The exploitation of nitrogen-functionalized reactive intermediates plays an important role in the synthesis of biologically relevant scaffolds in the field of pharmaceutical sciences. Those based on gold carbenes carry a strong potential for the design of highly efficient cascade processes toward the synthesis of compounds containing a fused indole core structure. This personal account gives a detailed explanation of our contribution to this sector, and embraces the reaction development of efficient gold-catalyzed cascade processes based on diversely functionalized azido-alkynes. Challenging cyclizations and their subsequent application in the synthesis of pharmaceutically relevant scaffolds and natural products conducted in an intra-or intermolecular fashion are key features of our research.

Because benzannulated and indole-fused mediumsized rings are found in many bioactive compounds, combining these fragments might lead to unexplored areas of biologically relevant and uncovered chemical space. Herein is shown that α-imino gold carbene chemistry can play an important role in solving the difficulty in the formation of medium-sized rings. Namely, phenylene-tethered azido-alkynes undergo arylative cyclization through the formation of a gold carbene intermediate to afford benzannulated indolefused medium-sized tetracycles. The reactions allow a range of different aryl substitution patterns and efficient access to these otherwise difficult-to-obtain medium-sized rings. This study also demonstrates the feasibility of the semihollowshaped C-dtbm ligand for the construction of a ninemembered ring.

Phenyl azidessubstituted by an (alkylphenyl)ethynyl group facilitate benzylic sp 3 (CÀ H) functionalization in the presence of a JohnPhosAu catalyst, resulting in indole-fused tetra-and pentacycles via divergent N-or C-cyclization. The chemoselectivity is influenced depending on the counter-anion, the electron density of the α-imino gold(I) carbene, and the alkyl groups stabilizing the benzylic carbocation originating from a 1,5-hydride shift. An isotopic labeling experiment demonstrates the involvement of an indolylgold(I) species resulting from a tautomerization that is much faster than the deauration. The formation of a benzylic sp 3 (CÀ H) functionalization leading to an indole-fused seven-membered ring is also demonstrated.

Herein, we describe a gold-catalyzed cascade cyclization of Boc-protected benzylamines bearing two tethered alkyne moieties in a domino reaction initiated by a 6endo-dig cyclization. The reaction was screened intensively, and the scope was explored, resulting in nine new Bocprotected dihydrobenzo[c]phenanthridines with yields of up to 98 %; even a π-extension and two bidirectional approaches were successful. Furthermore, thermal cleavage of the Boc group and subsequent oxidation gave substituted benzo [c] phenanthridines in up to quantitative yields. Two bidirectional approaches under the optimized conditions were successful, and the resulting π-extended molecules were tested as organic semiconductors in organic thin-film transistors.

Ag olden compass guides the adventurer's way in an unknown chemical space from the structures with one-and two-dimensional content towards those with an increased three-dimensional character.T hese three-dimensional compounds rise towards uncharted chemical space leaving the flatland behind, based on the cascade cyclization of alkynyl azides generating indole fused medium-sized rings.