Herein, we describe a facile approach towards the synthesis of diversely substituted 3‐aminothiophenes. A wide range of functional groups can be incorporated at the C(2), C(4), and C(5) positions of the thiophenes, and this route is also suitable for the synthesis of fused bicyclic heterocycles such as 3‐aminotetrahydrobenzothiophenes. This methodology relies on a 6π‐electrocyclization involving a vinyl sulfide linked to a keteniminium salt, the latter being formed in‐situ through activation of the corresponding amide with triflic anhydride.

A divergent total synthesis of three structurally distinct natural products from imine 9 was accomplished through an approach featuring: 1) a Pd-catalyzed decarboxylative cross-coupling, and 2) heteroannulation of 9 with bromoacetaldehyde and oxalyl chloride to give tetrahydroindolizine 6 and dioxopyrrole 7, respectively. The former was converted into (-)-rhazinilam, while the latter was converted into (-)-leucomidine B and (+)-leuconodine F. A substrate-directed highly diastereoselective reduction of a sterically unbiased double bond by using a homogeneous palladium catalyst was developed. A self-induced diastereomeric anisochronism (SIDA) phenomenon was observed for leucomidine B.

A predictive computational study was conducted in order to assess the efficiency of electrocyclization reactions of keteniminium salts, in an effort to form a variety of heterocyclic systems, namely, 3-amino­(benzo)­thiophenes, 3-amino­(benzo)­furans, 3-aminopyrroles, as well as 3-aminoindoles. A density functional theory (DFT) approach was utilized and the effect of heteroatoms (NMe, O, S) was thoroughly investigated by means of population analysis, QTAIM, NICS, ACID, and local reactivity descriptors (Parr and Fukui functions). The electrocyclization of enamines leading to 3-aminopyrroles was shown to be both kinetically and thermodynamically most favorable. Moreover, the pericyclic nature of the electrocyclizations was confirmed using FMO, QTAIM, NICS, and ACID methods. Additionally, substituent effects were investigated in order to give further insight on the reactivity of heteroatom containing keteniminium systems toward electrocyclization reactions. Finally, computational predictions were experimentally confirmed for a selection of keteniminium systems.

Dedicated to Professor Philippe Renaud for his 60 th birthday and in recognition of his great contributions to radical chemistryHerein, we describe a very straightforward and metal free method for the synthesis of benzazepinones through an intramolecular cyclization. This involves an ortho-vinyl-anilino-amide as starting material which is converted to a keteniminium intermediate that spontaneously cyclize to form a 7-membered ring iminium. Under slightly basic hydrolysis conditions, this latter is ultimately converted to the desired benzazepinone. Control experiments on the electron density of the nitrogen constituting the aniline were performed to support our proposed mechanism and rationalize the selectivity of the reaction.

the strategy involving the use of functionalized tetrahydro‐6H‐cycloocta[b]indol‐6‐one is reported as a key intermediate for synthesis of members of the sarpagine‐ajmaline‐macroline family of monoterpene indole alkaloids. The desired tricycle was synthesized through the following key steps: 1) Evans’ syn‐selective aldolization; 2) Liebeskind–Srogl cross‐coupling using the phenylthiol ester of 3‐chloropropanoic acid as a surrogate of acrylic thioester for the synthesis of 2,3‐disubstituted indoles; and 3) ring‐closing metathesis (RCM) for the formation of the eight‐membered ring. An N‐allylation followed by intramolecular 1,4‐addition was planned for synthesis of the vobasine class of natural products. However, attempted cyclizations under a diverse set of conditions involving anionic, radical, and organopalladium/organonickel species failed to produce the bridged ring system. On the other hand, esterification of the pendant primary alcohol function with acetoacetic acid, followed by intramolecular Michael addition, afforded the desired tetracycle with excellent diastereoselectivity. Subsequent functional group manipulation and transannular cyclization of the amino alcohol afforded the N(1)‐demethyl‐3,5‐diepi‐alstolactone. We believe that the same synthetic route would afford the alstolactone should the amino alcohol with appropriate stereochemistry be used as the starting material.