Diastereoselective Synthesis Research Articles

Diastereoselective dearomatization of indoles via photocatalytic hydroboration on hydramine-functionalized carbon nitride.

A protocol for trans-hydroboration of indole derivatives using heterogeneous photocatalysis with NHC-borane has been developed, addressing a persistent challenge in organic synthesis. The protocol, leveraging high crystalline vacancy-engineered polymeric carbon nitride as a catalyst, enables diastereoselective synthesis, expanding substrate scope and complementing existing methods. The approach emphasizes eco-friendliness, cost-effectiveness, and scalability, making it suitable for industrial applications, particularly in renewable energy contexts. The catalyst's superior performance, attributed to its rich carbon-vacancies and well-ordered structure, surpasses more expensive homogeneous alternatives, enhancing viability for large-scale use. This innovation holds promise for synthesizing bioactive compounds and materials relevant to medicinal chemistry and beyond.

Synthesis of Stereodefined Polysubstituted Bicyclo[1.1.0]butanes.

We report a highly diastereoselective synthesis of polysubstituted bicyclobutanes possessing up to three stereodefined quaternary centers and five substituents. Our strategy involves a diastereoselective carbometalation of cyclopropenes followed by a cyclization to furnish the bicyclobutane ring system. This straightforward approach allows for the incorporation of a diverse range of substituents and functional groups, notably without the need for electron-withdrawing functionalities.

One-pot formation of six bonds: pseudo-six-component diastereoselective synthesis of pyridinium-containing piperidin-2-ones

One-pot formation of six bonds: pseudo-six-component diastereoselective synthesis of pyridinium-containing piperidin-2-ones

Photocatalytic Bicyclization of Indole-Tethered 1,6-Enynes for Diastereoselective Synthesis of Pyrrolo[3,2,1-jk]carbazoles.

A visible-light-driven photocatalytic protocol is established for the diastereoselective synthesis of pyrrolo[3,2,1-jk]carbazoles via a radical-triggered multicomponent bicyclization reaction starting from readily available indole-tethered 1,6-enynes and α-benzyl-α-bromomalonates under mild conditions. This photocatalytic approach exhibits a wide substrate compatibility and excellent tolerability toward various functional groups and boasts the benefit of efficient ring formation and chemical bond creation.

Diastereoselective Synthesis of High Functionalized 4‐Imidazolidinone‐Tetrahydro‐β‐Carboline Hybrids via Divergent Post‐Ugi Transformation

AbstractAn easily scalable and highly diastereoselective synthesis of challenging 1,2,5,6,11,11b‐hexahydro‐3H‐imidazo[1′,2′:1,2]pyrido[3,4‐b]indol‐3‐ones is accomplished through divergent transformation of Ugi 4‐CR products. The trimethylsilyl trifluoromethanesulfonate (TMSOTf) mediated intramolecular condensation of a series of Ugi 4‐CR adducts generates a N‐acylimidinium intermediate which undergoes ring closure to selectively afford the target title compounds in good to high yields.

Transition Metal‐Free Diastereoselective Synthesis of β‐Carboline Tethered Dihydrofurocoumarin Derivatives

AbstractOne‐pot procedure has been developed for the synthesis of novel β‐carboline tethered trans 2,3‐furocoumarins via assembling 1‐formyl‐β‐carbolines, 4‐hydroxycoumarins, and phenacyl bromides in pyridine under transition metal‐free conditions. The strategy was also found applicable to gram scale synthesis and a library of 40 molecules has been developed. The significant features of this operationally facile approach includes high efficiency, short reaction time, excellent yields, multicomponent character of the reaction, metal‐free mild reaction conditions, and a column chromatography free purification procedure.

Visible-light-mediated synthesis, NMR analysis and X-ray crystal structure of dihydrocyclobuta[b]naphthalene-3,8-diones

An efficient, concise, and green visible-light-mediated [2 + 2] cycloaddition reaction for the diastereoselective synthesis of dihydrocyclobuta[b]naphthalene-3,8-diones starting from readily available 1,4-naphthoquinones and alkynes under mild and clean conditions without using any photocatalysts is reported. The products could be obtained under blue LED (460 nm) irradiation at ambient temperature in 4 h with perfect regioselectivity and remarkable functional group tolerance. To discuss the special patterns of cyclobutene protons, to identify its cis-conformation, NMR spectra analysis (1D-NMR and 2D-NMR) was conducted in details by the chemical shifts, couplings and correlations. X-Ray Diffraction of 3ak confirmed its cis-conformation, and all the compounds were unequivocally confirmed by NMR, HRMS and XRD analysis. XRD analysis of 3ak further aids to disclose the reason why the cyclobutene and benzene rings are almost in the same plane.

