Domino Addition/Cycloisomerization Reactions of 2-Alkynyl-Arylaldehydes: Silver Catalyzed Synthesis of 1,3-Dicarbo-Substituted Isochromenes

One of the most efficient methods for the construction of 1-substituted isochromenes (and related heteroaryl compounds) is the metal catalyzed regioselective domino cycloisomerization/nucleophilic addition reaction of a 2-alkynyl(hetero)arylaldehyde in the presence of a suitable nucleophile.(1) The reaction with oxygen nucleophiles is the probably the most studied one. Several metal catalyst have been used, and our group recently gave a contribution in the field of silver catalyzed(2) synthesis of 1-alkoxyisochromenes.(3) Conversely, the reaction with carbon nucleophiles, and in particular with enolizable carbonyl compounds, is relatively less investigated.(4) We report here our recent results regarding the silver catalyzed synthesis of 1,3-dicarbo-substituted isochromene derivatives starting from 2-alkynyl(hetero)arylaldehydes and enolizable carbonyl compounds.(5) The reaction proceeded in a cascade fashion under mild reaction conditions with absolute regioselectivity and moderate-to-good yields. In some cases, the reaction produced unexpected diastereoisomeric couple of homodimeric products. The divergent formation of the 1-carbosubstituted isochromenes and the alternative homodimeric products has been tentatively explained by some experiments and two conceivable competitive paths have been proposed

Silver Triflate/p-TSA Co-Catalysed Synthesis of 3-Substituted Isocoumarins from 2-Alkynylbenzoates

In this paper, we describe the silver triflate/p-toluensulfonic acid co-catalysed synthesis of seventeen isocoumarins and two thieno[2,3-c]pyran-7-ones starting from 2-alkynylbenzoates and 3-alkynylthiophene-2-carboxylates, respectively. The reactions proceed with absolute regioselectivity under mild reaction conditions and low catalyst loading, to give the desired products in good to excellent yields. A conceivable reaction mechanism is proposed and supported by isotope-exchange tests, and 1H NMR studies and ad-hoc experiments

Gold-catalyzed cascade reactions of 4H‐furo[3,2‐b]indoles with allenamides: synthesis of indolin-3-one derivatives

2-Spirocyclopentane-1,2-dihydro-3H-indol-3-ones (namely, spiropseudo-indoxyls) constitute privileged scaffolds in organic synthesis and represent core components of different indole alkaloids (e.g. aristotelone and brevianamide A) and of molecules applied as functional dyes. In addition, they have found also an application as useful intermediate in the total synthesis of minfiensine. Taking into account these premises and our expertise in gold-catalyzed indole functionalization, we tested the reactivity of 4H-furo[3,2-b]indoles in the presence of electrophilic gold(I) activate \u3c0-systems (allenamides) with the aim to develop a new cascade process for the synthesis of these relevant scaffolds (Scheme 1). In this poster we present the obtained results together with the scope and limitation of the method and the proposed reaction mechanism

Catalytic transformations of indoles: recent achievements and new perspectives for the synthesis of complex indole derivatives

Transformation of simple indoles into (polycyclic) complex scaffolds has become the object of intensive studies in synthetic organic chemistry due to ubiquitous occurrence of indole core in the structure of relevant molecules In particular, catalytic-promoted manipulation of indoles have become an incomparable tool to increase indole structural complexity working under exceedingly mild conditions and in a regio- and stereo-controlled fashion. In this context we reported in the last years the synthesis of complex carbazole derivatives through gold-catalyzed (4+2) cycloaddition reactions of vinylindoles with different \u3c0-systems and the functionalization of structurally simple indoles with challenging metal-activated electrophiles. Taking into account these premises, this oral communication will deal with our recent achievements in the field of cycloaddition reactions involving vinylindoles as 4\u3c0 systems and in gold-catalyzed cascade reactions on indole-based scaffolds. In particular we were able to extend cycloaddition of vinylindoles besides (4+2) processes to synthetize cyclohepta[b]indoles. Moreover, we explored the reactivity of 4H-furo[3,2-b]indoles with gold-activated \u3c0-systems to synthetize 2-spiro-3-oxindoles and 2-alkenyliden-indolin-3-ones selectively. Advantages of our methods as well as limitations and future perspectives will be discussed

