Lithiation-Borylation Methodology and Its Application in … · 2021. 2. 22. · 60% yield, 99% ee,...

Lithiation-BorylationMethodologyandItsApplicationinSynthesis

LiteratureSeminar2018/06/23

HongyuCHEN(M1)

Contents

•  Introduction

•  Part1:Factorsresponsibleforthe1,2-migration

•  Part2:Factorsresponsibleforstereocontrol

•  Part3:Applicationoflithiation-borylationreactioninsynthesis

•  Summary

AnatomyofTheLithiation-BorylationReaction

X

OLGR2

R1

Li

OLGR2

R1

B(OR)2

OLGR2

R1

R3

Lithiation

B(OR)2R3

1,2-MetallateRearrangement

B(OR)2

OLGR2

R1

R3

Stereoinvertive

Borylation

Stereoretentive

Borylation

1,2-MetallateRearrangement

B(OR)2

R2R3 R1

B(OR)2

R3 R1

R2

OLG = OCb or OTIB X = H or SnR3

Lithium carbenoid

Boronate complex Homologated product

Boronate complex Homologated product

・R1,R2andR3=Alkyl,AlkenylorAryl・ReagentControl・CompleteStereospecificity・ContiguousStereocenters・QuaternaryStereocenters・NaturalProductSynthesis・Assembly-LineSynthesis

ArylationAlkynylationOxidationFluorinationAssembly-LineSynthesis

http://www.chm.bris.ac.uk/org/aggarwal/research.php#li-b

TheFirstNonenzymaticAsymmetricSynthesis(H.C.Brown,1961)

)2BH)2B H HO H

+ BH3 DG0 ℃

[O]

90% yield, 87% ee

R* B

R*D

R*OH

R*CHO

R*CO2H

R*CH2OH R*NH2

R*R’NH

R*R’CHNH2R*COR’

R*COCCR’

R*R’CHOH

R*R2’COH

R*CH2CN

R*CH(CN)2

R*CH2COR’

R*CH2CO2Et

R*CCHR*CCR’

R*CH2CHCH2

R* R* R'

R*

R' R*

R’ R'

cis, cis; cis, trans; trans, trans etc.R*CHCHCHCHR’

GeneralAsymmetricSynthesisviaChiralOrganoboranes

Brown,H.C.etal.Pure&Appl.Chem.,1991,63,307.

ComplementaryRoutestoChiralBoronicEstersA)Matteson:Stepwisesubstrate-controlledapproach

B)Hoppe:Stepwisereagent-controlledapproach

C)Lithiation-Borylation:Iterativereagent-controlledapproach

O

OBR

R1

R1O

OB

R1

R1R

Cl

O

OB

R1

R1R

R2LiCHCl2 R2-MgBr

R OCb

Li

R B(pin)

R2 R3 OCb

Li

R

R2B(pin)

R3

R2-B(pin)

Aggarwal,V.K.etal.Acc.Chem.Res.,2014,47,3174.

R OCb

Li

R OCb

B(pin)

R B(pin)

R2B(Oi-Pr)3 R2-MgBr

then pinacol

Prof.VarinderKumarAggarwal1980-1983BA,UniversityofCambridge1983-1986PhD,UniversityofCambridge(Prof.StuartWarren)1986-1988PostdoctoralPosition,ColumbiaUniversity(Prof.GilbertStork)1988-1991LecturerinChemistry,UniversityofBath1991-1995LecturerinChemistry,UniversityofSheffield1995-1997ReaderinChemistry,UniversityofSheffield1997-2000ProfessorinChemistry,UniversityofSheffield2000-presentProfessorinSyntheticChemistry,UniversityofBristol

“Ourcurrentfocusisinthefieldoforganoboronchemistry,sinceboronseemstopossessauniqueabilitytoorchestratemanyprocessescleanlyandwithhighstereochemicalfidelity.”

CurrentResearchInterests:Stereoselectivesynthesis/Mechanisticstudies/Totalsynthesisofnaturalandnon-naturalproducts

Contents

•  Introduction




•  Summary

WhatAffectstheMigratoryAptitudeofAlkylGroups?(Steric&ElectronicFactors)

B XR1

YR3

R2B X

R1

R3

R2Y

Migrating terminus

Migrating origin

+

1,2-Rearrangementofboratecomplexes

1.Sterichindrancearoundboron.2.Sterichindrancearoundthemigratingterminus.3.Compressionofthebondanglesinthemigratinggroupatthetransitionstatefor

migration.

