Copper-CatalyzedReactionswithDiborons: FromtheBeginningtoRecentResults
HajimeIto,HokkaidoUniversity,Japan
HokkaidoUniversity
FacultyMembers:4000
HokkaidoUniversity
UndergraduateStudents:12000
GraduateStudents:6000
HokkaidoUniversity
FacultyMembers:4000
HokkaidoUniversity
UndergraduateStudents:12000
GraduateStudents:6000
AkiraSuzuki 2010NobelPrizeWinner
ResearchesinIto’sGroup
Cu catalysis (2000−)
Si-B/base Chemistry (2012−)
J. Am. Chem. Soc., 2012, 134, 19997; Chem. Sci. 2015, 6, 2943.
BorylationReactions
Angew. Chem., Int. Ed. 2015, 54, 8809. J. Am. Chem. Soc. 2015, 137, 420. J. Am. Chem. Soc. 2014, 136, 16515. J. Am. Chem. Soc. 2013, 135, 2635. Org. Lett. 2012, 14, 890. Angew. Chem., Int. Ed. 2011, 50, 2778. J. Am. Chem. Soc. 2010, 132, 11440. J. Am. Chem. Soc. 2010, 132, 1226 .
J. Am. Chem. Soc. 2010, 132, 5990. Angew. Chem., Int. Ed. 2010, 122, 570. Nature Chemistry 2010, 2, 972. J. Am. Chem. Soc. 2008, 130, 15774. Angew. Chem., Int. Ed. 2008, 47, 7424. J. Am. Chem. Soc. 2007, 129, 14856. J. Am. Chem. Soc. 2005, 127, 16034.
DFT calculation: J. Am. Chem. Soc. 2015, 137, 4090.
EWG(pin)B B(pin)
Cu cat.EWG
(pin)B
Ito, Hosomi Tetrahedron Lett. 2000, 40, 7807.(Ishiyama, Miyaura, Chem. Lett. 2000, 982.)
Chem. Sci., 2015, 6, 2187.
Mechano-ResponsiveMaterial
J. Am. Chem. Soc. 2008, 130, 10044.
Nature Comm. 2013, 4, 2009.
Angew. Chem., Int. Ed. 2013, 52, 12828, VIP.Chem. Sci., 2015, 6, 1491.
Chem. Sci., 2015, 6, 2187.
BoronicAcids:PreparationandApplicationsinOrganicSynthesis,MedicineandMaterials,2ndreviseded.; Hall,D.G.,Ed.;Wiley-VCH:Weinheim,2011.
B
R1 R1
H
C
R1 R1
H
HO
R1 R1
H
H2N
R1 R1
H
VersatileBuildingBlock
MajorSyntheticMethods・Hydroboration・Electrophilicreactionsofboronreagents・Pd-catalyzedreactionsofB2pin2(Miyaura’sprocedure)
OrganoboronCompounds
NopracticalnucleophilicreactionsofboronreagentsLowelectronegativityofB(2.0)makesgenerationofBaniondif@icult.
・Hydroboration
Hydroborationisnottheperfectsolution.
■Brown’sasymmetrichydroborationwithstoichiometricchiralgroup
BH2 +
H B(ipc)2 H OHoxidation
99% ee
OH+ 2
H. C. Brown (1961)
・Hydroboration
Hydroborationisnottheperfectsolution.
■Asymmetriccatalytichydroborationwaslimited.
Ph
[Rh(cod)2]BF4 (1 mol %)(R)-BINAP (1 mol %)
–78°C, 6 h
OHB
O+ Ph
B(cat)
91%, 96.2 % ee
Hayashi, T.; Matsumoto, Y.; Ito, Y. J. Am. Chem. Soc. 1989, 111, 3426.!
■Brown’sasymmetrichydroborationwithstoichiometricchiralgroup
BH2 +
H B(ipc)2 H OHoxidation
99% ee
OH+ 2
H. C. Brown (1961)
・RLi,RMgXandBoronElectrophiles
RLiandRMgBrstillhavelimitations.
M R X BX
X
−MXR B
X
X
Highlybasicconditions,lowfunctionalgroupcompatibility
・RLi,RMgXandBoronElectrophiles
RLiandRMgBrstillhavelimitations.
M R X BX
X
−MXR B
X
X
Highlybasicconditions,lowfunctionalgroupcompatibility
N
Ph O N(i-Pr)2
O
(-)-sparteine
s-BuLi–78°C
Ph O N(i-Pr)2
OLi
H
N
Ph O N(i-Pr)2
OB
H
OO
Et
Et BO
O
MgBr2
PhBO
OEt
90%, 96% ee
R Li BX
■ChiralOrganoboron(Aggarwaletal)
no reaction(DMI)nCu H(DMI)nCu
Cl
HSi
Cu Cl +
NN
O
(DMI)(THF)
O
H SiCH3
CH3
Copper-CatalyzedHydrosilylation
no reaction(DMI)nCu H(DMI)nCu
Cl
HSi
Ito, H.; Ishizuka, T.; Arimoto, K.; Miura, K.; Hosomi, A. Tetrahedron Lett. 1997, 38, 8887.
O
H Si+cat. CuCl
DMI, rt
O
H92%
H3O+CH3
CH3
Cu Cl +
NN
O
(DMI)(THF)
O
H SiCH3
CH3
Catalysis
Copper-CatalyzedHydrosilylation
StoichiometricReaction
OurPreliminaryCopper-CatalyzedReactions
■Hydorsilylaiton
CuCl / DMI / R3SiH:Ito, H.; Ishizuka, T.; Arimoto, K.; Miura, K.; Hosomi, A. Tetrahedron Lett. 1997, 38, 8887.
O
H Si+cat. CuCl
DMI, rt
O
H92%
H3O+CH3
CH3
CuX
SiH
Cu H
L
L
FCu(PPh3) / R3SiH: Mori, A.; Fujita, A.; Nishihara, Y.; Hiyama, T. Chem. Commun. 1997, 2159.
