A versatile strategy for C7-selective boronation of tryptophans, tryptamines, and 3-alkylindoles by way of a single-pot C2/C7-diboronation–C2-protodeboronation sequence is described. The combination ...of a mild iridium-catalyzed C2/C7-diboronation followed by an in situ palladium-catalyzed C2-protodeboronation allows efficient entry to valuable C7-boroindoles that enable further C7-derivatization. The versatility of the chemistry is highlighted by the gram-scale synthesis of C7-boronated N-Boc-L-tryptophan methyl ester and the rapid synthesis of C7-halo, C7-hydroxy, and C7-aryl tryptophan derivatives.
A new tris(1-benzyl-1H-1,2,3-triazol-4-yl)methanol ligand 3 has been prepared by a triple Cu(I)-catalyzed alkyne−azide 1,3-dipolar cycloaddition (CuAAC). Ligand 3 forms a stable complex with CuCl, ...which catalyzes the Huisgen 1,3-dipolar cycloaddition on water or under neat conditions. Low catalyst loadings, short reaction times at room temperature, and compatibility with free amino groups make 3·CuCl an outstanding catalyst for CuAAC.
A polystyrene-linked tris(triazolyl)methanecopper(i) cationic catalyst operates under heterogeneous conditions for the reaction of ethyl diazoacetate (EDA) with an array of substrates. ...Carbon-hydrogen as well as X-H (X = O, N) functionalization derived from the formal transfer of the carbene moiety (:CHCO
Et) from the copper center and subsequent insertion have been achieved, the reactions permitting repeated catalyst recycling and reuse. The addition of the same carbene unit to benzene leading to a cycloheptatriene derivative (Büchner reaction) or to phenylacetylene (cyclopropenation) took place at similar rates to the insertion processes and with the same catalyst recyclability. The use of this heterogenized cationic Cu catalyst in continuous flow has also been implemented. Key characteristics of the flow process are its high and constant turnover frequency (TOF) (residence times of 1 min still lead to full conversion in the reaction with ethanol after 48 h operation) and its suitability for the sequential performance of different types of carbene transfer reactions with a simple and affordable experimental setup.
We demonstrate that a simple Co(III)-complex can efficiently catalyze the cleavage of unstrained C–C bonds via the β-carbon elimination of secondary and tertiary alcohols bearing a directing group. ...The cobalt-aryl intermediate generated under the reaction conditions can be trapped by different electrophiles to generate a new carbon–carbon bond. Some essential features of this new Co-based mechanistic manifold were revealed by preliminary mechanistic studies.
A catalytic pinacol‐type reductive rearrangement reaction of internal 1,2‐diols is reported herein. Several scaffolds not usually amenable to pinacol‐type reactions, such as aliphatic ...secondary–secondary diols, undergo the transformation well without the need for prefunctionalization. The reaction uses a simple boron catalyst and two silanes and proceeds through a concerted, stereoinvertive mechanism that enables the preparation of highly enantiomerically enriched products. Computational studies have been used to rationalize the preference for migration over direct deoxygenation.
Opportunities for insiders: A catalytic pinacol‐type reductive rearrangement of 1,2‐internal diols was developed by the use of a simple boron catalyst and two silanes (see scheme). The reaction occurs through a concerted, stereoinvertive mechanism and is applicable to several substrate scaffolds not usually amenable to pinacol‐type reactions, such as aliphatic secondary–secondary diols, without the need for prefunctionalization.
A polymer-supported bifunctional thiourea organocatalyst (PS-TU) has been prepared and successfully used in the enantioselective alpha -amination of 1,3-dicarbonyl compounds with azodicarboxylates. ...In contrast to homogeneous thioureas, PS-TU is not irreversibly deactivated by the azodicarboxylate reagents, and simple washing with triethylamine between runs has allowed the reuse (9 cycles) of the PS-TU catalyst. The alpha -amination mediated by PS-TU has also been adapted to perform the enantioselective amination (93% ee) of ethyl 2-oxocyclopentanecarboxylate in continuous flow (7.5 h operation, 21 min residence time, TON = 37).
