an efficient strategy single-electron-transfer …ccc.chem.pitt.edu/wipf/current...

Yongzhao Yan Wipf Group Current Literature 9-5-2014

An Efficient Strategy Single-Electron-Transfer-Induced Tandem Anion–Radical Reactions

Frantisˇek Kafka, Martin Holan, Denisa Hidasovμ, Radek Pohl, Ivana Císarˇova,

Blanka Klepetμrˇovμ, and Ullrich Jahn*Angew. Chem. Int. Ed. 2014, 53, 9944 –9948

DOI: 10.1002/anie.201403776

Fe Fe+

NO

N+

O PF6-

PF6-

Nu- Nu

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SET-Mediated Transformation

✤ Radicals are generated from neutral precursors.

✤ Overall reactions are classified as neutral, oxidative and reductive.

✤ Stoichiometric amounts of SET agents.

1. Top. Curr. Chem. 2012, 320, 121–452

主要是oxi reduc两步set最后产生中性的产物

alkyl halides or sulfur electrophiles,

transition-metal-catalyzed atom-transfer radical reactions,

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Catalytic SET-Mediated Reactions✤ Reductive Titanium(III)-catalyzed reaction

1. Top. Curr. Chem. 2012, 320, 121–452

Ti promotes 2 SET

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Catalytic SET-Mediated Reactions

1. Org. Lett., 2008, 10 (19), pp 4383–4386

✤ Reductive Titanium(III)-catalyzed reactionjohn maciejsikiindoline scaffold synthesis

3mol%

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Catalytic SET-Mediated Reactions

1. Org. Lett., 2008, 10 (19), pp 4383–4386

✤ Reductive Titanium(III)-catalyzed reactiontrace O2 or H+ oxidize back

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Catalytic SET-Mediated Reactions✤ Ru(II) catalyzed photoredox reactions

1. Top. Curr. Chem. 2012, 320, 121–452

cat

cat

cat. = Ru(bipy)3Cl2

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Ferrocene/Ferrocenium Couple

1. Chem. Rev. 1996, 96, 877−910

mild Oxidantweak reductantrecommended by IUPAC for standard

0.40 V in MeCN

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Ferrocene/TEMPO Combination

1. Tetrahedron 2009, 65, 10917–10929

crappy yield in one-pothighest yield = 65%both 3 and 4 are used with 1 equiv.

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Ferrocene/TEMPO Combination

1. Tetrahedron 2009, 65, 10917–10929

Radical recombination faster than radical addition to alkene

without FeCp2

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1. Chem. Eur. J. 2009, 15, 58-62

Applications in Total Synthesis✤ Total Synthesis of 15-F2t-Isoprostane

✤ 39% desired isomer

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1. Tetrahedron 68 (2012) 1521-1539

Trapping Reagents

✤ CuCl2 and CuBr2 as oxidizing/trapping reagent

CuBr2 gave pdt with low stereoselectivity

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Ferrocene/TEMPO Redox Pair

Fe Fe+

NO

N+

O PF6-

PF6-

Nu- Nu

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all 2 3 trans 34 cis Ferrocene 1-10%

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Tandem Michael Addition/Radical Cyclization/Oxygenation Reactions

5 mol% 2 add TEMPO in the system to start with10a sele EWG sizetrans ewg and R1 major

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Tandem Michael Addition/Radical Cyclization/Oxygenation Reactions

5 exo to 6 endo

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Ferrocene/TEMPO Redox Pair

✤ Comparing with 52% and 47% (6:1)1

1. Eur. J. Org. Chem. 2012, 4461–4482

same distribution catalytic worked!

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TMP As Alcohol Protecting Group

1. Eur. J. Org. Chem. 2012, 4461–4482

Tolerance with reduction Zn cleavagemcpba directly oxidize it back

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Conclusion

✤ High stereoselectivity on several examples.

✤ TEMPO as a alcohol protecting group saving a protection step/excessive oxidant usage.

✤ Potentials in total synthesis

✤ SET oxidation by Ferroceium and combination with TEMPO

inseparable materialsONLY TEMPO?

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