Palladium-catalyzed cyclization-coupling reaction

The palladium-catalyzed cyclizative coupling reaction of a-allenols 41 with alkenyl halides was also explored. The transformation of allenols 41 into spirocyclic disubstituted dihydrofuran (3-lactams 43 was readily achieved in high yields, by treatment with allyl bromide or 2,3-dibromopropene in the presence of palladium (II) chloride (5 mol%) (Scheme 14) [60]. 

On the basis of this palladium-mediated Michael addition cyclization process, a novel two-step synthetic entry into functionalized furan derivatives 67 has also been devised (Scheme 28). Substitution of benzylidene (or alkyli-dene) malonates for their ethoxymethylene analog (65) as activating olefins gave rise to the formation of the corresponding 2-ethoxy-4-arylidene tetrahy-drofurans 66. An in situ addition of potassium ferf-buloxidc induced a decar-boxylative elimination reaction which was followed by an isomerization of the exocyclic double bond. The entire process successively involved a conjugate addition, a palladium-catalyzed cyclization-coupling reaction, a base-induced eliminative decarboxylation, and finally, a double bond isomerization [73]. 

Aurrecoechea and co-workers used a palladium(Il) catalyst to perform a palladium-catalyzed cyclization-coupling reaction to prepare... 

The palladium-catalyzed reductive coupling reactions were used in the synthesis of several natural products, including laurene [75], ceratopicanol [80], and dihydrostreptazolin 141 [81]. The cyclization leading to dihydrostrepta-zolin shown in Eq. 26 highlights the diastereoselectivity and functional group compatibility seen with this catalytic system. 

The [2,3- ]> [2,3- ]. and [i,Z-b] isomers of 2,3-disubstituted furopyridines can be obtained from alkynes and o-iodoacetoxypyridines by a palladium-catalyzed cross-coupling reaction followed by an electrophilic iodocyclization reaction or a palladium-catalyzed cyclization in the presence of CO, as illustrated in Scheme 32 for [2,3-3] and [3,2-3] derivatives. When the pyridine ring contains strongly electron-withdrawing substituents such as carboethoxy, the reaction proceeded smoothly with benzyloxyalkynylpyridines <20020L2409>. 

By contrast, for iodide 18 having the triple bond activated by a phenyl group, conversion to the cyclic organozinc species 25 occurred effectively and the latter could be efficiently functionalized, provided that traces of moisture were excluded by pre-treatment of zinc powder with Mel. The substituted benzylidene cyclopentanes 26 and 27 were respectively obtained after iodinolysis and palladium-catalyzed cross-coupling reaction with benzoyl chloride (equation 10). However, it could not be assessed whether the formation of organozinc 25 was attributable to an anionic or a radical cyclization pathway (or both) as, had iodide 26 been produced by a radical iodine atom-transfer, it would have been converted to 25 by reaction with metallic zinc due to the presence of the activating phenyl group21. 

An indium-mediated radical cyclization sequence has been used to synthesize stereoselectively 3-alkylideneoxindoles [65, 66]. The generation of predominantly the i -isomer, such as seen with 96 below, is attributed to the strong coordination of the indium to the carbonyl of the oxindole intermediate, and the transformation of various iodo-ynamides to the cyclized oxindoles occurred in good yield. Selective approaches to the E- and disubstituted 3-alkylideneoxindoles involving a tandem palladium-catalyzed cross coupling reaction were also highlighted in this report. 

The formation of 2-alkenyl-substituted furans was observed in the palladium-catalyzed cross-coupling reactions between benzyl, aryl, or allyl bromides and conjugated ene-yne-ketones. This reaction involved oxidative addition, alkyne activation-cyclization, palladium carbene migratory insertion, P-hydride elimination, and catalyst regeneration (13JA13502). 

In the total synthesis of (+)-lycopladine A by Toste et al. [30], a gold-catalyzed 5-endo cyclization of an iodoalkyne with a silyl enol ether has been used (Scheme 16.25). This transformation efficiently produces a -unsaturated bicyclic ketone that possesses the required quaternary asymmetric center at the position a to the carbonyl group. The vinyl iodide functionaiity generated during the cyclization was subsequently used in a palladium-catalyzed cross-coupling reaction in order to construct the pyridine ring of (-F)-lycopladine A. 

The authors further explored the chemistry on solid support by decorating the obtained resin-bound 2-aminobenzothiazoles using different palladium-catalyzed cross-coupling reactions (Scheme 8.24). Thus, the reaction product of 3-bromoaniline was subjected to bromine-mediated cyclization in AcOH at rt for 16 h, furnishing a 1 1 mixture of 5- and... 

Cacchi and Palmier (83T3373) investigated a new entry into the quinoline skeleton by palladium-catalyzed Michael-type reactions. They found that phenyl mercurial 134 was a useful intermediate for the synthesis of quinoline derivatives, and that by selecting the reaction conditions the oxidation level of the heterocyclic ring in the quinoline skeleton can be varied. On such example is shown in Scheme 16. PdCla-catalyzed coupling between organomercurial reagent 134 and enone 135 delivered adduct 136 which was subsequently cyclized to quinoline 137 under acidic conditions. 

Palladium-catalyzed cyclization reactions with aryl halides have been used to synthesize pyrazole derivatives. V-Aryl-lV-(c>-bromobenzyl)hydrazines 26 participated in a palladium-catalyzed intramolecular amination reaction to give 2-aryl-2W-indazoles 27 . Palladium-catalyzed cascade intermolecular queuing-cyclocondensation reaction of o-iodophenol (28) with dimethylallene and aryl hydrazines provided pyrazolyl chromanones 29 <00TL7129>. A novel one-pot synthesis of 3,5-disubstituted-2-pyrazolines 32 has been achieved with an unexpected coupling-isomerization sequence of haloarene 30, propargyl alcohol 31, and methylhydrazine <00ACIE1253>. 

A few synthetic applications of palladium catalysis appeared this year. The palladium-catalyzed cyclization of amino allenes 58 occurs with coupling of aryl iodides or vinyl triflates at the 3-position <990L717, 99SL324>. The cyclization can also proceed by the exo-trig pathway, but under suitable reaction conditions the piperidine 59 is prepared selectively. The intramolecular cyclization of amines onto N-allylbenzotriazoles similarly affords piperidines <99JOC6066>. 

The industrial synthesis of vinyl acetate [14] via palladium-catalyzed oxidative coupling of acetic acid and ethene using direct 02 reoxidation has already been mentioned (Scheme 3, d). Some NaOAc is required in the reaction medium, and catalysis by Pd clusters, as alternative to Pd(II) salts, was proposed to proceed with altered reaction characteristics [14]. Similarly, the alkenyl ester 37 (Table 5) containing an isolated vinyl group yields the expected enol acetate 38 [55] whereas allylphenol 39 cyclizes to benzofuran 40 with double bond isomerization [56]. 

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