Palladium-catalyzed ring closure

Synthesis of benzo[e]pyrrolo[l,2-a]azepinone 82 was accomplished by palladium catalyzed ring closure of ketone 81 (Scheme 16 (2005JMC1705)). 

The intramolecular palladium catalyzed ring closure of the tetrahydro-isoquinoline derivative depicted in 8.41. led to the formation of the aporphine derivative in good yield, which was then converted into racemic aporphine in three steps. In the ring closing step 20 mol% palladium acetate and 40 mol% tricyclohexylphosphine were used as catalyst. The removal of the hydroxyl group was also achieved by palladium catalysis through its conversion to triflate and the subsequent reduction with ammonium formate in the presence of palladium acetate and dppf.53... 

Related palladium-catalyzed ring closures permit simple and selective either cis or trans annulation processes via an almost 100% stereospecific C—O C— Pd C—C transfer. The diastereoselectivity... 

We attempted the palladium-catalyzed ring closure of 27a (Table 5). Treatment of 27a with palladium(Tf) acetate [Pd(OAc)2] (30 mol%) in the presence of triethylphosphite [( tO)3P] and sodium bicarbonate (NaHCOs) in aqueous tetrahydrofuran (THF) afforded the desired cyclized product 28a albeit in a poor yield (30%) (Table 5, Entry 1). Both the lack of base or the use of a strong base (NaH) in place of NaHCOs were detrimental, yielding thiophene 44 or 2-oxazolidinone derivative 45, respectively (Table 5, Entries 2 and 3). 

An intramolecular variation of the Heck reaction was used in the construction of the monoterpene alkaloid ( )-oxerime 395 [138]. Nucleophilic addition to 392 of an allyl anion equivalent produced 393, a precursor to an intramolecular Heck cyclization. Palladium-catalyzed ring closure afforded 394, an intermediate in the synthesis of the natural product 395. 

Several other syntheses of the lif-azepino[5,4,3-c,c/ indole ring system have been reported, including the Mitsunobo reaction <85TL4043>, an intramolecular, acid-catalyzed aminoalkylation <88JOC5128> and intramolecular imine formation <87H(26)1197> leading to total synthesis of clavicipitic acid. Palladium-catalyzed ring closure of (127) afforded the cyclized derivative (128) (Equa-... 

Three new syntheses of 7-methoxymitosene (3) were published in the last five years. They were based on entirely different approaches. The one by Luly and Rapoport was a forerunner of the decarbamoylaziridinomitosene synthesis described above, and the palladium-catalyzed ring closure was developed in it [33]. In this synthesis (Scheme 11), 5,6-dibromo-2-methoxy-3-methyl-l,4-benzoquinone (86) was treated with proline ethyl ester to give 87. Photochemical oxidation-reduction then afforded 88 in 71% overall yield. Palladium-catalyzed oxidation of 88 furnished 89, which was converted to 90 by palladium-acetate-catalyzed ring closure in 93% overall yield. The carbethoxy group was then transformed into a carbamoyloxymethyl substituent by standard procedures, affording 3 in 67% yield. 

Tetrakis(triphenylphosphine ) palladium ( 0 )jtriethylamine Palladium-catalyzed ring closure of benzyl halides... 

Tobe reported that palladium-catalyzed ring-closure reaction of 200 provides l,l -biindenylidene 201 by a domino-Heck-type double cyclization in moderate yields (Scheme 6.53) [124]. The reaction is appHcable to the synthesis of fulvalene derivatives involving thiophene ring(s) 202 and 203 [125]. The (Z)-isomers of the... 

W. Stadlbauer, R. Laschober, T. Kappe, Palladium-catalyzed ring closure reactions to benzofuranes a new and effective approach to... 

The synthetic plan for (-)-dactyloIide by Lee and co-workers in 2010 involved the distinctive transition-metal-catalyzed transformations, including the formation of the 2,6-cw-disubstituted tetrahydropyran via the tandem ruthenium-catalyzed Alder-ene reaction [197,198] and palladium-catalyzed ring closure. The Alder-ene... 

Palladium (II)-catalyzed ring closure of acyclic allylic 2-alkynoates of type 137 provides an efficient entry to stereodefined a-methylene-y-butyro-... 

The comparison of intramolecular carbopalladation reactions of allenes and alkenes outlined in Schemes 9-5 and 9-6 illustrates that not every transition metal catalyzed ring closure necessarily involves a template effect. Others, however, clearly benefit from it. A prototype example is the palladium catalyzed cycloisomerization of alkenyl epoxides carrying distal pre-nucleophiles [38, 39], representing one variant of the famous Tsuji-Trost allylation [40]. 

Scheme 7.52 Demanding palladium(ll)-catalyzed ring closure en route to okaramine N.

The parent system 4 has also been jnepared employing a double reductive ring closure of a dinitrodiphenylbenzene derivative (Scheme 25). The required starting material, 195, was prepared using a palladium-catalyzed coupling of 1,4-dibromo-2,5-dinittobenzene with phenylboronic acid and after reaction with tri-ethylphosphite in hot tert-butylbenzene, 4 could be isolated in a moderate yield (92JHC1237). 

The palladium-catalyzed cyclization of compound 138 amply demonstrates the utility of the Stille reaction as a macrocyclization method (see Scheme 37). This efficient ring closure is just one of many examples disclosed by J.E. Baldwin and his group at Oxford.58 Interestingly, compound 138 can be employed as a stereoisomeric mixture of vinylstannanes because both stereoisomers converge on the same cyclized product. To rationalize this result, it was suggested that the configuration of the vinylstannane moiety is conserved in the cyclization, but that the macrocycle resulting from the (Z)-vinylstannane stereoisomer isomerizes to the thermodynamically favored trans product under the reaction condi-... 

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>. 

Watanabe reports a new method for the direct conversion of o-choroacetaldehyde N,N-disubstituted hydrazones into 1-aminoindole derivatives 93 by palladium-catalyzed intramolecular ring closure of 92 in the presence of P Bu3 or the bisferrocenyl ligand 94 <00AG(E)2501>. When X = Cl, this cyclizative process can be coupled with other Pd-catalyzed processes with nucleophilic reagents (e.g., amines, azoles, aryl boronic acids) so as to furnish indole derivatives with substituents on the carbocyclic ring. 

---