Scaffold Diversity through a Branching Double-Annulation Cascade Strategy: Iminium-Induced One-Pot Synthesis of Diverse Fused Tetrahydroisoquinoline Scaffolds

Abstract

A branching double-annulation cascade (BDAC) strategy for diverse and complex fused THIQ scaffolds via a highly reactive iminium-induced one-pot double-cyclization sequence involving Pictect-Spengler-type cyclization has been developed for the first time. The salient features of this protocol are that it allows direct and rapid access to unprecedented diverse fused THIQ skeletons, is metal/catalyst free, has a cleaner reaction profile, provides good to excellent yields, and is a convenient approach. This catalyst-free domino process facilitates the double annulation with a variety of scaffold building agents via two C-N and one C-X (X = C, N, O) bond formation in a single step under uniform reaction conditions. Furthermore, we reveal an unusual dual BDAC sequence leading to N-N-linked isoquinoline dimer.

Comprehensive Strategies for the Synthesis of Isoquinolines: Progress Since 2008

“…[289] Sharada et al reported one-pot synthesis of tetrahydroisoquinolines 477 using iminium-induced branching double annulation cascade (BDAC) protocol. [290] This methods falls into the category of Pictet-Spengler type cyclization which was reported for the first time. This unprecedented method gives an easy and facile entry to diverse range of fused tetrahydroisoquinolines (Scheme 291).…”

Aryne and CO2-based formal [2 + 2 + 2] annulation to access tetrahydroisoquinoline-fused benzoxazinones

“…In 2016, a one-pot process was reported from anthranilic acid and 2-haloethylbenzaldehydes through an iminium-mediated branching double-annulation cascade process. 5 Furthermore, alternative pathways proceed through cross-dehydrogenative coupling (CDC) from THIQ fused benzoic acids under various oxidative conditions. 6 Based on the CDC strategy, 7 Ye group developed an N-heterocyclic carbene-catalyzed domino reaction of THIQ-fused aryl aldehydes with phenyliodine( iii ) diacetate through acyl azolium intermediates.…”

Quantum chemical approaches to [NiFe] hydrogenase

“…We will summarize the various quantum chemistry techniques that give insight into the (i) geometry, (ii) electronic structure, (iii) thermodynamics and (iv) kinetics properties of [NiFe] hydrogenase. In the process, we will touch on a range of technical challenges wide enough to be relevant to most other bioinorganic complexes in a variety of other research fields such as enzymology, [28][29][30][31][32] genetics, [33][34][35][36][37] regulation, [38][39][40][41] medicine [42][43][44][45][46] and environmental chemistry. [47][48][49][50] II.…”