Heterocycles from intramolecular nucleophilic

Figure 27 shows plots of all the available EM s for closures of small- and common-sized saturated carbocycles and heterocycles by intramolecular nucleophilic displacement. Clearly, a-values as small as 0.1 would be required in order to calculate extrathermodynamically from (67) EM-values comparable to those actually observed for ring-sizes 3 and 4, and an even smaller value would be necessary for ring-size 5. This would lead to the conclusion that the effect of ring strain on cyclisation rates is insignificant. The same conclusion was recently drawn by Benedetti and Stirling (1983), based on rates and activation parameters for the cyclisation of bis-sulphonyl-stabilised carbanions to 3-, 4-, and 5-membered bis-sulphonylcyloalkanes. 

Dihydroimidazo[2,l-b]oxazoles were prepared fi om an intramolecular nucleophilic ipso-substitution of 2-alkylsulfonylimidazoles <99S1613>. The synthesis of hitherto unknown 2-(2,4,6-triarylphenyl)substituted 4,5-dihydro-1/f-imidazolium perchlorates from 2-methyl imidazolium perchlorates and 2,4,6-triarylpyrylium perchlorate salts was published <99JC813>. Substituted aromatic heterocycles from reactions of 2,3-dihydrospiro[l/f-4-and... 

The intramolecular nucleophilic attack of a nitrogen atom on an allylpalladium complex was also used to construct a five and a six membered heterocycle in the same step. TV-substituted 2-iodobenzamides bearing an allene function in the appropriate distance from the iodine underwent cyclization through the carbopalladation of the allene moiety by the arylpalladium complex, formed in the first step of the catalytic cycle. The intermediate allylpalladium complex, part of a nine membered ring, cyclized readily to give the pyrroloisoquinolone derivative in excellent yield (4.23.). The nature of the added ligand and the solvent both had a marked influence on the efficiency of the transformation.26... 

The platinum-catalysed intramolecular domino annulation reaction of o-alkynylben-zaldehydes has been described as a versatile approach to naphthalenes with annulated carbocycles or heterocycles of various sizes (Scheme 32).94 A plausible mechanism for the platinum(II)-catalysed annulation reaction shows that the double annulation process most probably proceeds through the benzopyrylium cation (117), which results from the nucleophilic attack of the carbonyl oxygen at the alkyne, activated by the Lewis-acidic platinum salt. A subsequent intramolecular Huisgen-type 3 + 2-cycloaddition of the second alkyne is assumed to generate intermediate (118). Rearrangement to (119) and the formal 4 + 2-cycloaddition product (118) leads to the aromatized final (116), liberating the active catalyst. In the case of FeCl3 as the Lewis acid, we assume that intermediate (118) is oxidatively transformed to (121). 

A few representatives of this heterocyclic system 35 were synthesized in very high yield (85-90%) by the intramolecular nucleophilic cyclization of the acetylene derivatives 36 (81RTC10), which in turn were obtained by treatment of alkynyl(chloromethyl) sulfides with one equivalent of Na2Te, the latter being prepared from elemental sodium and tellurium in liquid ammonia. 

The reaction of perfluoro-4-methyl-2-pentene with ethylene glycol also leads to 2-fluoro-2-trifluoromethyl-3-(2,2,2-trifluoro-1 -trifluoromethylethy-lidene)-l,4-dioxane 106 (96ZOB1995). The formation of the six-membered heterocycle occurs via generation of the intermediate carbanion and fluoride ion elimination from the y-position. Subsequent intramolecular nucleophilic cyclization involving the O-nucleophilic center and the internal double bond leads to a 1,4-dioxane derivative (route e). 

Some noteworthy intramolecular nucleophilic ring openings have been reported in the recent literature, which can be used to prepare functionalized heterocycles of synthetic interest. For example, the highly oxygenated epoxide 100 undergoes rearrangement induced by boron trifluoride etherate, whereby anchimeric assistance from the pendant phenylthio substituent leads to an intermediate episulfonium ion 101 which subsequently suffers 5-e o-tet cyclization to form the tetrahydrofiiran derivative 102 <03TL5547>. 

The more electronegative the anion X in HgX2, the more six-membered rings are formed. There is a trans arrangement of the Hg and oxygen atom in each product i.e., reaction proceeds via intrafacial addition to the C=C bond. The intramolecular nucleophile can itself be generated from initial reaction of a diene. The eventual product is a bis-mercurated heterocycle, e.g. ... 

The reactivity of allenylpalladium species, derived from oxidative addition of propargyl alcohol derivatives to palladium (0), has attracted considerable attention in organic synthesis.283 Recently, the intramolecular reaction of the propargylic derivatives 665 with an oxygen and nitrogen nucleophile has been widely utilized for the synthesis of heterocyclic compounds. The key step of formation of a heterocyclic ring is intramolecular nucleophilic attack of a... 

Intramolecular nucleophilic attack onto the carbon centres of nitriles constitutes a common strategy employed in the synthesis of heterocyclic amines. However, a recent preparation of 5 -amino-m-terphenyls from arylidene and 1-arylethylidene-malononitriles has demonstrated that such reactions can be applied to the synthesis of carbocyclic amines (Scheme 3). 

Some interesting photo-NOCAS-type reaction (photochemical nucleophile-olefin combination, aromatic substitution) have been reported by three groups. Arnold has developed the photo-NOCAS reaction as three components photoaddition.Xu et al., reported the intramolecular photocyclization of A-(co-hydroxyalkyl)-tetrachlorophthalimide (138, 141) with alkenes to give medium- and large-ring heterocycles (140,143). These photoreactions proceeded via 1, n-biradicals generated from the nucleophilic attack of alcohols to alkenes between the radical anions of phthalimides and the radical cations of alkenes. 

---