We have developed a novel metal-catalyzed method for the synthesis of furans via cycloisomerization of diversely substituted allenyl ketones which involves a [1,2]-migration of alkyl- or aryl groups as the key step in this unique transformation. Thus, 4,4-disubstituted allenyl ketones underwent smooth cycloisomerization in the presence of catalytic amounts of oxophilic Lewis acids, such as Si-, Sn(II)-, and In(III)-, as well as carbophilic Ag(I)- and Au(I) triflates to produce up to tetrasubstituted and even fused furans in 62-94% yields. It was also demonstrated that a variety of functional groups were perfectly tolerated under these reaction conditions. [Angew. Chem Int. Ed. 2007, 46, 5195].

      Motivated by the successful 1,2-thio migration during the cycloisomerization reaction of alkynyl ketones and imines, we next incorporated 1,2-selenium migration into this cascade transformation. Thus, a novel Cu(I)-catalyzed method for the synthesis of diversely substituted seleno-furans and -pyrroles via 1,2-selenium migrative cycloisomerization of alkynyl ketones, aldehydes, and imines has been developed.  [J. Am. Chem. Soc. 2008, 130, 1440],  [Angew. Chem Int. Ed. 2007, 46, 5195].

     Our thorough studies revealed many similarities observed during cascade cycloisomerizations of C-4 diversely substituted alkynyl and allenyl systems involving 1,2-migration of various groups as the key step in the assembly of heterocyclic cores. It is believed that all of the reported 1,2-migration/cycloisomerization cascade transformations most likely proceed via allenyl intermediate. Considering all the experimental data, we propose a generalized mechanism for the synthesis of furans and pyrroles involving 1,2-migration of different migrating groups which is outlined below. Thus, a thermally induced and Cu-catalyzed 1,2-migration of chalcogenides (Y = SR and SeR) proceeds via paths A and B, respectively. Alternatively, Lewis or Brønsted acid-catalyzed cycloisomerization of allenones (X = O) involving 1,2-shifts of halogen (Y = Hal), alkyl, and aryl (Y = C) groups is postulated to follow path B, whereas carbophilic catalysts trigger through path C. Nevertheless, employment of transition metal catalysts in the 1,2-chalcogen migration/cycloisomerization cascade, such as Au(I), Au(III), Pd(II), and Pt(II), might involve a competitive -system activation pathway C proceeding via 1,2- or [1,5]-chalcogen migration in the carbenoid/oxonium intermediates. The observed competitive 1,2-migrations in case of pi-philic catalysts can be attributed to the 1,2-shifts to the electrophilic center (Path E). Alternatively, 1,2-shifts of these groups can also occur through the activated enone intermediate via equally feasible path D.  [J. Am. Chem. Soc. 2008, 130, 1440],  [Angew. Chem Int. Ed. 2007, 46, 5195].

     We developed a novel method for the synthesis of fused pyrroloheterocycles from diverse propargyl-substituted heterocycles in the presence of Au-catalyst. This method allows for mild and efficient synthesis of diverse C-2 substituted N-containing heterocycles such as indolizines, pyrroloquinolines, pyrroloisoquinolines, pyrrolothiazoles. The cascade transformation proceeds via alkyne-vinylidene isomerization with concomitant 1,2-shift of hydrogen, silyl, and stannyl groups. Remarkably, we also shown that previously unknown 1,2-migration of a germyl group upon alkyne-vinylidene rearrangement occurs under these reaction conditions. [J. Am. Chem. Soc. 2006, 128, 12050]

 We have developed an exceptionally mild, practical, and efficient method for synthesis of C-1-C-3 disubstituted N-fused heterocycles via a novel cycloisomerization protocol. The transformation can be efficiently performed at room temperature, it does not require any base or ligands. We demonstrated, that in the presence of Ag, Cu or Au catalyst, 2-propagyl pyridines, quinoxalines, and thiazoles undergo smooth and facile cycloisomerization resulting in the formation of C-1-C-3 disubstituted indolizines, pyrroloquinoxalines, and pyrrolothiazoles in good to excellent yields. This approach is complimentary to our previously developed methods for construction of related C-3 and C-1 - C-2 mono- and disubstututed heterocyclic systems. . [Org. Lett. 2007, 9, 3433-3436]

