Post on 18-Jul-2021
transcript
Lithiation-BorylationMethodologyandItsApplicationinSynthesis
LiteratureSeminar2018/06/23
HongyuCHEN(M1)
Contents
• Introduction
• Part1:Factorsresponsibleforthe1,2-migration
• Part2:Factorsresponsibleforstereocontrol
• Part3:Applicationoflithiation-borylationreactioninsynthesis
• Summary
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
• Part1:Factorsresponsibleforthe1,2-migration
• Part2:Factorsresponsibleforstereocontrol
• Part3:Applicationoflithiation-borylationreactioninsynthesis
• 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.
Example1.Iodine-InducedRearrangementofEthynyltrialkylborates(2)
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).
Example1.Iodine-InducedRearrangementofEthynyltrialkylborates(3)
S.W.Slayden.J.Org.Chem.,1981,46,2311.
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
• Part1:Factorsresponsibleforthe1,2-migration
• Part2:Factorsresponsibleforstereocontrol
• Part3:Applicationoflithiation-borylationreactioninsynthesis
• 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
LimitationsoftheMatteson-typeHomologation-Alkylation(2)
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
LimitationsoftheMatteson-typeHomologation-Alkylation(3)
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
• Part1:Factorsresponsibleforthe1,2-migration
• Part2:Factorsresponsibleforstereocontrol
• Part3:Applicationoflithiation-borylationreactioninsynthesis
• 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.
V.K.Aggarwal.etal.NatureChem.,2017,9,896.
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
V.K.Aggarwal.etal.NatureChem.,2017,9,896.
28
29
30
31
32
33
34 35
Contents
• Introduction
• Part1:Factorsresponsibleforthe1,2-migration
• Part2:Factorsresponsibleforstereocontrol
• Part3:Applicationoflithiation-borylationreactioninsynthesis
• Summary
Summary
• Severalfactorsshouldbeconsideredwhenthinkingabout1,2-migratonandstereoselectivityoflithiation-borylationreaction.
• Lithiation-Borylationisapowerfulmethodinassembly-linesynthesis.
ThankYou!
AppendixProposedcatalyticcycleforphotoredoxcleavageofaminosilane
V.K.Aggarwal.etal.NatureChem.,2017,9,896.