Oxygen heterocycles, formation

A closely related oxygenated heterocyclic system devoid of acidic groups interestingly shows quite different biological activity. Thus, condensation of the benzofuran hydroxyketone 66 with ethyl thiomethyl acetate (67) probably proceeds initially by formation of the acylation product 68. Intramolecular dehydration leads to formation of a pyran ring. There is thus obtained the hypo-cholesterolemic agent timefurone (69) [14],... 

The synthesis of oxygen heterocycles in which cyclization onto a pendant alkyne is a key step has also been achieved. Reaction (7.36) shows an example of iodoacetal 29 cyclization at low temperature that afforded the expected furanic derivative in moderate Z selectivity [47]. A nice example of Lewis acid complexation which assists the radical cyclization is given by aluminium tris(2,6-diphenyl phenoxide) (ATPH) [48]. The (3-iodoether 30 can be com-plexed by 2 equiv of ATPH, which has a very important template effect, facilitating the subsequent radical intramolecular addition and orienting the (TMS)3SiH approach from one face. The result is the formation of cyclization products with Z selectivity and in quantitative yield (Reaction 7.37). 

Yu and co-workers have expanded upon Ojima s work through development of an effective Rh-catalyzed protocol for the cyclization/hydrosilylation of allenyl carbonyl compounds to form silylated vinylcycloalkanols and heterocyclic alcohols.For example, reaction of tosylamide 44 (X = NTs, R = H, n= ) and triethylsilane catalyzed by Rh(acac)(GO)2 (1 mol%) under GO (10 atm) at 70 °G for 8h gave the silylated vinyl pyrrolidinol 45 (X = NTs, R = H, n= ) in 74% yield with exclusive formation of the m-diastereomer (Equation (29)). The rhodium-catalyzed reaction was also effective for the cyclization of alleneones and for the formation of carbocycles, oxygen heterocycles, and six-membered cyclic alcohols (Equation (29)). However, Rh-catalyzed cyclization/hydrosilylation of allenyl carbonyl compounds that possessed substitution on an allenyl carbon atom was not established (Equation (29)). The efficiency of the Rh-catalyzed reaction of allenyl carbonyl compounds depended strongly on GO pressure. Reactions run under 10 atm GO were more efficient than were... 

The formation of oxygen heterocycles through carbon-oxygen bond formation was also reported. Substituted 2-(o-halophenyl)-ethanols were converted to dihydrobenzofuranes using palladium and Buchwald s bulky biaryl-type ligands (3.43.). The reaction was also efficient in the formation of six and seven membered oxygen heterocycles.53... 

The palladium catalysed conversion of alkenes to enols, also known as the Wacker reaction, has also been used in the formation of oxygen heterocycles. In the example shown in 3.68. the subsequent formation of two carbon-oxygen bonds leads to the desired dioxabicyclo[3.2.1]octane derivative. The first Wacker reaction gives selectively a six membered ring formation (other possible routes would lead to even larger rings), while in the second Wacker reaction the selective formation of the five membered ring is observed.86... 

The palladium catalyzed iminoannulation and carboxyannulation of alkynes and an appropriate aryl/vinyl halide is an efficient tool to construct six membered nitrogen and oxygen heterocycles. The process encompasses the concomitant formation of a carbon-carbon and a carbon-heteroatom bond. 

Small radicals such as tert-butylperoxy and ethylperoxy can, however, react via 1,4 H-transfer only the strain energy involved in O-heterocycle formation is 28 kcal. per mole. In this case, k.4(x — 106 sec."1 whereas krta = 10r> 4 sec. 1 and when [02] = 200 mm. of Hg, ko[02] = 105,3 sec. 1, so that k.4ct < < (tkr,a + k [02]). The result is that in the oxidation of small alkyl radicals, the route via alkylperoxy radicals will be blocked because reverse Reaction —4 competes successfully with Reaction 5. Reaction 2 will thus be a more effective mode of reaction of alkyl radicals with oxygen and the conjugate alkene will be a major product. 

The photoaddition of alcohols and phenols to alkenes has been observed.404 The equivalent intramolecular process results in cyclization and the formation of oxygen heterocycles. Irradiation of 2-allyl-4-(-butylphenol (388) affords 2,3-dihydro-2-methyl-5-<-butyl-benzofuran (389), whereas o-3-methylbut-2-enylphenol (390) gives 2,2-dimethylchroman (391). In both cases, therefore, the addition can be said to occur in a Markovnikov direction. 

The photolysis of cyclic ketones, in general, results in homolytic cleavage of the carbon-carbon bond adjacent to the carbonyl function. For details of this process, the reader is referred to the review by Srinivasan.425 Included among the photoproducts are certain oxygen heterocycles, formed by cyclization of reactive intermediates. Thus, cleavage in a cyclic /3-diketone, such as tetramethylcyclobutane-1,3-dione or hexamethylcyclohexane-l,3,5-trione [Eq. (110)] is followed by cyclization on the oxygen atom to form a lactone.426,427 y-Lactone formation is also observed on photolysis of 2,2-diphenylindane-l,3-dione [Eq. (Ill)] in ether, and the process is reversible.428... 

P,O-Heterocycles, formation in reactions of P(I1I) chlorides with oxygen-containing reagents 90MI5, 90UK431. 

Oxygen Heterocyclics Generated by Ethylene Formation 4.552 Oxygen Heterocyclics Generated Butadiene Formation 4.55.3 Nitrogen Heterocyclics Generated by Ethylene Formation... 

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