A combination of directing groups and chiral anion phase-transfer catalysis for enantioselective fluorination of alkenes

Wu, Jeffrey C.S.; Wang, Yiming; Drljevic, Amela; Rauniyar, Vivek; Phipps, Robert J.; Toste, F. Dean

doi:10.1073/pnas.1304346110

Cited by 113 publications

(45 citation statements)

References 42 publications

(41 reference statements)

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“…As a consequence of the demonstrated success of the benzamide group in CAPT catalysis,1h–k our efforts began with the readily prepared tryptamine derivative 4 (Table 1). We were pleased to find that exposure of tryptamine 4 to 3 equivalents of Na 3 PO 4 , 1 equivalent of phenyldiazonium tetrafluoroborate, and 5 mol % of ( S )‐TCyP ( 6 ) in hexane provided the desired pyrroloindoline 5 with good conversion and moderate enantioselectivity (35 % ee ; Table 1, entry 1).…”

Section: Methodsmentioning

confidence: 99%

Chiral Anion Phase Transfer of Aryldiazonium Cations: An Enantioselective Synthesis of C3‐Diazenated Pyrroloindolines

et al. 2014

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Herein is reported the first asymmetric utilization of aryldiazonium cations as a source of electrophilic nitrogen. This is achieved through a chiral anion phase-transfer pyrroloindolinization reaction that forms C3-diazenated pyrroloindolines from simple tryptamines and aryldiazonium tetrafluoroborates. The title compounds are obtained in up to 99% yield and 96% ee. The air-and water-tolerant reaction conditions accommodate electronic and steric diversity of the aryldiazonium electrophile and of the tryptamine core. Keywordsphase-transfer catalysis; cyclization; asymmetric catalysis; photolysis; amination Chiral anion phase-transfer (CAPT) catalysis has recently arisen as an effective strategy in enantioselective catalysis (Figure 1a). [1] In particular, electrophilic halo-functionalization reactions of alkenes using Selectfluor (Figure 1b) and its derivatives have proven broadly effective, delivering a wide scope of valuable halogenated products in high yields and excellent enantioselectivities. [1f-m] Inspired by the substrate generality exhibited by CAPT halo-functionalization and other oxidative reactions, [1n-o] it has been a long-standing goal in our group to identify additional cationic electrophiles amenable to this strategy (Figure 1b).We were specifically interested in cations comprised of electrophilic nitrogen atoms, as asymmetric electrophilic C-N bond formation remains a synthetic challenge. [2] Aryldiazonium salts were recognized as candidates, as their N-electrophilicity has been exploited to diazenate several classes of carbon nucleophiles in a non-stereoselective fashion, including aromatics, [3] enolates, [4] and heteroaromatics. [5] Reports of GombergBachmann-Hey biaryl syntheses [3b] and azo-coupling reactions [3a,c] that utilize aryldiazoniums under phase-transfer conditions further encouraged our efforts in this area. ** We gratefully acknowledge NIHGMS (R01 GM104534) for financial support. H.M.N. would like to acknowledge the UNCF and Merck for generous funding. S.H.R. would like to acknowledge the Amgen Foundation for generous funding. The authors would like to thank Pascal Tripet for useful discussions.

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Section: Methodsmentioning

confidence: 99%

Chiral Anion Phase Transfer of Aryldiazonium Cations: An Enantioselective Synthesis of C3‐Diazenated Pyrroloindolines

et al. 2014

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“…[71] Related halogenation of enamides and alkenes without the addition of nucleophiles were also reported by Toste and co-workers. [72] Most of the alkenes involved in the intermolecular halofunctionalization have special functional groups, such as an allylic OH, allylic NH, or vinylic NH groups. Highly enantioselective halofunctionalization of nonfunctionalized alkenes has not been achieved and is obviously the next step, in addition to expanding the scope of nucleophiles.…”

