Cyclobutanone ring 7-lactones

A series of 2-vinyl-3-silyloxybicyclo[3.2.0]heptan-6-ones has also been converted to prostanoid lactones in excellent yield but variable regioselectivity. Some of the best regioselectivity was obtained using H202 in trifluoroethanol (see p. 1097).241 The strained cyclobutanone ring and the relatively unreactive terminal vinyl group favor the desired reaction in preference to alkene epoxidation. 

The synthesis of ( )-isodihydronepetalactone (114) is dependent upon the highly stereoselective hydrolysis of the cyclo-adduct (115) to (116) which on reductive cleavage of the cyclobutanone ring yields, after hydrolysis, (114) accompanied by minor amounts of the two lactones (117). Selective monohydroboration-... 

Hydrogen peroxide sodium hydroxide Baeyer-YUliger oxidation y-Lactones from cyclobutanone ring... 

Whereas lactone annulation invokes a relief of strain of the four membered ring by migration of the ring bond to an electron deficient oxygen, a similar migration to an election deficient carbon creates a cyclopentanone synthesis (Eq. 73). The release of approximately 84 kJ/mole (20 kcal/mole) provides a strong driving force. Thus, the 1,1-cyclobutanone annulation of ketones translates into a 1,1-cyclopentanone annulation. 

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. 

The benzene ring containing cyclobutanones (208), (210) and (212) were also oxidized to their y-lactones (209), (211) and (213) respectively71 These examples demonstrate convincingly the order of alkyl migration. 

Cyclobutanones were found to be much more reactive under these conditions, presumably due to relief of ring strain (131). Racemic cyclobutanone (192) is oxidized under the conditions described above to provide lactones 193 and 194 in a ratio of 55 45, Eq. 111. The expected lactone product 193 is formed in 67% ee while the abnormal product 194 is formed in 92% ee. The major enantiomers of the two products are complementary, resulting from enantiomeric ketones. 

The key steps in the ring expansion of the cyclobutanones (186) and (787) are the Baeyer-Villiger oxidation effected by H202—HOAc. It is noteworthy to point out that the Baeyer-Villiger oxidation is regiospecific and serves to be an excellent method for the preparation of y-lactone from cyclobutanones. 

A final oxidation type that has been observed is the catalysis of Baeyer-Villiger-type oxidations of cyclic ketones to lactones.53 Understandably, the strained cyclobutanone is the best substrate, giving 80% conversion after 24 h at 25°C (tert-butanol solvent). Larger ring ketones proceed more slowly, although selectivity remains high. Elevated temperatures increase the rate without sacrificing selectivity cyclopentanone is converted to the lactone in 72% yield after 1 h at 70°C in THF. Complex 4 was presumed to be the active species. 

In general, on reaction with selenic acid, cycloalkenones undergo ring contraction to cycloal-kanecarboxylic acids, while 2-alkylcycloalkanones give lactones.Depending on the experimental conditions, on treatment with selenium dioxide, cyclobutanone" underwent either oxidation to y-butyrolactone or ring contraction to cyclopropanecarboxylic acid (1). 

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... 

The thermal [2 + 2J cycloaddition of cumulenes with alkenes, imines, and carbonyl compounds is one of the most useful routes to four-membered ring compounds. Ketenes and keteniminium salts add to alkenes to give cyclobutanones (Houben-Weyl Vol. IV/4 pp 174 205) 41 al-lenes add to alkenes to give methylenecyclobutanes (Houben-Weyl Vol. IV/4 pp 151-173), ketenes add to carbonyl compounds to give //-lactones (Houben-Weyl Vol. VI/2 pp 520-527), ketenes add to imines to give /1-lactams, and isocyanates add to alkenes to give //-lactams (Houben-Weyl Vol. V/lb p 1098). 

An efficient conversion of cyclobutanone to a 7-lactone ring is part of a total synthesis of prostaglandins Among the various products obtained by reaction of acetylenes with carbon disulfide are those of special interest which originate by the addition of third components to intermediate 1,3-dithiolium carbenes to form 2-subst. 1,3-dithioles... 

Cyclopentane-ring Variants.- Full details have been published on the preparations of nor-PGs (Scheme 26). A key transformation en route to these compounds involves oxidative cleavage of the alkene unit in the bieyelohepteno 1 (179). The lactone (180) was formed and this compound was converted into the cyclobutanone (181). The ketone (181) was allowed to undergo ring expansion... 

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