Mild AgOTf Catalyzed Synthesis of 1-Carbosubstituted-isochromenes

One of the most efficient methods for the construction of 1-substituted isochromenes (and related heteroaryl compounds such as pyrano[4,3-b]pyridines) is the metal catalyzed regioselective domino cycloisomerization/nucleophilic addition reaction of a properly substituted 2-alkynyl(hetero)arylaldehyde in the presence of a suitable nucleophile. The reaction with oxygen nucleophiles is the most studied and several metal catalyst, i.e., Pd(II), Cu(I), Ag(I), Au(I) and In(III), demonstrated to be effective for synthesis of 1-alkoxyisochromenes. Conversely, the reaction with carbon nucleophiles, and in particular with enolizable carbonyl compounds, is relatively less investigated. In connection with our ongoing interest in the development of silver catalysed domino approaches involving alkyne derivatives, we report here a silver catalyzed domino approach to isochromenes starting from 2-alkynyl(hetero)arylaldehydes and enolizable carbonyl compounds. The reaction yields range from fair to very good. The reaction mechanism is also investigated and the formation of by-products discussed

Silver-catalysed A3-coupling reactions in phenylacetic acid/alkylamine N-oxide eutectic mixture under dielectric heating: An alternative approach to propargylamines

The development of alternative benign reaction conditions to perform multicomponent reactions is an interesting and desirable strategy to increase the sustainability of organic synthesis. In this paper, we report a new version of A3-coupling MCR for the preparation of differently substituted propargylamines starting from aldehydes, alkynes and amines in an acidic DES as reaction media, under dielectric heating, and in the presence of a tetraaza-macrocyclic silver complex as catalyst. The reaction scope is broad in terms of aldehyde partners. Electron-rich phenylacetylenes are the more reactive alkynes partners, whereas the nature of the amine is the more serious limitation as only secondary cyclic amines are tolerated

Gold-Catalyzed Cascade Reactions of 4H-Furo[3,2-b]indoles with Allenamides: Synthesis of Indolin-3-one Derivatives

Merging the ability of cationic gold(I) catalysts to activate unsaturated \u3c0-systems with the electrophiles driven ring-opening reactions of furans, we describe a new approach to 2-spiroindolin-3-ones from 4H-furo[3,2-b]indoles. The reaction occurs through a cascade sequence involving addition of a gold-activated allene to the furan moiety of the starting furoindole followed by a ring-opening/ring-closing event affording 2-spirocyclopentane-1,2-dihydro-3H-indolin-3-ones in moderate to good yields

Gold-Catalyzed Cascade Reactions of 4H‑Furo[3,2‑b]indoles with Propargyl Esters: Synthesis of 2-Alkenylidene-3-oxoindolines

2-alkenyliden-indolin-3-ones were synthesised in high yields via a cascade reaction between 4H\u2011furo[3,2\u2011b]indoles and propargyl esters. The cascade sequence involves initial formation of a gold-carbene specie via cationic gold(I) catalysed 1,2-acyloxy migration of properly substituted propargyl esters followed by gold-carbene to furoindole addition and successive furan ring-opening affording the final products. The obtained compounds contain an extended \uf070-system linked at the C2 of the indolin-3-ones, they are characterised by intense colouration (from yellow to purple) and were characterised by UV mesearurements

Gold(I)-catalyzed [4+2] cycloaddition reactions of vinylindoles and allenes

Carbazole and tetrahydrocarbazole rings are the key structural motif in a great number of biological active molecules, including natural alkaloids and synthetic products. For this reason, strategic syntheses of these indole derivatives are highly required, in particular when based on asymmetric methodologies. In this research field, 2- and 3-vinylindoles have become versatile 4C building blocks for the synthesis of complex tetrahydrocarbazole derivatives by means of [4+2] cycloadditions. Among dienophiles, it has been shown that gold activated allenes could participate in [4+2] processes and we published the first example of gold catalyzed reaction of 2- and 3-vinylindoles with allenamides and allenyl esters. In this latter work we reported also some preliminary investigations on enantioselective synthesis of tetrahydrocarbazoles, by conducting the reaction in the presence of a chiral gold(I) phosphoramidites. Prompted by these results and taking into account the importance of asymmetric tetrahydrocarbazole synthesis, we next explored the reactivity of 3/2-substituted-2/3-vinylindoles with N-allenamides under chiral gold(I) catalysis for the synthesis of a new series of dearomatized indoles bearing a quaternary C4a/C9a stereocenter (Scheme 1). The results obtained in this work will be presented in the context of our investigations on gold(I) catalyzed syntheses of tetrahydrocarbazoles