Cyclic intermediate

Complex reactions occur on the autoxidation of pyrroles (see Section 3.05.1.4) predictably, susceptibility to autoxidation increases with increasing alkyl substitution, llie photosensitized reaction of pyrrole and oxygen yields 5-hydroxy-A -pyrrolin-2-one, probably by way of an intermediate cyclic peroxide (Scheme 28) (76JA802). 

Electrophilic attack on the sulfur atom of thiiranes by alkyl halides does not give thiiranium salts but rather products derived from attack of the halide ion on the intermediate cyclic salt (B-81MI50602). Treatment of a s-2,3-dimethylthiirane with methyl iodide yields cis-2-butene by two possible mechanisms (Scheme 31). A stereoselective isomerization of alkenes is accomplished by conversion to a thiirane of opposite stereochemistry followed by desulfurization by methyl iodide (75TL2709). Treatment of thiiranes with alkyl chlorides and bromides gives 2-chloro- or 2-bromo-ethyl sulfides (Scheme 32). Intramolecular alkylation of the sulfur atom of a thiirane may occur if the geometry is favorable the intermediate sulfonium ions are unstable to nucleophilic attack and rearrangement may occur (Scheme 33). 

Hydrolysis of ribonucleic acids by snake venom was found to yield inorganic phosphate, nucleosides, and pyrimidine ribonucleoside diphosphates.197 These diphosphates were shown by their behavior toward various enzymes to be mixtures of 2,5- and 3,5-diphosphates, and it therefore seems likely that they were formed through intermediate, cyclic phosphates. Thus, although this evidence confirms the existence of 2(or 3) — 5 linkages, it does not distinguish between the 2- and 3-positions. 

The alcoholysis of the cyclic phosphate of catechol by alditols can lead, after acid hydrolysis of intermediate, cyclic phosphates, to the selective formation of phosphoric esters of the primary hydroxyl groups in the alditols. Thus, erythritol and D-mannitol afford, after chromatographic purification of the reaction products, their 1-phosphates in yields of 31 and 38%, respectively.217 The method was used to convert riboflavine into riboflavine 5 -phosphate.218 1-Deoxy-1-fluoro-L-glycerol has been converted into the 3-(dibenzyl phosphate) in 54% yield by selective reaction with dibenzyl phosphorochloridate. 219... 

The Wittig reaction consists in the replacement of carbonyl oxygen of aldehydes and ketones by a methylene group with the aid of phosphine-methylenes resulting in the formation of cis or trans olefines. The reaction proceeds through the nucleophilic addition of Wittig reagent (phosphine methylene) across the > C = O bond and formation of an intermediate cyclic. 

Criegee had earlier postulated the formation of an intermediate cyclic ester, but this was later ruled out and now the above mechanism has been established. 

Products. The work of Wagner (42,43) and Boeseken (44) established that the oxidation of alkenes under alkaline conditions results in a syn-addition of two hydroxyl groups. In order to account for this observation, Wagner suggested that the reaction must proceed by way of an intermediate cyclic manganate(V) diester, 1, as in equation 3. 

The aminosugar was allowed to react with phosphorus trichloride to give the intermediate cyclic phosphorochloridite (step a). The latter was trans-... 

On treatment with IBD, tetraketones 213 are transformed to pyrones 215. This reaction probably occurs via intermediate cyclic ene-hemiacetal 214. In contrast, lead tetra-acetate (LTA), which generally behaves similarly to IBD, shows a different reactivity pattern in the oxidation of 213, thereby yielding the isomeric pyrone 216 (80TL1575 83JHC1389). 

Slomkowski S, Szymanski R, Hofman A (1985) Formation of the intermediate cyclic six-membered oxonium ion in the cationic polymerization of P-propiolactone initiated with CHsCO SbFs. Makromol Chem 186 2283-2290... 

Radicals formed by intramolecular addition can be further extended by trapping the intermediate cyclic radical with an electrophilic alkene. 

Dye-sensitized photooxygenation of oxazoles (242) in aprotic solvents with 650 W halogen lamp leads to unstable 1,2,4-dioxazolines (244) via intermediate cyclic peroxides (243) (Scheme 49) <90JCS(Pl)10n, 91JCS(P2)1085>. 

From the same substrates, a different reaction took place when the electron-deficient phosphine was replaced by the electron-rich (p-MeOC6Fl4)3P phosphine. In the presence of this slightly modified catalytic system, the recovery of the organic ligand as a lactone was made possible by oxidation of the intermediate cyclic alkoxycarbene with N-hydroxysuccinimide, a mild oxidant which did not destroy the catalyst (Scheme 10.13) [52]. 

