Ketones alkenyl, cyclization

Several approaches to cyclic thio- and dithio-lactones have been described thus, the reaction of y-oxo-esters with HjS gave 5-mercaptothiolan-2-ones (123) (see Vol. 5, p. 249). A general approach to y- and -thiolactones, e.g. (124), involves the reaction of a bis-metallated thioacid with a- or /6-chloro-ketones and cyclization of the resulting y- or <5-chloro-y6-hydroxy-thioacids. Reactions of cyclic lactones with the dimeric phenylthionophosphine sulphide (125) gave dithiolactones. y-Dithiolactones, e.g. (126), were obtained from 2-alkenyl alkanedithioates, which... 

The reaction of alkenyl iodides or triflates, alkenylstannanes, and CO affords divinyl ketones[397,398]. Thus the capnellene skeleton 538 has been synthesized by the carbonylation of the cyclopentenyl triflate 536 with the alkenyltin 537[392], The macrocyclic divinyl ketone 540 has been prepared in a moderate yield by the carbonylative cyclization of 539[399]. 

The starting materials may easily be obtained from a commercially available ketone, which thus can be transformed in a short sequence into the cyclization substrates41. In addition, dienones containing the alkynylsilane terminator can also easily be transformed to m-fused cyclopcn-tanes with the synthetically useful angular alkenyl side chain41,45. 

Perez-Pietro et al. have introduced the dirhodium complex (105) with a unique o/7/io-metalated arylphosphine ligand. The complex is an efficient catalyst for the cyclization of alkenyl diazo ketones (Scheme 7S).288 289... 

Silyl enol ethers of alkenyl methyl ketones can be efficiently cyclized to cyclopentenones and cyclohexenones by treating them with stoichiometric amounts of palladium acetate244 an example indicating the elaboration of this approach to the synthesis of a reduced benzoxepinone derivative, and the suggested244 mechanism of the reaction, are depicted in Scheme 174. 

Elsewhere, Heaney et al. (313-315) found that alkenyloximes (e.g., 285), may react in a number of ways including formation of cyclic nitrones by the 1,3-APT reaction (Scheme 1.60). The benzodiazepinone nitrones (286) formed by the intramolecular 1,3-APT will undergo an intermolecular dipolar cycloaddition reaction with an external dipolarophile to afford five,seven,six-membered tricyclic adducts (287). Alternatively, the oximes may equilibrate to the corresponding N—H nitrones (288) and undergo intramolecular cycloaddition with the alkenyl function to afford five,six,six-membered tricyclic isoxazolidine adducts (289, R = H see also Section 1.11.2). In the presence of an electron-deficient alkene such as methyl vinyl ketone, the nitrogen of oxime 285 may be alkylated via the acyclic version of the 1,3-APT reaction and thus afford the N-alkylated nitrone 290 and the corresponding adduct 291. In more recent work, they prepared the related pyrimidodiazepine N-oxides by oxime-alkene cyclization for subsequent cycloaddition reactions (316). Related nitrones have been prepared by a number of workers by the more familiar route of condensation with alkylhydroxylamines (Scheme 1.67, Section 1.11.3). 

The 5-9-5 skeleton was assembled by the addition of the alkenyl cerate derived from 6 with the ketone 4, to give 7. -Cope rearrangement then gave the 5-9-5 enolate, which was quenched with methyl iodide to give 8. The ketone 8 underewent spontaneous intramolecular ene cyclization, to give 9. 

Several procedures are known, including Rh catalysis, for the exo cyclization of alkenyl aldehydes such as 1 to ketones such as 2. Kiyoshi Tomioka of Kyoto University recently reported (J. Org. Chem. 2005, 70,681) that efficient cyclization can be achieved by merely heating the aldehyde with a catalytic amount of a tertiary thiol, with A1BN as the initiator. Addition takes place even to unactivated aikcnes, and both five- and six-membered ring ketones can be formed. It is a measure of the mildness of the method that cyclization of 1 gives 2 as a 1 1 mixture, even though trans is much the more stable diasteromer. 

The isoxazolidines (47) and (48) were obtained by cyclization of the corresponding ketone-derived exocyclic nitrones (Scheme 11).22 Such reactions have been used for natural product sysnthesis, as in the conversion of isoxazolidine (49) to ( )-hirsutene. Methylation and catalytic hydrogenolysis provided a y-dimethylamino alcohol, which underwent Cope elimination to provide an alkenyl alcohol in a key step. A related synthesis of ( )-7,12-sechoishwaran-12-ol is also reported. 

Isotellurazoles 4 were obtained in low yields (3-11%) by the one-pot reaction of alkynyl ketones with hydroxylamino-O-sulfonic acid and K2Te in aqueous solution containing sodium acetate (83S824 87H1587). A plausible mechanism of the reaction includes formation of the oxime derivative and subsequent nucleophilic addition of telluride anion to the triple bond followed by cyclization to 4. The reaction is accompanied by the formation of telluro bis(alkenyl ketones) 5 in yields approximately equal to those of 4. When alkynyl aldehydes are used instead of ketones, the single reaction products are the tellurobis(alkenyl nitriles) 6 (83S824). 

There are still two other factors influencing the reactivity of ketones in the Norrish-Yang reaction. If functional groups with a relatively low oxidation potential (amino, alkenyl or aryl groups, thioethers) are present in the reactants, the excited state may be quenched by partial or complete charge transfer from these groups to the extited carbonyl group. The effects of such processes may vary from a complete loss of reactivity to an entirely new reaction mode - cyclization reactions ini-... 

The same group has further shown that the alkenyl double bond geometry of geraniol- as well as nerol-derived ketones 41 and 43 remains unaffected during the photocyclizations. This suggests that the rate of cyclization is much higher than the rotation about the double bond in the allylic radical center of the biradical (Scheme 8.12). 

Azole approach. 3-(4-Oxo-l-alkenyl)isoxazoles on acid catalysis will undergo cyclization at the nitrogen atom if the oxo group is part of an ester, a lactam is formed, e.g. (38) (80LA542). The hydrobromide of the betaine (40) has been prepared by ionic dibromination of the ketone (39), followed by elimination of HBr (71JCS(C)1196). 

Excitation of the ketone (226) brings about a 1,7-hydrogen transfer to afford the biradical intermediate (e.g., 227). Cyclization within this species yields the alkenyl-tetrahydrofurans (228) and (229) in the yields and ratios shown. The cyclization process is reasonably selective in that the geometry of the double bond is retained in the cyclized product. This was demonstrated for the enone (230) (a cis trans mixture of ratio 1 3), which gave the cyclized products (231—234) (Scheme 16). Two principal products (235, 15%) and (236, 60%) are obtained from irradiation of the ketone (237) in dioxan solution. " Two minor products (238)... 

Cinnolines are prepared by an intramolecular cyclization of o-alkenyl or o-alkynyl aryldiazonium salts. For instance, (o-aminophenyl)alkynes 6 or alkyl(o-aminophenyl)ketones 8 (via the enol form) yield 4-hydroxycinnolines 7 (the v. Richter and Borsche syntheses, respectively), o-Aminostyrenes 10 afford 3,4-disubstituted cinnolines 11 (Widman-Stoermer synthesis) ... 

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