Cyclization with ketenes

Vinyl etheis cyclize with ketenes to cyclobutanones (239). 

This method for the preparation of cyclobutanone via oxaspiropentane is an adaptation of that described by Salaiin and Conia. The previously known large-scale preparations of cyclobutanone consist of the reaction of the hazardous diazomethane with ketene, the oxidative degradation or the ozonization in presence of pjrridine of methylenecyclobutane prepared from pentaerythritol, or the recently reported dithiane method of Corey and Seebach, which has the disadvantage of producing an aqueous solution of the highly water-soluble cyclobutanone. A procedure involving the solvolytic cyclization of 3-butyn-l-yl trifluoro-methanesulfonate is described in Org. Syn., 54, 84 (1974). 

Additions of silylated ketene acetals to lactones such as valerolactone in the presence of triphenylmethyl perchlorate in combination with either allyltrimethylsilane 82, trimethylsilyl cyanide 18, or triethylsilane 84b, to afford substituted cyclic ethers in high yields have already been discussed in Section 4.8. Aldehydes or ketones such as cyclohexanone condense in a modified Sakurai-cyclization with the silylated homoallylic alcohol 640 in the presence of TMSOTf 20, via 641, to give unsaturated cyclic spiro ethers 642 and HMDSO 7, whereas the 0,0-diethyllactone acetal 643 gives, with 640, the spiroacetal 644 and ethoxytrimethylsilane 13b [176-181]... 

Compound 133 was synthesized by the one-pot intermolecular cyclization of ketene aminal 132 with alkyl isothiocyanate (Equation 15) <1995BML1541, 1997BML651, 2002BMC1275>. 

The cyclobutenone 70 is transformed to the r/4-vinylketene complex 72 with (t/5-indenyl)Co(PPh3)2 71. The vinylketene complex 72 undergoes cyclization with alkynes to produce the corresponding phenols 73. FeCl3 oxidation of the (2-phenylvinyl)ketene complex, however, leads to the naphthol 74. A catalytic synthesis of phenols via the vinylketene intermediates 72 is achieved by the use of Ni(COD)2 as a catalyst [36]. (Scheme 26)... 

A novel heterocyclic system has been achieved from methyl 3-aminopyra-zine-2-carboxylate and several aroyl chlorides, leading to 3-aroylamino derivatives the latter are cyclized with dibromotriphenylphosphorane to 2-arylpyrazino[2,3-rf][3,l]oxazin-4-one (94S405). Furthermore, vinylimino-phosphoranes and diphenylketene react (Scheme 87) to give nonisolable vinylketenimines (233) which afford, with a second equivalent of ketene in a [4 + 2]-cycloaddition, 1,3-oxazinones (234) [89JCS(P1)2140]. 

Esterification of linalool requires special reaction conditions since it tends to undergo dehydration and cyclization because it is an unsaturated tertiary alcohol. These reactions can be avoided as follows esterification with ketene in the presence of an acidic esterification catalyst below 30 °C results in formation of linalyl acetate without any byproducts [71]. Esterification can be achieved in good yield, with boiling acetic anhydride, whereby the acetic acid is distilled off as it is formed a large excess of acetic anhydride must be maintained by continuous addition of anhydride to the still vessel [34]. Highly pure linalyl acetate can be obtained by transesterification of tert-butyl acetate with linalool in the presence of sodium methylate and by continuous removal of the tert-butanol formed in the process [72]. 

The intramolecular cyclization dominates other possible reactions even in solvents highly susceptible to free radical attack (110). Thus, irradiation of 4,5-octanedione in butanal gives 2-hydroxy-3-methyl-2-propylcyclobutanone in 92% yield (110). Irradiation of 1,2-cyclo-decanedione (Formula 264) gives 1-hydroxybicyclo [6.2.0 ]decan-10-one (Formula 265) in 74% yield and cyclooctanone (Formula 266) in 9% yield (111). The cyclooctanone is produced together with ketene by a secondary photolysis of Formula 265 (111). 

