Pd -catalyzed intramolecular coupling

Hennings, D. D. Iwasa, S. Rawal, V. H. Anion-accelerated Pd-catalyzed intramolecular coupling of phenols with aryl halides./. Org. Chem. 1997, 62, 2-3. 

The Pd-catalyzed intramolecular coupling of aryl halides or triflates with aromatic rings to give biaryl compounds offers useful synthetic methods. Intramolecular aryla-tion of benzene derivatives was reported first by Ames. Cyclization of 102, catalyzed by Pd(OAc)2 in the presence of DBU, is an example [23]. Pyrimido[4,5-fe]indole was prepared by intramolecular arylation of 4-anilino-5-iodopyrimidine 103 in 86 % yield in the presence of Pd(OAc>2, PPh3 and AcONa in DMF [24]. Cyclization of the monobrominated diarylpyrazole 104 afforded pyrazolo[l,5-/]phenanthridine in 65 % yield in the presence of phosphine-free Pd(OAc>2, Bu NBr, LiCl and K2CO3 in DMF at 110°C [25]. 

In 2009, Majumdar and coworkers developed a new efficient route for the synthesis of polycyclic sultones via ligand-free Pd-catalyzed intramolecular coupling reaction (Scheme 4.15) [22]. Using the optimized condition [Pd(PPh3)4/ TBAB/KOAc/DMF/100°C], benzenesulfonic acid 2-bromophenyl esters were successfully cyclized to afford the sultone in 90% yield. 

Scheme 4.15 Pd-catalyzed intramolecular coupling reaction of benzenesulfonic acid 2-bromophenyl esters.

Scheme 4.18 Pd-catalyzed intramolecular coupling reaction to synthesize polycyclic sultams.

Scheme 5 Synthesis of 2-carboxyindoles via Pd-catalyzed intramolecular coupling and carbon-ylation from ort/to-gem-dibnnnovinylanilines...

Interestingly, treatment of diene 215a with methanesulfonic acid afforded 216 as a single diastereomer in 88% yield, the structure of which was confirmed by X-ray analysis (Scheme 60). The transformation of 216 into 217 started with an alkylation, followed by reductive desulfurization and triazene formation to afford compound 217 in 92% yield. Upon treatment with diiodomethane, triazene 217 was smoothly converted to aryl iodide 218 in 75% yield. Pd-catalyzed intramolecular Heck coupling of 218 led to the desired product 219b in 62% yield. 

Zhao and Larock have described the synthesis of carbazoles, indoles, and dibenzofurans 118 via a Ic type cyclization that follows a sequence of Pd-catalyzed cross-coupling of alkynes and aryl iodides 116, then nitrogen-directed palladium migration to an arylpalladium intermediate 117 that undergoes an intramolecular Mizoroki-Heck ring closure <06JOC5340>. 

The synthesis of lycorane (13) by Mori and Shiba-saki121 is breathtaking for its use of three consecutive Pd catalyzed C-C bond forming reactions. Thus, Pd-catalyzed asymmetric allylic substitution of a benzoate in meso 7 in the presence of the chiral bisphos-phine 8 leads to the regioselective formation of 10 in 40 % ee It is easy to overlook this low level of enantioselectivity when we are faced with the subsequent elegant Pd-catalyzed reactions Pd-catalyzed intramolecular animation is followed by a Pd-catalyzed Heck coupling to afford 12, which is then readily converted to the target molecule... 

Acylsilanes serve as acyl donors in the Pd-catalyzed cross-couplings with allyl trifluoroacetates,243 aryl halides,244 and alkenyl halides.2 Intramolecular acylation of alkynes with acylsilanes proceeds under catalysis by [RhCl(CO)2]2.246... 

Single crystal X-ray analysis of the ethynyl-l,5-azastibocine 5a showed the presence of intramolecular Sb---N interaction which should be responsible for the reactivity enhancement of the ethynyl-l,5-azastibocines in Pd-catalyzed cross-coupling reactions with organic halides (see Section 14.18.11). The distance between the antimony and nitrogen atoms (2.538(4) A) corresponds to 68% of the sum of the van der Waals radii of both elements (3.74 A). In the crystal central antimony atom exhibited a pseudo-trigonal-bipyramidal structure <2003TL8589>. 

