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

Wang, Leming; Jiang, Xiaomo; Chen, Jiean; Huang, Yong

doi:10.1002/anie.201902989

Cited by 25 publications

(15 citation statements)

References 55 publications

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“…Another hydrofluorination reaction, that was developed by Huang and coworkers uses NHC as a catalyst to perform the reaction [22] . This method enables the hydrofluorination and oxidation of α,β‐unsaturated aldehydes to α fluoro ester (Scheme 13).…”

Section: Electrophilic Hydrofluorinationmentioning

confidence: 99%

Hydrofluorination of Alkenes: A Review

Bertrand

Chabaud

Paquin

2021

Chemistry An Asian Journal

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In this minireview, we explore the different approaches used to perform the hydrofluorination reaction of alkenes. Contrary to other hydrohalogenation reactions, the hydrofluorination requires specific conditions due to the lower reactivity of HF. Over the years, many different approaches have been explored among which the use of HF complexes has particularly proved to be useful as these reagents are easier to handle. The enantioselective hydrofluorination has been demonstrated using electrophilic sources of fluorine, while radical fluorination proved compatible with a vast range of functional groups that are generally problematic with strong acids and some fluoride sources. This review will cover the different conditions developed through the years, starting with the first reported addition using gaseous HF, up to the most recent method described in October 2020.

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Section: Electrophilic Hydrofluorinationmentioning

confidence: 99%

Hydrofluorination of Alkenes: A Review

Bertrand

Chabaud

Paquin

2021

Chemistry An Asian Journal

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“…[71c] Because simple α-fluorinations utilizing MacMillan's method or Jørgensen's procedure are lacking novelty, this chapter focuses on reaction cascades utilizing these methods [64][65][66][67][68][69][70]79] and alternative systems for aldehyde fluorination instead. [73][74][75][76][77][78][80][81][82] Brenner-Moyer and coworkers reported a one-pot α-chlorination/α-fluorination cascade. The first step (α-chlorination) is catalyzed by L-proline, while the second step (enantioselective α-fluorination) utilizes Jørgensen catalyst (S)-CAT6.…”

Section: Fluorination Of Aldehydesmentioning

confidence: 99%

“…[79] NHC-catalyzed hydrofluorination of enals results in αfluoroesters due to oxidation of the aldehyde group during the reaction. [80] NHCs can also catalyze the asymmetric transformation of γ-aryl enals with a leaving group in γ-position into αfluorinated β,γ-unsaturated esters. In the latter case, sole NHC catalysis yields substrates with E geometry, [81] but combining NHC catalysis and photocatalysis provides the diastereomeric product with Z geometry (Scheme 42 shows the catalytic cycle).…”

Section: Fluorination Of Aldehydesmentioning

confidence: 99%

“…However, fluorination of α‐branched aldehydes with these methods is rarely efficient [71c] . Because simple α‐fluorinations utilizing MacMillan's method or Jørgensen's procedure are lacking novelty, this chapter focuses on reaction cascades utilizing these methods [64–70,79] and alternative systems for aldehyde fluorination instead [73–78,80–82] …”

Section: Asymmetric C−f Bond‐forming Reactions Using Organocatalysismentioning

confidence: 99%

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Asymmetric Methods for Carbon‐Fluorine Bond Formation

et al. 2021

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In memory of Ferenc FülöpAs a consequence of the ever-increasing relevance of fluorinated drugs in medicinal chemistry, organofluorine chemistry has become a hot topic research area during the last decade. Asymmetric carbon-fluorine bond-forming reactions have enormously developed in recent years with considerable findings related to novel reactions and synthetic approaches. These new synthetic efforts have contributed to the access to a growing number of fluorinated molecules and complex natural or synthetic products of high relevance in medicinal chemistry and drug research. Illustrative examples of novel synthetic methodologies, including organocatalytic processes, asymmetric syntheses or phase-transfer catalytic methods for the enantioselective incorporation of fluorine atom(s) into versatile molecular entities, are covered in the current Review, focusing on main contributions of the last ten years.

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“…Thermal ellipsoids for ORTEP structure shown at 50 %p robability. [16] Table 3: Scope with respect to the b-alkyl enals in the enantioselective hydrofluorination.…”

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

Cited by 25 publications

References 55 publications

Hydrofluorination of Alkenes: A Review

Hydrofluorination of Alkenes: A Review

Asymmetric Methods for Carbon‐Fluorine Bond Formation

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

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