4.Nonbondedinteractionsofthesubstituentsatthemigratingterminuswiththe

substituentsattachedtoboron.

5.Thestabilityofthemigratinggroupwhichcarriespartialnegativecharge.

Aggarwal,V.K.etal.Pure&Appl.Chem.,2006,78,215.

Example1.Iodine-InducedRearrangementofEthynyltrialkylborates(1)

BR1R2

R3B

R1

R3R2

I I

BR1

I

R3

R2

R1R3R2BI

I2

I

+

S.W.Slayden.J.Org.Chem.,1981,46,2311.



・Apartialrelativemigratoryaptitudeorder:bicyclooctyl>n-butyl>cyclohexyl,isobutyl,sec-butyl>thexyl.Generally1°>2°>3°(exceptforbicyclogroup).・Inexactorderingofthecyclohexyl,isobutyl,andsec-butylgroups.

Canbeexplainedbythestabilityofthemigratinggoupthatcarriespartialnegativecharge(factor5).



For4-6,Anapproximatetwo-foldincreaseinMintheseriesn-butyl<sec-butyl<isobutylbutnosuchregularityfor7-9.

CanbeexplainedbythestericaccelerationduetoBstrain(factor1).

Example2.Rearrangementof9-BBNDerivatives

B

H H

Rn-C8H17OC H

PhIB

H H

RPhI COn-C8H17

HB

H H

RH IPh

n-C8H17OCn-C8H17

OIPh

BR-9-BBNBR

n-C8H17OC

R = c-C5H9, c-C6H11, n-C6H13

BR

R1H

Br

Br

R1

BR-9-BBN R

R1

B-9-BBN

R1 = COR2, CO2R3, CN

Nonmigratinggroup

Migratinggroup

Conformationoftheatecomplexdominatesoutcome(factor4).

Torsionalstraininexpansionof9-BBN.

M.Ochiai.etal.Org.Lett.,2004,6,1505.

H.C.Brown.etal.J.Am.Chem.Soc.,1969,91,6852.H.C.Brown.etal.J.Am.Chem.Soc.,1969,91,6854.H.C.Brown.etal.J.Am.Chem.Soc.,1969,91,6855.

B

H H

R

B

H H

RI2

I2

R = n-Butyl, sec-Butyl, isobutyl

Example3.OxidationofTrialkylboranewithTMANO

BB O

t-Hx

NMe3n-Hxc-Hx

n-Hx

t-Hx

c-Hx NMe3t-Hx

c-Hx

n-Hx Me3Nc-Hx

n-Hx

t-Hx NMe3

OHOH

n-HxOH

TMANO

78% 20% 2%relative yield

Thebulkiergroupsarepreferentiallyoxidized(migratoryaptitudedecreasesintheorder3°>2°>1°).

Canbeaccountedforthepreferredconformationoftheatecomplex(factor4).

R3B R2BOR R2BOH ROH[O] H2O

R3B

R2BOR

RB(OR)2

B(OR)3

TMANO (1eq), 0 ℃

TMANO (2eq), 25 ℃

TMANO (3eq), reflux, 24h

+The intermediate alkoxyboranesare easy to be hydrolyzed.

The oxidation process can be controlleddepending on the stoichiometry andreaction conditions.

J.A.Soderquist.etal.J.Org.Chem.,1986,51,1330.

Example4.CarbonylationofOrganoboranes

R1R2R3BCO B C

R1R2

R3

OR2R3B R1

OR3B

O

R2

R1

R1 R2

O

R1R2R3BKCN B CN

R1R2

R3

TFAA BR1

CR3

R2 NO

CF3

NBO

R1

CF3R3

R2 NBO CF3

R1R2

R3

[O]

[O]

B

OH

(2) [O], pH 8

(1) CO

60% yield, 99% ee, >99% trans

(2) TFAA(3) [O], pH 8

(1) NaCNB

PhPh H

O

75% yield, 99% ee, 99% trans

Noketonesbearingthemosthinderedgroupwereisolated.Theorderinthemigrationstepis1°>2°>3°.

Suggestingthatthe1,2-migrationisdominatedbyelectronicfactorsrelatingtotheabilityofthemigratinggrouptocarrynegativecharge(factor5).

H.C.Brown.etal.J.Am.Chem.Soc.,1988,110,1529.

ShortSummary

•  Severalfactorsshouldbeconsideredwhenthinkingaboutwhichgroupwillmigratepreferentially.