OurPreliminaryCopper-CatalyzedReactions
■Silylationwithdisilanes
Si Ph+
cat. CuOTf PBu3
DMI, rt
H3O+O
SiPh
O
SiPh
Ito, H.; Ishizuka, T.; Tateiwa, J.; Sonoda, M.; Hosomi, A. J. Am. Chem. Soc. 1998, 120, 11196.
CuX
SiSi
Cu Si
L
L
■Hydorsilylaiton
CuCl / DMI / R3SiH:Ito, H.; Ishizuka, T.; Arimoto, K.; Miura, K.; Hosomi, A. Tetrahedron Lett. 1997, 38, 8887.
O
H Si+cat. CuCl
DMI, rt
O
H92%
H3O+CH3
CH3
CuX
SiH
Cu H
L
L
FCu(PPh3) / R3SiH: Mori, A.; Fujita, A.; Nishihara, Y.; Hiyama, T. Chem. Commun. 1997, 2159.
EarlyStudiesonDiboron/CuCatalysis
CuCl/KOAc: Takahashi, K.; Ishiyama, T.; Miyaura, N. Chem. Lett. 2000, 982. CuX/PR3: Ito, H.; Yamanaka, H.; Tateiwa, J.; Hosomi, A. Tetrahedron Lett. 2000, 41, 6821.
+
cat. CuX PR3
DMI, rt
H3O+
OO
BB B
O
OO
O
OO
87%
■FirstCu-CatalyzedFormalNucleophilicBorylation
EarlyStudiesonDiboron/CuCatalysis
CuCl/KOAc: Takahashi, K.; Ishiyama, T.; Miyaura, N. Chem. Lett. 2000, 982. CuX/PR3: Ito, H.; Yamanaka, H.; Tateiwa, J.; Hosomi, A. Tetrahedron Lett. 2000, 41, 6821.
+
cat. CuX PR3
DMI, rt
H3O+
OO
BB B
O
OO
O
OO
87%
■FirstCu-CatalyzedFormalNucleophilicBorylation
CuX
BB
Cu BL
L
✔Boryl-CopperIntermediateBoronNucleophilicity LigandControlledSelectivity
EarlyStudiesonDiboron/CuCatalysis
Segawa, Y.; Yamashita, M.; Nozaki, K. Science 2006, 314, 113.
NNBBr
iPr
iPr iPr
iPr
NNBLi
iPr
iPr iPr
iPrLi, naphthalene
THF
■Generationof”Boryl-Anion”wasdif]icult.
CuCl/KOAc: Takahashi, K.; Ishiyama, T.; Miyaura, N. Chem. Lett. 2000, 982. CuX/PR3: Ito, H.; Yamanaka, H.; Tateiwa, J.; Hosomi, A. Tetrahedron Lett. 2000, 41, 6821.
+
cat. CuX PR3
DMI, rt
H3O+
OO
BB B
O
OO
O
OO
87%
■FirstCu-CatalyzedFormalNucleophilicBorylation
CuX
BB
Cu BL
L
✔Boryl-CopperIntermediateBoronNucleophilicity LigandControlledSelectivity
EarlyStudiesonDiboron/CuCatalysis
CuCl/KOAc: Takahashi, K.; Ishiyama, T.; Miyaura, N. Chem. Lett. 2000, 982. CuX/PR3: Ito, H.; Yamanaka, H.; Tateiwa, J.; Hosomi, A. Tetrahedron Lett. 2000, 41, 6821.
+
cat. CuX PR3
DMI, rt
H3O+
OO
BB B
O
OO
O
OO
87%
■FirstCu-CatalyzedFormalNucleophilicBorylation
CuX
BB
Cu BL
L
✔Boryl-CopperIntermediateBoronNucleophilicity LigandControlledSelectivity
R M X B R B
FornmalNucleophilicborylation
▶ ▶Mildreactionconditions
B CuR X R B
Umpolung
▶Catalyticasymmetricsynthesis▶
Electrophilicborylation
HighlybasicconditionsStoichiometricreaction
M R
Xantphos/Cu shows High reactivity High regio- and E/Z selectivity
Ito, H.; Kawakami, C.; Sawamura, M. J. Am. Chem. Soc. 2005, 127, 16034.
Cu(O-t-Bu)/ ligand(5 mol %)
GC yield, %
dppf
100
3744
Xantphos
Ligand E : Z a
97 : 399 : 1
96 : 4> 99 : < 197 : 3 > 99 : < 1
11 62 : 38> 99 : < 1
γ : α
dppedppp
OPPh2Ph2P
+
2.0 equiv.
OB
O
OB
O
Xantphos:
Pd(dba)2 0 57 : 43
R
OCO2Me
R
B
R = (CH2)3Ph
O O
γ
THF, rt, 3 h
BCu
OR
L
B
AllyboronSynthesis:Xantphos/Cu
S R
2.4 equiv.
Bu
B(pin)MeO2CO Bu(pin)B B(pin)+
THF, 0 °C, 40 h
10 mol% Cu(O-t-Bu)ーXantphos
88%, 97% eeγ:α = >99:1, E:Z = >99:1
97% ee
Ito, H.; Kawakami, C.; Sawamura, M. J. Am. Chem. Soc. 2005, 127, 16034.
C CR2C
H R1R3
OR
HC C
B
R1R2
H
CR3H
C CR2C
H R1R3
OR
H
Cu BLL Cu B
■Cu/Xantphos:anti-SN2’reaction
AllyboronSynthesis:AsymmetricReactions
S R
2.4 equiv.
Bu
B(pin)MeO2CO Bu(pin)B B(pin)+
THF, 0 °C, 40 h
10 mol% Cu(O-t-Bu)ーXantphos
88%, 97% eeγ:α = >99:1, E:Z = >99:1
97% ee
Ito, H.; Kawakami, C.; Sawamura, M. J. Am. Chem. Soc. 2005, 127, 16034.
C CR2C
H R1R3
OR
HC C
B
R1R2
H
CR3H
C CR2C
H R1R3
OR
H
Cu BLL Cu B
■Cu/Xantphos:anti-SN2’reaction
AllyboronSynthesis:AsymmetricReactions
■AsymmetricCu-catalyzedAllylboronSynthesis
Ito, H.; Ito, S.; Sasaki, Y.; Matsuura, K.; Sawamura, M. J. Am. Chem. Soc. 2007, 129, 14856.
