Heterocycles reductive cleavage

Amino-4-phenylthiazole when heated with Raney Ni is reported to yield acetophenone (469). In the course of a general study on reductive cleavage in heterocyclic systems Hoff et al. studied the reaction of 2-amino-4-methylthiazole with Na in liquid ammonia. Two equivalents of Na are necessary to obtain a mixture of 4-methyl-3-thiazoline (240) and... 

Reductive cleavage of the N-N bond in bicyclic systems containing a ring junction hydrazine subunit presents a facile route to medium-sized heterocycles containing two or more nitrogen atoms and the subject was duly covered in CHEC-II(1996) <1996CHEC-II(8)747>. No substantial progress has been reported since its publication. 

Reductive cleavage of the thiazoline C-S bond in heterocycle 193 with -Bu3SnH <1986T3537> followed by in situ hydrolysis of the resulting hemiaminal and protection of nitrogen as its benzyl carbamate gave 194 in 64% overall yield. This was then converted in several steps to potent marine neurotoxin Kainic acid 195 in racemic form (Scheme 27) <1994JOC2773>. 

Also, a danger of potential instability toward n-doping of the thiophene-5,5-dioxide containing oligomeric and polymeric EL materials can be foreseen, based on the known instability of other classes of heterocyclic systems with SO2 fragment in the cycle toward reductive cleavage. However, it should be mentioned that such a behavior has not, so far, been reported for the above thiophene-5,5-dioxide-containing materials. 

The reductive cleavage of phosphonio-substituents attached to other heterocyclic frameworks was first demonstrated in the reaction of the 3,5-bis-phosphonio-l,2,4-diazaphospholide 15 with NaBH4 or LiBEt3H to yield the zwitterionic borane-complexes 27. Liberation of the free zwitterion 28 was readily feasible by treatment of the complexes with an excess of NEt3 (Scheme 9) [34]. 

This chapter deals mainly with the 1,3-dipolar cycloaddition reactions of three 1,3-dipoles azomethine ylides, nitrile oxides, and nitrones. These three have been relatively well investigated, and examples of external reagent-mediated stereocontrolled cycloadditions of other 1,3-dipoles are quite limited. Both nitrile oxides and nitrones are 1,3-dipoles whose cycloaddition reactions with alkene dipolarophiles produce 2-isoxazolines and isoxazolidines, their dihydro derivatives. These two heterocycles have long been used as intermediates in a variety of synthetic applications because their rich functionality. When subjected to reductive cleavage of the N—O bonds of these heterocycles, for example, important building blocks such as p-hydroxy ketones (aldols), a,p-unsaturated ketones, y-amino alcohols, and so on are produced (7-12). Stereocontrolled and/or enantiocontrolled cycloadditions of nitrones are the most widely developed (6,13). Examples of enantioselective Lewis acid catalyzed 1,3-dipolar cycloadditions are summarized by J0rgensen in Chapter 12 of this book, and will not be discussed further here. 

Dipolar cycloaddition reactions between nitrile oxides and aUcenes produce 2-isoxazolines. Through reductive cleavage of the N—O bond of the 2-isoxazohnes, the resulting heterocycles can be readily transformed into a variety of important synthetic intermediates such as p-hydroxy ketones (aldols), p-hydroxy esters, a,p-unsaturated carbonyl compounds, y-amino alcohols, imino ketones and so forth (7-12). 

Similar results were also obtained starting from 1,4-hexadiene in this case no trace of four-mem-bered heterocycles was observed. For example, when carbamates or tosylamides were reacted with 1,4- or 1,5-hexadiene by using mercury(II) nitrate as the electrophile in dichloromethane, the thermodynamically more stable civ-.V-substituted 2,5-dimcthylpyrrolidincs 8 were obtained after reductive cleavage. This result is ascribed to a double A1,2 strain in the cyclization which occurs under thermodynamic control90,91. 

Reductive cleavage of a C—O bond of 1,3-dioxolanes may be achieved by a variety of methods commonly chemical reductants are employed and, although LAH alone is ineffective, the mixed reductants LAH/AlCb or LAH/AlBrs cleave 2-substituted dioxolanes (241) to hydroxy ethers (242), sometimes with a high degree of diastereotopic selectivity. This is usually explained in terms of the selective complexation of the reagent with one of the oxygen atoms of the ring, which then allows the delivery of hydride ion to one face of the heterocycle, rather than to the other. 

Reductive cleavage of a C-0 bond requires activation of the bond such activation can be obtained in different ways. Conjugated carbinols, like allylic and benzylic alcohols, tt-electron-deficient heterocyclic carbinols, and a-hydroxyketones and the ethers of these compounds, may be reductively cleaved. Reductive elimination of two vicinal hydroxyl groups or derivatives thereof may also be possible. These reactions have been exploited in the electrochemical removal of protecting groups [40,41]. 

The reductive cleavage of several aryl disulphides to thiols by their reaction with triphenylphosphine in aqueous dioxan has been reported. Several examples have been reported of the cleavage by phosphines and phosphites of S—SandS—N bonds contained in heterocyclic ring systems. Examples include (73) and (74). ... 

Heavily substituted l,2-dihydroquinazolin-4-ones were reduced with lithium aluminum hydride to 1,2,3,4-tetrahydroquinazolines without reductive cleavage of the heterocyclic ring. Several 1,2,3,4-tetrahydroquinazolines (65 X = Hj) were prepared in this way, and their structures were confirmed by syntheses from o-substituted aminomethylanilines and 5-chloropentan-2-one. ... 

There are many reactions that result in the conversion of dihydrothiazines into other heterocycles. They may be divided into three categories those that involve a nonoxidative and nonreductive cleavage, those that require an oxidative cleavage, and those that proceed by a reductive cleavage of the dihydrothiazine ring. 

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