Ketenes electrocyclization

An alternative end-game has the CO insert into the Cr=C bond of the allylidenechromium compound to give a Cr complex of a ketene. Electrocyclic ring closing of the ketene would then give the product. 

Pharmaceutically important 3-substituted-[l,8]naphthyridine-2,4-diones have been prepared by the reaction of 2-methyl-477-pyrido[2,3-r/][3,l]oxazin-4-one with active methylene compounds (Scheme 66) <1997J(P1)1487, 2003JOC4567> and by the same group via an intramolecular azadiene-ketene electrocyclization reaction of amino-nicotinic acid derivatives in a related process <2001JOC4413>. 

An intramolecular ketene electrocyclization also seems to occur in the Conrad-Limpach quinoline synthesis. In the heating of the 6-anilinocrotonic acid ester in a high-boiUng solvent at 240-250 °C, the ketene 466 is generated, which undergoes inttamolecular cy-clization to form a quinoline derivative 467 ... 

The proposed mechanism for the Conrad-Limpach reaction is shown below. Condensation of an aniline with a 3-keto-ester (i.e., ethyl acetoacetate 5) with loss of water provides enamino-ester 6. Enolization furnishes 10 which undergoes thermal cyclization, analogous to the Gould-Jacobs reaction, via 6n electrocyclization to yield intermediate 11. Compound 11 suffers loss of alcohol followed by tautomerization to give 4-hydroxy-2-methylquinoline 7. An alternative to the proposed formation of 10 is ejection of alcohol from 6 furnishing ketene 13, which then undergoes 671 electrocyclization to provide 12. 

We break the C4-C6 bond, and we form C3-C8 and C4-C9. The formation of the latter two bonds and the fact that we re forming a cyclobutanone suggests a [2+2] cycloaddition between a ketene at C3=C4=0 and the C8=C9 n bond. We can generate the requisite C3=C4 n bond by electrocyclic ring opening of the cyclobutene ring in the S.M. 

Disubstituted 2,4-cyclohexadienones (112) undergo photoinduced electrocyclic ring opening to the transient ketene derivatives 113, which can be trapped by nucleophiles to prepare the corresponding carboxylic acid derivatives (114 equation 44)196 197 j le reaction has been employed successfully for the synthesis of various carboxylic acids, esters and amides. 

Vollhardt s investigations100 into electrocyclic transformations on a CpCo template produced the following unusual result. After photolysis of CpCo(CO)2 in the presence of the tosyl hydrazone of trans-4-pheny -3-buten-2-one, the only isolated product was the vinylketene complex 123. Note that the tricarbonyliron analogue of this complex has also been isolated.3,87 The mechanism of formation was not discussed, but it seems likely that the ketene carbonyl originated as a carbonyl ligand that replaced the hydrazone moiety, perhaps via a vinylcarbene intermediate. 

Stabilized ketene 6S. For l, 2 -disubstituted epoxide, species 6S undergoes 6-endo-dig electrocyclization (path b) [24] to form the six-membered ketone 66, ultimately giving naphthol products. l, 2, 2 -Trisubstituted epoxide species 6S undergoes 5-endo-dig cyclization (path a) to give the ketone species 67, finally producing l-alkylidene-2-indanones. The dialkyl substituent of the epoxide enhances the 5-endo-dig cyclization of species 65 via formation of a stable tertiary carbocation 67. We observed similar behavior for the cyclization of (o-styryl)ethynylbenzenes [15, 16]. Formation of 2,4-cyclohexadien-l-one is explicable according to 6-endo-dig cyclization of a ruthenium-stabilized ketene, vhich ultimately afforded the observed products [25]. 

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... 

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... 

Abstract The main computational studies on the formation of (3-lactams through [2+2] cycloadditions published during 1992-2008 are reported with special emphasis on the mechanistic and selectivity aspects of these reactions. Disconnection of the N1-C2 and C3-C4 bonds of the azetidin-2-one ring leads to the reaction between ketenes and imines. Computational and experimental results point to a stepwise mechanism for this reaction. The first step consists of a nucleophilic attack of the iminic nitrogen on the sp-hybridized carbon atom of the ketene. The zwitterionic intermediate thus formed yields the corresponding (3-1 actant by means of a four-electron conrotatoty electrocyclization. The steroecontrol and the periselectivity of the reaction support this two-step mechanism. The [2+2] cycloaddition between isocyanates and alkenes takes place via a concerted (but asynchronous) mechanism that can be interpreted in terms of a [n2s + (n2s + n2s)] interaction between both reactants. Both the regio and the stereochemistry observed are compatible with this computational model. However, the combination of solvent and substituent effects can result in a stepwise mechanism. 

Fig. 4 Optimized geometric features of the electrocyclic transition structures associated with the conrotatory (a) and disrotatory (b) ring closure of the zwitterionic intermediates resulting from the interaction between ketene and prop-2-en-l-imine. Bond distances are given in A...

