Spiro ketone

Antithetic conversion of a TGT by molecular rearrangement into a symmetrical precursor with the possibility for disconnection into two identical molecules. This case can be illustrated by the application of the Wittig rearrangement transform which converts 139 to 140 or the pinacol rearrangement transform which changes spiro ketone 141 into diol 142. 

The pinacol rearrangement reaction is of limited synthetic importance although it can be a useful alternative to the standard methods for synthesis of aldehydes and ketones." Especially in the synthesis of ketones with special substitution pattern—e.g. a spiro ketone like 5—the pinacol rearrangement demonstrates its synthetic potential ... 

In a total synthesis of (—)-/J-vetivone, the key step involves intramolecular alkylation of the bromo ketone 108 to give spiro ketone 111 (equation 47)169. The 5-Eto-Tet... 

In like manner, the addition product (110) of cyclopropanone and cyclopentadienyl Grignard reagent readily rearranges to the spiro ketone... 

In the study of a model for the possible synthesis of concentrine, 3,4-dihy-dropapaverine has been condensed with cyclohexane- 1,2-dione in the presence of base (preferably Triton B) to give the spiro-ketone (14). The reaction presumably proceeds via the carbanion (10) and the intermediates (11), (12), and (13). A similar reaction with benzil affords the diphenyl ketone (15). Catalytic reduction of the ketone (14) yields the corresponding alcohol.26... 

The present radical formation was then applied to intramolecular cyclization. 3-Substituted cyclohexenone derivative 64 which has a (tributylstannyl)methylthio group in the side chain was irradiated (hv > 300 nm) in methanol. The desired spiro compound 65 was, however, obtained in low yield (23%) along with methyl sulfide 66 (60%) and dienone 67 (S%). In contrast, when 64 was irradiated in the presence of a 0.3 molar amount of 1,4-dicyanonaphthalene (DCN) as sensitizer in acetonitrile with 5 molar amounts of water, spiro ketone 65 was produced in 84% yield without a detectable amount of 66 and 67. Thus, by employing the DCN-mediated one-electron oxidation, the intramolecular coupling reaction proceeds smoothly (Scheme 27). 

In the case of the tricyclic epoxides la-c the outcome of the reaction depends on the ring size. The formation of 2 and 3 was explained by the following mechanism. Cleavage of the epoxide ring with boron trifluoride diethyl ether complex gives the zwitterionic intermediate 4. Subsequent transfer of fluoride anion to the cationic center C2 leads to fluoroborate 5 (path a), which is hydrolyzed to yield 2. Spiro ketone 3 is obtained by a 1,2-alkyl shift in 4 (path b). 

However, the normal course for base-catalysed ring-opening of the alcohol (13) could be effected by converting the substrate to its sodium salt (14) (by NaH) followed by quenching with methanol the spiro ketone (15) obtained in this reaction results from retention in the protonation step (equation 13). ... 

The cis- and frans-hydrindandiols (26) are both converted exclusively to the spiro ketone (27) on brief treatment with cold concentrated sulfuric acid (equation 16). Plausible alternative products, the epoxide and spiro[5.3]nonanone, could not be ruled out as intermediates, since both were prepared by independent routes and found to give (27) under the reaction conditions. 

Alternatively, trialkylstannylcesium compounds can be prepared by fluoride ion-induced desilylation. Treatment of (trimethysilyl)tributylstannane with cesium fluoride affords a tributylstanyl anion. The anion reacts with a C-I bond to form a vinyl anion that promotes intramolecular cyclization [6]. The spiro ketone obtained is converted into a natural sesquiterpene acorone (Scheme 2.3). 

The benzylic carbanion from papaverine has been converted into a variety of substituted bases of general structure (30) by treatment with alkyl halides, aminoalkyl halides and ethyl acrylate (A. Buzas and G. Lavielle, Patent, Chem.Abs., 1981, 95, 25378, 150978) and the ion from dihydropapaverine (31) has been found to react with cyclohexan-1,2-dione in the presence of excess base to give the spiro ketone (35) presumably via the intermediates (32), (33) and (34). 

The bromoketones (94) undergo SET induced conversion into the spiro ketones (95). The electron transfer occurs on irradiation from an amine to afford the radical anion of the keto group. Loss of bromide affords the radical (96), which cyclizes to yield the products. The outcome of these photoreactions were compared with others using samarium iodide as the route to the radicals. This treatment afforded different products. ... 

The tnmv-diol 12 is obtained under mild conditions (activated alumina, ethanol, 48 h, 20 °C) from the polycyclic spiro ketone 11204. 

