main-group elements (bi) in catalysis for organic synthesis · 18/03/2020 · the application of...

Main-group Elements (Bi) in Catalysis for Organic Synthesis

Xiaheng ZhangMacMillan Group Meeting

March 18th 2020

XR

LX

R

L

Mechanisms of Activation Mode for Main-group Elements

■ Activation mode of transition metal elements

XR

LX

R

L

M

! donation into empty d-orbital

M

" donation from d-orbital into "∗-orbital

! donation into empty p-orbital " donation from p-orbital into "∗-orbital

■ Activation mode of main-group elements

Activation of Small Molecules by Main-group Elements

Frustrated Lewis pairs activation

Stephan, D. W. et al. Science 2006, 314, 1124.

Activation of H2 by carbenes

iPr2N

Mes2P B

F4

H2 25 oC

> 100 oCMes2P B

F4

H H

Stephan, D. W. et al. Science 2016, 354, aaf7229.

Me

MeMe H2 35

oCiPr2N

Me

MeMe

Frey, G. D.; Lavallo, V.; Donnadieu, B.; Schoeller, W. W.; Bertrand, G. Science 2007, 316, 439.

H H

Catalysis Enabled by Main-group Elements

Frustrated Lewis pairs catalyzed hydrogenation

Chernichenko,K.;Madaraśz,A.;Paṕai,I.;Nieger,M.;Leskela,̈ M.;Repo,T. Nat. Chem. 2013, 5, 718.

FLP catalyzed C-H activation

H2 FLP (5 mol%)

Leǵare,́M.-A.;Courtemanche,M.-A.;Rochette,É.;Fontaine,F.-G. Science 2015, 349, 513.

BuPh

Bu

Ph

H

H

N

B(C6F5)2

Me

Me

FLP (Cat.)

N

Me

HN

Me

BpinH-Bpin FLP (2.5 mol%)N

BH2

R

R

FLP (Cat.)

Catalysis Enabled by Main-group Elements

C-H silylation catalyzed by alkali metal catalyst

Toutov, A. A.; Liu, W.-B.; Betz, K. N.; Fedorov, A.; Stoltz, B. M.; Grubbs, R. H. Nature 2015, 518, 80.

Imine hydrogenation catalyzed by alkaline earth metal catalyst

KOt-Bu (20 mol%)

Harder, S. et. al. Nat. Catal. 2018, 1, 40.

H2 Ca (10 mol%)

N

Me

H

Et3SiHN

Me

SiEt3

MeMe

NMe

MeMe

NMe

H

H


■ The facts of bismuth

■ Synthesis of organobismuthines

■ The application of organobismuthines in organic synthesis

■ Redox chemistry of bismuth

Outline

Why do people care about bismuth catalysis

Bi

Peptobismol OTC

stomach disorders

■ naturally abundant

■ ‘green element’ even less toxic than NaCl■ widely used in industry, antibiotics, radiopaque bone cements, polymers

electron configuration: 4f145d106s26p3

common oxidation state: +1, +3, +5

Can we discover new reactivity that is unique to bismuth catalysis?






Outline

Synthesis of organobismuthines

■ Synthesis of trivalent organobismuthines

BiCl3ArMgBr, ArLi or ArBr, CoBr2, Zn

BiAr3

BiCl3 (0.5 eq)BiAr2Cl

BiCl3 (2.0 eq)BiArCl2

■ Synthesis of highly functionalized trivalent organobismuthines

Gagnon, A. et. al. J. Org. Chem. 2016, 81, 5401.

Bi

OH

3

NaBH4 Bi

OH

3

97% yield

BrCH2CO2EtPPh3Bi 3

CO2Et

80% yield

Bi3

Me

99% yield

HO

MeMgBr Bi 3

82% yield

Ph3PCH3It-BuOK

Synthesis of organobismuthines

■ Synthesis of pentavalent organobismuthines

Michaelis, A. Ber. Dtsch. Chem. Ges. 1887, 20, 52.Barton, D. H. R.; Finet, J.-P. Pure Appl. Chem. 1987, 59, 937.

Bi3

Br2

Cl2 or PhICl2

Bi3

Cl

Cl

NaF or AgFBi

3

F

F

K2CO3O3CBi3

RCO2H, H2O2Bi

ROCO

ROCO 5Bi

3

Br

Br






Outline

Organobismuth as arylation reagents

■ The first arylation reaction using organobismuthines

75% yield

N

MeO

HO NPh3BiCO3

DCMN

MeO

ON

N

MeO

ON

Ph

Barton, D. H. R.; Lester, D. J.; Motherwell, W. B.; Papoula, M. T. B. J. Chem. Soc., Chem. Commun. 1980, 246.

