Halides reductive cyclization

Bond constructions similar to those just discussed can be achieved using an alkylidene malonate which is tethered to an alkyl bromide [72]. Of particular interest in this context is the controlled potential reductive cyclization of 263. As illustrated, the method provides a reasonably facile and modestly efficient entry to cyclobutanes 264. Presumably, the process is initiated by reduction of the alkylidene malonate rather than the alkyl halide, since alkyl bromides are more difficult to reduce. The same substrate, when reduced with L-Selectride undergoes conjugate addition of hydride and a subsequent cyclization leading to the five-membered ring 265. The latter transformation constitutes an example of a MIRC reaction [71-73], a process which is clearly complementary to the... 

Phenyl o-radicals generated by reduction of aryl halides can also interact with an intramolecular alkene bond. Ihe method has been developed for the formation of dihydroindoles by reductive cyclization of N-allyl-2-chloroacetanilides. The results indicate the importance of a time interval between electron addition to give a radical-anion and the fragmentation of this species to give the active a-radical, The time interval allows the radical-anion to diffuse away from the electrode surface so that when the a-radical is foimed, it has time to cyclize before it can be reduced at the surface. 

When steric hindrance in substrates is increased, and when the leaving anion group in substrates is iodide, SET reaction is much induced (Cl < Br < I). This reason comes from the fact that steric hindrance retards the direct nucleophilic reduction of substrates by a hydride species, and the a energy level of C-I bond in substrates is lower than that of C-Br or C-Cl bond. Therefore, metal hydride reduction of alkyl chlorides, bromides, and tosylates generally proceeds mainly via a polar pathway, i.e. SN2. Since LUMO energy level in aromatic halides is lower than that of aliphatic halides, SET reaction in aromatic halides is induced not only in aromatic iodides but also in aromatic bromides. Eq. 9.2 shows reductive cyclization of o-bromophenyl allyl ether (4) via an sp2 carbon-centered radical with LiAlH4. 

On reduction of aryl halides the initially formed ion radical decomposes to halide ion and aryl radical [13-16]. In appropriate substituted compounds the radical may in an intramolecular attack effect a ring closure. This is exemplified in the reductive cyclization of 5-(2-chlorophenyl)-l-phenylpyrazole to pyrazolo[l, 5-/]phenanthridine [13] and iV-allyl-... 

The carbon-halogen bond is stronger in vinyl halides than in alkyl halides, and Ni complexes with slightly lower reduction potentials have to be used to catalyze the reductive cyclization of vinyl halides on to alkene functions. Using conditions similar to those for the alkyl and aryl halides, 5-c.vo-cyclized products were obtained from 88 [237]. In a single case (methyl substitution at the position of S- .vc-attack), only the 6- /o-product was obtained [Eq. (53)] [237]. 

Not surprisingly, Ni(I)-catalyzed reductive cyclization of halides onto alkynes requires conditions similar to the Ni(I)-catalyzed reductive cyclization of halides onto alkenes. The alkynes are converted into alkylidene- or benzylidene-substituted five-mem-bered rings [234-236,243]. 

Diketones are also readily sulfenylated in the 2-position by benzenesulfenyl halides, and Shvedov et al. have reported the reductive cyclization of products such as 94 with zinc in acetic acid to benzothiazines... 

A well-established preparative method of alkynyl ketones 110 is the Sonogashira-type carbonylation of aryl halides in the presence of terminal alkynes. (Trimethylsi-lyOpyridylethyne (111), deprotected in situ, reacted with 3-iodotoluene and CO to give the alkynyl m-tolyl ketone 112 using DPPF as a hgand. Pd-catalyzed reductive cyclization of 112 using HCO2H afforded the 1,8-naphthyridine 113 [48]. 

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