Regio- and Diastereoselective Synthesis of E-Allylic Amines through Hydroalkylation of Terminal Alkynes

Regio- and Diastereoselective Synthesis of <i>E</i>-Allylic Amines through Hydroalkylation of Terminal Alkynes

Diastereoselective Synthesis of NH-Unprotected Spiropyrrolidines via the Huisgen Reaction of Acenaphthoquinone-Derived Azomethine Ylides with β-Nitrostyrenes

Abstract4′-Nitro-2H-spiro[acenaphthylene-1,2′-pyrrolidine]-2-one derivatives are prepared via [3+2] cycloaddition reactions of azomethine ylides, generated in situ from acenaphthoquinone and primary amines, with β-nitrostyrenes in the presence of ( i Pr)2NEt in methanol. Evidence for the structures of the products was obtained from single-crystal X-ray analysis. The important feature of this diastereoselective synthesis of NH-unprotected spiropyrrolidines is the formation of four contiguous stereogenic centers, one of which is quaternary, with high selectivity.

Natural product inspired diastereoselective synthesis of sugar-derived pyrano[3,2-c]quinolones and their in-silico studies

Herein, we report the development of a diastereoselective and efficient route to construct sugar-derived pyrano[3,2-c]quinolones utilizing 1-C-formyl glycal and 4-hydroxy quinolone annulation. This methodology will open a route to synthesize nature inspired pyrano[3,2-c]quinolones. This is the first report for the stereoselective synthesis of sugar-derived pyrano[3,2-c]quinolones, where 100% stereoselectivity was observed. A total of sixteen compounds have been synthesized in excellent yields with 100% stereoselectivity. The molecular docking of the synthesized novel natural product analogues demonstrated their binding modes within the active site of type II topoisomerase. The results of the in-silico studies displayed more negative binding energies for the all the synthesized compounds in comparison to the natural product huajiosimuline A, indicating their affinity for the active pocket. Ten out of the sixteen novel synthesized compounds were found to have comparative or relatively more negative binding energy in comparison to the standard anti-cancer drug, doxorubicin. Additionally, the scalability and viability of this protocol was illustrated by the gram scale synthesis.

Diastereoselective Synthesis of Dihydrobenzofuran Spirooxindoles and Their Transformation into Benzofuroquinolinones by Ring Expansion of Oxindole Core.

A mild and efficient approach for the diastereoselective synthesis of dihydrobenzofuran spirooxindoles using 3-chlorooxindoles and imines is presented. This process involves a formal [4 + 1] annulation, yielding the product with excellent diastereoselectivity. Furthermore, a novel method for constructing benzofuroquinolinone scaffolds through the ring expansion of oxindoles has been established. This method involves a lactam ring expansion to the quinolinone skeleton. Besides, a one-pot procedure for creating benzofuroquinolinone scaffolds from 3-chlorooxindoles and imines is also provided.

Synthesis of Borylated Carbocycles by [2 + 2]-Cycloadditions and Photo-Ene Reactions.

Saturated bicyclic compounds make up a valuable class of building blocks in the development of agrochemicals and pharmaceuticals. Here, we present the synthesis of borylated bicyclo[2.1.1]hexanes via crossed [2 + 2]-cycloaddition. Due to the presence of the C-B bond, a variety of structures can be easily prepared that are not accessible by other methods. Moreover, a rare photo-ene reaction is also disclosed, allowing for the diastereoselective synthesis of trisubstituted borylated cyclopentanes.

Synthesis of stereo-enriched bis glyco-cyclohexylamines by a one pot dual Petasis reaction

A one pot dual Petasis reaction of sugars, styrene boronic acid and cis/trans 1,2-cyclohexyldiamines was done for the diastereoselective synthesis of bis glyco-cyclohexylamines, which have multiple stereogenic centres and coordinating heteroatoms. The products were isolated and characterized by HMBC, HSQC, 1H, 13C NMR experiments, and X-ray single crystallographic analysis. A plausible mechanism for the dual Petasis reaction was proposed that involves hydroxyl directed borylation for the anti-diastereoselectivity along with N,N'-chelate tetracoordinated organoboron complex assisted syn-diastereoselectivity based on the experimental findings.

Stereocontrolled Synthesis of Phosphoproline Analogues Containing a trans-Fused Octahydroindole Bicyclic System.

Herein we report for the first time the diastereoselective synthesis of (2R,3aR,7aS)- and (2S,3aS,7aR)-octahydroindole-2-phosphonic acid (OicP trans-fused stereoisomers) from diethyl (R)- and (S)-phosphopyroglutamate derivative. The key steps of this procedure are the ruthenium tetroxide oxidation of enantiomerically pure diethyl (R)- and (S)-phosphoprolinate obtained through Katritzky's benzotriazole-oxazolidine methodology, a highly diastereoselective successive double 4,5-diallylation of diethyl (R)- and (S)-phosphopyroglutamate with allyl bromide and allyltrimethylsilane with a trans-addition mode, and a ring-closing metathesis with Grubbs' first-generation ruthenium catalyst.