N
N P
P
t-BuMe
t-Bu Me
(R,R)-QuinoxP*
R OCO2Me B BO
OO
O+
5 mol% Cu(O-t-Bu)/ chiral ligand
THF, 0 °C20 h R
BOO
78%, 96% eeR = PhCH2CH2
EarlyStudiesonDiboron/CuCatalysis
Mun, S.; Lee, J. E.; Yun, J. Org Lett. 2006, 8, 4887, Lee, J.-E.; Yun, J. Angew. Chem., Int. Ed. 2008, 47, 145.
R EWG B BO
OO
O+
cat. CuCl/Na(O-t-Bu)
chiral ligand, ROHR EWGB
OO Fe PPh2
PCy2
(R)-(S)-Josiphos*
■FirstEnantioselectiveReactionsbyYun
EarlyStudiesonDiboron/CuCatalysis
Mun, S.; Lee, J. E.; Yun, J. Org Lett. 2006, 8, 4887, Lee, J.-E.; Yun, J. Angew. Chem., Int. Ed. 2008, 47, 145.
R EWG B BO
OO
O+
cat. CuCl/Na(O-t-Bu)
chiral ligand, ROHR EWGB
OO Fe PPh2
PCy2
(R)-(S)-Josiphos*
■FirstEnantioselectiveReactionsbyYun
■FirstIsolationofBorylcopperSpecies
Efficient Homogeneous Catalysis in the Reduction of CO2 to CODavid S. Laitar, Peter Muller, and Joseph P. Sadighi*
Department of Chemistry, Massachusetts Institute of Technology, 77 Massachusetts AVenue,Cambridge Massachusetts 02139
Received September 28, 2005; E-mail: [email protected]
Nature uses carbon dioxide, on a massive scale, as a one-carbonbuilding block for the synthesis of organic molecules.1 An importantpathway for the consumption of CO2 is its reduction to CO by theenzyme acetyl-CoA synthase/CO dehydrogenase (ACS-CODH).2Due to the large energy input required to generate it from CO2,CO is produced industrially from fossil fuels.3 Even with strongreducing agents, however, overcoming the OdCO bond enthalpyof 532 kJ/mol4 often presents kinetic difficulties.5,6Certain metal complexes abstract oxygen readily from CO2,7 but
the resulting metal-oxygen bonds are necessarily strong, andcatalytic turnover is rare.8 Photolytic9 and photocatalytic10 ap-proaches show promise, and synthetic electrocatalysts have achievedimpressive yields and selectivities in the reduction of CO2 to CO.11However, the chemical processes involved are obscure, making itdifficult to improve these systems by design, and CODH remainsnotably the most efficient catalyst for this reduction.12 We reportherein that a new carbene-supported copper(I) boryl complexabstracts oxygen from CO2 and undergoes subsequent turnoverreadily. Using an easily handled diboron reagent as the net oxygenacceptor,13 these key steps permit unprecedented turnover numbersand frequencies for the chemical reduction of CO2 to CO in ahomogeneous system.While exploring the chemistry of organocopper(I) complexes
supported by N-heterocyclic carbene (NHC) ligands,14 we soughtto synthesize a copper(I) boryl complex and explore its reactivitytoward CO2. Metal boryls often display distinctive reactivity,15catalyzing a number of remarkable transformations.16 AlthoughC-B bond-forming reactions have been achieved using diboroncompounds with catalytic17a or stoichiometric17b copper(I), well-defined copper boryl complexes have not been described.The known (IPr)Cu(Ot-Bu) reacts rapidly with bis(pinacolato)-
diboron (pinB-Bpin), forming a product identified as (IPr)Cu(Bpin)(1, Scheme 1) by 1H and 11B NMR spectroscopy. Diffusion ofhexane vapor into a concentrated solution of 1 in toluene, carriedout at -40 °C to avoid thermal decomposition,18 produces singlecrystals suitable for analysis by X-ray diffraction. The resultingstructure (Figure 1a) shows a monomeric, nearly linear coordinationgeometry with a Cu-B distance of 2.002(3) Å.Complex 1 reacts with CO2 under atmospheric pressure in C6D6
solution, quantitatively forming a new complex within minutes. Theresonance for 1 in the 11B NMR spectrum, a broad singlet at 41.7ppm, is replaced by a singlet at 21.8 ppm, indicative of boron boundto three oxygen atoms.19 Single crystals of this new copper complexare grown by diffusion of hexane vapor into a concentrated toluenesolution. The X-ray crystal structure (Figure 1b) reveals the productto be (IPr)Cu(OBpin) (2): The copper boryl complex abstractsoxygen from CO2, implying the release of CO as the byproduct.To confirm the formation of CO, 13C-labeled CO2 is introduced
to a resealable NMR tube containing a solution of 1 in THF-d8 at-80 °C. After 30 min of gradual warming, analysis by 11B (Figure2a) and 1H NMR spectroscopy at -40 °C indicates complete
conversion of 1 to 2. The sole labeled products visible in the 13CNMR spectrum (Figure 2b) are 13CO (δ 184 ppm) and an adduct(δ 164 ppm) formed reversibly from CO and borate 2.20Treatment of 2 in C6D6 solution with pinB-Bpin smoothly
regenerates 1, forming the stable byproduct pinB-O-Bpin,21 overa reaction time of about 20 min. The success of this turnover stepcloses a catalytic cycle for the deoxygenation of CO2. Addition ofa THF solution of (IPr)Cu(Ot-Bu) to a 100-fold excess of pinB-Bpin under an atmosphere of CO2 results in the complete conversionof pinB-Bpin to pinB-O-Bpin within 20 h at ambient temper-ature, as judged by 11B NMR analysis of an aliquot from the reactionmixture (Figure 3a). When labeled CO2 is used as the limitingreagent, in the presence of ca. 2 mol % of precatalyst 1, the 13CNMR spectrum indicates complete consumption of CO2, with COrepresenting the sole significant product (Figure 3b).In the absence of copper catalyst, under otherwise identical
conditions, no pinB-O-Bpin is detected, demonstrating that thediboron compound by itself is kinetically unable to reduce CO2 toany observable extent. Control reactions run using copper precata-lyst and pinB-Bpin in the absence of CO2 (under an atmosphere
Scheme 1 a
a Isolated yield, contains some 2 (5 mol % by 11B NMR); (b) reaction iscomplete in <10 min at ambient temp; (c) L ) IPr or ICy.