•  Thereisnomigrating/nonmigratinggroupabsolutely.

•  Aconsiderationoftheconformationrequiredformigrationoftheatecomplexisimportant.

Contents

•  Introduction




•  Summary

Stereocontrol:SubstrateControlVSReagentControl

R1 BOR*

OR*B

R1

Cl OR*

OR** B

R1

Cl OR*

R2OR*

* M

R2 BOR

OR

R1 LG

M*

BR1

LG OR

R2OR

* M

BR1

R2 OR*

OR**

-MCl

-MLG

LiCHCl2-LiCl R2M

Substratecontrol(Matteson)

Reagentcontrol(Aggarwal)

Complementaryroutestohomochiralorganoboranesinvolving1,2-metallaterearrangement

V.K.Aggarwal.etal.ChemicalRecord.,2009,9,24.

SubstrateControl:AnatomyAndApplicationMattesonhomologation-alkylationsequence

SyntheticApplications

D.S.Matteson.etal.J.Org.Chem.,2013,78,10009.

O

O

C8H17

Japonilure

OHO

OH

OHHO

L-(+)-ribose

O

O

Me

O

(2S,3R,1’R)-Stegobinone

ŏ

O OH

Serricornin

OB

O

R

R

R1

OB

O

R

RR1

Cl OB

O

R

RR2

R1

OO

BR1

ClHCl

R

RO

OBR1

ClHCl

R

R

ZnCl2LiCHCl2THF, -78℃

ZnCl2r.t.

OB O

R

R

R1

Cl

HCl

ZnCl

Cl OB O

R

R

R1

Cl

ClH

ZnCl

Cl

OO

BR2

ClH

R1R

RO

OBR2

ClH

R1R

R

MgXOB O

R

R

R2

Cl

HR1

MX

XR2MgX MgX

Favoured Disfavoured1 2 3 3 4

5 6 7 7 8

LimitationsoftheMatteson-typeHomologation-Alkylation(1)

Reactionofdiastereomericboronicesterswithgrignardreagentsleadtodifferentoutcome.

D.S.Matteson.etal.Synthesis.,1990,200.

B

ClO

O

Ph

MeMgBr

B

ClO

O

Ph

B

MeO

O

Ph

B

MeO

O

Ph

O

BO Me

PhH

BO

OCl

H

BnMe

MgX

X

BO

OCl

Bn

HMe

MgX

X

O

O BMe

H

BnCl

MgX

X

BMe

OO

RR

Cl

Bn

MgX

X H

MeMgBr

MeMgBr

9 10 11

12 13 14

15 15 16


Additionalstepsarerequiredwhenchangingthestereochemistryofboronicester.

D.S.Matteson.etal.J.Org.Chem.,1996,61,6047.

OB

OCy

Cy

MeO

BOCy

Cy

Me

OBn

(1) LiCHCl2(2) LiOBn

(1) NaOH (HOCH2)3C-R

(2) H+

Cy OH

OHCy

BHO

HO Me

OBn

HO

Cy Cy

OH

OB

OCy

Cy

Me

OBn(2) MeMgBr

(1) LiCHCl2

O BO

Cy

CyOBn

OH OBn

+

17 18 19

202122

23

ent-19


Limitedsuccessforthesynthesisofquaternarystereocenters.

OBO

R

LiCH3

ClCl

ZnCl2

OBOR

Cl OBOR

Cl

+

R S

R

Et

PhBu

Cy

i-Pr

H3COBn

H3C

OO

a

bc

d

e

f

g

R/S = 8

dr

S/R = 24R/S = 1.04

S/R = 1.5

?/? = 40

?/? = 10

R/S = 1.5

・Variablelevelsofselectivitywereobtained.・Thesenseofasymmetricinductionwasunpredictable.

D.S.Matteson.J.Org.Chem.,2013,78,10009.

ReagentControl:Homologation-AlkylationofBoronicEstersandBoranesusingChiralCarbanions

R1 BOR*

OR*B

R1

Cl OR*

OR** B

R1

Cl OR*

R2OR*

* M

R2 BOR

OR

R1 LG

M*

BR1

LG OR

R2OR

* M

BR1

R2 OR*

OR**

-MCl

-MLG

LiCHCl2-LiCl R2M

Substratecontrol(Matteson)

Reagentcontrol(Aggarwal)

Complementaryroutestohomochiralorganoboranesinvolving1,2-metallaterearrangement

V.K.Aggarwal.etal.ChemicalRecord.,2009,9,24.

