organic electron donors - department of chemistry - uc ... · organic electron donors oeds:...

Organic Electron DonorsYang Li

Zakarian Research Group Department of Chemistry and Biochemistry

University of California, Santa Barbara 11/15/2018

N

NN

NMe Me

N

NN

N

NN

Me2N NMe2

Me2N NMe2

Me2N NMe2

S S

S S

TAF1 TDAE TAF2 TTF BPL

Outlines

Organic Electron Donors Background

Organic reactions with electron transfers Common electron donor reagents and reduction potentials

Typical organic electron donors Early development (TTF, TDAE) ‘Super electron donors’ (TAFs, bispyridinylidene) Application in organic synthesis

Application in mechanism studies Transition metal free reaction w/ DMEDA

2

N

NN

NMe Me

N

NN

N

NN

Me2N NMe2

Me2N NMe2

Me2N NMe2

S S

S S


Outlines





3

N

NN

NMe Me

N

NN

N

NN

Me2N NMe2

Me2N NMe2

Me2N NMe2

S S

S S


Background

Organic reactions with electron transfers Single electron transfer (SET) is an important process in various redox- and radical-type organic reactions.

4

R X R XD

D X

RH Solvent

R HReductive termination

DR D

NuR Nu

RE

R ED

D

Conversion into an electrophile

Conversion into a nucleophile

SET

DET

Organic reactions with electron transfers

Common electron donors reagents: Active metals: alkali metals, alkali earth metals Low valent metallic reagents: SmI2, TiCl3 Organic metallic reagents: Sodium naphthaline, CpTiIII

Background

4

R X R XD

D X

RH Solvent

R HReductive termination

DR D

NuR Nu

RE

R ED

D

Conversion into an electrophile

Conversion into a nucleophile

SET

DET

J. Broggi, et al. Angew. Chem. Int. Ed. 2014, 53, 384–413 L. Zhang, L. Jiao, Chem. Sci. 2018, 9, 2711-2722

Classic reactions involved electron donors:

Background

5

Birch reduction

Na, NH3, MeOH

44 %

H3C OCH3 H3C OCH3

Birch, A. J. J. Chem. Soc. 1944, 430-436Acyloin condensations

CO2Me

CO2MeCO2Me O

OHMeO2C

HH

HH H H

HH

Na, Et2O, NH3, MeOH

-78 °C, 15 min48 %

Lawton, R. G. J. Am. Chem. Soc. 1971, 93, 1730

Grigard reaction

Cl Cl+ e -Cl + e MgCl

Mg

J. Broggi, et al. Angew. Chem. Int. Ed. 2014, 53, 384–413 L. Zhang, L. Jiao, Chem. Sci. 2018, 9, 2711-2722

Organic electron donors OEDs: neutral, ground state organic molecules that reduce substrates by single electron transfer. Advantages: tunable reducing ability, mild reaction conditions

Background

6

J. Broggi, et al. Angew. Chem. Int. Ed. 2014, 53, 384–413

Common organic electron donors

S

S

S

S

Me2N

Me2N

NMe2

NMe2

N

NN

N

NN

Me2N NMe2

N

NN

NMe Me

Tetrathiafulvalene (TTF)Tetrakis(demethylamine)ethlyene (TDAE)

Diimidazo-TetraazafulvaleneDiimidazo-TAF

TAF2

Bispyridinylidene BPL

Dibenzo-TetraazafulvaleneDibenzo-TAF

TAF1

Reduction potential

Background

7

Reduction potential reflects ability to donate electrons Which functional group can accept the electron

-3.5 E (V)

-3.0 -2.5 -2.0 -1.5 -1.0 -0.5 0.0 +0.5 +1.0

Cl Br I N2

MeBr MeI CBr4

N

NN

N

TAF2E = -1.20 V

NN

Me2N NMe2N

NN

NMe Me

Me2N

Me2N

NMe2

NMe2

S

S

S

S

TAF1E1 = -0.82 VE2 = -0.76 V

TDAEE1 = +0.32 VE2 = +0.71 V

TTFE =+0.33 V

BPLE = -1.24 V

-e

+e

Outlines





8

TDAE as an electron donor In 1950, discovery of tetrakis(dimethylamino)ethene (TDAE) in industry Its ability to reduce electron poor perfluoro substrates

