Synthesis of CF<sub>3</sub>-Containing 3,3′-Cyclopropyl Spirooxindoles by Sequential [3 + 2] Cycloaddition/Ring Contraction of Ylideneoxindoles with 2,2,2-Trifluorodiazoethane

Li, Tianren; Duan, Shu‐Wen; Ding, Wei; Liu, Yi‐Yin; Chen, Jia‐Rong; Lu, Liang‐Qiu; Xiao, Wen‐Jing

doi:10.1021/jo500019a

Cited by 94 publications

(25 citation statements)

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“…Thereaction of tert-butyl diazoacetate with oxindole 1 in toluene at ambient temperature only gave the spiropyrazole cycloadduct 25 (66 %). [26] Similar pyrazoles have been reported to contract to cyclopropanes upon heating, [28][29][30] but this possibility was ruled out when starting materials were returned upon the treatment of spiropyrazole 25 with 3-bromopyridine and [Fe(TPP)Cl] (10 mol %) in toluene at room temperature.C yclopropanes could also undergo non-catalyzed ring expansion with pyridine, [31,32] but only starting materials were obtained from…”

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confidence: 99%

Stereoselective Synthesis of Tetrahydroindolizines through the Catalytic Formation of Pyridinium Ylides from Diazo Compounds

2016

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confidence: 99%

Stereoselective Synthesis of Tetrahydroindolizines through the Catalytic Formation of Pyridinium Ylides from Diazo Compounds

2016

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“…The reaction of tert ‐butyl diazoacetate with oxindole 1 in toluene at ambient temperature only gave the spiropyrazole cycloadduct 25 (66 %) . Similar pyrazoles have been reported to contract to cyclopropanes upon heating, but this possibility was ruled out when starting materials were returned upon the treatment of spiropyrazole 25 with 3‐bromopyridine and [Fe(TPP)Cl] (10 mol %) in toluene at room temperature. Cyclopropanes could also undergo non‐catalyzed ring expansion with pyridine, but only starting materials were obtained from a reaction of cyclopropane 3 under the latter reaction conditions.…”

Section: Methodsmentioning

confidence: 99%

Stereoselective Synthesis of Tetrahydroindolizines through the Catalytic Formation of Pyridinium Ylides from Diazo Compounds

2016

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Commercially available iron(III) and copper(I) complexes catalyzedm ulticomponent cycloaddition reactions between diazocompounds,pyridines,and electrophilic alkenes to give alkaloid-inspired tetrahydroindolizidines in high yield with high diastereoselectivity.Hitherto,the catalytic formation of versatile pyridinium ylides from metal carbenes has been poorly developed;t he broad utility demonstrated herein sets the stage for the invention of further multicomponent reactions in future.Indolizidines are found in many bioactive alkaloids, [1] whereas their unsaturated indolizine counterparts have valuable photochemical properties. [2,3] Both structures are valued for their therapeutic potential. [4][5][6] Spirooxindoles have also been identified as privileged scaffolds for drug discovery.[7] Efficient and versatile routes toward these structural motifs are therefore highly desirable.Thec onvergent synthesis of tetrahydroindolizidines is possible by 1,3-dipolar cycloaddition of pyridinium ylides with electrophilic alkenes.The resulting products may then be converted into indolizines by oxidation, [8][9][10] or into indolizidines by reduction or other types of functionalization (Scheme 1). [11,12] Ty pically,pyridinium ylides are formed by deprotonation of the corresponding salts,b ut this method produces stoichiometric conjugate-acid waste and usually requires as eparate alkylation step to prepare the pyridinium salts.S uch drawbacks significantly restrict the utility of otherwise versatile synthetic intermediates.In principle,c atalytic reactions that directly transform pyridines into their corresponding ylides under aprotic conditions,a nd in the presence of electrophilic alkenes, open up the prospect of more powerful multicomponent reactions to prepare tetrahydroindolizidines.T he addition of Lewis bases to metal carbenes to form ylides has been widely developed for synthesis, [13][14][15][16][17][18][19][20] but there are few reports of catalyzed reactions of pyridines with diazo compounds. [21,22] Theg eneration of pyridinium ylides in this way has received surprisingly little attention;infact, we could find only asingle example of this type of catalyzed three-component reaction to form an indolizine.[23]Herein, we describe anew,multicomponent reaction that produces highly functionalized tetrahydroindolizidines in good yields with generally excellent diastereoselectivity (Scheme 2). These reactions involve the catalytic generation of pyridinium ylides via metallocarbenes and in situ cycloaddition with electrophilic alkenes.This highly efficient route generates nitrogen as the only by-product. Ther eaction