ChiralCarbanionsDerivedfromSulfurYlides

S

O

BF4

BR3+Ph R

OH/NH2

(1) 1.2 eq, LiHMDSdioxane, THF, 5℃

(2) BF3(3) H2O2, NaOHor NH2OSO3H 68-73% yield

95-97% ee

PhS

O

H

Et3BPhS

O

HBEt3

Ph Et

BEt2

majorproduct

HS

O

PhHH

Et3B

Ph Et

BEt2HS

O

PhBEt3

ΔE = 4.37 kcal/mol

minorproduct

V.K.Aggarwal.etal.J.Am.Chem.Soc.,2005,127,1642.

Outcomeofthe1,2-MetallateRearrangementAteComplexesResultingfromthe9-BBNDerivatives

SPh

BF4 BR

+(1) LiHMDS, -78℃

(2) -100℃ to r.t.(3) H2O2, NaOH HO

OH

PhH Ph

OH

R+

Entry

1

2

3

4

5

6

7

8

R

Hexyl

Allyl

Benzyl

i-PrCyclopropyl

Ph1-Hexenyl

1-Hexynyl

Yield

56%

51%

51%

Trace

89%

Trace

Trace

92%

Yield

41%

39%

35%

77%

Trace

94%

21%

Trace

BR S

HPh

BR H

PhS

BR Ph

SH

HH

V.K.Aggarwal.etal.J.Am.Chem.Soc.,2007,129,14632.a b c

ChiralCarbanionsofLithiatedAlkylChlorides

p-TolSO

Cl

PhnBuLiorEtMgCl

THF,-78℃ Cl

MPh

M = Li or MgCl

OB

OR1

-78Ȣ

B(neo)

ClBnH

R1 R1

B(neo)BnH

R1 = Ph, nBu, Ph(CH2)2, c-hex

ArSO

Bn

Cl

tBuLi(2eq) Bn

Cl

Li Bn B(pin)O

BO

Bn

Cl

Bn

Bn(pin)B

Bn

(1) LiCH2Cl

(2) a(3) H2O2

Bn

Bn

Bn

OH

Bn B(pin)

Bn

Bn

Bn

OH

Bn

Bn

Bn

OH

Bn

Bn

Bn

OHor or

(R,S) (S,S) (S,R)97:3 er, 81:19 dr 99:1 er, 76:24 dr 99:1 er, 80:20 dr

a

(R,R)38% yield99:1 er, 79:21 dr

(1) a or ent-a(2) LiCH2Cl

(3) a or ent-a(4) H2O2

P.R.Blakemore.etal.J.Am.Chem.Soc.,2007,129,3068.

24 25 26

27

ChiralCarbanionsofLithiatedCarbamates(1)

V.K.Aggarwal.etal.AngewChemIntEd.,2007,46,7491.

R1 OCb

HH sBuLi

Et2O, -78℃(-)-sparteine

O

O

NiPr2

LiR1

H

NN (1) R2B(R3)2

(2) Lewis Acid OCb

B(R3)2

R1H

R2

B(R3)2

R2

R1H

(1) warm

(2) H2O2 OH

R2

R1H

ChiralCarbanionsofLithiatedCarbamates(2)

Ph OCb

Ph OCb

Li-sp

Ph

B(pin)

sBuLi(-)-sparteine

EtB(pin)

(78% yield, er = 98:2)

OCb

Li-sp

OCb

Li-sps

Ph

HO

Ph

HO

Ph OCb

Ph OCb

Li-sps

Ph

B(pin)

OCb

Li-sp

OCb

Li-sps

Ph

HO

Ph

HO

N

H

N

H

sBuLi(+)-sparteine surrogate

EtB(pin)

(75% yield, er = 97:3)

N

H

NMe

(-)-Sparteine (sp) (+)-Sparteine surrogate (sps)

82% yielder > 98:2, dr = 96:4

63% yielder > 98:2, dr = 94:6

64% yielder > 98:2, dr = 94:6

63% yielder > 98:2, dr = 90:10

ShortSummary•  Substratecontrolandreagentcontrolaretworoutestohomochiralorganoboranesinvolving1,2-metallaterearrangement.

•  Althoughapowerfultransformation,Matteson’shomologation-alkylationsequence(substratecontrol)suffersfromanumberofdrawbacks(limitation1-3).

•  Thereactionsbetweenchiralcarbanionsbearingpotentialleavinggroupswithachiralboronicesters(reagentcontrol)iscomplementarytotheMattesonapproach.

