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

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

Reachability analysis for neural agent-environment systems

We develop a novel model for studying agent-environment systems, where the agents are implemented via feed-forward ReLU neural networks. We provide a semantics and develop a method to verify automatically that no unwanted states are reached by the system during its evolution. We study several reachability problems for the system, ranging from one-step reachability, to fixed multi-step and arbitrary-step to study the system evolution. We also study the decision problem of whether an agent, realised via feed-forward ReLU networks will perform an action in a system run. Whenever possible, we give tight complexity bounds to decision problems intro- duced. We automate the various reachability problems stud- ied by recasting them as mixed-integer linear programming problems. We present an implementation and discuss the ex- perimental results obtained on a range of test cases

Verification of RNN-based neural agent-environment systems

We introduce agent-environment systems where the agent is stateful and executing a ReLU recurrent neural network. We define and study their verification problem by providing equivalences of recurrent and feed-forward neural networks on bounded execution traces. We give a sound and complete procedure for their verification against properties specified in a simplified version of LTL on bounded executions. We present an implementation and discuss the experimental results obtained

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

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