Intramolecular reductive coupling synthesis

J. L. Chiara, J. Marco-Contelles, N. Khira, P. Gallego, C. Destabel, and M. Bemabe, Intramolecular reductive coupling of carbonyl-tethered oxime ethers promoted by samarium diiodide A powerful method for the stereoselective synthesis of aminocyclopentitols, J. Org. Chem., 60 (1995) 6010-6011. 

Vogel and coworkers have also explored an alternative approach to the synthesis of isocorroles. This more rational approach involves the low-valent titanium-mediated intramolecular reductive coupling of an a,co-formyl-substituted linear tetrapyrrolic species. Specifically, ring closure of the linear species 2.272, carried out under these McMurry-type conditions, afforded the etioisocorrole 2.270 in 10% yield (Scheme 2.2.4). The putative corrologen , thought to occur as an intermediate in this reaction, was not isolated. Rather, oxidation by molecular oxygen or FeCls during workup was presumed to occur spontaneously. 

In an analogous manner, novel 2-(2-hydroxyaryl)quinolines can be prepared via a one-pot synthesis from intramolecular reductive coupling reactions of 2 -hydroxy-2-nitro-chalcones [75]. Accordingly, 2 -hydroxy-2-nitrochalcones 177a-b were treated with ammonium formate and Pd/C at room temperature to give a mixture of 2-(2-hydroxy-aryl)quinolines 178a-b and 2-(2-hydroxyaryl)quinoline-N-oxides 179a-b. 

Acyl)anilides 78 can be cydized by intramolecular reductive coupling of the two carbonyl moieties mediated by low-valent titanium (abbreviated [Ti]), thus creating the C-2/C-3 bond of 2,3-disubstituted indoles 79 (Furstner synthesis) [166] ... 

Thiophenes and selenophenes While the intramolecular reductive coupling of di-keto sulfides or selenides has been known since 1985, with the synthesis of a series of symmetrically and unsymmetrically substituted 2,5-dihydrothiophenes and se-... 

The first synthesis of cyclopropenes by the intramolecular reductive coupling of non-enolizable 1,3-diones, with TiCl3-LiAlH4, has been published, e.g. 

A third method for the synthesis of cycl[3.2.2]azines, from iV-(aroylmethyl)pyridinium salts via indolizines, involves intramolecular (reductive) McMurry coupling of the latter. For example, 3,5-dibenzoylindolizines, obtained from 2-benzoyl-iV-phenacylpyridinium bromide as shown (Scheme 91), are cyclized using zinc and titanium(iv) chloride to give the 3,4-diphenylcyclazines 352 in high yield (>90%). The reaction cannot be applied, however, to... 

Addition to cyclic iminium salts has been utilized in alkaloid synthesis. A zinc-promoted reductive coupling reaction of iminium salts and alkyl halides has been reported by Shono et al. (Scheme 8). Evidence delineating the mechanistic course (organozinc addition or electron transfer reaction) of the addition has not been established. In contrast to organolithium or Grignard additions, aromatic halogen and alkoxycarbonyl substituents are compatible with this methodology. The intramolecular version of this reaction has been employed for the synthesis of tricyclic amines (53 equation 9). 

The BiBrs-Sm binary reagent promotes reductive C-S and C-Se bond formation between benzyl and allyl bromides and diorganyl disulfides and diselenides in aqueous media, affording the corresponding sulfides and selenides, respectively (Scheme 14.105) [217, 218]. Intramolecular reductive C-S bond formation by use of a BiCl3-M (M = Sn, Zn) redox system is used in the synthesis of 3-hydroxyceph-ems and 2-exo-methylenepenams (Scheme 14.106) [219]. Alkyl and arylsulfonyl chlorides couple with allylic halides in the presence of Bi to afford the corresponding allylic sulfones [220]. 

A one-pot synthesis of phenanthrenes from ortho-alkoxy a re ne aldehydes and ketones has been accomplished using TiCl3-Li-THF [103]. The 2,2 dialkoxystil-benes, resulting from a classical McMurry coupling [80], are subjected to a reductive dealkoxylation and under the reaction conditions applied [103] form the intramolecular CC coupling products in moderate overall yields (25-38%). 

---