A set of six solid-supported diarylprolinol catalysts (varying on the anchoring strategy and the type of polymeric support) has been prepared and applied to the enantioselective cyclopropanation reaction. The selected candidate allows implementation of a long flow experiment (48 h) and generates a library of 12 cyclopropanes by sequential flow experiments. The mildness and utility of the method have enabled a telescoped process in which the outstream is directly used in a Wittig flow reaction.
The preparation of a small library of modular tris(triazolyl)methane ligands for coppercatalyzed 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 onestage, 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/ H 2 O 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.
UPDATESErhan Ozkal et al.
Scheme 2.Optimized procedure for the large-scale production of 1a.Scheme 3. Etherification of 1a leading to 2c, 2d.
The importance of discovering the true catalytically active species involved in photocatalytic systems allows for a better and more general understanding of photocatalytic processes, which eventually may help to improve their efficiency. Bi2O3 has been used as a heterogeneous photocatalyst and is able to catalyze several synthetically important visible-light-driven organic transformations. However, insight into the operative catalyst involved in the photocatalytic process is hitherto missing. Herein, we show through a combination of theoretical and experimental studies that the perceived heterogeneous photocatalysis with Bi2O3 in the presence of alkyl bromides involves a homogeneous BinBrm species, which is the true photocatalyst operative in the reaction. Hence, Bi2O3 can be regarded as a precatalyst which is slowly converted in an active homogeneous photocatalyst. This work can also be of importance to mechanistic studies involving other semiconductor-based photocatalytic processes.
SummaryThe application of polystyrene-immobilized proline-based catalysts in packed-bed reactors for the continuous-flow, direct, enantioselective α-aminoxylation of aldehydes is described. The system allows the easy preparation of a series of β-aminoxy alcohols (after a reductive workup) with excellent optical purity and with an effective catalyst loading of ca. 2.5% (four-fold reduction compared to the batch process) working at residence times of ca. 5 min.
The
two-step flow asymmetric synthesis of chiral γ-nitrobutyric
acids as key intermediates of the GABA analogues baclofen, phenibut,
and fluorophenibut is reported on a multigram scale. The telescoped
process comprises an enantioselective Michael-type addition facilitated
by a polystyrene-supported heterogeneous organocatalyst under neat
conditions followed by
in situ
-generated performic
acid-mediated aldehyde oxidation. Simple access to valuable optically
active substances is provided with key advances in terms of productivity
and sustainability compared to those of previous batch approaches.
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