The Applications of Catalytic Asymmetric Halocyclization in Natural Product Synthesis
TL;DR: A review of the applications of catalytic asymmetric halocyclization in natural product synthesis can be found in this paper, with a focus on the use of halonium-induced nucleophilic addition as a practical strategy for constructing cyclic skeletons.
Abstract: Halocyclization of olefinic substrate enables establishment of cyclic skeletons via intramolecular halonium-induced nucleophilic addition, which have been well utilized as a practical strategy for constructing cyclic skeleton in natural product synthesis. Recently, the renaissance and rapid evolution of organocatalysis accelerate the development of catalytic asymmetric halocyclization. In this context, natural product synthesis powered by catalytic asymmetric halocyclization has also received considerable progresses in recent years. In seom cases, these newly developed protocols enable more concise synthetic routes for accessing enantioenriched natural products. To this end, this review summarized the applications of catalytic asymmetric halocyclization in natural product synthesis.
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19 Oct 2022
TL;DR: In this article , a review of the advances in preparing functionalized heterocycles promoted by chiral organocatalysts or metal-based catalysts is presented. But this review is limited to halogen and chalcogen electrophiles.
Abstract: Halogen (fluorine, chlorine, bromine, iodine) or chalcogen (sulfur, seleno)-containing heterocycles are widely recognized as key building blocks in many natural products and bioactive targets. Catalytic asymmetric halogenation/chalcogenation of carbon-carbon unsaturated bonds via onium ion transformations are efficient methods to obtain diverse chiral heterocyclic backbones. In the past few years, catalytic enantioselective versions of halo/thio/seleno-functionalizations with various halogen and chalcogen electrophiles have experienced constant development. This review highlights those advances in preparing functionalized heterocycles promoted by chiral organocatalysts or metal-based catalysts.
7 citations
TL;DR: It is reported that an efficient Lewis basic chiral sulfide-catalyzed approach enables electrophilic iodinative difunctionalization of alkenes to give a variety of iodine-functionalized chiral molecules in good yields with excellent enantio- and diastereoselectivities.
Abstract: Electrophilic halogenation of alkenes is a powerful transformation offering a convenient route for the construction of valuable functionalized molecules. However, as a highly important reaction in this field, catalytic asymmetric intermolecular iodinative difunctionalization remains a formidable challenge. Herein, we report that an efficient Lewis basic chiral sulfide-catalyzed approach enables this reaction. By this approach, challenging substrates such as γ,γ-disubstituted allylic sulfonamides and 1,1-disubstituted alkenes with an allylic sulfonamide unit undergo electrophilic iodinative difunctionalization to give a variety of iodine-functionalized chiral molecules in good yields with excellent enantio- and diastereoselectivities. A series of free phenols as nucleophiles are successfully incorporated into the substrates. Aside from phenols, primary and secondary alcohols, fluoride, and azide also serve as efficient nucleophiles. The obtained iodinated products are a good platform molecule, which can be easily transformed into various chiral compounds such as α-aryl ketones, chiral secondary amines, and aziridines via rearrangement or substitution. Mechanistic studies revealed that the chiral sulfide catalyst displays a superior effect on control of the reactivity of electrophilic iodine and the enantioselective construction of the chiral iodiranium ion intermediate and catalyst aggregates might be formed as a resting state in the reactions.
7 citations
TL;DR: In this paper , the role of various catalysts, such as from metal-catalysts to organocatalysts, under different conditions to synthesize various halocyclized products is discussed.
5 citations
TL;DR: In this article , a phase-transfer catalyst and a chiral phosphate catalyst were combined for asymmetric bromocyclization in an electrochemical medium with NaBr as the bromine source.
Abstract: Electricity-driven asymmetric catalysis is an emerging powerful tool in organic synthesis. However, asymmetric induction so far has mainly relied on forming strong bonds with a chiral catalyst. Asymmetry induced by weak interactions with a chiral catalyst in an electrochemical medium remains challenging due to compatibility issues related to solvent polarity, electrolyte interference, etc. Enabled by a properly designed phase-transfer strategy, here we have achieved two efficient electricity-driven catalytic asymmetric bromocyclization processes induced by weak ion-pairing interaction. The combined use of a phase-transfer catalyst and a chiral phosphate catalyst, together with NaBr as the bromine source, constitutes the key advantages over the conventional chemical oxidation approach. Synergy over multiple events, including anodic oxidation, ion exchange, phase transfer, asymmetric bromination, and inhibition of Br2 decomposition by NaHCO3, proved critical to the success.
2 citations
TL;DR: In this paper , two approaches to resolve the inhibition were presented, enabling the (DHQD)2PHAL loading to be dropped from 10 to 1 mol % while maintaining high bromoester conversions in 8 h or less.
Abstract: Kinetic profiling has shown that a (DHQD)2PHAL-catalyzed intermolecular asymmetric alkene bromoesterification reaction is inhibited by primary amides, imides, hydantoins, and secondary cyclic amides, which are byproducts of common stoichiometric bromenium ion sources. Two approaches to resolving the inhibition are presented, enabling the (DHQD)2PHAL loading to be dropped from 10 to 1 mol % while maintaining high bromoester conversions in 8 h or less. Iterative post-reaction recrystallizations enabled a homochiral bromonaphthoate ester to be synthesized using only 1 mol % (DHQD)2PHAL.
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TL;DR: My opinion on why the field of organocatalysis has blossomed so dramatically over the past decade is presented.
Abstract: The use of small organic molecules as catalysts has been known for more than a century. But only in the past decade has organocatalysis become a thriving area of general concepts and widely applicable asymmetric reactions. Here I present my opinion on why the field of organocatalysis has blossomed so dramatically over the past decade.
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