Figure 1. X-ray crystal structures, shown as 50% thermal ellipsoids, ofboryl complex 1‚C6H14 (a), and borate 2‚C7H8 (b). Hydrogen atoms (calcd)and solvent are omitted for clarity. Selected bond lengths (Å) and angles(deg), (a): Cu(1)-B(1) 2.002(3), Cu(1)-C(1) 1.937(2), C(1)-N(1) 1.363(3),C(1)-N(2) 1.363(3), C(1)-Cu(1)-B(1) 168.07(16), N(1)-C(1)-N(2)102.97(18); (b): Cu(1)-O(1) 1.8096(16), O(1)-B(1) 1.306(3), Cu(1)-C(1) 1.857(2), C(1)-N(1) 1.355(3), C(1)-N(2) 1.364(3), C(1)-Cu(1)-O(1) 174.85(10), B(1)-O(1)-Cu(1) 133.61(16), N(1)-C(1)-N(2) 103.09(18).
Published on Web 11/18/2005
17196 9 J. AM. CHEM. SOC. 2005, 127, 17196-17197 10.1021/ja0566679 CCC: $30.25 © 2005 American Chemical Society
NN
Cu
tBuOiPr
iPr
iPr
iPr
NN
CuiPr
iPr
iPr
iPr
B(pin)
(pin)B-B(pin)
Laitar, D. S.; Müller, P.; Sadighi, J. P. J. Am. Chem. Soc. 2005, 127, 17197.
EarlyStudiesonDiboron/CuCatalysis
Mun, S.; Lee, J. E.; Yun, J. Org Lett. 2006, 8, 4887, Lee, J.-E.; Yun, J. Angew. Chem., Int. Ed. 2008, 47, 145.
R EWG B BO
OO
O+
cat. CuCl/Na(O-t-Bu)
chiral ligand, ROHR EWGB
OO Fe PPh2
PCy2
(R)-(S)-Josiphos*
■FirstEnantioselectiveReactionsbyYun
■ChiralNHCLigand
Lee, Y.; Hoveyda, A. J. Am. Chem. Soc. 2009, 131, 3160.
N N
Ph Phi-Pr
i-Pr i-Pr
SO3–
Ph (pin)B B(pin)+cat.CuCl/K(O-t-Bu)
THF, –50°C, 48 h, MeOH, 2.0 equiv
+
PhB(pin)
80%, 98% ee
■FirstIsolationofBorylcopperSpecies
Efficient Homogeneous Catalysis in the Reduction of CO2 to CODavid S. Laitar, Peter Muller, and Joseph P. Sadighi*
Department of Chemistry, Massachusetts Institute of Technology, 77 Massachusetts AVenue,Cambridge Massachusetts 02139
Received September 28, 2005; E-mail: [email protected]
Nature uses carbon dioxide, on a massive scale, as a one-carbonbuilding block for the synthesis of organic molecules.1 An importantpathway for the consumption of CO2 is its reduction to CO by theenzyme acetyl-CoA synthase/CO dehydrogenase (ACS-CODH).2Due to the large energy input required to generate it from CO2,CO is produced industrially from fossil fuels.3 Even with strongreducing agents, however, overcoming the OdCO bond enthalpyof 532 kJ/mol4 often presents kinetic difficulties.5,6Certain metal complexes abstract oxygen readily from CO2,7 but
the resulting metal-oxygen bonds are necessarily strong, andcatalytic turnover is rare.8 Photolytic9 and photocatalytic10 ap-proaches show promise, and synthetic electrocatalysts have achievedimpressive yields and selectivities in the reduction of CO2 to CO.11However, the chemical processes involved are obscure, making itdifficult to improve these systems by design, and CODH remainsnotably the most efficient catalyst for this reduction.12 We reportherein that a new carbene-supported copper(I) boryl complexabstracts oxygen from CO2 and undergoes subsequent turnoverreadily. Using an easily handled diboron reagent as the net oxygenacceptor,13 these key steps permit unprecedented turnover numbersand frequencies for the chemical reduction of CO2 to CO in ahomogeneous system.While exploring the chemistry of organocopper(I) complexes
supported by N-heterocyclic carbene (NHC) ligands,14 we soughtto synthesize a copper(I) boryl complex and explore its reactivitytoward CO2. Metal boryls often display distinctive reactivity,15catalyzing a number of remarkable transformations.16 AlthoughC-B bond-forming reactions have been achieved using diboroncompounds with catalytic17a or stoichiometric17b copper(I), well-defined copper boryl complexes have not been described.The known (IPr)Cu(Ot-Bu) reacts rapidly with bis(pinacolato)-
diboron (pinB-Bpin), forming a product identified as (IPr)Cu(Bpin)(1, Scheme 1) by 1H and 11B NMR spectroscopy. Diffusion ofhexane vapor into a concentrated solution of 1 in toluene, carriedout at -40 °C to avoid thermal decomposition,18 produces singlecrystals suitable for analysis by X-ray diffraction. The resultingstructure (Figure 1a) shows a monomeric, nearly linear coordinationgeometry with a Cu-B distance of 2.002(3) Å.Complex 1 reacts with CO2 under atmospheric pressure in C6D6