Discovery of Organic electron donors

9

TDAE oxidized to its radical anion 4 and di-anion 5 Electron rich ethene & heteroatoms as OEDs

Industrial application of TDAE reduction

F3C

C2F5 CF3

C2F5F

CF3CF3

CF3CF3

FMe2N

Me2N

NMe2

NMe2

DCM, 0C to roomtemp90 %2 3

F3C

C2F5 CF3

FF

CF3

+ e

F3C

C2F5 CF3

F CF3

F

CF3CF3

CF3CF3

FF+ e- F

Me2N

Me2N

NMe2

NMe2

Me2N

Me2N

NMe2

NMe2

- F

F

4

5

F

F

Lafferty, R. H., Jr. J. Am. Chem. Soc. 1950, 72, 3646

TTF as organic electronic material In 1970, inspired by powerful electron donating properties of TDAE, Fred Wudl applied Tetrathiafulvalene (TTF) to organic electronics.


10

F. Wudl, et al. J. Am. Chem. Soc. 1972, 94, 670–672. F. Wudl, et al. Chem. Commun. 1970, 1453

“TTF as an excellent organic solid semiconductor.” - F. Wuld Aromatic stabilization energy

S

S

S

S

S

S

S

S+ Cl

hv, -e+e

ρ = 3.7 ± 1 Ω cm

ρ = 1012 Ω cm

(4n + 2) π electrons


11


12

Chem. Commun. 1993, 295−297.

TTF as organic donor In 1990s, J. A. Murphy used alkene to trap the benzyl radical generated when treating arenediazonium with TTF.

Radical-Polar crossover reaction using TTF

N2BF4

O

R1

R2 S

S

S

S

acetoneH2O O

R1

OHR2

7a: R1 = Me, R2 = H (72%)7b: R1 = R2 = Me (56%)

6a, 6b

SET

O

R1

R2

O

R1

R2

O

R1

S+TTFR2

SSS

O

R2R1H2O

N2

N

NHCOCF3

MsN H

F3COCHNOH

S

S

S

S

acetoneH2O MsH N H

N

H

Et

8 9 aspidospermidine

Application in total synthesis

Reduction potential

Background

-3.5 E (V)

-3.0 -2.5 -2.0 -1.5 -1.0 -0.5 0.0 +0.5 +1.0

Cl Br I N2

MeBr MeI CBr4

N

NN

N

TAF2E = -1.20 V

NN

Me2N NMe2N

NN

NMe Me

Me2N

Me2N

NMe2

NMe2

S

S

S

S

TAF1E1 = -0.82 VE2 = -0.76 V

TDAEE1 = +0.32 VE2 = +0.71 V

TTFE =+0.33 V

BPLE = -1.24 V

-e

+e

13

Organic electron donors

TDAE: a moderate electron donor

N2

N

Br

Ms

NMe2

NMe2Me2N

Me2N

DMF74%

NMs

Br

NMs

J. A. Murphy, Beilstein J. Org. Chem. 2009, 19

NO

NPh

CF2Br+

N CHONMe2

NMe2Me2N

Me2N NO

NPh N

OHFF

M. Medebielle J. Org. Chem. 1998, 5385

NO

NPh

FF OHMeOEtO

(55%)

O

N F2C S

(60%)M. Medebielle, tetrahedron lett. 2001, 3463

Radical cyclization from benzodiazonium with TDAE

Radical difluoroalkyl addition to electrophiles

70%

10 11 12

13 14 15

16 17

(1 eq.)

DMF, 90 min(5 equiv.)

14



Radical trifluoromethyl addition to electrophiles

W. R. Dolbier, Org. Lett, 2001, 4271

Ar R

OTDAE (2.2 equiv.)CF3I (2.2 equiv.)

DMF, -20 °C to rt Ar R

HO CF3

(68%-95%)

TDAE (2.2 equiv.)CF3I (5 equiv.)

DMF, 0 °C to rtN

S S

N

N

SCF3

W. R. Dolbier, Org. Lett, 2004, 301

quant.