B(C6F5)3-Catalyzed Diastereoselective Synthesis of Carbocyclic β-Amino Acid (CBAA) Derivatives

B(C6F5)3-Catalyzed Diastereoselective Synthesis of Carbocyclic β-Amino Acid (CBAA) Derivatives

Brønsted Acid-Catalyzed Diastereoselective Synthesis of Spiroisoindolinones from Enamides.

A highly diastereoselective synthesis of spiroisoindolinones from enamides and 3-hydroxy-isoindolinones is reported. The reaction proceeds rapidly in the presence of p-toluenesulfonic acid as a Brønsted acid catalyst and affords a variety of densely substituted spiroisoindolinones with three contiguous stereogenic centers in high yields (≤98%) and diastereoselectivities (up to dr >98:<2:0:0).

CAN Interceded Oxidative Coupling of β‐Dicarbonyl Compounds to 2‐Aryl/Heteroarylchromenes: A Regio‐ and Diastereoselective Synthesis of Tetrahydro‐benzofuro[3,2‐c]chromenones

AbstractA promising and useful method has been accomplished for regio‐ and diastereoselective synthesis of tetrahydro‐benzofuro[3,2‐c]chromenones through ceric(IV) ammonium nitrate (CAN) mediated oxidative coupling of cyclic/acyclic 1,3‐dicarbonyl compounds to 2‐aryl/heteroarylchromenes followed by a base assisted cyclization. The significant features of the method encircle easy accessibility of the starting materials, high air stability and low toxicity of oxidant CAN, high product yield, operationally simple and eco‐friendly reaction conditions. Trapping of a radical intermediate with radical scavenger TEMPO (detected by LC–MS) from the reaction mixture proved that the oxidative coupling is a radical mediated process.

Highly Regio- and Diastereoselective Synthesis of 6,7-Dihydro-4H-furo[3,4-c]pyran Derivatives through Pd-Catalyzed Formal (3 + 3) Allylic Cycloaddition of 2-Butene-1,4-diols with 2-(1-Alkynyl)-2-alken-1-ones.

A highly efficient synthesis of 7-vinyl-6,7-dihydro-4H-furo[3,4-c]pyran derivatives from 2-butene-1,4-diols and 2-(1-alkynyl)-2-alken-1-ones has been achieved with high regio- and diastereoselectivity (dr > 20:1) by Pd-catalyzed tandem heterocyclization/cross-coupling. The π-allyl palladium species Int II generated from 2-butene-1,4-diol by direct cleavage of the C-OH bond is the key to the success in this formal (3 + 3) cycloaddition reaction.

Accessing Rare α-Heterocyclic Aziridines via Brønsted Acid-catalyzed Michael Addition/Annulation: Scope, Limitations, and Mechanism.

We report an approach to the diastereoselective synthesis of 1,2-disubstituted heterocyclic aziridines. A Brønsted acid-catalyzed conjugate addition of anilines to trisubstituted heterocyclic chloroalkenes provides an intermediate 1,2-chloroamine. Diastereocontrol was found to vary significantly with solvent selection, with computational modelling confirming selective, spontaneous fragmentation in the presence of trace acids, proceeding through a pseudo-cyclic, protonated intermediate and transition state. These chloroamines can then be converted to the aziridine by treatment with LiHMDS with high stereochemical fidelity. This solvent-induced stereochemical enrichment thereby enables an efficient route to rare cis-aziridines with high dr. The scope, limitations, and mechanistic origins of selectivity are also presented.

Diastereoselective ZnCl2-Mediated Joullié-Ugi Three-Component Reaction for the Preparation of Phosphorylated N-Acylaziridines from 2H-Azirines.

We disclose a direct approach to the diastereoselective synthesis of phosphorus substituted N-acylaziridines based on a one-pot ZnCl2-catalyzed Joullié-Ugi three-component reaction of phosphorylated 2H-azirines, carboxylic acids and isocyanides. Hence, this robust protocol offers rapid access to an array of N-acylaziridines in moderate-to-good yields and up to 98:2 dr for substrates over a wide scope. The relevance of this synthetic methodology was achieved via a gram-scale reaction and the further derivatization of the nitrogen-containing three-membered heterocycle. The diastereo- and regioselective ring expansion of the obtained N-acylaziridines to oxazole derivatives was accomplished in the presence of BF3·OEt2 as an efficient Lewid acid catalyst.