Intramolecular nucleophilic ring-opening

An intramolecular nucleophilic ring opening of a dioxanone was reported <1996TL3199>. Exposure of compound 178 to LDA affords the allylic anion which attacks the carbonyl group to give spirodiketone 179 in 42-61% yield (Scheme 34). 

However, these have not been the only approaches to the synthesis of these ring systems. For example, Sasaki et al. were able to use an intramolecular nucleophilic ring opening of an epoxide with sodium dimsylate to form the oxepane ring as illustrated in the conversion of 34 to 35 <99JOC9399>. 

Intramolecular nucleophilic ring opening of 4-methoxycarbonyl-l-azaphenanthrene 5,6-oxide (262) has been utilized in the total synthesis of eupolaramine (263).155... 

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>. 

Intramolecular nucleophilic ring-opening reactions of oxazolines are also known. Hydrozirconation of A -allylox-azolidine 141 gave a zirconocene intermediate 142, which reacted with TiCh to afford the corresponding 2-substituted pyrrolidine 143 in good yield and diastereoselectivity (Scheme 36) <2005OL4887>. 

Under basic conditions // a 5-2-hydroxymethyl-l-acylcyclopropanes can be transformed into c/i-isomers, and this occurs by an intramolecular nucleophilic ring-opening and subsequent ring-reclosure mechanism. ... 

This entailed the lengthy and difficult successive constraction of the three missing rings F, G, and C. The synthesis of the F ring is the least troublesome, as it succeeds in only three steps and with 67 % yield (rac-45 rac-47) (Scheme 7). The key step is the intramolecular nucleophilic ring-opening of the unisolated epoxide rac-45 the thermodynamically controlled reaction yields rac-46 exclusively. 

Intramolecular Nucleophilic Ring-Opening of Epoxides 2.3.7 Five-Membered Rings to Medium-Ring Size... 

Key steps, as shown in Scheme 4-15, involve the formation of a urethane intermediate 37 by treating epoxide 36 with methyl isocyanate in the presence of sodium hydride. Intramolecular A-nucleophilic ring opening of oxirane affords oxazolidine 38. Subsequent treatment furnishes product 34. 

Few solid-phase syntheses of oxazoles have been reported (Table 15.17). The most general strategy is the dehydration of a-(acylamino) ketones (Entry 2, Table 15.17) or 2-(acylamino)phenols (Entry 1, Table 15.17). Oxazolidin-2-ones have been prepared by intramolecular nucleophilic cleavage of carbamates from insoluble supports (Entries 5 and 6, Table 15.17). Resin-bound 2-aminoethanols, which are accessible by nucleophilic ring-opening of oxiranes with amines, undergo cyclocondensation with aldehydes to yield oxazolidines [220,221]. These compounds are unstable towards acids, and can be released from the support only under neutral or basic reaction conditions. 

Another example is compound 214, which imitates the trombin-bound structure of the fibrin peptide A, and is an inhibitor of this protease. The first step of this synthesis, Scheme 63, involves opening of 208 to the seven-membered ring compound 209. Subsequent acylation with 210 to form 211 is followed by an intramolecular oxidative cycloaddition to provide tricyclic lactam 212. Nucleophilic ring opening proceeds readily with glycine methyl ester to afford lactam 213 in 88% yield, which was transformed into 214 using solid-phase protocols [161]. 

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