solution, quantitatively forming a new complex within minutes. Theresonance for 1 in the 11B NMR spectrum, a broad singlet at 41.7ppm, is replaced by a singlet at 21.8 ppm, indicative of boron boundto three oxygen atoms.19 Single crystals of this new copper complexare grown by diffusion of hexane vapor into a concentrated toluenesolution. The X-ray crystal structure (Figure 1b) reveals the productto be (IPr)Cu(OBpin) (2): The copper boryl complex abstractsoxygen from CO2, implying the release of CO as the byproduct.To confirm the formation of CO, 13C-labeled CO2 is introduced
to a resealable NMR tube containing a solution of 1 in THF-d8 at-80 °C. After 30 min of gradual warming, analysis by 11B (Figure2a) and 1H NMR spectroscopy at -40 °C indicates complete
conversion of 1 to 2. The sole labeled products visible in the 13CNMR spectrum (Figure 2b) are 13CO (δ 184 ppm) and an adduct(δ 164 ppm) formed reversibly from CO and borate 2.20Treatment of 2 in C6D6 solution with pinB-Bpin smoothly
regenerates 1, forming the stable byproduct pinB-O-Bpin,21 overa reaction time of about 20 min. The success of this turnover stepcloses a catalytic cycle for the deoxygenation of CO2. Addition ofa THF solution of (IPr)Cu(Ot-Bu) to a 100-fold excess of pinB-Bpin under an atmosphere of CO2 results in the complete conversionof pinB-Bpin to pinB-O-Bpin within 20 h at ambient temper-ature, as judged by 11B NMR analysis of an aliquot from the reactionmixture (Figure 3a). When labeled CO2 is used as the limitingreagent, in the presence of ca. 2 mol % of precatalyst 1, the 13CNMR spectrum indicates complete consumption of CO2, with COrepresenting the sole significant product (Figure 3b).In the absence of copper catalyst, under otherwise identical
conditions, no pinB-O-Bpin is detected, demonstrating that thediboron compound by itself is kinetically unable to reduce CO2 toany observable extent. Control reactions run using copper precata-lyst and pinB-Bpin in the absence of CO2 (under an atmosphere
Scheme 1 a
a Isolated yield, contains some 2 (5 mol % by 11B NMR); (b) reaction iscomplete in <10 min at ambient temp; (c) L ) IPr or ICy.
Figure 1. X-ray crystal structures, shown as 50% thermal ellipsoids, ofboryl complex 1‚C6H14 (a), and borate 2‚C7H8 (b). Hydrogen atoms (calcd)and solvent are omitted for clarity. Selected bond lengths (Å) and angles(deg), (a): Cu(1)-B(1) 2.002(3), Cu(1)-C(1) 1.937(2), C(1)-N(1) 1.363(3),C(1)-N(2) 1.363(3), C(1)-Cu(1)-B(1) 168.07(16), N(1)-C(1)-N(2)102.97(18); (b): Cu(1)-O(1) 1.8096(16), O(1)-B(1) 1.306(3), Cu(1)-C(1) 1.857(2), C(1)-N(1) 1.355(3), C(1)-N(2) 1.364(3), C(1)-Cu(1)-O(1) 174.85(10), B(1)-O(1)-Cu(1) 133.61(16), N(1)-C(1)-N(2) 103.09(18).
Published on Web 11/18/2005
17196 9 J. AM. CHEM. SOC. 2005, 127, 17196-17197 10.1021/ja0566679 CCC: $30.25 © 2005 American Chemical Society
NN
Cu
tBuOiPr
iPr
iPr
iPr
NN
CuiPr
iPr
iPr
iPr
B(pin)
(pin)B-B(pin)
Laitar, D. S.; Müller, P.; Sadighi, J. P. J. Am. Chem. Soc. 2005, 127, 17197.
Cu BO
OL
C C
C CC C
Cu Bor
C CH B
C CB
C CB
X
CuC C
BCu
X
C CB
n
Cu ORL(pin)B B(pin)
C CE B
H+orE
R X
Ar Xor
R BO
O
OC
R'R
NC
R'R
R''or
CR'R
OHBC
R'R
NHR"B
CatalysisDesign
allylic substitution
borylativecyclization
alkyl-, aryl-substitution
aldehyde, imineaddition
X X X X
XX
Cu BO
OL
C C
C CC C
Cu Bor
C CH B
C CB
C CB
X
CuC C
BCu
X
C CB
n
Cu ORL(pin)B B(pin)
C CE B
H+orE
R X
Ar Xor
R BO
O
OC
R'R
NC
R'R
R''or
CR'R
OHBC
R'R
NHR"B
CatalysisDesign
allylic substitution
borylativecyclization
alkyl-, aryl-substitution
aldehyde, imineaddition
X X X X
XX
Ito, 2000–Miyaura, 2000–Yun, 2006–Marder, 2007–Molander, 2008–Kanai, 2009–Hoveyda, 2009–Santos, 2010–McQuade, 2010–Cordova, 2011–Hall, 2010–Carretero, 2011–Fernandez, 2011–Lam, 2012–
