Search

[This corrects the article DOI: 10.1039/D3SC04478E.].

We report the modular preparation of dihydro-1,2,5-thiodiazole dioxide heterocycles starting from methyl ketones and primary amines. This one-pot, three-component coupling employs 2,3-dimethylimidazole-1-sulfonyl azide triflate as a coupling reagent and oxidant. The transformation is scalable and various ketones and amines can be used, yielding thiodiazole dioxide products in up to 89% yield. In addition, 15N- and 13C-labeling studies suggest a mechanism involving a 1,2-nitrogen migration. Together with the mechanistic studies, DFT calculations provide insight into the reaction pathway and set the stage for further exploration of the mechanistic nuances of reactions that use sulfamoyl azides. In combination with the demonstrated modularity of the approach reported herein, the derivatization of the thiodiazole dioxide products highlights the potential of this methodology to rapidly access diverse chemical structures.

Azabicyclo[2.1.1]hexanes (aza-BCHs) and bicyclo[1.1.1]pentanes (BCPs) have emerged as attractive classes of sp3-rich cores for replacing flat, aromatic groups with metabolically resistant, three-dimensional frameworks in drug scaffolds. Strategies to directly convert, or "scaffold hop", between these bioisosteric subclasses through single-atom skeletal editing would enable efficient interpolation within this valuable chemical space. Herein, we describe a strategy to "scaffold hop" between aza-BCH and BCP cores through a nitrogen-deleting skeletal edit. Photochemical [2+2] cycloadditions, used to prepare multifunctionalized aza-BCH frameworks, are coupled with a subsequent deamination step to afford bridge-functionalized BCPs, for which few synthetic solutions currently exist. The modular sequence provides access to various privileged bridged bicycles of pharmaceutical relevance.

The hetisine-type natural products exhibit one of the most complex carbon skeletons within the diterpenoid alkaloid family. The use of network analysis has enabled a synthesis strategy to access alkaloids in this class with hydroxylation on the A-ring. Key transformations include a benzyne acyl-alkylation to construct a key fused 6-7-6 tricycle, a chemoselective nitrile reduction, and sequential C-N bond formations using a reductive cyclization and a photochemical hydroamination to construct an embedded azabicycle. Our strategy should enable access to myriad natural and unnatural products within the hetisine-type.

The secondary metabolites that comprise the diterpenoid alkaloids are categorized into C18, C19, and C20 families depending on the number of contiguous carbon atoms that constitute their central framework. Herein, we detail our efforts to prepare these molecules by chemical synthesis, including a photochemical approach, and ultimately a bioinspired strategy that has resulted in the development of a unifying synthesis of one C18 (weisaconitine D), one C19 (liljestrandinine), and three C20 (cochlearenine, paniculamine, and N-ethyl-1α-hydroxy-17-veratroyldictyzine) natural products from a common intermediate.

The denudatine-type diterpenoid alkaloids cochlearenine, N-ethyl-1α-hydroxy-17-veratroyldictyzine, and paniculamine have been synthesized for the first time (25, 26, and 26 steps from 16, respectively). These syntheses take advantage of a common intermediate (8) that we have previously employed in preparing aconitine-type natural products. The syntheses reported herein complete the realization of a unified strategy for the preparation of C20, C19, and C18 diterpenoid alkaloids.

Lewis acid catalyzed ring opening of 1,1-cyclopropanediesters by the hydroxyl group of a propargyl alcohol sets up a subsequent Conia-ene cyclization to produce substituted tetrahydropyrans in a one-pot, high-yielding procedure.

The preparation of the ferrocene-based reagents FcSSiMe3 ( 1) and fc(SSiMe3)2 ( 2) [Fc = (η5-C5H5)Fe(η5-C5H4)-; fc = Fe(η5-C5H4)2-] is reported together with their use in the formation of the tetrahedral zinc complexes [( N, N′-tmeda)Zn(SFc)2] ( 3a) and [( N, N′-tmeda)Zn(S2fc)] ( 4a), respectively (tmeda = tetramethylethylenediamine). The structures of these coordination complexes are compared to the new ferroceneselenolates [( N, N′-tmeda)Zn(SeFc)2] ( 3b) and [( N, N′-tmeda)Zn(Se2fc)] ( 4b), themselves prepared using FcSeSiMe3 and fc(SeSiMe3)2, respectively. The synthesis and characterization of dimeric [Cd2(µ-EFc)2(EFc)2(PPr3)2] ( 5a, E = S; 5b, E = Se) are also described. [ABSTRACT FROM AUTHOR]

The secondary metabolites that comprise the diterpenoid alkaloids are categorized into C 18 , C 19 , and C 20 families depending on the number of contiguous carbon atoms that constitute their central framework. Herein, we detail our efforts to prepare these molecules by chemical synthesis, including a photochemical approach, and ultimately a bioinspired strategy that has resulted in the development of a unifying synthesis of one C 18 (weisaconitine D), one C 19 (liljestrandinine), and three C 20 (cochlearenine, paniculamine, and N-ethyl-1α-hydroxy-17-veratroyldictyzine) natural products from a common intermediate.

A Zn(NTf(2))(2) catalyzed tandem reaction consisting of a nucelophilic ring opening of 1,1-cyclopropanediesters by 2-alkynyl indoles followed by a Conia-ene ring closure results in the efficient one-step synthesis of tetrahydrocarbazoles. The adducts may be further elaborated to carbazoles.

The first total syntheses of clausamines A-C and clausevatine D are reported. The key step involves a Diels-Alder reaction between an imine quinone and cyclic diene, allowing for the subsequent construction of the carbazole core in a regiospecific manner. Stereochemistry of the natural products is also discussed.

The Diels-Alder reaction between a quinone monoimine and cyclic diene allows for the construction of substituted carbazoles in a regiospecific manner. This methodology has sucessfully been employed in a divergent strategy, culminating in the synthesis of eustifolines A-D and glycomaurrol.