Lactones cyclobutanes

Jeffares and McMurray have isolated the cyclobutane lactones (78) in low yield from the photochemical rearrangement of the 6-hydroxycyclohexenones (79). These are the first examples of products derived from cyclohexenones by an a-cleavage process. Irradiation in the presence of triplet quenchers such as ferrocene improves the yields somewhat. 

After separation of the diastereoisomers, cleavage of the tether afforded the cyclobutane lactones in good yield and in enantiomerically pure form. This strategy has been applied in a synthetic approach to (-)-italicene and (-l-)-isoitalicene. ... 

Chiral Alcohols and Lactones. HLAT) has been widely used for stereoselective oxidations of a variety of prochiral diols to lactones on a preparative scale. In most cases pro-(3) hydroxyl is oxidized irrespective of the substituents. The method is apphcable among others to tit-1,2-bis(hydroxymethyl) derivatives of cyclopropane, cyclobutane, cyclohexane, and cyclohexene. Resulting y-lactones are isolated in 68—90% yields and of 100% (164,165). 

Conjugate bases of relati-.- ly strong carbon acids like esters and nitriles react with oxiranes. The former give lactones (Scheme 56) (64HC(19-1)418) while the latter provide a route to cyclobutanes (Scheme 57) (74JA5270). 

The ring expansion of cyclobutane derivatives to other carbocycles remains to be one of the most powerful tool in synthetic organic chemistry. Cyclobutanones are exceptionally facile starting materials for the preparations of y-lactones as well as cyclopentanones. 

A new method, reported by Pearlman (262), for the preparation of Woodward s key building block also constitutes a new synthesis of reserpine as well as deserpidine. In the key step of the synthesis an internal (2ir + 2-tt] photocycliza-tion of dienone 518 gave cyclobutane derivative 519 with the established stereochemistry. Methanolysis and subsequent peracid treatment of 520 yielded lactone ester 521. Repeated methanolysis and retroaldol fission of the cyclobutane... 

Diketen und die meisten dimeren Aldoketene sind keine Cyclobutan-derivatc, sondem ungesattigte /5-Lactone 190), 184), 165). 

Ketene dimerization is the principal synthetic route to 4-methylene-2-oxetanones. This reaction proceeds very satisfactorily for ketene and methylketene, but disubstituted ketenes dimerize only to cyclobutane-1,3-diones. The cycloaddition reaction of r-butylcyanoketene to ketene and to methylketene gives a-cyanoalkylidene-/3-lactones in about 40% yield in addition to the cyclobutane-1,3-dione dimer of f-butylcyanoketene. A mechanism has been proposed for the formation of both types of dimers from a common zwitterionic intermediate (equation 111), with the relative amount of each product determined by the configurational equilibrium of the intermediate (80JOC4483, 75JOC3417). 

Cycloaddition is, in general, an effective way of generating cyclobutane rings. The lactone (304) is converted in this way on irradiation into both head-to-tail (305) and head-to-head (306) dimers.248 Direct irradiation of 5,7-dimethoxycoumarin in acetonitrile or benzene similarly affords the syn head-to-tail dimer via the singlet excited state, whereas... 

Addition to six-membered oxygen heterocycles is also common. The photocycloaddition of 5,7-dimethoxycoumarin to tetramethylethylene has been described,269 and 4-hydroxycoumarin (326) undergoes facile addition to cyclohexene on direct irradiation to give the cyclobutane (327)270 analogous additions to a variety of other alkenes have been reported, and the cycloaddition of 4-methoxycoumarin to 2-methylpropene has been employed in a synthesis of l,2-dihydrocyclobuta[c]coumarin.271 Photoaddition of the 1,2-bisenol lactone (328) to tran.s-stilbene yields propellane (329),272 and [ 2 + 2] cycloaddition is observed along with other competing photoreactions on irradiation of chromone in the presence of alkenes.273... 

Irradiation of lactone 131 with ( )-anethole in benzene gave cyclobutane 132 together withp-methoxybenzaldehyde [215] (Scheme 43). Similar irradiation of lactone 133 gave both cyclobutane 134 and an olefin 136 derived from an oxe-tane precursor 135. 

