A conceptually novel approach for asymmetric intramolecular hydroamination, hydroalkoxylation and hydrocarbonation of alkynes using chiral palladium catalysts are described. The reactions of the aminoalkynes 5, alkynols 7, and alkynylmethines 9 in the presence of Pd2(dba)3 x CHCl3/PhCOOH/renorphos 4 in benzene (or benzene-hexane) at 100 degrees C gave the corresponding cyclization products (nitrogen heterocycles 6, oxygen heterocycles 8, and carbocycles 10) in good yields with good enantioselectivities. The origins of enantioselectivities in the hydroamination reaction are discussed based on DFT computations.

The cyclization of 2-(1-alkynyl)-2-alken-1-ones 1 proceeded very smoothly in the presence of alcohols 2 with a catalytic amount of Cu(I)Br in DMF at 80 degrees C, leading to the formation of highly substituted furans 3. The catalytic system reported herein is easy to handle, compared to the previously known system wherein the reaction between 1 and 2 needed to use moisture sensitive gold(III) chloride.

A general protocol for the synthesis of functionalized indenes from o-alkynylbenzaldehyde acetals and thioacetals has been elaborated. Acetals uniformly give cyclization products having the alkyl group from the starting acetylene migrated to the alpha-position, whereas the cyclization of the corresponding thioacetals proceeds without alkyl migration. Optimization of the catalytic system for the cyclization of o-alkynylbenzaldehyde acetals revealed an unknown activation effect: PtCl(2) was found to be a better catalyst for the cyclization of acetals in the presence of olefins than without. A similar catalytic system (PtCl(2)/benzoquinone) has been found to be appropriate for the cyclization of cyclic acetals, whereas the optimal catalyst for the reaction of thioacetals is PdI(2). NMR monitoring of two reactions, acetal 3a + Pd(CH(3)CN)Cl(2) in CD(3)CN and thioacetal 5j + PdI(2) in CD(2)Cl(2), revealed that in both reactions similar cationic species are formed at the early stage of the transformation. Computational data (B3LYP/SDD level of theory) suggest that the difference in the reaction pathways for acetals and thioacetals can be rationalized by taking into account the relative stabilities of the corresponding vinylpalladium intermediates (22 vs 20 and 19 vs 21), which suggests a reversible thermodynamically controlled alkyl migration in the intermediate vinylcationic species.

The cyclization of amino-alkynes 1 in which an amino group is attached to the aromatic ring, proceeded smoothly using a catalytic amount of Pd(PPh3)4 and benzoic acid in toluene at 120 degrees C, leading to the formation of the 2-substituted tetrahydroquinolines 2. An asymmetric variant of the reaction using the chiral palladium catalyst (prepared in situ by mixing Pd2(dba)3.CHCl3 and (R,R)-RENORPHOS) was also explored. The absolute configuration of the enantiomerically enriched tetrahydroquinolines, obtained in this way, was determined by converting them to the known compounds and was found to be R. The alkaloids such as (+/-)-galipinine, (+/-)-angustureine, and their optically active form were synthesized by using this reaction as a key step.

The allylation of aromatic amines with alkynes proceeded smoothly in the presence of catalytic amounts of Pd(PPh(3))(4) and benzoic acid. The allylation products were obtained in high yields in a regio- and stereoselective manner. The effect of various groups on the nitrogen atom of anilines was studied. Regardless of the substituent (electron withdrawing or electron donating) on the aromatic ring, the reaction proceeded well. Various functionalities, including -CH(3), -OMe, -Cl, -CN, -COOMe, -NO(2) and -COCH(3) were tolerated under the reaction conditions. Similarly, the allylation of alpha-aryl aldehydes proceeded well with the same level of regio- and stereoselectivity as the allylation of aromatic amines. This reaction provides the second example of the transition metal catalyzed direct alpha-allylation of aldehydes.