Divergent Synthesis of Highly Substituted Pyridines and Benzenes from Dienals, Alkynes, and Sulfonyl Azides

Abstract

Divergent synthesis is extremely important for the highly efficient preparation of structurally diverse target molecules. Herein, we describe a multicomponent cascade reaction, which allows access to highly substituted pyridines and benzenes by combining four individual steps in a one-pot manner from the same set of readily available starting materials. The azepine intermediates were first used as the precursors for 6π-electrocyclization to construct highly substituted pyridines and benzenes in a tunable manner.

Recent advances in 8π electrocyclization reactions

“…Recently, our group reported a Cu( i )/Rh( ii )-catalyzed three component cascade reaction to access cis -substituted 2,3-dihydroazepines from readily available dienal, alkyne and sulfonyl azide substrates (Scheme 2). 18 Specifically, the copper-catalyzed reaction of sulfonyl azides with alkynes generated the corresponding N -sulfonyl-1,2,3-triazoles that served as α-imino diazo precursors to provide metal-stabilized carbenoids by Rh( ii ) catalysis. Subsequently, the reaction of the carbenoid with an aldehyde group forms an oxazoline by means of a formal [3 + 2] cycloaddition reaction.…”

Recent Applications on Dual-Catalysis for C–C and C–X Cross-Coupling Reactions

“…34,37,[47][48][49] The use of dual-metal catalytic systems in the synthesis of new compounds has increased significantly during the past twenty years. [50][51][52] In addition to improving selectivity and reactivity, these novel methods can also greatly enhance the reaction processes that would not be feasible with a single metal catalyst, enabling the synthesis of novel compounds and molecular frameworks. Synergistic catalysis has often been studied by combining a transition metal catalyst with Lewis acids, 53,54 organocatalysts (e.g., Brønsted acids, N-heterocyclic carbenes, chiral amines, and Lewis bases), [55][56][57][58][59][60][61][62][63][64][65][66][67] or Lewis acids with N-heterocyclic carbenes.…”

Synergism of Fe/Ti Enabled Regioselective Arene Difunctionalization

“…Ethyl olivetolate ( 8 ) was conveniently prepared from 2,4-dimethoxylphenyl magnesium bromide by one-pot successive alkylation and acylation with the problems of regioselectivity and alkyl chain isomerization in conventional methods being well addressed. For pharmaceutical synthesis, Pitofenone ( 9 ) and CF 3 -substituted Pitofenone ( 10 ) were successfully synthesized in a one-pot manner, where the introduction of the ketone and carboxyl groups at designated positions in preparing a substituted Pitofenone ( 10 or analogues) remains a challenge to other methods. Late-stage diversification of Estrone ( 11 ) was also achieved in a one-pot manner using the present ODF, providing a shortcut for the synthesis of drug-like compounds.…”