     We have discovered that N-fused pyrroles and imidazoles can be easily accessed via novel transannulation of 1,2,3-triazoles with terminal alkynes and nitriles. Readily available, stable, storable, and easy to handle N-fused 1,2,3-triazoles serve as very convenient precursors for a-imino diazocompounds, which upon reaction with Rh(II) carboxylates produce Rh-carbenoids. Subsequent transannualtion with alkynes and nitriles produces multisubstituted N-fused heterocycles, important biological scaffolds.. [Angew. Chem. Int. Ed. 2007, 46, 5195]

      We have developed a novel regiodivergent transition metal-catalyzed rearrangement of 3-imino cyclopropenes into N-fused heterocycles.  A choice of the metal catalyst (Rh or Cu) completely controls the regioselectivity of cycloisomerization. Thus, this method allows for highly efficient synthesis of 1,3- and 1,2-disubstituted N-fused pyrroloheterocycles, including indolizines, pyrrolooxozole and pyrroloisoquinoline.  We have also demonstrated that previously unavailable 3-imino cyclopropenes can conveniently be synthesized from 1,2,3-triazoles via the Rh(II)-catalyzed cyclopropenation of alkynes.   [Org. Lett. 2007, 9, 4463]

     We have also developed the direct, efficient, regioselective C-3 aryl- and heteroarylation of indolizines.  Our mechanistic studies strongly supported electrophilic substitution as the mechanism for this transformation.  A variety of substituents both on the indolizine and aryl bromide are tolerated, providing rapid access to substituted indolizines in good to very high yields.  [Org. Lett. 2004, 6, 1159], [Chem. Soc. Rev. 2007, 36, 1173]

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     We have developed a highly efficient method for the synthesis of multisubstituted 1,2,3-triazoles via a direct arylation protocol. It was found that arylation, in the presence of Pd-catalyst and tetrabutylammonium acetate in NMP, proceeded smoothly to provide C-5 arylated triazoles in good to excellent yields. This methodology appeared to be general with regard to electronic nature of aryl group. Thus, 1,4-disubstituted 1,2,3-triazoles, containing electron withdrawing aryl or carbethoxy groups, electron donating aryl groups, as well as aliphatic secondary alcohol at C-4, were smoothly arylated at C-5. A variety of functional groups were tolerated under the reaction conditions. It was also shown that aryl bromides bearing 2-naphthyl, bulky 1-naphthyl, and electron deficient heteroaromatic 3-pyridyl moiety can also be employed in this reaction. [Org. Lett.  2007, 9, 2333], [Chem. Soc. Rev. 2007, 36, 1173]

We have found that N-benzyl monosubstituted triazole undergoes regioselective arylation at C-5 with different aryl bromides under these reaction conditions. We believe that this methodology allows to extend the scope of the existing methods toward 1,5-disubstituted 1,2,3-triazoles.[Org. Lett.  2007, 9, 2333], [Chem. Soc. Rev. 2007, 36, 1173]

     We developed a mild and effective method for direct palladium-catalyzed sp2-sp carbon-carbon bond forming reaction of electron-rich heterocycles with alkynyl-halides. Existing methods for direct C-H functionalization of heterocycles, such as arylation and vinylation, are limited to sp2-sp2 carbon-carbon bond-forming reactions. Our conceptually new approach provides straightforward and efficient access to diverse alkynyl heterocycles.[J. Am. Chem. Soc.  2007, 129, 7742], [Chem. Soc. Rev. 2007, 36, 1173]

We found that a variety of easily available bromoalkynes bearing a variety of functional groups (such as alkyl, mono- and fused aryls, alkene, TMS, and ester) afford the corresponding alkynylated products in good to very high yields. Also, we demonstrated this method to be general with regard to electron-rich heterocyclic coupling partner: indolizines, pyrroloisoquinoline, densily substituted pyrroloxazole, pyrroloquinoline can be alkynylated in good to very high yields. Notably, bis-pyrrolopyrimidine underwent double alkynylation in good yield.

      We have developed a novel gold(I)-catalyzed method for the synthesis of unsymmetrically substituted naphthalenes via cycloisomerization of propargylic esters. This transformation features an unprecedented tandem sequence of 1,3- and 1,2-migration of two different migrating groups. Thus, benzyl-substituted propargyl phosphates and acetates underwent smooth cycloisomerization in the presence of catalytic amounts of cationic Au(I) triflate to produce multisubstituted and even fused naphthalenes in 30-94% yields. It was also demonstrated that a variety of functional groups were perfectly tolerated under these reaction conditions. [Org. Lett. 2008, 10, 1465-1468.]