Several new synthetic routes to acorane sesquiterpenoids have been published during the past year cf. Vol. 8, p. 76). In the first of these routes spiroannulation of the pyrrolidine enamine (201) derived from cyclopentene aldehyde (200) provided an enone (202) which was subsequently converted into (-)-acorenone (203) (Scheme 19). In an alternative synthetic route,Robinson annulation of the aldehyde (204) with methyl vinyl ketone provided a spiro-ketone (205) which served as a common intermediate in the synthesis of (-)-acorenone (203) and (-)-acorenone-B (211) (Scheme 20) cf. Vol. 7 pp. 63, 64). To explain the conversion of (206) into (209), it has been suggested that the intermediate 1,2-borane borate (207) undergoes elimination followed by hydroboration. 

Radical ring expansion of propenylcyclobulanesf The substrates (2) arc obtained by alkylation of a spirocyclobutanone 1 with 1,3-dibromopropcnc. Treatment of 2 with Bu-,SnH/AIBN in refluxing benzene provides the tricyclic spiro ketone 3 together with the reduction product 4. 

There is no reason why ),6-difunctionalised compounds should not be made by conventional methods, essentially ignoring the 1,6-relationship. The symmetrical spiro ketone (28) disconnects to l,6 dicarbonyl compound (29) which could no doubt be made by cleavage of (30). An alternative approach is to disconnect the ring from the chain to give (31) easily made from butyro-lactone (32) (Table 25.1). 

Diels Alder reaction, and to some spiro-ketones by cyclisation of 91... 

Elimination of the silyl group affords the final products (34). The reaction has been extended to provide a path to larger ring ketones such as the cyclization of (35) to yield (36) and also to the synthesis of spiro ketones (37) from (38). 

Reaction of the organobiscuprate (45) with chloroenones (46) gives the spiro-ketone (47) in about 50% yield. In contrast, reaction with 3-acetoxycyclohex-3-... 

Acid-catalysed decomposition of the diazo-ketone (330) results in cyclization to the spiro-ketone (331) in the first recorded example of Ar,-4 participation. ... 

The keten (695) has been obtained by irradiation of benzocyclobutenone. Photolysis of the diketones (696 n = 5—7) in methylene chloride affords mixtures of olefins (697 n = 5—7) and ketens, whereas (696 n = 4) gives mainly the lactone (698). The behaviour of these spiro-ketones in methanol is different, the larger ring systems (696 n = 5—7) giving esters (699) and ketones (700) and also, in the cases where n = 6 or 7, the unstable, air-sensitive cyclopropanone hemiketal (701X which oxidizes to (702) on work-up cf. ref. 84). 

Lightner has reported the first simple cases of ketones with only a dissymmetric front octant perturber. The spiro-ketone (11) was made from (-f )-7,7-dimethoxybicyclo-[2,2,l]heptan-2-ol using a Trost spiroannelation procedure. The methyl group is subject to large downfield shifts in benzene or in presence of [Eu(dpm)3], confirming the relative stereochemistry. The ketone shows a strong positive Cotton effect near... 

The full paper on the preparation and properties of monomeric selenoketones and their conversion into olefins by two-fold extrusion processes has now appeared. The preparation of the spiro-ketones (459)—(461) from 7-norbornen-one has been described. Thus, treatment of 7-norbornenone with cyclopropyl-... 

A domino process of enamine 136 formation, N-allylation, aza-Claisen rearrangement and a final Mannich condensation was introduced by Florent [22g]. Aldehyde 135 was subsequently treated with pyrrolidine and allyl iodide 137 to give an E/Z mixture of the ammonium salts 138. Heating to 80 °C induced the Claisen rearrangement. The newly formed iminium ions 139 underwent intramolecular Mannich cycUzations. The final amine eUmination delivered the spiro ketones 140 with 38% yield as a 2 1 mixture of diastereomers. The formed material should serve as a key compound in diverse cyclopentenone prostaglandine total syntheses (Scheme 10.30). 

Enediynyl ethyl ethers like 12 have been applied by Wang s group as precursors of enyne-ketenes 13, which underwent the Moore cyclization reaction to form diradicals. The intermediate 14 and (after 1,5-hydrogen shift) new diradical 15, form, upon the cascade transformations, the final products mainly chromanol 16 and spiro ketone 17. The latter is a result of subsequent intramolecular reaction of intermediates o-quinones methide and spiro ketone (not illustrated). ... 

While S-3 participation in carbocation reactions is common, cyclo-propylcarbinyl cations such as (31) preferentially lead to ring enlargement, and a synthetic procedure for obtaining cyclobutanones has been devised based on this observation. " Thus the tertiary alcohol (32) is ether, upon treatment with aqueous fluoboric acid, gives the spiro ketone (33) quanti-... 

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