■ The first C-arylation of phenols organobismuthines

OH Ph3BiCO3

TMG

OH

Ph

76% yield


■ O-arylation and C-arylation controlled by condition

90% yield 90% yield

91% yield 57% yield

Me

Me

O

Me

BiPh3X

Me

Me

O

Me

Ph

Me

Me

O

MePh

Ph4BiO2CCF3

TMG

basic conditions

Ph4BiO2CCF3

Cl3CCO2H

acidic or neutral conditions

OH

PhOPh

O

PhCO2Et

OPh

CO2Et

Me

Me

OPhMe

Me

OPh

72% yield 58% yield

Barton, D. H. R. et. al. J. Chem. Soc., Chem. Commun. 1980, 827. Barton, D. H. R. et. al. J. Chem. Soc., Chem. Commun. 1981, 503.


■ O-arylation of alcohols, diols, aminoalcohols

73% yield

Me

MeOH Ph4BiO2CCF3 or Ph3Bi(OAc)2

DCM or toluene

David, S.; Thieffry, A. J. Org. Chem. 1983, 48, 441. Barton, D. H. R. et. al. J. Chem. Soc., Chem. Commun. 1986, 65.

Me

MeO

Ph

tBu

OPh

OH

OPh

OHMe

88% yield

PhHNOH

51% yield

HO OPhMe Me

99% yield

MeOOPh

86% yield

PhPh

O

OPh

88% yield

HOOPh

80% yield


■ O-arylation of tertiary alcohols via Cu catalysis

OH

Me

Me Ph3Bi(OAc)2, Cu(OAc)2, Cy2NMe, O2

DCM or toluene

Ikegai, K.; Fukumoto, K.; Mukaiyama, T. Chem. Lett. 2006, 35, 612. Mukaiyama, T.; Sakurai, N.; Ikegai, K. Chem. Lett. 2006, 35, 1140.

89% yield

EtO2C

O

Me

Me

EtO2CPh

O

Me

Me

EtO2CPh

89% yield

OMe

EtO2CPh

Ph

94% yield

O

Me

EtPh

88% yield

OPh

BnN

Ph

87% yield

O

Me

Me

MePh

50% yield

O

Me

MePhTBSO

O

N


■ Cu catalyzed arylation of N, S-nucleophiles

Nu

Me

Me Ph3Bi(OAc)2 or Ar3Bi, Cu(OAc)2, O2

Gagnon, A. et. al. Synthesis 2017, 49, 1707.

96% yield

Nu

Me

MePh

HN

Ph

80% yield 91% yield

Me

Me

HN

OBn

Ph

Ph

O

O NH

HN

O

PhtBu

N

MeO2C

Ph-pMe

87% yield

N

N

Ph

87% yield

N N

N

Ph

60% yield

N NN

N

Ph

87% yield

Ph

S

Ph

84% yield

MeO


■ Cu catalyzed arylation of N, S-nucleophiles

Nu

Me

Me Ph3Bi(OAc)2 or Ar3Bi, Cu(OAc)2, O2

Gagnon, A. et. al. Synthesis 2017, 49, 1707.

96% yield

Nu

Me

MePh

HN

Ph

80% yield 91% yield

Me

Me

HN

OBn

Ph

Ph

O

O NH

HN

O

PhtBu

N

MeO2C

Ph-pMe

87% yield

N

N

Ph

87% yield

N N

N

Ph

60% yield

N NN

N

Ph

87% yield

Ph

O

NMe

52% yield

Me3Bi

Cross-coupling using organobismuth

Pd

Rh

CO2EtPh3Bi

CO2EtPh

Pd

Ph3BiN

N Cl

FGN

N Ph

FG

Pd

Ph3BiPO

Ph

EtOH P

OPh

EtOPh

Pd

c-Pr3BiN Cl

CN

N

CN

Gagnon, A.; Duplessis, M.; Alsabeh, P.; Barabé, F. J. Org. Chem. 2008, 73, 3604.

Wang, T.; Sang, S.; Liu, L.; Qiao, H.; Gao, Y.; Zhao, Y. J. Org. Chem. 2014, 79, 608.Kawamura, T.; Kikukawa, K.; Takagi, M.; Matsuda, T. Bull. Chem. Soc. Jpn. 1977, 50, 2021.

Gagnon, A. J. Org. Chem. 2016, 81, 5401.