Intramolecular Pd-catalyzed cross-coupling of bromothiophene derivatives 423 and 425 gives dithienothiophenes 424 and 426, respectively (Equation 14) <1997TL4581>. Synthesis of benzonaphthothiophene-6,ll-diones 428 by Pd(OAc)2-mediated cyclization of 427 has been reported <2005H(65)1205>. 

Pd-catalyzed Stille-Kelly coupling Pd-catalyzed intramolecular biaryl coupling of aryl halides or aryl triflates in the presence of distannanes. 440... 

A series of 2-aryloxazoloquinolones 32 having high affinity for the GABA receptor were prepared via a Pd-catalyzed intramolecular diaryl coupling of ethyl 5-bromo-2-phenyl-oxazole-4-carboxylate with 2-aminophenylboronic acid followed by cyclization [37]. This one-pot intramolecular Suzuki reaction was followed by cyclization to afford a tricyclic compound 32. 

A novel five-membered ring annulation reaction based on Pd(O)-catalyzed intramolecular coupling of vinyl iodide has been developed by taking advantage of the vinylgermane strategy (Scheme 11.49) [72]. 

As shown in the following scheme, a SEM-ether derived phenyl acetylene was treated with PtClj in the presence of CO to give a benzo[4>]furan, which was first subjected to desilylation, followed by Pd-catalyzed intramolecular etherification, affording the tetracyclic skeleton of pterocarpane family of phytoalexins <05JA15024>. A similar type of synthetic transformation was so applied to make a key intermediate in the total synthesis of vibsanol <05JA15022>. 2,3-Disubstituted benzo[h]furans were prepared under very mild reaction conditions by the Pd/Cu-catalyzed cross-coupling of various o-iodoanisoles and terminal... 

In a Pd-catalyzed intramolecular cross-coupling reaction aryl halides containing an ortho-(y-hydroxy)alkyl side chain are cyclized to give 2,2-disubstituted chromanes [43]. 

A series of Pd-catalyzed intramolecular Heck reactions of N-(2-halophenyl)-substituted enaminones was performed by Pombo-Villar et al. [114]. The reactions were performed in the presence of palladium acetate with a phosphonium ligand as catalyst, sodium acetate, and tetrabutylammonium chloride (TBACl) as the PTC catalyst in DMF solution to afford desired coupling product in 25 to 99% yields (Eq. 79). 

Pd-catalyzed intramolecular arylation of some aromatics proceeds smoothly, offering a useful method of aryl-aryl coupling. However, the reaction is not mechanistically simple [la], and several mechanisms (paths a, b, c, and d) for the arylation... 

F-Alkenyltin compounds may be prepared by transmetallation using triorganyltin halides. Several ( )-alkenylstannyl alcohols have been prepared from intramolecular cross-coupling in the synthesis of zearalenone shown in Scheme 12. ... 

The a-substituted alkenylmetals used in Pd-catalyzed cross-coupling have been mainly those containing Mg, Zn, B, and Sn, as shown in Table 12 as well as Schemes 54-57. Of these, a-substituted alkenylmetals containing Mg and Zn can readily be prepared by direct oxidative metaUation of 2-halo-l-alkenes that are easily accessible by Markovnikov addition of HX to 1-alkynes (Scheme 54). a-Substituted alkenyltin compounds have been prepared and used in the construction of bicyclic diene systems via intramolecular Stille coupling, as shown in Scheme 55. ... 

Another noteworthy earlier example is the synthesis of humulene, albeit in 32% yield, via Pd-catalyzed intramolecular alkenyl-allyl coupling shown in Scheme... 

The Pd-catalyzed intramolecular cascade CTOss-coupling of l-halo-l,(< l)-dienynes [for 2-halo-l,(ft> l)-dienynes see Scheme 32] with a terminal double bond leads to 2-methylenecycloalkyIidenecycloalkenes (Sch ne 29), ° whereas halodienynes with the initiating iodoalkenyl unit incorporated in the chain between the alkynyl relay and the alkenyl terminator yield methylenebicycloalkadienes (Scheme 29). ° ... 

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