18 19

20 21

15



DMF, -20 °C to rthv, 82%

SET to aldehyde by light

OMeMeMe

MeOMe

Cl 4NO2-Ph

O

H+

NMe2

NMe2Me2N

Me2NOMe

MeMe

MeOMe

O 4-NO2Ph

OTDAE, hv

4NO2-Ph

O

H 4NO2-Ph

O

HOMe

MeMe

Me O 4-NO2Ph

O24NO2-Ph

O

O

Cl Ar

Cl ArO2

OMe

2223

25-2

25-1

24

16

Reduction potential

Background

-3.5 E (V)

-3.0 -2.5 -2.0 -1.5 -1.0 -0.5 0.0 +0.5 +1.0

Cl Br I N2

MeBr MeI CBr4

N

NN

N

TAF2E = -1.20 V

NN

Me2N NMe2N

NN

NMe Me

Me2N

Me2N

NMe2

NMe2

S

S

S

S

TAF1E1 = -0.82 VE2 = -0.76 V

TDAEE1 = +0.32 VE2 = +0.71 V

TTFE =+0.33 V

BPLE = -1.24 V

-e

+e

17


Super electron donors : TAFs and bispyridinylideneTetraazafulvalene or NHC?

N

N

N

NR R

R RN

N

N

NR R

R RStrongly favor NHC carbenetetraazafulvalene

Earliest TAFs by J.A. Murphy contained methylene bridges

N

NN

NMe Me

KHMDS

DMF

I

N

NN

NMe Me

26

N

NN

N

TAF2E = -1.20 V

NN

Me2N NMe2BPLE = -1.24 V

TAF1E1 = -0.82 VE2 = -0.76 V

J. A. Murphy, Angew. Chem. Int. Ed. 2005, 1356J. A. Murphy, Angew. Chem. Int. Ed. 2007, 5178

J. A. Murphy, Org. Lett. 2008, 1227

Features: Neutral organic molecules Low reduction potential: SET to benzyl iodi

(TAF2 and BPL) DET and anionic cyclization 18


Super electron donors : SET v.s. DET

N

N

N

N

Me MeN

N

N

N N N

NMe2Me2NTAF1 TAF2 BPL

O

I CO2Et

MeMe Super electron donors

DMF, ΔO Me

MeO

H CO2Et

MeMe

O

(51%)(21%)

J. A. Murphy, Angew. Chem. Int. Ed. 2007, 5178

SET

O

CO2Et

MeMe

O

CO2Et

MeMe

TAF2(83%)(8%)BPL

(77%)TAF127

30 31

DET?

O MeMe

OOEt

HAT(0%)

32

28 29

19


Super electron donors : SET v.s. DET

N

N

N

N

Me MeN

N

N

N N N


N

OMsI

Ms

TAF1, KHMDSDMF, rt

PhMe, Δ N

OMs

Ms90%

N

OMs

Ms

+e-I

N

OMs

Ms

HAT

N

OMs

Ms

+e

NMs (not observed)

N

OMs

Ms

+e

N

OMs

MsJ. A. Murphy, Angew. Chem. Int. Ed. 2005, 1356

(not observed)

33 34

20


Super electron donors : Reactions of Diimidazol-TAF

N

N

N

N

Me MeN

N

N

N N N


Br H

Cl HTAF2 (6 equiv.)DMF, 110 °C, 4h

PhO2S SO2Ph PhO2S H

96%

NMs

NH

91%

ItBu tBu

tBu

BPL DMF

91%

HtBu tBu

tBu

TAF2 (3 equiv.)DMF, 110 °C

TAF2 (1.5 equiv.)DMF, 100 °C

TAF2 (1.5 equiv.)DMF, 100 °C

99%

99%

J. A. Murphy, J. Am. Chem. Soc. 2007, 129 , 13368J. A. Murphy, Angew. Chem. Int. Ed. 2007, 5178

21


Super electron donors : bispyridinylidene

SET to benzenes

O

OEt

nBuOMe

BPL (3 equiv.)hv, DMF, rt

91%HO

OEt

nBu

cis:trans 70:3066%

6%

OBPL (6 equiv.)hv, DMF, rt

73%

OMe

Me Me

Me

OH Me Me

Me

Murphy, Angew. Chem. Int. Ed. 2012, 3673



BPLhv, DMF, rt

22

Synthetic applications of organic electron donors

Electron Donor ET Redox potential (vs SCE) Reduced bond Promoted reaction

S

S

S

S

TTF

1 e- +0.32 V, +0.71 V (CH3CN) Ar-N2+ BF4-radical cyclizationradical translocation