O

Ph3Bi

O

Ph

Li, C.-J. et. al J. Am. Chem. Soc. 2001, 123, 7451.

OPh3BiCl2, PBu3

OPh

Krische, M. J. J. Am. Chem. Soc. 2004, 126, 5350.

Bi redox chemistry is unclear with rare examples






Outline

Bi(III)/Bi(V) redox activation

Jurrat, M.;Maggi, L.;Paṕai,I.;Lewis, W.;Ball, L. T. Nat. Chem. 2020, 12, 260.

SO O

Bi X B(OH)2 SO O

Bi OH

[O]OH

ortho-Arylation of phenols via Bi(III)/Bi(V) redox activation

OH

HO

iPr

Me

Liganasantibacterial, cyctotoxic

OH

CO2H

NH

N

NN

OAr

Pharmaceuticalsaplastic anemia

N

N

OH

Cl

Agrochemicalsherbicide


■ Current approaches for the preparation of 2-hydroxybiaryls


H

OH

R

H

O

R

H, X, Li

PG, DG

H, X, Li OR

OH

R

2-hydroxybiaryls

OBiPh3XPh4BiO2CCF3

TMG

basic conditions

Ph4BiO2CCF3

Cl3CCO2H

acidic or neutral conditions

OH

Ph

OPh

■ Barton’s pioneer discovery

■ O or C arylation is highly dependent on the nature of the organobismuth and reaction conditions■ multistep synthesis of arylbismuth reagents, transfer one of the aryl groups in the organobismuth■ lack of systematic studies of mechanism which impedes practical exploration of the method



SO O

Bi X B(OH)2 SO O

Bi OH

[O]OH

ortho-Arylation of phenols via Bi(III)/Bi(V) redox activation

■ one-pot boron-to-bismuth transmetallation ■ commercially available starting materials■ completely prevents the formation of O-arylated products■ operates under air in non-anhydrous conditions

Bi(III)/Bi(V) redox activation for ortho-Arylation of phenols


■ Reaction design

SO O

Bi X

SO O

Bi

B(OH)2

B-to-Bi transmetallation

mCPBA

Bi(III) to Bi(V) oxidationBi

OOH

SO

O

O

Cl

OH

phenol deprotonation

Bi

OO

SO

O

O

Cl

HO

arylated product

exocyclicaryl group



SO O

Bi OTs SO O

Bi


B(OH)2

(1.1 equiv.)

K2CO3 (1.2 equiv.)

PhMe/water (99/1), 60 oC, 2h

SO O

Bi F

SO OLi Li

SO OnBuLi

ArBiBr2BiBr3 Ar3Bi

■ Transmetallation to universal bismacyclic precursor

TsOH



SO O

Bi OTs SO O

Bi

B(OH)2

(1.1 equiv.)

K2CO3 (1.2 equiv.)

PhMe/water (99/1), 60 oC, 2h

■ Transmetallation to universal bismacyclic precursor

>99% yield

SO O

Bi NMe2

>99% yield

SO O

Bi CN

>99% yield

SO O

Bi

F3CO

>99% yield

SO O

Bi

Me

Me

Me

>99% yield

SO O

Bi

>99% yield

SO

BiNBoc

>99% yield

SO

Bi

>99% yield

SO

BiN

O

Me

MeN

OMe

NH



SO O

Bi OTs SO O

Bi

B(OH)2

(1.1 equiv.)

K2CO3 (1.2 equiv.)

■ One-pot, Bi(V)-mediated arylation of phenols and naphthols

69% yield

OH

OH

mCPBA, r.t., 10 min

OH

77% yield

OHMeO

OMe

F

59% yield

OH

F

Br

OH

Me

Me Me

89% yield

OH

87% yield

Br

OH

59% yield

OHN

93% yield

p-F

OH

90% yield

p-F

HN

N

SMe



SO O

Bi OTs SO O

Bi

B(OH)2

(1.1 equiv.)

K2CO3 (1.2 equiv.)

■ One-pot, Bi(V)-mediated arylation of phenols and naphthols

OH

OH

mCPBA, r.t., 10 min

+

SO O

Bi OmCBAcOH elution

SO O

Bi OAc

B(OH)2

96%



SO O

Bi OTs SO O

Bi

B(OH)2

(1.1 equiv.)