Kobayashi, 2012–Tsuji, 2012–de Vries, 2012–Ma, 2010–Zhu, 2013–Caser, 2013–Chun, 2013–Yoshida, 2014–Xiao and Fu, 2015–Feringa, 2015–Quiling, 2015–……
> 180 publications
Cu BO
OL
C C
C CC C
Cu Bor
C CH B
C CB
C CB
X
CuC C
BCu
X
C CB
n
Cu ORL(pin)B B(pin)
C CE B
H+orE
R X
Ar Xor
R BO
O
OC
R'R
NC
R'R
R''or
CR'R
OHBC
R'R
NHR"B
CatalysisDesign
allylic substitution
borylativecyclization
alkyl-, aryl-substitution
aldehyde, imineaddition
X X X X
X
Ito, 2000–Miyaura, 2000–Yun, 2006–Marder, 2007–Molander, 2008–Kanai, 2009–Hoveyda, 2009–Santos, 2010–McQuade, 2010–Cordova, 2011–Hall, 2010–Carretero, 2011–Fernandez, 2011–Lam, 2012–
Kobayashi, 2012–Tsuji, 2012–de Vries, 2012–Ma, 2010–Zhu, 2013–Caser, 2013–Chun, 2013–Yoshida, 2014–Xiao and Fu, 2015–Feringa, 2015–Quiling, 2015–……
> 180 publications
Cu BO
OL
C C
C CC C
Cu Bor
C CH B
C CB
C CB
X
CuC C
BCu
X
C CB
n
Cu ORL(pin)B B(pin)
C CE B
H+orE
R X
Ar Xor
R BO
O
OC
R'R
NC
R'R
R''or
CR'R
OHBC
R'R
NHR"B
CatalysisDesign
allylic substitution
borylativecyclization
alkyl-, aryl-substitution
aldehyde, imineaddition
X X X X
Ito, 2000–Miyaura, 2000–Yun, 2006–Marder, 2007–Molander, 2008–Kanai, 2009–Hoveyda, 2009–Santos, 2010–McQuade, 2010–Cordova, 2011–Hall, 2010–Carretero, 2011–Fernandez, 2011–Lam, 2012–
Kobayashi, 2012–Tsuji, 2012–de Vries, 2012–Ma, 2010–Zhu, 2013–Caser, 2013–Chun, 2013–Yoshida, 2014–Xiao and Fu, 2015–Feringa, 2015–Quiling, 2015–……
> 180 publications
Cu BO
OL
C C
C CC C
Cu Bor
C CH B
C CB
C CB
X
CuC C
BCu
X
C CB
n
Cu ORL(pin)B B(pin)
C CE B
H+orE
R X
Ar Xor
R BO
O
OC
R'R
NC
R'R
R''or
CR'R
OHBC
R'R
NHR"B
CatalysisDesign
allylic substitution
borylativecyclization
alkyl-, aryl-substitution
aldehyde, imineaddition
X X X
Ito, 2000–Miyaura, 2000–Yun, 2006–Marder, 2007–Molander, 2008–Kanai, 2009–Hoveyda, 2009–Santos, 2010–McQuade, 2010–Cordova, 2011–Hall, 2010–Carretero, 2011–Fernandez, 2011–Lam, 2012–
Kobayashi, 2012–Tsuji, 2012–de Vries, 2012–Ma, 2010–Zhu, 2013–Caser, 2013–Chun, 2013–Yoshida, 2014–Xiao and Fu, 2015–Feringa, 2015–Quiling, 2015–……
> 180 publications
Ito, H.; Okura, T.; Matsuura, K.; Sawamura, M. Angew. Chem., Int. Ed. 2010, 49, 560.
RO
(pin)Bdiboron
Cu(O-t-Bu)/(R,R)-QuinoxP* (5.0 mol %)
baseH2O
iPrOCO2H
Ph
OHPhCHO (1.0 eq.)
0 °C, 18 hrt, 2 hRO- = i-PrOCO2 87%, 97% ee
dr >99:1
ORRO
AllylicSubstitutions,Meso-andPropargyls
Ito, H.; Okura, T.; Matsuura, K.; Sawamura, M. Angew. Chem., Int. Ed. 2010, 49, 560.
RO
(pin)Bdiboron
Cu(O-t-Bu)/(R,R)-QuinoxP* (5.0 mol %)
baseH2O
iPrOCO2H
Ph
OHPhCHO (1.0 eq.)
0 °C, 18 hrt, 2 hRO- = i-PrOCO2 87%, 97% ee
dr >99:1
ORRO
AllylicSubstitutions,Meso-andPropargyls
OTIPSN
NN
N
NH2
Cl
AntiVirusDrugPrecursor
H
OTBS
CO2Me
OH
H
97% ee, >98% dsFourChiralCenters
Ito, H.; Okura, T.; Matsuura, K.; Sawamura, M. Angew. Chem., Int. Ed. 2010, 49, 560.
RO
(pin)Bdiboron
Cu(O-t-Bu)/(R,R)-QuinoxP* (5.0 mol %)
baseH2O
iPrOCO2H
Ph
OHPhCHO (1.0 eq.)
0 °C, 18 hrt, 2 hRO- = i-PrOCO2 87%, 97% ee
dr >99:1
ORRO
CCCBu
B(pin)
MeH
74%, 97% ee
10 mol %Cu(O-t-Bu)/Xantphos
THF, 50 °C, 5 h97% ee
Me C C C Bu
OCO2Me
H
(S)
(S)
2.0 equiv.
OB
O
OB
O+
■Allenylboroncompoundswithhighee.
Ito, H.; Sasaki, Y.; Sawamura, M., J. Am. Chem. Soc. 2008, 130, 15774.
AllylicSubstitutions,Meso-andPropargyls
OTIPSN
NN
N
NH2
Cl
AntiVirusDrugPrecursor
H
OTBS
CO2Me
OH
H
97% ee, >98% dsFourChiralCenters
Ito, H; Kunii, S; Sawamura, M. Nature Chem. 2010, 2, 972.
Cu(O-t-Bu)(R,R)-QuinoxP*(5.0 mol %)
(pin)B B(pin)(1.5 equiv)Et2O, 24 h
OCH3Ph
racemic 98% yield97% ee
Ph
BO
O
DirectEnantio-ConvergentReaction
Ito, H; Kunii, S; Sawamura, M. Nature Chem. 2010, 2, 972.
Cu(O-t-Bu)(R,R)-QuinoxP*(5.0 mol %)
(pin)B B(pin)(1.5 equiv)Et2O, 24 h
OCH3Ph
racemic 98% yield97% ee
Ph
BO
O
DirectEnantio-ConvergentReaction
OCH3Ph
CH3OPh
OCH3Ph
CH3O Phracemic
CuB
L*
CuB
L*
Ph
BO
O
anti-SN2'
syn-SN2'
■Onecatalystconvergetwosubstrateenantiomersintooneproduct enantiomer.
Ito, H; Kunii, S; Sawamura, M. Nature Chem. 2010, 2, 972.
