Chemo- and Regioselective 4CR Synthesis of Oxathiaaza[3.3.3]propellanes via Sequential C–S, C–N and C–O Bond Formation in a Single Pot

Abstract

Oxathiaaza[3.3.3]propellane derivatives were prepared by reaction of in situ generated asymmetric thioureas with intermediate Knoevenagel adducts resulting from ninhydrin and malononitrile. This four-component sequential transformation performed in one reaction flask represents a general route to this unexplored valuable class of sulfur-nitrogen heterocycles. The chemoselectivity and regiochemistry of the products were established by IR, NMR and single crystal X-ray analysis.Multicomponent reactions (MCRs) offer an expedient route to complex targets since the combination of three or more reactants within a single reaction typically leads to a shorter reaction sequence and fewer purification steps. 1 Moreover, multicomponent products are comparatively far more elaborate than their starting material counterparts and, by altering a single reactive component, a wide range of diversity can be achieved. 2 For these reasons, the development of new multicomponent reactions has broad implications in synthetic methodology, library production, and biological screening. 3Propellane systems, which belong to the wide group of tricyclic compounds with one of the C-C bonds shared by three rings (so called conjoining bond), have attracted attention as structures of chemical and synthetic interest, 4 and because of their presence in certain non-naturally and naturally occurring products 5 having many applications, including bioactive medicinal compounds 6 or polymers. 7 Among them, nitrogen-containing propellanes and analogues have attracted much attention due to their presence in biologically active natural products and pharmaceuticals such as the periglaucine A, sinoacutine and hasubanan alkaloids (Figure 1). 8The first propellanes were synthesized in the 1930s during investigations into the Diels-Alder reaction. 9 However, the first 'propellane by design' was synthesized much later, in 1965. 10,11 Since their discovery in 1965, these polycyclic structures have received attention by many research groups due to their extended use and challenging architecture. Significant research in the field of the synthesis of propellanes (about 100 papers) has been carried out by Ashkenazi and co-workers. 12 The synthesis of propellanes containing carbonyl groups is of great interest and the rearrangement of spiroketones 13 and Diels-Alder reactions 14 are used for their synthesis. In general, modern synthetic approaches to form carbocyclic or heterocyclic propellanes include [4+2] cycloadditions, 15 palladium 16 or manganese 17 catalysis, and nucleophilic substitutions of 1,1,2,2-tetrasubstituted alkenes. 18 The majority of these synthetic approaches to propellanes rely on the formation of a third ring on the framework of a fused bicyclic structure.Against this background, and also in the context of our investigations designed to develop the synthesis of biologically important N-fused polycyclic heterocycles via multicomponent reactions, 19 herein we report a chemo-/ regioselective approach to oxathiaaza[3.3.3]propellanes that can be achi...

Modification of magnetic mesoporous N-doped silica nanospheres by CuO NPs: a highly efficient catalyst for the multicomponent synthesis of some propellane indeno indole derivatives

“…Propellanes as annulated tricyclic systems with a common carbon–carbon covalent bond, have many applications in synthesis of bioactive medicinal compounds 1 or polymers. 2 These tricyclic systems are part of many natural products, such as modhephene 1, 3 canataxa 2 (ref. 4 ) and hasubanan alkaloids 3 (ref.…”

“…In 2012, Alizadeh and his co-workers have successfully reported the catalyst free synthesis of the heterocyclic [3.3.3] propellanes by the domino four-component reactions. 3 In 2013 Some of heterocyclic propellanes were prepared using Et 3 N in ethanol by Yan et al 14 Due to the limitations of homogeneous catalysts, heterogeneous catalysts were used to synthesis of propellane indeno indoles. In 2017, these compounds were prepared using CSB-Ni( ii ) as a heterogeneous catalyst 15 and in 2021, the hollow mesoporous boron nitride spheres decorated by CuO was successfully prepared and used as an efficient catalyst for the synthesis of [3.3.3] propellane indeno[1,2- b ] indole derivatives.…”

Design, synthesis, and DNA interaction studies of furo-imidazo[3.3.3]propellane derivatives: Potential anticancer agents

“…Several methods are reported for the synthesis of heterocylic [3.3.3]propellanes. Oxa-aza [3.3.3]propellanes were synthesized by Alizadeh et al [4,[22][23][24], Yavari et al [25], Chen et al [26] and Zhang et al [27]. Hassan et al reported the formation of oxaaza-and bisoxathia-aza [3.3.3]-propellanes via nucleophilic addition of symmetrical and unsymmetrical N 1 ,N 2 -disubstituted-1,2-dicarbothioamides on dicyanomethylene-1,3-indanedione 1 [28].…”

Synthesis of 5-amino-N′-(9H-fluoren-9-ylidene)-8-nitro-7-aryl-1,2,3,7-tetrahydroimidazo[1,2-a]pyridine-6-carbohydrazide derivatives based on heterocyclic ketene aminals

“…Some other novel synthetic approaches have been established in recent years for the synthesis of tetrahydroimidazo[1,2-a]pyridines by heterocyclic ketene aminals (HKAs). [25][26][27][28][29] Heterocyclic ketene aminals (HKAs) have been proven to be efficient synthons in the synthesis of heterocyclic systems. During the past few years, reactions of cyclic ketene aminals with a variety of biselectrophilic compounds have been applied to make veand six-membered fused heterocycles.…”