Diversity‐Oriented Synthesis of 2‐Iminothiazolidines: Pushing the Boundaries of the Domino Nucleophilic Displacement/Intramolecular anti‐Michael Addition Process

Abstract

Methods for the synthesis of a variety of functionalized 2‐iminothiazolidines and related heterocycles through a base‐mediated domino nucleophilic displacement/intramolecular anti‐Michael addition process involving electron‐deficient allylic bromides and 1,3‐ambident nucleophiles derived from thiourea were developed. These transformations proceed under mild and simple conditions and different functional groups are well tolerated. The scope and limitations of this protocol are dependent on the structure of the allylic bromide and 1,3‐ambident nucleophile involved. The synthetic versatility of 2‐iminothiazolidines was further demonstrated through a series of chemoselective modifications, giving rise to a wide range of thiazolidine frameworks of structural complexity. In particular, the reductive cyclization of 2‐nitrobenzyl‐substituted 2‐iminothiazolidines furnished novel spiroquinolones in good to fair yields. The structural assignment of key products was unequivocally achieved by X‐ray diffraction analysis and two‐dimensional NMR techniques.

Synthesis, spectral characteristics and molecular structure of 2H‐1,3,5‐oxadiazine‐2,4(3H)‐diimine derivatives

“…Recently, acyl thioureas have successfully been used for the synthesis of some heterocyclic compounds, for example, derivatives of 2‐iminothiazolidines [19], benzothiazole [20], 1,2,4‐triazole [21], pyrimidine [22], thiazinone [23], tetrazole [24] and others [1]. We have lately reported the successful use of acylated thioureas 1 for the synthesis of 2 H ‐1,3,5‐oxadiazine‐2,4(3 H )‐diimine 2 derivatives (Scheme 1) [25].…”

Palladium-Catalyzed anti-Michael-Type (Hetero)arylation of Acrylamides

“…The scarcity of cases arises from the higher electrophilicity of the β-position compared to that of the α-position, necessitating the overwhelming of this unfavorable electronic bias for achieving the anti -Michael-type addition reaction (Scheme A). Previous reports on overcoming the electronic bias can be categorized into two strategies: (1) restricting the addition position by a substrate structure, such as an intramolecular reaction, , or (2) changing the electronic bias by introducing a strong electron-withdrawing group at the β-position (Scheme B). , Despite these strategies representing significant advances in anti -Michael-type addition reactions, applying the methodology to the complex molecule synthesis faces a crucial restriction; these strategies are significantly constrained by the structure of the starting materials. − Recently, transition-metal-catalyzed α-hydroarylations of α,β-unsaturated carbonyl compounds have emerged as a state-of-the-art methodology for accessing anti -Michael-type adducts. − Although these reactions offer rare solutions to critical challenges associated with anti -Michael-type addition reactions, certain limitations persist. For instance, the formation of β-adducts is occasionally observed. , In another case, the versatility of these reactions is limited by the aryl groups, necessitating the introduction of strong electron-withdrawing groups .…”

“…The scarcity of cases arises from the higher electrophilicity of the β-position compared to that of the α-position, necessitating the overwhelming of this unfavorable electronic bias for achieving the anti-Michael-type addition reaction (Scheme 1A). Previous reports on overcoming the electronic bias can be categorized into two strategies: (1) restricting the addition position by a substrate structure, such as an intramolecular reaction, 8,9 or (2) changing the electronic bias by introducing a strong electron-withdrawing group at the β-position (Scheme 1B). 10,11 Despite these strategies representing significant advances in anti-Michael-type addition reactions, applying the methodology to the complex molecule synthesis faces a crucial restriction; these strategies are significantly constrained by the structure of the starting materials.…”

Palladium-Catalyzed anti-Michael-Type Hydroamination of N-(Quinolin-8-yl)acrylamide with 2-Pyridones

“…Among N -alkylated 2-pyridones, N -substituted 2-pyridone carboxylic acids and their derivatives are of considerable significance. This prominence largely arises from the frequent presence of the 2-pyridone motif at the α-position of carbonyl groups (Scheme A). − An ideal synthetic approach for these compounds involves α-addition to α,β-unsaturated carbonyl compounds, i.e., anti -Michael-type addition, yet this method presents substantial challenges. − The reaction between 2-pyridones and α,β-unsaturated carbonyl compounds typically results in the formation of a new chemical bond at the β-position of the α,β-unsaturated carbonyl compounds . Conversely, achieving the less common α-addition requires an inverse electron-demand nucleophilic addition process.…”