Cu(O-t-Bu)(R,R)-QuinoxP*(5.0 mol %)
(pin)B B(pin)(1.5 equiv)Et2O, 24 h
OCH3Ph
racemic 98% yield97% ee
Ph
BO
O
PhCHO
Ph
B
CO
HPh Ph
HO
Ph
85% yield, 97% ee
DirectEnantio-ConvergentReaction
OCH3Ph
CH3OPh
OCH3Ph
CH3O Phracemic
CuB
L*
CuB
L*
Ph
BO
O
anti-SN2'
syn-SN2'
■Onecatalystconvergetwosubstrateenantiomersintooneproduct enantiomer.
Cu BO
OL
C C
C CC C
Cu Bor
C CH B
C CB
C CB
X
CuC C
BCu
X
C CB
n
Cu ORL(pin)B B(pin)
C CE B
H+orE
R X
Ar Xor
R BO
O
OC
R'R
NC
R'R
R''or
CR'R
OHBC
R'R
NHR"B
CatalysisDesign
allylic substitution
borylativecyclization
alkyl-, aryl-substitution
aldehyde, imineaddition
X X X
Cu BO
OL
C C
C CC C
Cu Bor
C CH B
C CB
C CB
X
CuC C
BCu
X
C CB
n
Cu ORL(pin)B B(pin)
C CE B
H+orE
R X
Ar Xor
R BO
O
OC
R'R
NC
R'R
R''or
CR'R
OHBC
R'R
NHR"B
CatalysisDesign
allylic substitution
borylativecyclization
alkyl-, aryl-substitution
aldehyde, imineaddition
X X
Cu(I) cat.(pin)B–B(pin)
Cu BL
OR
RORE
RERO
RE
Cu BL B(pin)
RERE = SiR3, Arβ LCuOR+
AsymmetricBorylativeCyclizations
Cu(I) cat.(pin)B–B(pin)
Cu BL
OR
RORE
RERO
RE
Cu BL B(pin)
RERE = SiR3, Arβ LCuOR+
(pin)B B(pin)
Cu(O-t-Bu) / ligand
R XTHF, 30 °C
B(pin)
RR = R3Si, Ar, HetAr
B(pin)
NBoc
B(pin)
S
B(pin)70%, 92% ee90%, 92% ee 70%, 92% ee
X = OCO2R, OPO(OR)2
B(pin)
Me3Si
94%, 94% ee
B(pin)
BnMe2Si
83%, 94% ee
Ito, H.; Kosaka, Y.; Nonoyama, K.; Sasaki, Y.; Sawamura, M. Angew. Chem., Int. Ed. 2008, 47, 7424.Zhong, C.; Kunii, S.; Kosaka, Y.; Sawamura, M.; Ito, H. J. Am. Chem. Soc. 2010, 132, 11440.
AsymmetricBorylativeCyclizations
a The endo-cyclization product was detected (7%).
(pin)B
4 h, 86%
(pin)B
Me
Me
4 h, 90%
(pin)B
4 h, 84%
(pin)B
6 h, 87%d.r. = 1.1:1
Si(pin)BMe
Me
4 h, 74%a
5 mol % CuCl5 mol % Xantphos(pin)B-B(pin) (1.2 equiv)
K(O-t-Bu) (1.2 equiv)THF, 30 °C
nCC
Cu
(pin)B – CuBrC n
n = 1−3 n = 1−3CC
BrBr C
(pin)B
L
complex mixtureb
Br
(pin)B
4 h, 95%d.r. = 1.4:1
(pin)B
MeMe
4 h, 83%
Kubota, K.; Yamamoto, E.; Ito, H. J. Am. Chem. Soc. 2013, 135, 2635.
b The six-membered ring product was detected (4%).
BorylativeCyclizationofTerminalAlkenes
B
B 88%
O
O
O
O
OB
OB
O
O
(1.2 equiv)
Br
Br
+
10 mol % CuCl10 mol % Xantphos
K(O-t-Bu) (2.0 equiv)THF, 30 °C, 4 h
Highexo/endoselectivity
Kubota, K.; Yamamoto, E.; Ito, H. J. Am. Chem. Soc. 2013, 135, 2635.
SpiroCompounds
5 mol % CuCl / Xantphos(pin)B-B(pin) (1.2 equiv)
t-BuOK (1.2 equiv)THF, 30 °C, 4 h, 82%
B(pin)
NS
O O
NS
O O
BrBorylativecyclization
Kubota, K.; Yamamoto, E.; Ito, H. J. Am. Chem. Soc. 2013, 135, 2635.
ShortSynthesisofDrugCandidate
5 mol % CuCl / Xantphos(pin)B-B(pin) (1.2 equiv)
t-BuOK (1.2 equiv)THF, 30 °C, 4 h, 82%
B(pin)
NS
O O
NS
O O
BrBorylativecyclization
1. NaBO3/4H2O THF/H2O, rt, 1 h
2. Jones Reagent acetone, 0 °C, 1 h 64% (2 steps)
C-OBondformation
Condensation
HistamineH3ReceptorLigand
O
NSO O
HO
O
NSO O
NN
NHN
HBTU, iPr2NEtDMF, rt, 2 h, 91%
Kubota, K.; Yamamoto, E.; Ito, H. J. Am. Chem. Soc. 2013, 135, 2635.
ShortSynthesisofDrugCandidate
Cu BO
OL
C C
C CC C
Cu Bor
C CH B
C CB
C CB
X
CuC C
BCu
X
C CB
n
Cu ORL(pin)B B(pin)
C CE B
H+orE
R X
Ar Xor
R BO
O
OC
R'R
NC
R'R
R''or
CR'R
OHBC
R'R
NHR"B
CatalysisDesign
allylic substitution
borylativecyclization
alkyl-, aryl-substitution
aldehyde, imineaddition
X X
v
■FirstAsymmetric1,2-Monoborylationof1,3-Dienes
Sasaki, Y.; Zhong, C.; Sawamura, M.; Ito, H. J. Am. Chem. Soc. 2010, 132, 1226.
(pin)B (pin)B+
THF, MeOH (2.0 equiv)–40°C, 24.5h
Cu(O-t-Bu)–(R,R)-Me-DuPhos(5.0 mol %)(pin)B B(pin) (1.5 equiv)
96%, 96% ee, dr >99:1H
AsymmtericMonoboryaltion
v
■FirstAsymmetric1,2-Monoborylationof1,3-Dienes
Sasaki, Y.; Zhong, C.; Sawamura, M.; Ito, H. J. Am. Chem. Soc. 2010, 132, 1226.
