Cyclic cleavage

Ring cleavage. Cyclic 1,3-diketones and 3-keto esters undergo oxidative cleavage in a copper(II) perchlorate-mediated process. 

Ether cleavage. Cyclic ethers, particularly tetrahydrofuranes, are cleaved by magnesium bromide and acetic anhydride in acetonitrile to oj-bromoacetates. The reaction occurs with inversion (8 2). 

The following mechanism for the reaction has been suggested. It postulates formation of an intermediate paraconic ester (A) the irreversible alkoxlde cleavage of this cyclic ester drives the reaction to completion ... 

Regioselectivity of C—C double bond formation can also be achieved in the reductiv or oxidative elimination of two functional groups from adjacent carbon atoms. Well estab llshed methods in synthesis include the reductive cleavage of cyclic thionocarbonates derivec from glycols (E.J. Corey, 1968 C W. Hartmann, 1972), the reduction of epoxides with Zn/Nal or of dihalides with metals, organometallic compounds, or Nal/acetone (seep.lS6f), and the oxidative decarboxylation of 1,2-dicarboxylic acids (C.A. Grob, 1958 S. Masamune, 1966 R.A. Sheldon, 1972) or their r-butyl peresters (E.N. Cain, 1969). 

The most common stereoselective syntheses involve the formation and cleavage of cyclopentane and cyclohexane derivatives or their unsaturated analogues. The target molecule (aff-cts)-2-methyl-l,4-cyclohexanediol has all of its substituents on the same side of the ring. Such a compound can be obtained by catalytic hydrogenation of a planar cyclic precursor. Methyl-l,4-benzoquinone is an ideal choice (p-toluquinone M. Nakazaki, 1966). 

Overall the reaction leads to addition of two hydroxyl groups to the double bond and IS referred to as hydroxylation Both oxygens of the diol come from osmium tetraox ide via the cyclic osmate ester The reaction of OSO4 with the alkene is a syn addition and the conversion of the cyclic osmate to the diol involves cleavage of the bonds between oxygen and osmium Thus both hydroxyl groups of the diol become attached to the same face of the double bond syn hydroxylation of the alkene is observed... 

A carbonyl group can be protected as a sulfur derivative—for example, a dithio acetal or ketal, 1,3-dithiane, or 1,3-dithiolane—by reaction of the carbonyl compound in the presence of an acid catalyst with a thiol or dithiol. The derivatives are in general cleaved by reaction with Hg(II) salts or oxidation acidic hydrolysis is unsatisfactory. The acyclic derivatives are formed and hydrolyzed much more readily than their cyclic counterparts. Representative examples of formation and cleavage are shown below. 

This reaction is referred to as the type-I or a-cleavage reaction of carbonyl omnpnunds. This type of reaction is not so common in solution, although some cyclic ketooes do undergo decarbonylation ... 

With cyclic ketones, the a-cleavage can also be followed by intramolecular bydn en abstraction that leads eventually to an unsaturated ring-opened aldehyde ... 

The reductive cleavage of -bromo ethers is a related reaction. If the ether is cyclic, the reverse reaction takes place on treatment with NBS ... 

A classical method for the vicinal hydroxylation of a double bond involves treatment with osmium tetroxide to give a cyclic ester, followed by reductive cleavage to the glycol ... 

By changing from the simplest to larger aliphatic and cyclic ketones, structural factors may be introduced which favor alternative unimolecular primary photoprocesses or provide pathways to products not available to the simple model compound. In addition, both the increase in molecular size and irradiation in solution facilitate rapid vibrational relaxation of the electronically excited reactant as well as the primary products to thermally equilibrated species. In this way the course of primary and secondary reactions will also become increasingly structure-selective. In a,a -unsym-metrically substituted ketones, the more substituted bond undergoes a-cleavage preferentially. 

According to Quinkert, photoexcited cyclic ketones may be transformed to open-chain unsaturated carboxylic acids in the presence of molecular oxygen. This reaction may compete efficiently with a-cleavage and secondary transformations thereof. Thus, both stereo iso meric 17-ketones (109) and (110) yield as much as 20% of the unsaturated acid (111) when irradiated in benzene under a stream of oxygen. This photolytic autoxidation has been used notably for partial syntheses of naturally occurring unsaturated 3,4-seco-acids from 3-oxo triterpenes (for references, see ref. 72). 

Serini reaction, 167 Simmons-Smith reaction, 107 Sodium acetylide, 138 Sodium bismuthate, 147, 149 Sodium bistrimethylsilylamide, 90 Sodium chloroacetylide, 68 Solvolytic cleavage of cyclic ethers, 267 3- (5 -Spiro-2, 2 -dimethyloxazolidi nyl) -cholestane, 360... 

In contrast to hydrogen-type ethers, a-haloethers, both linear and cyclic, are relatively easily cleaved by anhydrous hydrogen fluoride. Bis( 1,1 -difluoroalkyl) ethers are converted to 1,1,1 -trifluoroalkanes and alkanoyl fluorides The cleavage temperature depends on the substituents present ethers having no electronegative substituents other than a-fluorines are readily cleaved below 20 °C, 3-halo-1,1-di fluoroethers require approximately 70 °C, but 2-halo-1,1-difluoroethers are prac tically resistant toward hydrogen fluoride [/I (equation 1)... 

In the field of nucleosides, an interesting example of a cleavage of a nonfluor-inated six-membered cyclic ether containing oxygen and nitrogen atoms to give a fluoro nucleoside has been reported [5] (equation 5)... 

Oxidation of tim5-4-(2,2,2-tnfluoro-l-hydroxy 1 tnfluoromethylethyl)cyclo-hexanol with pyridinium chlorochromate results m the correspondmg cyclic ketone whereas oxidation with nitnc acid m the presence of a catalyst causes ring cleavage [50] (equation 46)... 

Irradiation of cyclic ketones having perfluoroalkyl groups causes cleavage of a ring to yield acyclic products [I74 (equation 44) Similarly, perfluonnated ketones undergo decarbonylation when irradiated [775]. Gas-phase photolysis of perfluorodiazoketones, in the presence of a trapping agent, yields fluorinated furan as a major product [176] (equation 45)... 

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