The initial step of this condensation appears to be the attack of the primarily formed imidochloride R—C( NH)C1 (or [R—C=NH+]C1 ) at the sulfur of the thioamide. The resulting diimido-sulfide (77) then rearranges irreversibly to the more stable end-product (78),presumably via an intermediate cyclic stage.108... 

Considering that 112 would be the favored orientation for the initial addition-compound (when the starting sugar is acyclic), the intermediate cyclic structure for migration would be 113, in which a... 

The photosensitized reaction of pyrrole and oxygen yields 5-hydroxy-A3-pyrrolin-2-one, probably by way of an intermediate cyclic peroxide (Scheme 45) (76JA802). 

Of course, the PCC-induced formation of tetrahydrofurans from 5, 6-dihydroxyalkenes fails when structural constrains prevent the approach of the intermediate cyclic chromate ester to the alkene.286... 

Cyclic siloxanes are important precursors in the silicon industry, being formally dimers or trimers of silanone (R2Si=0), a known intermediate. Cyclic siloxanes have been synthesized by four routes, the conventional methods being the condensation of silanediol or the hydrolysis of species such as halosilanes or aminosilanes (Scheme l)16-20. Alternatively, oxidation of disilene by triplet oxygen (equation l)21-27 or oxidation of oxadisiliranes by singlet oxygen (equation 2)28-31 may be utilized. 

Clearly such a method is of limited preparative value, but an important exception is the oxidation of cyclic secondary alcohols which on oxidation with nitric acid give good yields of dicarboxylic acids by way of the intermediate cyclic ketone, e.g. adipic acid from cyclohexanone, Expt 5.123. 

The cyclohexene 121, which was readily accessible from the Diels-Alder reaction of methyl hexa-3,5-dienoate and 3,4-methylenedioxy-(3-nitrostyrene (108), served as the starting point for another formal total synthesis of ( )-lycorine (1) (Scheme 11) (113). In the event dissolving metal reduction of 121 with zinc followed by reduction of the intermediate cyclic hydroxamic acid with lithium diethoxyaluminum hydride provided the secondary amine 122. Transformation of 122 to the tetracyclic lactam 123 was achieved by sequential treatment with ethyl chloroformate and Bischler-Napieralski cyclization of the resulting carbamate with phosphorus oxychloride. Since attempts to effect cleanly the direct allylic oxidation of 123 to provide an intermediate suitable for subsequent elaboration to ( )-lycorine (1) were unsuccessful, a stepwise protocol was devised. Namely, addition of phenylselenyl bromide to 123 in acetic acid followed by hydrolysis of the intermediate acetates gave a mixture of two hydroxy se-lenides. Oxidative elimination of phenylselenous acid from the minor product afforded the allylic alcohol 124, whereas the major hydroxy selenide was resistant to oxidation and elimination. When 124 was treated with a small amount of acetic anhydride and sulfuric acid in acetic acid, the main product was the rearranged acetate 67, which had been previously converted to ( )-lycorine (108). 

A review cataloging intramolecular Diels-Alder reactions as key steps in the total synthesis of natural products has been published.78 A key step in the total synthesis (g) of (+)-dihydrocompactin (66) is the intramolecular ionic Diels-Alder reaction of the trienone (63) to yield the (+)-compactin core compound (65) via the intermediate cyclic vinyloxocarbenium ion (64) (Scheme 17).79 The intramolecular Diels-Alder reaction of the Asp-Thr tethered compound (67) produced the cycloadduct (68) with high regio- and stereo-selectivity (Scheme 18).80 Mixed quantum and molec- (g) ular mechanics (QM/MM) combined with Monte Carlo simulations and free-energy perturbation (FEP) calculations have been used to show that macrophomate synthase... 

An alternative protocol towards pyrazino 2,l-b]quinazolines 79 relied on cyclocondensation of diketopiperazine-derived lactim ethers with anthranilic acid. Microwave dielectric heating in a domestic oven (600 W irradiation power) furnished heterocycles 79 within 3-5 min, while the corresponding reaction in an oil-bath required 2 hours heating at 120-140 °C [129]. The use of N-protected co-amino acids 83 in the microwave-assisted reaction with anthranilic acid 71 furnished pyrrolo 2, -b]quinazolines 85 via transannu-lar cyclization of the intermediate cyclic diamide 84 [126]. Subsequent in situ condensation with a variety of aldehydes furnished isaindigotone 86 and analogues, possessing cytotoxic activity (Scheme 51). 

Nitrogen heterocycles more electrophilic than benzene are susceptible to attack by hydride ion from a complex metal hydride anion. In protic solvents the intermediate cyclic enamines can undergo further reduction. The proper choice of reducing agent and reaction conditions thus allows the preparation of many partially reduced nitrogen heterocycles unavailable by other routes. These reduction procedures provide a valuable adjunct to catalytic hydrogenation155 for the syntheses of saturated nitrogen heterocycles. 

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