A highly thermally stable saturated Pd–NHC acts only as a catalyst precursor in Mizoroki Heck catalysis to highly active Pd species when it is immobilized.
A saturated Pd-N-heterocyclic complex was ...immobilized on an amorphous silica. The complex itself is of very high thermal stability. However, TEM observations, hot filtration, reusability, and poisoning tests all revealed that the complex acted only as a precatalyst to highly active Pd species in Mizoroki–Heck reactions when immobilized. The complex appears more stable when used under homogeneous reaction conditions. The immobilized complex afforded high turnover numbers, 10
4–10
5. The higher turnover frequencies were realized at the lower Pd concentrations, which is a characteristic property of ligand-free Pd catalyzed reactions.
The preparation of a small library of modular tris(triazolyl)methane ligands for copper‐catalyzed azide–alkyne cycloaddition (CuAAC) reactions is reported. The synthesis of the first generation ...ligand, tris(1‐benzyl‐1H‐1,2,3‐triazol‐4‐yl)methanol (1a), suitable for work in aqueous systems, is reported at the 50–100 mmol scale through a one‐stage, environmentally benign procedure. One‐stage procedures for the synthesis of tris(aryltriazolyl)methanol structures (1b, phenyl; 1c, para‐trifluoromethylphenyl; 1d, para‐methoxyphenyl) designed for electronic fine‐tuning of catalytic properties, and of 1a‐derived ethers 2c (OBn) and 2d (OMe), designed for CuAAC reactions in organic solvents, are also reported. The complete set of ligands (1a–d, 2c–d) has been tested in the reaction of phenylacetylene with benzyl azide in six different solvents (water, hexane, toluene, dichloromethane, tetrahydrofuran, and acetonitrile), and this has allowed the identification of 1b, 1c and 2c as the ligands depicting the highest tolerance to changes in solvent polarity within the considered family. The comparative performance of ligands 1b–d and 2c in the cycloaddition of a small family of alkynes with benzyl azide in two very different reaction media (1:1 t‐BuOH/H2O and toluene) has been studied as a guide for catalyst selection in specific applications. The applicability of 1c in CuAAC reactions involving functional substrates in toluene has been explored under thermal and microwave‐accelerated (tandem azide formation plus CuAAC reaction) reaction conditions.
A polymer-supported bifunctional thiourea organocatalyst (
PS-TU
) has been prepared and successfully used in the enantioselective α-amination of 1,3-dicarbonyl compounds with azodicarboxylates. In ...contrast to homogeneous thioureas,
PS-TU
is not irreversibly deactivated by the azodicarboxylate reagents, and simple washing with triethylamine between runs has allowed the reuse (9 cycles) of the
PS-TU
catalyst. The α-amination mediated by
PS-TU
has also been adapted to perform the enantioselective amination (93% ee) of ethyl 2-oxocyclopentanecarboxylate in continuous flow (7.5 h operation, 21 min residence time, TON = 37).
A PS-immobilized thiourea catalyses the enantioselective α-amination of dicarbonyl compounds at room temperature. It is not deactivated by azodicarboxylate reagents, allowing multiple recycling in batch as well as use in flow (21 min residence time).
Tris(1-benzyl-1H-1,2,3-triazol-4-yl)methanol (3), a highly efficient ligand for CuAAC reactions, has been immobilized onto Merrifield resins through different strategies. The SN2-supported Cu complex ...(8) is stable in water and under air; it is active at low catalyst loadings (1 mol%) and at low concentration (down to 0.125 M) in both aqueous and purely organic media. Resin 8 can be repeatedly reused in 1 : 1 MeOH-water for short reaction times (4 h) with the only precaution of Cu(i) reloading every five cycles.
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