Asymmetric Fluorolactonization with a Bifunctional Hydroxyl Carboxylate Catalyst

Egami, Hiromichi; Asada, Junshi; Sato, Kentaro; Hashizume, Daisuke; Kawato, Yuji; Hamashima, Yoshitaka

doi:10.1021/jacs.5b06546

Cited by 105 publications

(46 citation statements)

References 34 publications

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“…4,5 In reported efforts directed toward enantioselective fluorolactonization reactions, electrophilic fluorinating reagents have been shown to afford γ-butyrolactone products with exocyclic fluoromethyl substituents in moderate-to-high enantioselectivity (Scheme 1, top). 6 We hypothesized that a hypervalent iodine catalysis of a nucleophilic fluorination pathway (“F − ”) could provide a complementary approach to regioisomeric fluorolactone products containing a C–F stereogenic center (Scheme 1, bottom), in a manner analogous to that observed in recently described enantioselective acetoxylactonization reactions. 7 Herein, we report the development of an enantioselective, catalytic fluorolactonization reaction for the preparation of 4-fluoroisochromanones in high enantio- and diastereoselectivity.…”

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confidence: 99%

Enantioselective, Catalytic Fluorolactonization Reactions with a Nucleophilic Fluoride Source

2016

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The enantioselective synthesis of 4-fluoroisochromanones via chiral aryl iodide-catalyzed fluorolactonization is reported. This methodology uses HF•pyridine as a nucleophilic fluoride source with a peracid stoichiometric oxidant, and provides access to lactones containing fluorine-bearing stereogenic centers in high enantio- and diastereoselectivity. The regioselectivity observed in these lactonization reactions is complementary to that obtained with established asymmetric electrophilic fluorination protocols.

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confidence: 99%

Enantioselective, Catalytic Fluorolactonization Reactions with a Nucleophilic Fluoride Source

2016

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“…To address this issue,w ed ecided to introduce two separate modifiers for b-protonation and afluorination, respectively.Acombination of quinuclidine and carboxylic acid should be the most promising.T oste and coworkers reported carboxylic/phosphoric acids accelerate fluorine transfer from Selectfluoro by phase-transfer catalysis. [15] In this scenario,aproper choice of carboxylic acids may also facilitate highly selective a-fluorination. Compared to other carboxylic acids,1 -adamantanecarboxylic acid (1-AdCO 2 H) quickly emerged as as uperior fluorination promotor for this transformation.…”

Section: Angewandte Chemiementioning

confidence: 99%

Enantio‐ and Diastereoselective Hydrofluorination of Enals by N‐Heterocyclic Carbene Catalysis

et al. 2019

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In contrast to well-established asymmetric hydrogenation reactions,e nantioselective protonation is an orthogonal approach for creating highly valuable methine chiral centers under redox-neutral conditions.R eported here is the highly enantio-and diastereoselective hydrofluorination of enals by an asymmetric b-protonation/a-fluorination cascade catalyzedb yN -heterocyclic carbenes (NHCs). The two nucleophilic sites of ah omoenolate intermediate,g enerated from enals and an NHC,a re sequentially protonated and fluorinated. The results show that controlling the relative rates of protonation, fluorination, and esterification is crucial for this transformation, and can be accomplished using ad ual shuttling strategy.S tructurally diverse carboxylic acid derivatives with two contiguous chiral centers are prepared in asingle step with excellent d.r.and ee values.There is much interest in the development of general synthetic strategies towards fluorine-containing compounds because of their broad applications of in pharmaceuticals and agrochemicals. [1] Direct, asymmetric hydrofluorination is particularly attractive given the abundance of common olefinic chemical feedstocks. [2] However,i ntroduction of two contiguous chiral centers,o ne of which bears af luorine,i n as ingle process is very challenging.A symmetric metal hydride addition to olefins followed by trapping of the corresponding organometallic species with af luorine source has been reported (Scheme 1A). [3] MacMillan et al. reported af ormal asymmetric addition of H À F + to electron-deficient olefins using iminium/enamine catalysis (Scheme 1B). [4] These approaches use reducing reagents for the hydride transfer and oxidative conditions for the fluorination, and proceeds in either as equential or stepwise manner. Herein, we report ac omplementary strategy of formal asymmetric addition of H + F + to enals by an enantioselective b-protonation/diastereoselective a-fluorination/esterification cascade (Scheme 1C). This redox neutral transformation demonstrates wide functional-group tolerance across various structural motifs.Recently,a symmetric protonation reactions catalyzed by N-heterocyclic carbenes (NHC) emerged as ageneral, redox-neutral strategy for the synthesis of b-chiral carboxy derivatives.I n2 015, Scheidt et al. reported asymmetric hydrogenation of b-ester enals,areaction which was later extended to b,b-aryl, alkyl enals by the same group. [5] In 2017, our group reported enantioselective hydrogenation of enals using bridgehead nitrogen amines as as elective proton-transfer agent. [6] Subsequently,w ed iscovered that the same transformation can be accomplished with ab roader substrate scope by using acombination of an achiral NHC and achiral phosphoric acid. [7] We recently applied this strategy to the synthesis of b-chiral amides,hydrazides,acid, esters,peresters, and heterocycles. [8] However,a ll asymmetric b-protonation reactions mentioned above are only applicable to products lacking an a-chiral center.W ee nvisioned that upon b-protonation of th...

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“…Organocatalytic halolactonizations have attracted much attention from the viewpoint of “green” chemistry. Therefore, a variety of organocatalysts has been developed, such as alkyl‐ or amino‐thiocarbamate, catalysts based on iodine, phosphite, substituted imidazoles, squaramides, peptides, and others (Scheme 2 Β) . However, most of them require cryogenic conditions that limit applications in industry.…”

Section: Introductionmentioning

confidence: 99%

Organocatalytic Synthesis of Lactones by the Oxidation of Alkenoic Acids

et al. 2017

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Along the lines of modern sustainable oxidation, a green and mild organocatalytic synthetic procedure for the synthesis of hydroxylactones from alkenoic acids is described. The reaction includes the activation of H2O2 by an organocatalyst (2,2,2‐trifluoromethylacetophenone), the oxidation of an olefinic group to the corresponding epoxide, and intramolecular lactonization to afford a variety of substituted γ‐ or δ‐lactones with multiple substitution patterns in good to high yields. The product can be obtained with high purity after simple extraction if the conversion is quantitative. Attempts to render the process asymmetric met with limited success.

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Asymmetric Fluorolactonization with a Bifunctional Hydroxyl Carboxylate Catalyst

Cited by 105 publications

References 34 publications

Enantioselective, Catalytic Fluorolactonization Reactions with a Nucleophilic Fluoride Source

Enantioselective, Catalytic Fluorolactonization Reactions with a Nucleophilic Fluoride Source

Enantio‐ and Diastereoselective Hydrofluorination of Enals by N‐Heterocyclic Carbene Catalysis

Organocatalytic Synthesis of Lactones by the Oxidation of Alkenoic Acids

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