Regioselective palladium-catalyzed cycloaddition reactions

The reactions between benzotriafulvenes and transition metals (Pt and Rh) afford metallacyclobutane derivatives 41 as stable crystalline compounds in good yields. Recently, Huang developed the highly regioselective palladium-catalyzed [i+2] cycloaddition reactions of 34 (R = Ph) with arynes or alkynes to provide fluorene 42 and rndene derivatives 43, respectively (Scheme 6.4) [24]. 

Dipolar cycloaddition reaction of trimethylstannylacetylene with nitrile oxides yielded 3-substituted 5-(trimethylstannyl)isoxazoles 221. Similar reactions of (trimethylstannyl)phenylacetylene, l-(trimethylstannyl)-l-hexyne, and bis (trimethylsilyl)acetylene give the corresponding 3,5-disubstituted 4-(trimethyl-stannyl)isoxazoles 222, almost regioselectively (379). The 1,3-dipolar cycloaddition reaction of bis(tributylstannyl)acetylene with acetonitrile oxide, followed by treatment with aqueous ammonia in ethanol in a sealed tube, gives 3-methyl-4-(tributylstannyl)isoxazole 223. The palladium catalyzed cross coupling reaction of... 

A similar pressure effect on regioselectivity was reported for palladium-catalyzed [3-I-2]-cycloadditions [19]. In the reaction of the trimethylenemethane (TMM) precursor 61 with the alkene 62 the two regioisomeric cycloadducts 63 and 64 are possible while 64 is mainly formed at 1 bar, the only product observed at 10 kbar is 63. A possible explanation of this dramatic change in selectivity could be the increased rate of the bimolecular reaction of 65 and 62 to give 63 compared to the unimolecular isomerization of the TMM complexes 65 and 66. Thus, the kineti-cally formed complex 65 is effectively trapped under pressure by the alkene 62. 

Methylenecyclopropane is also a convenient TMM precursor for the cycloaddition reaction. Both nickel(O) and palladium(O) complexes can catalyze the [3 + 2] cycloaddition of aUcylidenecyclopropanes with aUcenes and alkynes (Scheme 12). ° Unlike the Ni-catalyzed reaction, the regioselectivity in the Pd-catalyzed reaction with alkene is independent of the structure of the starting aUcylidenecyclopropanes, which indicates that this reaction also proceeds via TMM-Pd as mentioned above. The TMM-Pd generated from aUcylidenecyclopropanes can undergo a stereoselective intramolecular cycloaddition with alkynes,and the regiochemistry is different from the Ni-catalyzed reaction... 

V. Gevorgyan, U. Radhakrishnan, A. Takeda, M. Rubina, M. Rubin, Y. Yamamoto, J. Org. Chem. 2001, 66, 2835-2841. Palladium-catalyzed highly chemo- and regioselective formal [2+2+2] sequential cycloaddition of alkynes a renaissance of the well known trimerization reaction ... 

In palladium-catalyzed [2 - - 2 - - 2] cycloaddition, arynes can be used as alkyne components. In 1994, Pena, Romero, and co-workers reported palladium-catalyzed homo-[2- -2- -2] cycloaddition of arynes (Scheme 6.9) [12]. The reactions of 2-silylaryl trifluoromethanesulfonates 26 with CsF generated the corresponding arynes 27, which were trimerized in the presence of a catalytic amount of Pd(PPh3)4 or Pd2(dba)3 to afford substituted triphenylenes 28. In the reactions of unsymmetric arynes, moderate to high regioselectivities were observed. A mechanism via pallada-cycle intermediates, generated through the oxidative cyclization of two molecules of arynes, was proposed. 

The complexes [Ni(acrylonitrile)2] and [Ni(COD)2] catalyze [3 + 2] cycloadditions of (26) with electron deficient l,2 isubstituted alkenes to afford 2,3- or 3,4-disubstituted methylenecyclopentanes such as (32) and (33). Similar reactions have been reported by use of tertiary phosphine complexes of nickel(0) and palladium(0) (equation 13 and Table 1). The reaction proceeds regioselectively to give (32) or (33) depending on both the alkene stmcture and catalytic system. Reactions catalyzed by phos-phine-palladium(0) complexes afford only products of the type (32), via selective cleavage of the C(2)— C(3)bondof(26). 

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