Synthesis of Chiral α‐Fluoroketones through Catalytic Enantioselective Decarboxylation

Nakamura, Masaharu; Hajra, Alakananda; Endo, Kohei; Nakamura, Eiichi

doi:10.1002/ange.200502703

Cited by 84 publications

(26 citation statements)

References 48 publications

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“…[13] Other novel approaches towards chiral quaternary carbon centers bearing a fluorine atom include the enantioselective decarboxylation of a-fluoro-bketoesters. [14] To the best of our knowledge, a highly enantioselective and diastereoselective reaction using a fluorocarbon nucleophile has not yet been reported.We are keen to develop bicyclic guanidines as general Brønsted base catalysts, and we found that these bases work particularly well with conjugate addition type reactions providing adducts with high ee values. [15] We have previously shown that adduct 1 can be obtained by the guanidinecatalyzed addition of ethyl benzoylacetate and N-ethyl maleimide with an ee value of 90 % and a d.r.…”

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Synthesis of a Chiral Quaternary Carbon Center Bearing a Fluorine Atom: Enantio‐ and Diastereoselective Guanidine‐Catalyzed Addition of Fluorocarbon Nucleophiles

et al. 2009

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The CÀF bond is highly polarized and its unique properties are often understood by considering its stereoelectronic interactions with neighboring bonds or lone pairs of electrons. [1] Whereas natural organofluoro compounds are rare, synthetic fluorinated compounds are useful in areas such as materials, agrochemicals, pharmaceuticals, and fine chemicals. [2] Strategic fluorination is commonly used in contemporary medicinal chemistry to improve metabolic stability, bioavailability, and protein-drug interactions. [3] The replacement of metabolically active hydrogen atoms with fluorine atoms increases the in vivo lifetime of drugs. As such, fluorine-containing compounds are ubiquitous in blockbuster drugs, for example, fluoxetine (antidepressant), atorvastatin (cholesterol-lowering), and ciprofloxacin (antibacterial). The specific incorporation of fluorine in a regio-and stereoselective manner has thus become the most pivotal consideration in the synthesis of fluorinated compounds. To date, both nucleophilic fluorination [4] and electrophilic fluorination [5] methods have been developed.With the huge number of potential applications, asymmetric CÀF bond formation has been become a subject of intense research and has emerged as an important goal in organic chemistry. [6] Hintermann and Togni reported the first example of an enantioselective catalytic electrophilic afluorination using a titanium/taddol complex (taddol = tetraaryl-1,3-dioxolane-4,5-dimethanol) and Selectfluor. [7] The emergence of other stable sources of electrophilic fluorinating agents such as N-fluorobenzenesulfonimide (NFSI) and the use of other metal complexes allowed the scope of asymmetric C À F bond formation to be dramatically expanded. [8] Organocatalytic approaches for asymmetric C À F bond transformation using proline and cinchona alkaloids and their derivatives as catalysts have recently been shown to be a viable alternative. [9] Catalytic enantioselective nucleophilic fluorination is not common; however, one example is the ring opening of epoxides with fluoride sources using salen/ chromium complexes (salen = bis(salicylidene)ethylenediamine) as catalysts. [10] The use of a fluorocarbon nucleophile such as 1-fluorobis(phenylsulfonyl)methane (FBSM) as a synthetic equivalent of monofluoromethane was effectively exploited in a Mitsunobu reaction, [11] Michael reaction, [12a] Mannich reaction, [12b] and palladium-catalyzed allylation. [12c] The amination of 2-fluoro-tert-butyl benzoylacetate under phase-transfer conditions was found to proceed with moderate enantioselectivity. [13] Other novel approaches towards chiral quaternary carbon centers bearing a fluorine atom include the enantioselective decarboxylation of a-fluoro-bketoesters. [14] To the best of our knowledge, a highly enantioselective and diastereoselective reaction using a fluorocarbon nucleophile has not yet been reported.We are keen to develop bicyclic guanidines as general Brønsted base catalysts, and we found that these bases work particularly well with conjugate additi...

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Synthesis of a Chiral Quaternary Carbon Center Bearing a Fluorine Atom: Enantio‐ and Diastereoselective Guanidine‐Catalyzed Addition of Fluorocarbon Nucleophiles

et al. 2009

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“…The successes of Stoltz [16] and Trost [17] on asymmetric Tsuji decarboxylative allylations [18] prompted us to attempt the asymmetric version of the intramolecular decarboxylative allylation of a-trifluoromethyl b-keto esters by the use of chiral bisphosphine ligands like the Trost ligand, P,N ligands or the like. A racemic allyl 2-trifluoromethyl-1-indanonecarboxylate (1a) was tested to be converted into the corresponding optically active 2-allyl-2-trifluoromethyl-1-indanone (2a) by palladium-catalyzed extrusion of carbon dioxide (Scheme 6).…”

Section: Towards Asymmetric Reactionsmentioning

confidence: 99%

Construction of Trifluoromethyl‐Bearing Quaternary Carbon Centers by Intramolecular Decarboxylative Allylation of α‐Trifluoromethyl β‐Keto Esters

et al. 2011

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International audienceA new palladium-catalyzed decarboxylative allylation of allyl α-trifluoromethyl-β-keto esters was developed in the presence of tris(dibenzylideneacetone)dipalladium [Pd2(dba)3] and 1,2-bis(diphenylphosphino)ethane (dppe) in THF. α-Trifluoromethyl ketones featuring a quaternary carbon center were produced in good yields and the dreaded α,β-unsatd.-β,β-difluoro ketones resulting from β-elimination of a fluoride ion were not obsd

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“…The target compound 6 might be elaborated in multiple steps by conventional methods such as enantioselective fluorination, [2] catalytic enantioselective decarboxylation, [3] and diastereomeric salt resolution of racemates. [4] Due to the cis configuration of the piperidine substituents, AHH of a tetrasubstituted dehydropiperidine was an attractive approach to 6.…”

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Kilogram‐Scale Asymmetric Ruthenium‐Catalyzed Hydrogenation of a Tetrasubstituted Fluoroenamide

Stumpf¹,

Reynolds²,

Sutherlin³

et al. 2011

Adv Synth Catal

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Synthesis of Chiral α‐Fluoroketones through Catalytic Enantioselective Decarboxylation

Cited by 84 publications

References 48 publications

Synthesis of a Chiral Quaternary Carbon Center Bearing a Fluorine Atom: Enantio‐ and Diastereoselective Guanidine‐Catalyzed Addition of Fluorocarbon Nucleophiles

Synthesis of a Chiral Quaternary Carbon Center Bearing a Fluorine Atom: Enantio‐ and Diastereoselective Guanidine‐Catalyzed Addition of Fluorocarbon Nucleophiles

Construction of Trifluoromethyl‐Bearing Quaternary Carbon Centers by Intramolecular Decarboxylative Allylation of α‐Trifluoromethyl β‐Keto Esters

Kilogram‐Scale Asymmetric Ruthenium‐Catalyzed Hydrogenation of a Tetrasubstituted Fluoroenamide

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