Addition of diethylaminopropyne to C60 resulted in a [2+2] cycloadduct that can be ring-opened under acidic conditions, while, when followed by oxidative cy-clization in the presence of activated carbon, novel fullerene lactones were formed [62]. Further work on the reaction of C60 with propiolates in the presence of triph-enylphosphine resulted in the construction of bismethanofullerenes and a [2+2] cycloadduct consisting of a cyclobutane ring fused to a 6,6 ring junction [63]. 

The fadal diastereoselectivity of intermolecular cyclopentenone [2 + 2]-photocy-cloaddition reactions is predictable if the cyclopentenone or a cyclic alkene reaction partner is chiral. Addition occurs from the more accessible side, and good stereocontrol can be expected if the stereogenic center is located at the a-position to the double bond. In their total synthesis of ( )-kelsoene (11), Piers et al. [22] utilized cyclopentenone 9 in the [2 + 2]-photocycloaddition to ethylene (Scheme 6.5). The cyclobutane 10 was obtained as a single diastereoisomer. In a similar fashion, Mehta et al. have frequently employed the fact that an approach to diquinane-type cis-bicydo [3.3.0]octenones occurs from the more accessible convex face. Applications can be found in the syntheses of (+)-kelsoene [23], (—)-sulcatine G [24], and ( )-merri-lactone A [25]. 

Liu has reported recently a new Co2(CO)8-mediated tandem [5+ 1]/ [2 + 2+ 1]-cycloaddition reaction that gives tricyclic 5-lactones from cis-epoxy enynes 186. This process possibly involves an initial opening of the epoxide in the cobalt hexacarbonyl complex 187 to from the complexed al-lene 189 via 188. Further coordination of the tethered olefin leads to 190 and further oxidative cyclization gives cobaltacycle 191 which inserts CO leading to the final compound 192. When performing the reaction under N2,191 suffers a reductive elimination to give cyclobutane 193 (Scheme 55) [172],... 

The cycloaddition of the allenes (63) to cyclopentenone results in the formation of the two adducts (64) and (65) in a ratio of 4 1. The addition reaction occurs primarily across the less substituted double bond of the aliens. Cycloaddition of acetylene and but-l-yne to the enones (66) can be brought about using left-circularly polarised light. The resultant cyclobutane derivatives are readily converted to the optically active enones (67). The photoaddition of hex-1-yne to the lactone (68) affords the two isomeric adducts... 

Numerous examples of [ 2 -I- 2] photocycloaddition of five-membered oxygen-containing heterocycles to alkenes have been reported, many of which have useful synthetic applications. The regiochemistry and stereochemistry of each adduct has not always been fully established. The lactone (311) undergoes photoaddition to cyclopentene to afford the cis,anti,cis adduct (312), whereas three stereoisomeric adducts were obtained with cyclohexene. Analogous additions of substituted lactones to alkenes have been employed in the syntheses of ( )-dihydrofomannosin acetate and cyclobutane analog of chrysanthemumic acid. The photoaddition of... 

Subsequently, the absolute configuration of the natural lineatin was determined as (lR,4S,5R,7R)-77 by our second synthesis, as shown in Figure 4.16.35 The first step was the cycloaddition of dichloroketene to isoprene to construct a cyclobutane ring. The symmetrical cyclobutanone A was then converted to ( )-bicyclic lactone B. Enantiomer separation (optical resolution) of ( )-B was executed as follows. Reaction of ( )-B with the resolving agent C (derived from chrysanthemic acid) yielded a diastereomeric mixture... 

Das gleiche Cyclobutan-Dcrivat I laBt sich aueh durch Belichtung von 2,3-Diphenyl-Acrylsaure in 2,3-Dimethyl-buten-(2) mit 67%iger Ausbeute gewinnen. Dabei ist das /3-Lacton II Zwischenprodukt3. Durch Oxidation von I (N-Brom-succinimid-Methode) wird 3,3,4,4-Tetramethyl-l,2-diphenyl-cyclobuten (III 80% d.Th.) zuganglich. 

Acetone sensitized reaction of the enantiomerically pure lactone 28 with ethylene gave a diastereomeric mixture of cyclobutanes (17 ,4S,5S)-29 and (1 S,4S,5R)-29 in high chemical yield84 8 Y By decreasing the reaction temperature the diastereoselectivity can be improved (e.g., +14 C de 29 % — 85 °C de 47 %). The least hindered attack of the alkene onto lactone 28 affording isomer (17 ,45,5S)-29 is preferred. 

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