Section: Intermolecular Halofunctionalization Of Alkenesmentioning

confidence: 99%

Cinchona Alkaloids as Organocatalysts in Enantioselective Halofunctionalization of Alkenes and Alkynes

et al. 2014

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Naturally occurring cinchona alkaloids include quinine, quinidine, cinchonine, and cinchonidine. Many of their derivatives are also readily available. This Focus Review summarizes recent applications of cinchona alkaloid derivatives, an important class of organocatalysts, in enantioselective halofunctionalization of alkenes and alkynes. Most successful examples in this area are intramolecular halofunctionalizations, where the nucleophile is tethered with the alkene or alkyne substrate. Only a few catalytic enantioselective intermolecular halofunctionalization of alkenes have been realized. Dimeric cinchona alkaloids are the most frequently used catalysts in asymmetric halofunctionalizations. Most other catalysts have an appended functional group on the C9 position of the cinchona alkaloids. These functional groups include (thio)urea, thiocarbamate, and sulfonamides.

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“…Asymmetric electrophilic reactions have been realized in which the electrophile is associated with a chiral anion responsible for the phase transfer catalyzed process (chiral anion phase-transfer (CAPT) catalysis) [305][306][307]. An example is given with the enantioselective electrophilic fluorination of alkenes developed by Toste and co-workers (Scheme 44) [308,309]. Chiral anion transfer of arenediazonium cations has permitted the enantioselective synthesis of C(3)-diazenated pyrroloindolines in a similar way [310].…”

Section: Asymmetric Ion-pairing Catalysismentioning

confidence: 99%

“…Catalysts 2016, 6, 128 32 of 62 [308,309]. Chiral anion transfer of arenediazonium cations has permitted the enantioselective synthesis of C(3)-diazenated pyrroloindolines in a similar way [310].…”

Section: Asymmetric Ion-pairing Catalysismentioning

confidence: 99%

Organocatalysis: Fundamentals and Comparisons to Metal and Enzyme Catalysis

et al. 2016

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Catalysis fulfills the promise that high-yielding chemical transformations will require little energy and produce no toxic waste. This message is carried by the study of the evolution of molecular catalysis of some of the most important reactions in organic chemistry. After reviewing the conceptual underpinnings of catalysis, we discuss the applications of different catalysts according to the mechanism of the reactions that they catalyze, including acyl group transfers, nucleophilic additions and substitutions, and C-C bond forming reactions that employ umpolung by nucleophilic additions to C=O and C=C double bonds. We highlight the utility of a broad range of organocatalysts other than compounds based on proline, the cinchona alkaloids and binaphthyls, which have been abundantly reviewed elsewhere. The focus is on organocatalysts, although a few examples employing metal complexes and enzymes are also included due to their significance. Classical Brønsted acids have evolved into electrophilic hands, the fingers of which are hydrogen donors (like enzymes) or other electrophilic moieties. Classical Lewis base catalysts have evolved into tridimensional, chiral nucleophiles that are N-(e.g., tertiary amines), P-(e.g., tertiary phosphines) and C-nucleophiles (e.g., N-heterocyclic carbenes). Many efficient organocatalysts bear electrophilic and nucleophilic moieties that interact simultaneously or not with both the electrophilic and nucleophilic reactants. A detailed understanding of the reaction mechanisms permits the design of better catalysts. Their construction represents a molecular science in itself, suggesting that sooner or later chemists will not only imitate Nature but be able to catalyze a much wider range of reactions with high chemo-, regio-, stereo-and enantioselectivity. Man-made organocatalysts are much smaller, cheaper and more stable than enzymes.

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A combination of directing groups and chiral anion phase-transfer catalysis for enantioselective fluorination of alkenes

Cited by 113 publications

References 42 publications

Chiral Anion Phase Transfer of Aryldiazonium Cations: An Enantioselective Synthesis of C3‐Diazenated Pyrroloindolines

Chiral Anion Phase Transfer of Aryldiazonium Cations: An Enantioselective Synthesis of C3‐Diazenated Pyrroloindolines

Cinchona Alkaloids as Organocatalysts in Enantioselective Halofunctionalization of Alkenes and Alkynes

Organocatalysis: Fundamentals and Comparisons to Metal and Enzyme Catalysis

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