Halides reductive intramolecular coupling

Intramolecular reductive coupling between the isoquinolinium systems (107) and an attached aromatic halide [Eq. (67)] [308], gives products similar to those obtained by the intramolecular coupling of aromatic halides with other aryl groups (Sec. V.B). 

The macrocycles of nickel and cobalt that stabilize the metal(I) oxidation state allowing the use of M(II)L/M(I)L couples to be used for the catalytic reduction of alkyl halides [13,14]. With alkyl bromides with alkene and alkyne substituents, the reactions can lead to interesting cyclic molecules by intramolecular coupling [15-17]. 

The radicals R" generated by reduction of the halides RX (R = alkyl or aryl X = Cl, Br, I, etc.) by Sml2 (see Chap. 12.4.2) can be reduced (formation of RH by trapping an H atom from the solvent) or couple onto a carbonyl (aldehydes, ketones Barbier reaction), an olefin or an alkyne. For coupling reactions, the competitive reduction to RH indicated above must be avoided. The intramolecular coupling with formation of 5- or 6-atom rings, of synthetic interest, are promoted by the entropic factor. ... 

The cross-coupling of alkynylzinc halides or fluorinated alkenylzinc halides with fluori-nated alkenyl iodides allows the preparation of a range of fluorinated dienes or enynes - Functionalized allylic boronic esters can be prepared by the cross-coupling of (dialkylbo-ryl)methylzinc iodide 428 with functionalized alkenyl iodides. The intramolecular reaction provides cyclized products, such as 429 (Scheme 109) ° °. In some cases, reduction reactions or halogen-zinc exchange reactions are observed. 

Lithium butyldimethylzincate, 221 Lithium sec-butyldimethylzincate, 221 Organolithium reagents, 94 Organotitanium reagents, 213 Palladium(II) chloride, 234 Titanium(III) chloride-Diisobutylalu-minum hydride, 303 Tributyltin chloride, 315 Tributyl(trimethylsilyl)tin, 212 3-Trimethylsilyl-l, 2-butadiene, 305 Zinc-copper couple, 348 Intramolecular conjugate additions Alkylaluminum halides, 5 Potassium t-butoxide, 252 Tetrabutylammonium fluoride, 11 Titanium(IV) chloride, 304 Zirconium(IV) propoxide, 352 Miscellaneous reactions 2-(Phenylseleno)acrylonitrile, 244 9-(Phenylseleno)-9-borabicyclo[3.3.1]-nonane, 245 Quina alkaloids, 264 Tributyltin hydride, 316 Conjugate reduction (see Reduction reactions)... 

Intramolecular reductive couplings between alkenes and aromatic halides have been mentioned in sec. IV.B.5 and IV.B.6. Here, discussion centers on reductive coupling either between two aromatic rings or between an aromatic ring and another, nonolefinic molecule. 

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 Stille-Kelly coupling consists of two connected catalytic cycles and the following steps 1) the oxidative addition of the Pd ° complex into one of the C-X bond of the aryl halide 2) transmetallatlon with the distannane followed by reductive elimination to afford the organostannane 3) oxidative addition of the Pd ° complex into the C-X bond of the organostannane 4) intramolecular transmetallatlon, and 5) reductive elimination to give the coupled product. 

Whether the reaction is inter- or intramolecular, the Heck reaction generates vinyl(hetero)arenes or dienes from an alkene and a (hetero)aryl or alkenyl halide [130]. This reaction has great versatility and is applicable to a wide range of aryl and alkene species. Mechanistically, the Heck reaction varies from that depicted in Fig. 4.3. While the oxidative addition of the halogen species occurs, the transmetalation step is replaced by the coordination of the alkene. This is followed by a migratory insertion which essentially substitutes for the cross-coupling step. The product is released not by a reductive elimination, but by a 3-hydride elimination sequence (Fig. 4.5). 

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]. 

Conditions first described by Fagnou were used to affect the C-H to C-H bond cyclization, which proceeded in 47% yield. Mechanistically the direct coupling reaction is thought to proceed via intramolecular nucleophilic attack of the pyrrole moiety onto the Pd(II) centre. It was postulated that the electron rich DavePhos ligand facilitates both oxidative addition and forms a more reactive cationic Pd(II) species by dissociation of the halide. Following a deprotonation step, reductive elimination of Pd(0) then resulted in formation of the biaryl bond, completing the core framework. Application of this direct palladium-catalyzed biaryl coupling facilitates a very efficient and concise synthesis of rhazinilam as a racemate. 

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