Spontaneous Cyclization of peri-Diiminonaphthalenes Leading to the Formation of Benzo[de]isoquinolines and Stable Benzo[de]isoquinoliniums

Abstract

The interaction of peri-dilithionaphthalenes with organic cyanides was studied. Instead of the expected peri-diimines, the reaction leads to the formation of three types of benzo­[de]­isoquinolines. Treatment of unsubstituted 1,8-dilithionaphthalene with aromatic nitriles results in the formation of 1-amino-1,3-diaryl-1H-benzo­[de]­isoquinolines. In contrast, 4,5-dilithio-1,8-bis­(dimethylamino)­naphthalene gives an aromatic isoquinolonium cation via elimination of ammonia under the same condition. Upon treatment with tert-butylcyanide, both dilithionaphthalenes undergo a transformation to 1-amino-3,4-di-tert-butyl-4H-benzo­[de]­isoquinolines. The observed reactivity was supported by quantum chemical calculations.

Transition‐Metal‐Free Synthesis of 2‐Substituted Benzo[cd]Indoles via the Reaction of 1‐Halo‐8‐lithionaphthalenes with Nitriles

“…We believe that the selectivity of the protonation of 11 originates from the abovementioned strong conjugation of the 5‐NMe 2 group with an aromatic core: the stabilization of form 11’ boosts the basicity of the indole nitrogen on the one hand, and prevents the protonation of the non‐conjugated NMe 2 group by inducing a positive charge in close proximity, on the other hand (Scheme 5). A similar effect was previously observed in the case of cations 14 , where the conjugation of the 1‐NMe 2 group with the aromatic system also prevented the protonation of the molecule [35] . Additionally, the abovementioned “clothespin effect” in the case of 11 leads to the decrease of the basicity of the “proton sponge” moiety: the annulation of the 5‐membered cycle to the peri ‐positions of 1,8‐bis(dimethylamino)naphthalene leads to the increase of the internitrogen distance [49,51,52] .…”

“…A similar effect was previously observed in the case of cations 14, where the conjugation of the 1-NMe 2 group with the aromatic system also prevented the protonation of the molecule. [35] Additionally, the abovementioned "clothespin effect" in the case of 11 leads to the decrease of the basicity of the "proton sponge" moiety: the annulation of the 5-membered cycle to the peri-positions of 1,8bis(dimethylamino)naphthalene leads to the increase of the internitrogen distance. [49,51,52] Indeed, performed quantum chemical calculations (for R = tert-Bu) have demonstrated that formation of form 15 is thermodynamically less favourable than 11 • H + : ΔΔG (11 g • H + !15 g) = + 8.0 kcal/mol (Figure 2).…”

“…[33,34] Thus, an effective utilisation of lithionapthalenes for the synthesis of benzo[de]isoquinolines, benzo[h]quinazolines, and benzo[g]indoles has been demonstrated in the past decade. [35][36][37][38][39] The concept of utilisation of aryllithiums containing a group suitable for nucleophilic substitution is very promising for the heterocyclic moiety annulation. As a development of this concept, we present our simple and effective organometallic approach to the synthesis of 2-substituted benzo [cd]indoles based on the interaction of easily available 1-halo-8-lithionaphthalenes with nitriles (Scheme 1c).…”

“…Consequently, they not only maintain their solid positions as indispensable tools for modern organic synthesis but also open up new possibilities through novel applications discovered in recent years [33,34] . Thus, an effective utilisation of lithionapthalenes for the synthesis of benzo[ de ]isoquinolines, benzo[ h ]quinazolines, and benzo[ g ]indoles has been demonstrated in the past decade [35–39] …”