K2CO3 (1.2 equiv.), 1h

■ Mechanistic studies for the reaction

FF

SO O

Bi OH H2OS

O OBi O

S

O

O

Bi

>99%

K2CO3,PhMe/water

30 minr.t., 99%

B(OH)2

F

isolated

plausible pre-transmetallation intermediate



■ Reaction design

SO O

Bi X

SO O

Bi

B(OH)2


mCPBA

Bi(III) to Bi(V) oxidationBi

OOH

SO

O

O

Cl

OH

phenol deprotonation

Bi

OO

SO

O

O

Cl

HO

arylated product

exocyclicaryl group



SO O

Bi


F1) mCPBA, PhMe2) DBU

Bi

OO

SO

O

Bi

SO

O

F

F

(X-ray)

Bi(V) dimer

Bi(V) dimermCPBA

Bi

OmCBOH

SO

O

mCPBA

Bi

OmCBOmCB

SO

O

mCBA/Bi = 1.3 2NMR ratio

HO

F

PhOHPhOH



SO O

Bi


F1) mCPBA, PhMe2) DBU

Bi

OO

SO

O

Bi

SO

O

F

F

(X-ray)

Bi(V) dimer

Bi(V) dimermCPBA

Bi

OmCBOH

SO

O

mCPBA

Bi

OmCBOmCB

SO

O

mCBA/Bi = 1.3 2NMR ratio

HOPhOH

Fk > 40 M-1S-1

PhOH



SO O

Bi


F

d0-PhOH (5.0 eq)d5-PhOH (5.0 eq)

OH

F

mCPBA, PhMe, r.t.

kH/kD = 1.03

SO O

Bi F

OH

F

mCPBA, PhMe, r.t.

kH/kD = 0.83

OH

D

H



SO O

Bi


F

Bi

OmCBOH

SO

O

Bi

OmCBO

SO

O

FF

k > 40 M-1S-1k > 1.6 M-1S-1RDS

PhOH

-H2O

OH

F

PhOH, mCPBA

PhMe, r.t.

mCPBA

What about Bi(III)/Bi(V) redox catalysis?

Planas, O.; Wang, F.; Leutzsch, M.; Cornella, J. Science. 2020, 367, 313.

■ Fluorination of arylboron via Bi(III)/Bi(V) redox catalysis

Bpin F

Bi

SON

F3C

BF4

Bi(III) (10 mol%)NaF (5.0 eq), CDCl3, 90 oC

NCl Cl

F

BF4 (1.0 eq)

90% yield

F

TMS

71% yield

F

Ph

77% yield

F

Me

55% yield

FMeO

36% yield

FCl

84% yield

FMe

Me

Br

45% yield

F

Me

F

49% yield

Fluorination of arylboron via Bi(III)/Bi(V) redox catalysis


■ Proposed mechanism for Bi(III)/Bi(V) redox catalysis

BY2F

Bi

SON

F3C

X

C-F bond formation

Bi

SON

F3C

F-X

OA

Bi

SON

F3C

PhF

X

RETM

electrophile



■ Proof of concept study

Bi

SOO

Me

XeF2 (1.0 eq)

CHCl3, 0 oC

>95% isolated

Bi

SO

O

Me

F F

FBi

SOO

Me

F

X-ray

Bi

SOO

F

Me

F110 oCCDCl3

45% yieldreductive elimination

from Bi(V) center



■ Ligand effect for the reductive elimination

Bi

SOO

Me

XeF2 (1.0 eq)

F

45% yield

then 110 oC

Bi

SON

F3C

Bi

SON

Me

XeF2 (1.0 eq)

F

28% yield

then 110 oC

XeF2 (1.0 eq)

F

94% yield

then 110 oC



■ Kinetic analysis of the reductive elimination

Bi

SON

F3C

XeF2 (1.0 eq) F 110 oCBi

SON

F3C

F

F

R

R

R



■ Mechanism study of the reductive elimination

FBi

SO

NCF3

F

F slower decay in the presence of Bu4NF

CD3Cl, 90 oC, 6hBi

SON

F3C

F

F

C-F bond R.E.