Contents

•  Introduction




•  Summary

WideApplicationofLithiation-BorylationReaction

Secondary boronicesters and derivatives

R2

OH

HR1 R2

NHBn

HR1

50-94% yield, >95:5 er

Tertiary benzylic boronic esters and derivatives

OH

R2R1

Ar

OH

R2 ArR1

60-91% yield,>95:5 er

69-95% yield,>95:5 er

1,2-diols

OH

EtOH

Et

70% yield, 99:1 er,>95:5 dr

ǃ-Amino alcoholsOH

PhNHBoc

i-Pr

90% yield, >99:1 er,>95:5 dr

PhNHBus

OHR1

80-87% yield,>99:1 er

Allylic boronic esters and homoallylic alcohols

R3

OH

R2 R154-91% yield, >95:5 er,>99:1 dr

R3

OH

R2

R1

46-59% yield, 99:1 er,>99:1 dr

R3

OH

R2

R1

51-67% yield, >95:5 er,>99:1 dr

ǃ-Hydroxy allylsilanes

R1 SiMe3

OH

R2

74-96% yield, >94:6 er,>25:1 dr

R1 SiMe3

OH

R2

64-67% yield, >93:7 er,>25:1 dr

ǂ-Silyl boronic esters

R

Bpin

SiMe2Ph

68-69% yield,>96:4 er

Bpin

R2 R1

Si

52-84% yield,>97:3 er

Tertiary allylic boronicesters and derivatives

OH

R4R3

R2 R1

Tertiary propargylic boronic esters and derivatives

OH

R2R1

tBu42-58% yield,>95:5 er

Tertiary alkyl boronicesters and derivatives

OH

R3 R2

R1

35-80% yield,>97:3 er

Contiguous quaternary stereocenters

HO Ar

R1Ar32-85% yield, >95:5 dr,>99:1 er

Acyclic γ-dimethylamino tertiary boronic esters

Ph

BpinR

N

44-75% yield

1,3-Bis(boronic esters) and derivatives

R3

OH OH

R1

R2

43-94% yield, >95:5 dr,99:1 er

72-92% yield,>98:2 er

Lithiation-BorylationinTotalSynthesis

O

OH

OHOH

O

OO

NH N

OH OH

OTBS

F

O

NHPh

C14H29

OH

OH

OH OH

( )5

O

O OH OH

OO

OH

H

C5H11

OH

OH

H

HO

O

O

MeOOMe

OMe

OH

O O

OH

HH

H

O

O

O

O OH

MeOOMe

OMe

Sch725674(-)-Stemaphylline

Atorvastatin (Lipitor) Derivative

(+)-Giganin

(+)-Erogorgiaene

Mycolactone Core

Solandelactone E

(-)-Clavosolide AO

Br

ClCl

NHMe

ONC

F

NMe2

O

O

HOOH

OH

HOO

OHOH

(-)-Decarestrictine

Escitalopram

(-)-Filiforminǂ-1 Hormone (+)-Sertraline

Assembly-LineSynthesisExamples

N

SN

O

(+)-kalkitoxin

OMe

OMe

MeO

MeO

OMe

OMe

OMe

OMeMeO

Tatanan A

O

Ph

Bpin

All-Syn Helical Structure

HO2COH

C15H31

(+)-Hydroxyphthioceranic Acid

HO

OH

OH OH OH O

R

Baulamycin A (R = CH2CH3)Baulamycin B (R = CH3)

(+)-Faranal

IterativeAssembly-LineSynthesis

Ph

BpinTIBO

Li

MeH

TIBO

Li

MeH

TIBO

Li

MeH

TIBO

Li

MeH

TIBO

Li

MeH

TIBO

Li

MeH

TIBO

Li

MeH

TIBO

Li

MeH

TIBO

Li

MeH

Ph

Bpin

Bpin

99.3:0.7 er

99.3:0.7 er

98.7:1.3 er

58% yield (9 steps)

44% yield (9 steps)

45% yield (9 steps)

