Oxygen 4 + 2 ketene cycloaddition

Heterocyclic derivatives can be prepared by this route when one of the tether atoms is a nitrogen or an oxygen. Again this route is more efficient than the corresponding intramolecular ketene cycloaddition method for monosubstituted ketenes. Examples are the formation of 17,17 18,18 19 and 20,19 21,19 and 22.19... 

The psudoexcitation preferentially occurs in ketenes. The energy gap is smaller between and of ketenes than between n and it of alkenes. The orbital of ketene is raised in energy by the interaction with the n orbital on the carbonyl oxygen above n of alkenes. The orbital of ketenes is lower in energy than n of alkenes. The pseudoexcitation is preferred in ketenes and occurs through the interaction. The [2h-2] cycloaddition reactions take place across the C=C bond of ketenes rather than C=0 bond. 

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. 

The reaction of diphenylketene with 1,3,2-diazaboroles 234 in hexane at — 20 °C leads to the formation of 1,3,2-oxazaborolidines 238 in 64-70% yield. The reaction proceeds via the coordination of the ketene oxygen to boron 236 followed by a [2+3] cycloaddition yielding the bicyclic intermediate 237. Fission of B-N bond leads to the product formation as yellow to colorless crystals (Scheme 40) <20000M5791>. 

CYCLOADDITIONS f-Butyicyanoketene. a-Chloro-N-cyclohexylpropanaldoxime. Chlorosulfonyl isocyanate. Dichloroke-tene. Dimethyl acetylenedicarboxylate. Diphenyl ketene, 2-Methoxyallyl bromide. 2-Methoxy-6-methyl-l,4,3,5-oxathiadia-zine 4,4-dioxide. Oxygen, singlet. 4-Phen-yl-l,2,4-triazoline-3,5-dione. Silver fluoro-borate. Trimethylsilyldiazomethane. 

The polymer-supported Zr catalyst (12) is useful for asymmetric aza-Diels-Alder cycloaddition of benzaldehyde imine to Danishefsky diene [9]. The 6-substituted BINOL-Zr(IV) catalyst is useful for the enantioselective anft -preferred aldol reaction of benzaldehyde with ketene silyl thioacetal (15) (Scheme 5.5) [ 10]. The calculated charge densities on the oxygen atoms of the BINOL derivatives revealed that there is a good correlation between the charge density and the reactivity of 6-substituted BINOL [ 10]. 

The cycloaddition of ketenes to carbonyl compounds also shows the expected regioselectivity. In this case, both HOMO(ketone)/LUMO(ketene) and LUMO(ketone)/HOMO(ketene) interactions may be important, but they lead to the same conclusions about regioselectivity, with the carbonyl oxygen atom bonding to the carbonyl carbon atom of the ketene as in the reactions of the quinone 6.384 and formaldehyde... 

AAAcylimines, e.g., 4, are the most widely recognized and the most extensively investigated hetero-2-azadiene system capable of participation in Diels-Alder reactions, and comprehensive reviews have been published.7,71 In general, substituents X and Y are strongly electron-withdrawing groups and consequently the AAacylimines participate as electron-deficient partners in cycloaddition reactions with electron-rich dienophiles. Diels-Alder reactions of electron-deficient /V-acylimines with vinyl ethers, enamines, olefins, sulfenes, acetylenes, and the carbon-carbon or carbon-oxygen double bond of ketenes have been detailed.57 71 This 47t participation of electron-deficient AAacylimines does complement the ability of many simple AAacylimines to behave as 2ir dienophile components in Diels-Alder reactions with typical electron-rich dienes.6... 

Other heterocycles have also been allowed to react with ketenes via (2 + 2)-cycloaddition of an imino group. Heterobicyclic compounds related to the penicillins or the cephalosporins in which the sulfur atom is replaced by oxygen (0-penam and O-cepham)103 were obtained... 

DicWoroketene is particularly reactive, and reductive dechlorination of the product with zinc and acetic acid allows access to the cyclobutanone from formal addition of ketene itself. Thus, cycloaddition of dichloroketene with cyclopentadiene, followed by dechlorination and Baeyer-Villiger oxidation gave the lactone 173, a usehil precursor to various oxygenated cyclopentane products (3.117). Intramolecular cycloaddition reactions of ketenes can allow the formation of bicyclic and polycyclic products using otherwise unstable ketene intermediates. ... 

In 1978, BelluS and Malherbe described this variant of the Claisen rearrangement in the course of studies toward the [2 + 2] cycloaddition of ketene 234 and allylic ether 235. The presence of the y,<5-unsaturated ester 239 in the product mixture along with the expected product 237 led to the rationale which roposed formation of zwitterionic intermediate 238 resulting from the trapping of ketene by the ether oxygen. 

The lactam is an important class of heterocycles and has been investigated due to its potent anti-bacterial activity. Among the multiple synthetic approaches, a [2 -i- 2] cycloaddition of a ketene with an imine, is one method to provide quick access to cis P lactams. The typical prerequisite for these protocols involves the generation of the ketene from an activated carboxylic acid derivative (often an acyl chloride), which limits the scope of this pathway. Lee and coworkers developed a rhodium-catalyzed oxygenative addition reaction that furnishes the acyl chloride equivalent from a more stable terminal alkyne 41. An intermediate rhodium vinylidene then undergoes a [2 -i- 2] cyclization with imines (42) to provide the P-lactam 4. This reaction pathway enables more easily accessible alkynes to be employed as substrates for tran -P-lactam formation. 

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