A model compound 15 containing an indole (3-lactam moiety in chartellines was synthesized from the Mannich reaction of isatin imine with ketene silyl acetal, followed by (3-lactam formation through cyclization of the resulting (3-amino acid 14 (Scheme 5) [52]. L-Proline-catalyzed direct asymmetric Mannich reactions of... 

The use of substituted pyridines in organic synthesis has broad application. The activation of the pyridine ring toward nucleophilic attack is well known in the literature. The products of such reactions are often dihydropyridines which can serve as intermediates in more complex synthetic strategies. Rudler and co-workers have reported on the nucleophilic addition of bis(trimethylsilyl)ketene acetals to pyridine (26). The 1,4-addition product 27 was then cyclized with iodine to afford bicycle 28 in 90% overall yield <02CC940>. Yamada has elegantly shown that facial selectivity can be achieved and chiral 1,4-dihydropyridines accessed in high yield and de (29—>30) <02JA8184>. 

Allene carboxylic acids have been cyclized to butenolides with copper(II) chloride. Allene esters were converted to butenolides by treatment with acetic acid and LiBr. Cyclic carbonates can be prepared from allene alcohols using carbon dioxide and a palladium catalyst, and the reaction was accompanied by ary-lation when iodobenzene was added. Diene carboxylic acids have been cyclized using acetic acid and a palladium catalyst to form lactones that have an allylic acetate elsewhere in the molecule. With ketenes, carboxylic acids give anhydrides and acetic anhydride is prepared industrially in this manner [CH2=C=0 + MeC02H (MeC=0)20]. 

Chloroacetylacetone and ketene 378 are other bifunctional electrophiles investigated in cyclizations with 1-aminopyrazoles [Eq. (92)] (78TL1291 83H1271). 

Cyclization or2-aminophenoI with ketene in liquid sulphur dioxide at or below 0°C gives a modest yield of this fused ring compound. 

The high reactivity of iV-substituted pyridincs (review (1870]) is exemplified in the mild conditions needed to cyclize the A -allyiic side-chain of the pyridinium salt (42.1). Evidence for the participation of pyridinium ylides in this reaction is provided by adding ethyl propynoate and carbonate to the pyridinium salt [2469, 2471, 2518]. The pyridinium salt (42.2, R = Et) reacts with ketene dithioacetals (review [3712]) to give 3-substituted indolizines [2881] the behav-... 

Thiazolium bromide (108) reacts with keten thioacetals (MeS)2C=C(CN)2, etc., in the presence of NaH or EtaN, to afford iminothiazolines [109 Z = (NC)2C, Me02CC(CN), or tosylimino] Treating (109) with NaOMe results in cyclization to give imidazo[2,l-h] thiazoles [110 = C02Me, = CH-... 

The electron-rich character of keten acetals (36) means that they undergo cycloaddition with ketens with judicious choice of reactants, this results in the formation of dihydropyran-2-ones, e.g. (37), which are hydrolysed to the dioxo-derivative (38). /3-Keto-esters are cyclized by their reaction with 3-hydroxy-aldehydes and titanium(rv) chloride to form 5,6-dihydropyran-2-ones. Aroylarylacetylenes condense with either ethyl cyanoacetate or aceto-acetate in the presence of a base to form 4,6-diarylpyran-2-ones (39)." ... 

The synthesis of indolizines by 1,5-dipolar cyclization, the reaction of picolinium salts with ketene dithioacetals, the reaction of 2-pyridyl ketene dithioacetals with halogencarbonyls, and a reaction of A7-imines or S-imines with ketene dithioacetals have been reviewed <85YGK669>. 

Formation of the oxazolo[3,4-Z ][l,2,4]triazine ring system (27) was first observed in the phototransformation of (140) with ketene which gave the product (141) (Equation (39)) <88CPB3354>. The proposed mechanism involves formation of the biradical (142), its cyclization to the fused aziridine (143), ring opening of the three-membered ring to give the zwitterion (144), which upon reaction with a further molecule of ketene affords the final product (141). 

Deoxy-l-methylaminoalditols (546) undergo condensative cyclization with benzaldehyde (71ZC306) or ketene dithioacetals (86JPR21) to 2-substituted 5-(alditol-l-yl)-3-methoxyoxazolidines (547) (Scheme 145). 

---