9-mer:10-mer:11-mer = 1:97:2

9-mer:10-mer:11-mer = 1:94:5

9-mer:10-mer:11-mer = 0:97:3

Ph

Bpin

Ph

BpinTIBO

Li

HMe

TIBO

Li

MeH

TIBO

Li

HMe

TIBO

Li

MeH

TIBO

Li

HMe

TIBO

Li

MeH

TIBO

Li

HMe

TIBO

Li

MeH

TIBO

Li

HMe

TIBO

Li

HMe

TIBO

Li

HMe

TIBO

Li

MeH

TIBO

Li

MeH

TIBO

Li

HMe

TIBO

Li

HMe

TIBO

Li

MeH

TIBO

Li

MeH

TIBO

Li

HMe

Bpin

・Tencontiguous,stereochemicallydefinedmethylgroups.・Totalstereocontrol.・Noextramanipulationrequired.R

Bpin

Bpin

RHMe

B

TIBO MeH

ROO

Re-entry intoiterative cycle

TIBO

Li

MeH

V.K.Aggarwal.etal.Nature.,2014,513,183.

IterativeAssemblyLineSynthesisofPolypropionates

TIBO

Li

MeH

TIBO

Li

HMe Li Cl

Si

Li

HCl

N

OMe

Si

Li

ClH

N

OMe

[Me] [Me] [C]

[Si] [Si]

= = =

= =

[Ir]LEDs

Photoredox cleavage=

・Fivecontiguousstereocenters.・Fullstereocontrolinaneffectively‘one-pot’process.・Purificationofintermediatesisnot　required.

V.K.Aggarwal.etal.NatureChem.,2017,9,896.

Bn BpinSi

Bn Bpin

OMeSi

BnSi Bpin

OMe OMe[SI] [Ir] [Me]

LEDs

[SI] [Ir] [Me]

LEDs

[C] m-CPBA

KHF2, DMF

OHBn

OH OH

70% yield, >95:5 dr 58% yield, 94:6 dr 66% yield, >95:5 dr

OHBn

OH OH

75% yield, >95:5 dr

OHBn

OH OH

52% yield, >95:5 dr

OH OH OH

71% yield, >95:5 dr

StereocontrolledHomologationofLithiatedα-chloromethylsilanewithboronicesters

Si

N

OMe

Cl

HCl

s-BuLi, Et2O

-78℃, 1hSi

LiN

OMe

Cl

R-Bpin, Et2O

-78℃Si

BN

OMe

ORO

ClH

-78℃ to rt

1hSi

N

OMe

Bpin

R

R = alkanes, aromatic substituted alkanes, alkenes, protected alcohols, tert-butyl esters, azides

60%-92% yield, >85:15 dr

・Sincetheboronatecomplexispronetoundergoβ-eliminationratherthanthedesired1,2-migration,theoxygenfunctionalityismaskedasasilylgroup.

・Thesilylgrouprendersanadjacentcarbanionconfigurationallyunstableevenatlowtemperature,lithiatedbenzylsilanebearingatetheredchiralmethoxymethylpyrrolidinomethylmoietyisused.

・Thepronouncedtetrahedralnatureoforganoithiumtogetherwithitspotentialtocomplexwiththeoxygenatomsoftheboronicesterdirectsthereagenttothesamefaceasthelithiumatom,accountsfortheoriginoftheretentionofconfigurationobserved.

・AgoodleavinggroupCl-isusedtoimprovethereactivityofthe1,2-migrationinsteadofutilizingadditivessuchasMg(ClO4)2.


AssemblyLineSynthesisProtocolfortheconstructionofpolypropionates

Bn[Si]

Bpin

Li

TIBO HMe

BnMe2Si

Bpin

NOMe

61% yield, >95:5 dr

Si

Li

ClH

N

OMe

No reaction

[Ir]

LEDs BnMe2Si

Bpin

OMe

79% yield

Li

TIBO HMe

Bn BpinMe2Si

OMe Si

Li

ClH

N

OMe

Bn

[Si]

Bpin

SiOMe

[Ir]

LEDs

Li

TIBO HMe

Si SiOMe OMe

Bn

Bpin

59% yield, >95:5 dr

I2, NaOMe(1)

(2) Urea-H2O2, KF KHCO3, THF, MeOH

Li

BnOH OH

92% yield, >95:5 dr


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34 35

Contents

•  Introduction




•  Summary

Summary

•  Severalfactorsshouldbeconsideredwhenthinkingabout1,2-migratonandstereoselectivityoflithiation-borylationreaction.

•  Lithiation-Borylationisapowerfulmethodinassembly-linesynthesis.

ThankYou!

AppendixProposedcatalyticcycleforphotoredoxcleavageofaminosilane


Lithiation-Borylation Methodology and Its Application in … · 2021. 2. 22. · 60% yield, 99% ee,...

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