Me2N

Me2N

NMe2

NMe2

TDAE

1 e- -0.78 V, -0.61 V (CH3CN)-0.62 V (DMF)

Ar-N2+ BF4-

ArCCl3CF3I/CF3BrC(O)CHRBr

radical cyclizationradical addition (CHO, RSSR)trifluoromethylation

1 e- -0.76 V, -0.82 V (DMF) Ar-I radical cyclizationN

N

N

N

Me Me

N

N

N

N

N N

NMe2Me2N

2 e- -1.20 V (DMF) Ar-IArBrArClCSO2PhNTs

2 e- -1.24 V (DMF) OTfNTfC(O)NOMe

anionic cyclizationreduction of haloarenereductive cleavage of sulfone and sulfonamide

anionic cyclizationreduction of haloarenereductive cleavage of sulfone and sulfonamidetriflate ester, Weinreb amide

23

More than organic electron donors

24

NPh + B2Pin2 MeOK+

(1 equiv.) (1.1 equiv.) (1.1 equiv.)

18-C-6 (1.1 equiv.)

THF, rt, 2 h77 % yield

NNB

OO

PhPhH

H

K 18-C-6

B(super electron donor)

E = -1.1 V (SCE)

N NH

NPh

(20 mol%)B2Pin2 (1.3 eq.)MeOK (1.3 eq.)MTBE, 85 °C, 12 h

(86%)

A

A (40 mol%)B2Pin2 (1.3 eq.)MeOK (1.3 eq.)

B2Pin2 (1.3 eq.)MeOK (1.3 eq.)MTBE, 85 °C, 1 h

N

OMe

OMeN

OMe

H(96%)

L. Zhang and L. Jiao, Chem. Sci. 2018, 9, 2711

Ts

Cl

F

CeCl3 (1 eq.)0.1 M Et4Cl in CH3CN

Black light CFLsN2, 40 h

H

F

via [CeCl6]3- electron donor: E = -3.45 V (Cp2Fe)

M. Anna and E. J. Schelter, J. Am. Chem. Soc. 2016, 138, 16266

In-situ generated super electron donor

Photosynsitizer for Ar-Cl

69%

Transient electron donor

Me I H+ 20 mol% DMEDA

NH HN MeMe

KOBut, 80 °CMe

Lei, A. W. J. Am. Chem. Soc. 2012, 132, 16737-16740

Reaction:

Mechanism:

organic additiveDMEDA

Strong electron donor

base

?SET

Me I

Me

I−

HAr1

H Base

addition

cleavage SET

protonabstraction

Me

Me I

Me

Chain Propagation

Chain Initiation

Tuttle, T., Murphy, J. A., J. Am. Chem. Soc. 2014, 136, 17818

25

Transient electron donor

What is the Electron donor that traggers the reaction?a. Initiation mechanism 1:

b. Initiation mechanism 2:

Me NH

HN Me

(as an electron donor?)Strong electron donor?

Me NH

HN Me

Ar1-X Ar1-X

Me NH

HN Me

(as a ligand?)

t-BuOKNH

NHK

Me

Me

OtBu

Strong electron donor?

Ar1-X Ar1-X NH

NHK

Me

Me

OtBu

c. Initiation mechanism 3:

(as a precursorto electron donor)

NH

NH

Me

Me

t-BuOKN

NH

Me

MeStrong electron donor?

Ar1-X Ar1-XN

NH

Me

Me

t-BuOKN

NH

Me

Me

SET

SET

SET

Tuttle, T., Murphy, J. A., J. Am. Chem. Soc. 2014, 136 , 17818Jiao, L., J. Am. Chem. Soc. 2016, 138 , 7151-7160

26

Thank you！Yang Li

Zakarian Research Group Department of Chemistry and Biochemistry

University of California, Santa Barbara 11/15/2018

N

NN

NMe Me

N

NN

N

NN

Me2N NMe2

Me2N NMe2

Me2N NMe2

S S

S S


TAF1 as a one electron donor

N

OMsI

Ms

TAF1, KHMDSDMF, rt

PhMe, Δ N

OMs

Ms90%

N

OMs

Ms

+e-I

N

OMs

Ms

HAT

N

OMs

Ms

+e

NMs (not observed)

N

OMs

Ms

+e

N

OMs

MsMurphy, Angew. Chem. Int Ed. 2005, 1356

(not observed)

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