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“…In 2013, Mykhailiuk and co‐workers reported the [3 + 2] cycloaddition of N ‐benzylmaleimides with CF 3 CHN 2 followed by a thermally‐induced ring contraction to provide 6‐trifluoromethyl‐3‐azabicyclo[3.1.0]hexanes . In 2014, Lu, Xiao and co‐workers reported a similar process from ylideneoxindoles to provide the CF 3 ‐containing 3,3′‐cyclopropyl spirooxindoles …”

Section: Optimization Of Reaction Conditions For Cyclopropanation Witmentioning

confidence: 99%

Trifluorodiazoethane (CF₃CHN₂) in the Uncatalyzed Cyclopropanation of 3‐Arylmethylenebenzofuran‐2(3 H)‐ones

Zhu

Cahard

2015

Asian J Org Chem

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The uncatalyzed cyclopropanation of 2,2,2-trifluorodiazoethane onto 3-arylmethylenebenzofuran-2(3 H)ones leads to highly functionalized trifluoromethylated spirocyclopropanes. At hermal activation mode not requiring the additiono fatransition metal provided high product yields, whereas as alt effect benefited the diastereomeric ratios obtained. The products are readily elaborated to non-spiro derivatives.2,2,2-Trifluorodiazoethane( CF 3 CHN 2 )h as emerged as av ery attractive CF 3 -containing synthon for the construction of fluorinated molecules featuring aC F 3 structural subunit. This gaseous and explosive reagent is conveniently generated in situ by conversion of trifluoroethylamine hydrochloride in the presence of sodium nitrite. Alternatively,g aseous CF 3 CHN 2 can be draggedo ff by argon flow into ad ifferent reaction vessel or stock solutionso fC F 3 CHN 2 can be prepared. Recently,C F 3 CHN 2 has demonstrated aw ider ange of applicationsi nvarious reactions such as 1,3-dipolar cycloaddition, [1] cyclopropenation, [2] cyclopropanation, [3] aziridination, [4] trifluoroethylation of terminal alkynes, [5] reactionw ith organoborons, [3d, 6] and otherr eactions. [7] Cyclopropanation by means of CF 3 CHN 2 has attracted much attentionn ot only because cyclopropanei saw idespread motif in natural and synthetic compounds, but also because fluorine strongly influences electronic and steric properties as well as physiological properties, bioactivity,a nd metabolic stabilityo f fluorinated molecules. [8] Early studies focused on photolysis of CF 3 CHN 2 to generate the trifluoromethylcarbene, [9] whereas more recent cyclopropanation reactions were catalyzed by transition metals, for example, Fe, [3a,e,i] Co, [3h] Cu, [3b,c,f,k] Ru, [3a] Rh, [3c,g] or Pd. [3d] Metal-free conditions for cyclopropanation by means of CF 3 CHN 2 are less studied. In 2013, Mykhailiuk and co-

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Synthesis of CF₃-Containing 3,3′-Cyclopropyl Spirooxindoles by Sequential [3 + 2] Cycloaddition/Ring Contraction of Ylideneoxindoles with 2,2,2-Trifluorodiazoethane

Cited by 94 publications

References 50 publications

Stereoselective Synthesis of Tetrahydroindolizines through the Catalytic Formation of Pyridinium Ylides from Diazo Compounds

Stereoselective Synthesis of Tetrahydroindolizines through the Catalytic Formation of Pyridinium Ylides from Diazo Compounds

Stereoselective Synthesis of Tetrahydroindolizines through the Catalytic Formation of Pyridinium Ylides from Diazo Compounds

Trifluorodiazoethane (CF₃CHN₂) in the Uncatalyzed Cyclopropanation of 3‐Arylmethylenebenzofuran‐2(3 H)‐ones

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Synthesis of CF3-Containing 3,3′-Cyclopropyl Spirooxindoles by Sequential [3 + 2] Cycloaddition/Ring Contraction of Ylideneoxindoles with 2,2,2-Trifluorodiazoethane

Cited by 94 publications

References 50 publications

Stereoselective Synthesis of Tetrahydroindolizines through the Catalytic Formation of Pyridinium Ylides from Diazo Compounds

Stereoselective Synthesis of Tetrahydroindolizines through the Catalytic Formation of Pyridinium Ylides from Diazo Compounds

Stereoselective Synthesis of Tetrahydroindolizines through the Catalytic Formation of Pyridinium Ylides from Diazo Compounds

Trifluorodiazoethane (CF3CHN2) in the Uncatalyzed Cyclopropanation of 3‐Arylmethylenebenzofuran‐2(3 H)‐ones

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Synthesis of CF₃-Containing 3,3′-Cyclopropyl Spirooxindoles by Sequential [3 + 2] Cycloaddition/Ring Contraction of Ylideneoxindoles with 2,2,2-Trifluorodiazoethane

Trifluorodiazoethane (CF₃CHN₂) in the Uncatalyzed Cyclopropanation of 3‐Arylmethylenebenzofuran‐2(3 H)‐ones