Thus, nucleophilic attack of the nitrogen of the a, 3-unsaturated imine (21) (Scheme 6) on the electrophilic carbon atom of ketenes (2) leads to the formation of zwitterionic intermediates (22) in the (3 and 8 conformations. The thermally allowed [n4c] reaction (22(3) leads to the formation of (3-lactams (23), whereas the [n6d] electrocyclization of (228) leads to the formation of the corresponding 8-lactams (24) (Scheme 6). 

Thus, ketenes (2) can react as dienophiles with (E)-l,3-diazabuta-l,3-dienes (E)-(25) to yield either [4 + 2] cycloaducts (26) or (27) depending on the participation of the C = C or C = O moieties of the ketenes (Scheme 7). Claisen rearrangement of 3,6-dihydro-2-methylene-2//-l,3,5-oxadiazines (27) yields the p-lactams (28). Alternatively, reaction between ketenes (2) and (Z)-l,3-diaza-buta-1,3-dienes (Z)-(25) leads to the usual zwitterionic intermediates (29), whose conrotatory electrocyclation leads to p-lactams (28). No computational data including solvent effects have been reported for these reactions. 

Computational studies [89] on the model reactions shown in Scheme 22 at the RHF/6-31G, MP2/6-31G, B3LYP/6-31G in vacuo and including solvent effects via SCRF methods showed that both processes take place via stepwise mechanisms similar to those found for the reaction between ketenes and imines. In both cases the nucleophilic attack of the iminic moiety was the rate-limiting step, the electrocyclic ring closure of intermediates (93, 96) being much faster. However, the first... 

It was found that one possible mechanism, denoted as (A) in Scheme 31, consists of the nucleophilic attack of imine (66) in the chromacyclopropanone complex (120) to yield intermediate (121). Isomerization of this [Cr]-C complex leads to [Cr]-0 zwitterionic intermediate (122), whose electrocyclic reaction yields O-coordinated (3-lactam (123). Alternatively, isomerization of (120) to the O-complexed ketene (124) permits the direct formation of zwitterionic intermediate... 

There is a general agreement on the stepwise nature of the [2+2] cycloaddition between ketenes and imines. The first step consists of a nucleophilic attack of the iminic lone pair on the v/ -hybridized atom of the ketene to form a zwitterionic intermediate. The subsequent four-electron conrotatory electrocyclization leads to the corresponding (3-lactam. The final stereochemical outcome of the reaction depends on the combination of the following features (1) endo/exo attack of the imine on the ketene (2) inward outward disposition of the substituents at the conrotatory transition structure and (3) relevance of the isomerization pathways, including those of the starting imines. 

Flash vacuum pyrolysis (FVP) of the indenone epoxides 795 results in a thermal rearrangement to form the intermediate ketene, which can undergo electrocyclization to afford isocoumarins in high yield (Scheme 221) <2000TL3677>. 

The benzannulation reaction tolerates a range of alkyl and aryl allcynes, which may bear additional functionalities. The simultaneous presence of two bulky substituents directly attached to the C=C bond, as for example in bis(trimethylsilyl)ethyne, however, blocks the final electrocyclization and causes the reaction to stop at the vinyl ketene stage [44]. Neither very electron-rich nor very electron-poor allcynes can undergo benzannulation. Strongly electron-deficient allcynes such as hexafluorobut-2-yne cannot adequately compete with car-... 

The isomeric precursor 37 cyclizes efficiently under the same conditions to give the pyrrolizin-3-one 39 (via [1,5]-sigmatropic shift of the phenyl group, regiospecifically to the 5-position, followed by elimination of methanol to generate the ketene 38 and its electrocyclization to product 39) (Scheme 11) <2007ARK85>. 

Wolff rearrangement of /)-diazenyl-a -diazo ketone 83 in the presence of water, methanol (or even with primary and secondary amines) under varied reaction conditions comes with surprise Instead of the expected homologous acid 89, methyl ester 90 (or the respective amide), 2-phenylcinnolin-3(2E0-one (91) is the only product indicative of the anticipated in situ formation of ketene intermediate 88 (Scheme 22). Obviously, the apparent 67r-electrocyclization reaction prevails forming the isolated heterocyclic product 91, a so far unknown compound. 

Few reactions of alkynes with C—X bonds are valuable for the preparation of four-membered hetero-cycles. Ynatnines react with aldehydes and ketones in the presence of Lewis acids to give unstable oxetene derivatives which undergo electrocyclic opening (Scheme 43). Open-chain products are also obtained with thiocarbonyl compounds,Schiff bases and iminium salts. Reactions of ynamines with carbon dioxide, ketenes, - ketenimines and isocyanates " often give mixtures of products and are of little preparative value. 

---