Cyclization pathway rearrangement

N-Heterocyclics. The reaction of primary amines with the carbonyl products derived from lipid oxidation is a major pathway in lipid-protein interactions. Formation of Schiff s base intermediates followed by cyclization and rearrangement can yield imines, pyridines and pyrroles (5,15,30,31). For example, 2-pentylpyridine may result from the reaction of ammonia with 2,4-decadienal, one of the principle aldehydes from the autoxidation of linoleate (5). 

Benzyl carblnols react with fluorosulfurlc acid through various reaction pathways (rearrangement, dehydration, cyclization, ring expansion), depending on the substrate (eq 6). ... 

A f-BuONa-mediated synthesis of 3,3-disubstituted aza-oxindoles via a Truce-Smiles rearrangement-cyclization pathway has been reported (Scheme 181). ... 

Thermal and photochemical cycloaddition reactions always take place with opposite stereochemistry. As with electrocyclic reactions, we can categorize cycloadditions according to the total number of electron pairs (double bonds) involved in the rearrangement. Thus, a thermal Diels-Alder [4 + 2] reaction between a diene and a dienophile involves an odd number (three) of electron pairs and takes place by a suprafacial pathway. A thermal [2 + 2] reaction between two alkenes involves an even number (two) of electron pairs and must take place by an antarafacial pathway. For photochemical cyclizations, these selectivities are reversed. The general rules are given in Table 30.2. 

Another example of a zwitterionic product of a cycloaromatization reaction was given by Kerwin and coworkers. Their skipped (aza)enediynes rearranged to yield (aza)eneyne-allenes that subsequently cyclized under addition of methanol (in a byproduct), which is consistent with a partitioning between a diradical and a zwitterionic reaction pathway (Scheme 15).66... 

A related dienediol-phenol rearrangement which can occur by different pathways was reported as a new method for synthesis of the oxepine system180. Protonation of the starting diol 344 produces a cation 345 which can follow normal dienone-phenol rearrangement (path a) when the substituents R2 = Me, Ph and R1 = t-Bu are eliminated in the step 346 — 347. However, when R1 = t-Bu and R2 is a substituted phenyl which decreases the nucleophility, the cationoid intermediate 345 cyclizes to the oxonium ion 348 (path b) which then undergoes deprotonation to give the oxepine 349 (equation 124)180. 

The production of 69 and 70 in this photoreaction is in accord with the operation of mechanistic pathways involving the generation and competitive cleavage of aziridinyl-dicarbinyl biradical 71 (Scheme 12). Thus, the major photoproduct 69 is formed by C—N bond cleavage in 71 (path a). The alternative fragmentation of the C—C bond in 71 affords intermediate 72, which cyclizes yielding aziridine 70 (path b). As such, this represents the first example of a 2-aza-di -rr-methane (2-ADPM) rearrangement that occurs via a three-membered-... 

The amide derived from the carboxylic acid in Ugi adducts is in most cases tertiary, and therefore it cannot serve as nucleophilic partner in post-condensation transformations, unless a post-Ugi rearrangement converts it into a free amine [52, 54]. An exception is represented by Ugi adducts derived from ammonia, which give rise to two secondary amides, each of them potentially involved, as nucleophile, in nucleophilic substitution processes. Four competitive pathways are in principle possible (N- or 0-alkylations of the two amides), and the reaction is mainly driven by the stability of the formed rings. In the example shown in Fig. 12, 0-alkylation of the carboxylic-derived amide is favoured as it generates a 5-membered ring (oxazoline 62), while the alternative cyclization modes would have formed 3- or 4-membered rings [49]. When R C02H is phthalic acid, however, acylaziridines are formed instead via Walkylation [49]. In both cases, the intramolecular 8 2 reactions takes place directly under the Ugi conditions. 

A new synthetic method of benzofuran was reported (equation 39). The [3,31-sigma-tropic rearrangement of Af-trifluoroacetyl enehydroxylamines 136 obtained in situ by acylation of oxime ethers 135 in the presence of trifluoroacetic anhydride lead to the synthesis of cyclic or acyclic dihydrobenzofurans 138. The effects of base and temperature on the reaction products were studied. A similar pathway to that of Fisher indolization was proposed. The acylimine formed by the [3,3]-sigmatropic rearrangement of the V-trifluoroacetyl enehydroxylamine 136 gave the dihydrobenzofuran 137 by an intramolecular cyclization or the benzofuran 138 after elimination. 

The intermediate may be trapped by other nucleophiles (different from water) and diverse products may be obtained. The interception of the intermediate may occur inter- or intra-moleculary, the latter providing a helpful tool to produce a new ring system (Scheme 9, pathway 2). These reactions are sometimes referred to, respectively, as Beckmann rearrangement-addition and Beckmann rearrangement-cyclization reactions. 

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