloadditions benzofurans. On dehydrochlorination with triethylamine in refluxing C6H6, these acid chlorides are converted into (o-acylphenoxy)ketenes, which undergo a [2 + 2]cycloaddition reaction to form p-lactones, which are converted to benzofurans by spontaneous decarboxylation in 53-82% yield.1... 

The 2 + 2-cycloaddition reaction of a-alkoxyketene-derived imines yields /l-lactams with quaternary stereogenic centres at C(4).33 The 2 + 2-cycloaddition of chiral aminoketenes with chiral imines yields cis-fi-lactams with the absolute stereochemistry of file C(3) and C(4) positions being controlled by the ketene partner only.34 The 2 + 2-cycloaddition of ketenes with (W)-2-/-butyldihydrooxazole (19) yields predominately the regioisomer (20) from steric control rather than the expected electronic control (Scheme 7).35 The double 2 + 2-cycloaddition reaction between ketenylidenetriphe-nylphosphorane (21) and carbon suboxide (22) produces the bis(ylidic) spirocyclobut-anedione (23) (Scheme 8).36 Semiempirical and ab initio calculations have been used to investigate the Lewis acid-promoted 2 + 2-cycloaddition leading to the formation of jS-lactones.37... 

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>... 

Various methods have been explored for the synthesis of lactones by cycloaddition reactions. The most common of these types of reaction is the [2+2] cycloaddition of aldehydes and ketene. Palladium(ll) complexes, [Pd(dppb)2(PhCN)2](BF4)2, have been shown to be efficient catalysts for this reaction (Equation 34) <2000CC73>. 

A diastereoselective Mukaiyama aldol lactonization between thiopyridylsilylketene acetals and aldehydes was used to form the /3-lactone ring in the total synthesis of (-)-panclicin D <1997T16471>. Noyori asymmetric hydrogenation was a key step in a total synthesis of panclicins A-E and was used to establish the stereocenter in aldehyde 140, which in turn directed the stereochemistry of subsequent reactions <1998J(P1)1373>. The /3-lactone ring was then formed by a [2+2] cycloaddition reaction of 140 with alkyl(trimethylsilyl)ketenes and a Lewis acid catalyst. 

Although the earliest syntheses of the Corey lactone, using a cyclopentadienyl-thallium species, were not very attractive, it was soon found that the lactone could be usefully generated by a Baeyer-Villiger reaction on a bicycloheptenone.8 In turn, this derives from an easy [2 + 2] cycloaddition reaction between dichloroketene and cyclopentadiene (Scheme 30.2).9 Additionally, an intermediate of the lactone could be resolved by way of the a-methylbenzylamine salt of its opened hydroxyacid, bringing the resolution step earlier in the synthesis than previously.10... 

The acceptor quality of vinyl ketones liberated from methyl 2-alkenyl 2-siloxycyclo-propanecarboxylates can also be used in cycloaddition reactions. Thus y-oxoester 147 adds smoothly to 2-siIoxybutadien 146 affording a cyclohexene derivative which after desilylation gives the tricarbonyl compound 148. This crucial intermediate can be obtained from vinyl cyclopropane 132 as a precursor of 147 in 72 % overall yield 85). Its chemoselective methylation, lactonization, and dehydration make norbisabolid available — a constituent of the root bark of atalantia monophylla. 

A recent study provides comments on the mechanism and origin of stereoselectivity in the Lewis acid catalyzed [2+2] cycloaddition reaction between ketenes and aldehydes to give P-lactones. The observations made in this study highlight the broad range of factors which must be pondered in order to understand and control stereoselectivity in a multistep reaction <02AG(E)1572>. 

Liu has reported recently a new Co2(CO)8-mediated tandem [5+ 1]/ [2 + 2+ 1]-cycloaddition reaction that gives tricyclic 5-lactones from cis-epoxy enynes 186. This process possibly involves an initial opening of the epoxide in the cobalt hexacarbonyl complex 187 to from the complexed al-lene 189 via 188. Further coordination of the tethered olefin leads to 190 and further oxidative cyclization gives cobaltacycle 191 which inserts CO leading to the final compound 192. When performing the reaction under N2,191 suffers a reductive elimination to give cyclobutane 193 (Scheme 55) [172],... 

Not only thermal [2 + 2] cycloaddition reactions but also the corresponding [2 + 2] cycloreversions are subject to large solvent effects. A good example is the thermal decarboxylation of the y9-lactone trani -3- -butyl-4-phenyloxetan-2-one, as described in Eq. (5-36). 

Ab initio MO calculations for the uncatalyzed [2 + 2]cycloaddition reaction between ketenes e.g. chloroketene) and carbonyl compounds e.g. formaldehyde) to yield oxetan-2-ones (y9-lactones) predict a relatively synchronous, concerted process, with a [ 2s + 2s +, i2s)] arrangement of the reactants in the activated complex and a negligible solvent effect [813],... 

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