94% yield

proposed cationic intermediates

Bi

SON

F3C

PhF

FB F

F F

fast dissociation of labile BF4- ligand

CD3Cl, 60 oC, 5min

NMR, HRMS

Bi

SON

F3C

F

BF4

C-F bond R.E. F

85% yield

1.0 eq BF3·Et2OCH3Cl, -45 oC

5 min>99% yield



■ Fluoropyridinium as fluorinating reagent

CD3Cl, 60 oC, 2hBi

SON

F3C

F

BF4

F

85% yield

Bi

SON

F3C

NCl Cl

F

BF4

(1.2 eq)

Bi

SO

NF3C

F

N ClCl BF4

ligand exchange



■ Transmetallation of arylborone to Bi

Bi

SON

F3C

BF4

Bi

SON

F3C

Ph-B, KF, MeCN, 90 oC

B(OH)2

95% yield

Bpin

67% yield

B

72% yield

O

O

Me

Me

PhB

80% yield

OB

OB

O

Ph

Ph



■ Merging element steps together for Bi(III)/Bi(V) redox catalysis

Bi

SON

F3C

BF4

Bi

SON

F3C


CD3Cl, 60 oC, 2hBi

SON

F3C

NCl Cl

F

BF4

(1.2 eq)F

85% yield



■ Merging element steps together for Bi(III)/Bi(V) redox catalysis

Bi

SON

F3C

BF4

Bi

SON

F3C


Bpin F

Bi

SON

F3C

BF4

Bi(III) (10 mol%)NaF (5.0 eq), CDCl3, 90 oC

NCl Cl

F

BF4 (1.0 eq)

First Bi(III)/Bi(V) redox catalysis

What about Bi(I)/Bi(III) redox catalysis?

Wang, F.; Planas, O.; Cornella, J. JACS 2019, 141, 4235.

■ Bi(I) catalyzed transfer hydrogenation

Bi(I) (1 mol%)NH3BH3 (1.0 eq), H2O (1.0 eq)

THF, 35 oCN

NPh

PhN

NPh

Ph

H

H

N

BiN

tBu

tBu

Bi(I) catalyst

N

BiN

tBu

tBu

H

H

via Bi(III) hydride

What about Bi(I)/Bi(III) redox catalysis?


■ Bi(I) catalyzed transfer hydrogenation


THF, 35 oC

97% yield

NN

PhPh

NN

PhPh

H

H

N

BiN

tBu

tBu

Bi(I) catalyst

NN

H

H

Me

Me

99% yield

NN

H

H

CF3

F3C

98% yield

NN

H

HBr

99% yield

NN

H

H

NMe2

I

98% yield

NN

H

H

Me

Me

Me

MeNN

H H

99% yield

Transfer hydrogenation via Bi(I)/Bi(III) redox catalysis


■ Bi(I) catalyzed transfer hydrogenation of nitroarenes

Bi(I) (1 mol%)NH3BH3 (1.0 eq)

dioxane, 35 oC

97% yield

N

BiN

tBu

tBu

Bi(I) catalyst

NO2 N

H

Me

OH

N

H

Me

OH

88% yield

N

H

I

OH

67% yield

N

H

OH

82% yield

N

H

OH

75% yield

N

H

OH

22% yield

N

H

OH

Me

Me




THF, 35 oCN

NPh

PhN

NPh

Ph

H

H

N

BiN

tBu

tBu

H

H

via Bi(III) hydride

Effect of water



Bi(I) (1 mol%)Dn-NH3BH3 (1.0 eq), D2O

THF, 35 oC

NN

PhPh

NN

PhPh

H

H

N

BiN

tBu

tBu

H

H

via Bi(III) hydride

KIE experiments

Both N-H and B-H bonds are cleaved in the rate-determining step



Bi(I) (1 mol%)NH3BH3 (1.0 eq), H2O

THF, 35 oC

Competition experiment study

■ azoarenes are not participating in the RDS of this transformation

■ Bi(I) and AB are both involved in the RDS

NN

H

H

Me

Me

NN

Me

Me

Bi(I) (1 mol%)NH3BH3 (1.0 eq), H2O

THF, 35 oC

NN

H

H

F

F

NN

F

F

Product 1:1 ratio observed



■ Stoichiometric study for Bi(III)—H species

PhSiH

■ Bi(I) and H2 was detected during the reaction■ proton is from hydridic sources

N

BiN

tBu

tBu

H

H

putative Bi(III) hydrideintermediate

NN

PhPh

H

H

NN

PhPh

H

H

NN

PhPhN

BiN

tBu

tBu

F

F

N

BiN

tBu

tBu

Cl

Cl

NaBH3CNN

NPh

Ph

71% yield

98% yield



■ Mass-spectrometry study for Bi(III)—H species

N

BiN

tBu

tBu

H

H

putative Bi(III) hydrideintermediate

N

BiN

tBu

tBu

20 mol%

NH3BH3 (1.0 equiv)

ND3BD3 (1.0 equiv)

N

BiN

tBu

tBu

H

HRMS-ESI

main-group elements (bi) in catalysis for organic synthesis · 18/03/2020 · the application of...

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