Cyclization reactions mechanisms

A unique method to generate the pyridine ring employed a transition metal-mediated 6-endo-dig cyclization of A-propargylamine derivative 120. The reaction proceeds in 5-12 h with yields of 22-74%. Gold (HI) salts are required to catalyze the reaction, but copper salts are sufficient with reactive ketones. A proposed reaction mechanism involves activation of the alkyne by transition metal complexation. This lowers the activation energy for the enamine addition to the alkyne that generates 121. The transition metal also behaves as a Lewis acid and facilitates formation of 120 from 118 and 119. Subsequent aromatization of 121 affords pyridine 122. 

Highly electron-deficient 1,3,6,8-tetranitronaphthalene 443 was reported to react in ethanol with A -methyl phenylacetamidines, e.g. 444, to give the corresponding benzoquinoline derivatives, e.g. 446 (77JOC435). Though the reaction mechanism of this double nitro group displacement is not known, formation of intermediate 445 and its following cyclization is probably the most reasonable explanation (Scheme 70). 

Throughout each chapter, clear structures, schemes, and figures accompany the text. Mechanism, reactivity, selectivity, and stereochemistry are especially addressed. Special emphasis is also placed on introducing both the logic of total synthesis and the rationale for the invention and use of important synthetic methods. In particular, we amplify the most important developments in asymmetric synthesis, catalysis, cyclization reactions, and organometallic chemistry. 

Chemistry, reaction mechanisms, and properties have been extensively reviewed.4,5,10-20 Hie present chapter deals witii only one type of fully cyclized aromatic heterocyclic polymers die high-molecular-weight linear polymer witii a special emphasis on die synthesis and structure—property relationships for specific applications. 

Examples of the intermolecular C-P bond formation by means of radical phosphonation and phosphination have been achieved by reaction of aryl halides with trialkyl phosphites and chlorodiphenylphosphine, respectively, in the presence of (TMSlsSiH under standard radical conditions. The phosphonation reaction (Reaction 71) worked well either under UV irradiation at room temperature or in refluxing toluene. The radical phosphina-tion (Reaction 72) required pyridine in boiling benzene for 20 h. Phosphinated products were handled as phosphine sulfides. Scheme 15 shows the reaction mechanism for the phosphination procedure that involves in situ formation of tetraphenylbiphosphine. This approach has also been extended to the phosphination of alkyl halides and sequential radical cyclization/phosphination reaction. ... 

Until recently the products of all nitrile cyclizations by the Thorpe reaction had been formulated as imines, although the products were found in 1955 to be better written as the enamine structure. In order to verify the reaction mechanism of the Thorpe reaction, the solid-state reaction of 84 and Bu OK was monitored by measurement of IR spectra in Nujol mulls. As the reaction proceeds (Scheme 14), the CN absorption of 84 at 2250 cm" decreases and a new CN absorption of the imine intermediate (87) arises at 2143 cm As 87 is converted into 88 by a proton migration, the CN absorption of 87 at 2143 cm" disappears, and only the CN absorption of 88 at 2189 cm remains finally [13]. 

The structure of the reagent, the mechanism of epoxide opening, deoxygenations, dimerizations and intermolecular additions will be discussed first before covering the preparatively much more important cyclization reactions [36]. 

Interestingly, the nucleophilic addition of water in the sequence of events giving rise to 41 represents a relevant model system for investigating the mechanism of the generation of DNA-protein cross-links under radical-mediated oxidative conditions [80, 81]. Thus, it was shown that lysine tethered to dGuo via the 5 -hydroxyl group is able to participate in an intramolecular cyclization reaction with the purine base at C-8, subsequent to one electron oxidation [81]. 

The cyclic phosphonium salts 140,141,143,145, and 146 so obtained are evidence for the mechanism of the oxaphospholic cyclization and especially for the main role of the tertiary carbocation formation during the process. The additional data which support this assumption, come from the investigation of the same reaction, but with different substrate, i.e., dimethyl(l,2-hexadienyl)phosphine oxide 147. In this case, the reaction mechanism involved formation of secondary carbocation that gives oxaphosphole product 148 only in 10% yield (Scheme 60) [124],... 

The Nazarov cyclization of vinyl aryl ketones involves a disruption of the aromaticity, and therefore, the activation barrier is significantly higher than that of the divinyl ketones. Not surprisingly, the Lewis acid-catalyzed protocols [30] resulted only in decomposition to the enone derived from 46,47, and CO. Pleasingly, however, photolysis [31] readily delivered the desired annulation product 48 in 60 % yield. The photo-Nazarov cyclization reaction of aryl vinyl ketones was first reported by Smith and Agosta. Subsequent mechanistic studies by Leitich and Schaffner revealed the reaction mechanism to be a thermal electrocyclization induced by photolytic enone isomerization. The mildness of these reaction conditions and the selective activation of the enone functional group were key to the success of this reaction. 

In polysiloxanes the random scission mechanism is combined with cyclization reactions, and oligomeric cycles with a number of structural units ranging from 3 to 7 are formed in large amounts. 

A novel series of 5//-thiazolo[3,2-a]pyridine-5-ones 64 is prepared by addition of malonic esters 59 to 2-alkynylthiazoles 60 <06H(67)523>. A plausible reaction mechanism involves an intramolecular cyclization of the initial adduct 61 to give the cyclobutenoxide intermediate 62. Ring-opening of this intermediate and subsequent cyclization lead to 5//-thiazolo[3,2-a]pyridine-5-one 64. 

To probe the reaction mechanism of the silane-mediated reaction, EtjSiD was substituted for PMHS in the cyclization of 1,6-enyne 34a.5 The mono-deuterated reductive cyclization product 34b was obtained as a single diastereomer. This result is consistent with entry of palladium into the catalytic cycle as the hydride derived from its reaction with acetic acid. Alkyne hydrometallation provides intermediate A-7, which upon cw-carbopalladation gives rise to cyclic intermediate B-6. Delivery of deuterium to the palladium center provides C-2, which upon reductive elimination provides the mono-deuterated product 34b, along with palladium(O) to close the catalytic cycle. The relative stereochemistry of 34b was not determined but was inferred on the basis of the aforementioned mechanism (Scheme 24). 

The reaction mechanism was considered to be oxidative cyclization, and pal-ladacyclopentene 32 was formed. Reductive elimination then occurs to give cyclobutene 33, whose bond isomerization occurs to give diene 28. The insertion of alkyne (DMAD) into the carbon palladium bond of 32 followed by reductive elimination occurs to give [2+2+2] cocyclization product 27. Although the results of the reactions of E- and Z-isomers of 29 with palladium catalyst 26a were accommodated by this pathway, Trost considered the possibility of migration of substituents. Therefore, 13C-labeled substrate 25 13C was used for this reaction. 

Hegedus proposed the probable course of the cyclization reaction, which follows a Wacker-type reaction mechanism. Coordination of the olefin to Pd(II) results in precipitate 110, which upon treatment with Et3N undergoes intramolecular amination to afford intermediate 111. As expected, the nitrogen atom attack occurs in a 5-exo-trig fashion to afford 112. Hydride... 

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