(pin)B (pin)B+
THF, MeOH (2.0 equiv)–40°C, 24.5h
Cu(O-t-Bu)–(R,R)-Me-DuPhos(5.0 mol %)(pin)B B(pin) (1.5 equiv)
96%, 96% ee, dr >99:1H
AsymmtericMonoboryaltion
(pin)B (pin)B 96 % eechiral Cu catalystB2(pin)2(1.5 equiv)
THF, t-BuOH (5.0 equiv)room temp.77% (dr 92:8)
chiral Cu catalystB2(pin)2(1.5 equiv)
THF, MeOH (5.0 equiv)–40°C 87% (dr 7:93)
v
■FirstAsymmetric1,2-Monoborylationof1,3-Dienes
Sasaki, Y.; Zhong, C.; Sawamura, M.; Ito, H. J. Am. Chem. Soc. 2010, 132, 1226.
(pin)B (pin)B+
THF, MeOH (2.0 equiv)–40°C, 24.5h
Cu(O-t-Bu)–(R,R)-Me-DuPhos(5.0 mol %)(pin)B B(pin) (1.5 equiv)
96%, 96% ee, dr >99:1H
v MeMe
BuB(pin) B(pin)
BuMe
Bucat. Cu(OtBu)/diphosphine
(pin)B B(pin)THF, MeOH
cat. Cu(OtBu)/PPh3
(pin)B B(pin)THF, MeOHup to 84% ee
■Enantio-andRegioselectiveBorylationof1,3-Enynes
Sasaki, Y.; Horita, Y.; Zhong, C.; Sawamura, M.; Ito, H. Angew. Chem., Int. Edit. 2011, 50, 2778.
AsymmtericMonoboryaltion
(pin)B (pin)B 96 % eechiral Cu catalystB2(pin)2(1.5 equiv)
THF, t-BuOH (5.0 equiv)room temp.77% (dr 92:8)
chiral Cu catalystB2(pin)2(1.5 equiv)
THF, MeOH (5.0 equiv)–40°C 87% (dr 7:93)
Cu BO
OL
C C
C CC C
Cu Bor
C CH B
C CB
C CB
X
CuC C
BCu
X
C CB
n
Cu ORL(pin)B B(pin)
C CE B
H+orE
R X
Ar Xor
R BO
O
OC
R'R
NC
R'R
R''or
CR'R
OHBC
R'R
NHR"B
CatalysisDesign
allylic substitution
borylativecyclization
alkyl-, aryl-substitution
aldehyde, imineaddition
X X
Cu BO
OL
C C
C CC C
Cu Bor
C CH B
C CB
C CB
X
CuC C
BCu
X
C CB
n
Cu ORL(pin)B B(pin)
C CE B
H+orE
R X
Ar Xor
R BO
O
OC
R'R
NC
R'R
R''or
CR'R
OHBC
R'R
NHR"B
CatalysisDesign
allylic substitution
borylativecyclization
alkyl-, aryl-substitution
aldehyde, imineaddition
X
BorylSubstitutionofC(sp3)−X
Br +
CuCl / Xantphos (3 mol %)K(O-t-Bu) (1.0 equiv)
THF, rtB(pin)Alkyl AlkylB B
O
OO
O
1.2 equiv
B(pin)B(pin)
4 h, 85% 5 h, 91%
B(pin)
5 h, 90%
B(pin)
44 h, 0%
B(pin)
48 h, 17%
B(pin)
5 h, 51%
B(pin)
B(pin)
24 h, 62%a
B(pin)B(pin)
30 h, 68%a
aReaction was carried out at 40°C with 15 mol % of catalyst, 2.2 equiv of B2pin2 and 2.0 equiv of base.
B(pin)
5 h, 84%
B(pin)
4 h, 92%
Alkyl X Alkyl BCu cat.
B BO
OO
O+
X = Cl, Br, I O
O
base
Alkyl MgX or LiXB(pin)
CuCl / Xantphos: Ito, H.; Kubota, K. Org. Lett. 2012, 14, 890. CuI / PPh3: Yang, C.-T.; Steel, P. G.; Marder, T. B.; Liu, L. et al. Angew. Chem., Int. Ed. 2012, 51, 528.
K. Kubota
BorylSubstitutionofC(sp3)−X
Br +
CuCl / Xantphos (3 mol %)K(O-t-Bu) (1.0 equiv)
THF, rtB(pin)Alkyl AlkylB B
O
OO
O
1.2 equiv
B(pin)B(pin)
4 h, 85% 5 h, 91%
B(pin)
5 h, 90%
B(pin)
44 h, 0%
B(pin)
48 h, 17%
B(pin)
5 h, 51%
B(pin)
B(pin)
24 h, 62%a
B(pin)B(pin)
30 h, 68%a
aReaction was carried out at 40°C with 15 mol % of catalyst, 2.2 equiv of B2pin2 and 2.0 equiv of base.
B(pin)
5 h, 84%
B(pin)
4 h, 92%
Alkyl X Alkyl BCu cat.
B BO
OO
O+
X = Cl, Br, I O
O
base
Alkyl MgX or LiXB(pin)
CuCl / Xantphos: Ito, H.; Kubota, K. Org. Lett. 2012, 14, 890. CuI / PPh3: Yang, C.-T.; Steel, P. G.; Marder, T. B.; Liu, L. et al. Angew. Chem., Int. Ed. 2012, 51, 528.
Ni catalyst: Dudnik, A. S.; Fu, G. C. J. Am. Chem. Soc. 2012, 134, 10693.
Pd catalyst: Joshi-Pangu, A.; Ma, X.; Diane, M.; Iqbal, S.; Kribs, R. J.; Huang, R.;
Wang, C.-Y.; Biscoe, M. R. J. Org. Chem. 2012, 77, 6629.
Pd, Ni catalyst: Yi, J.; Liu, J. H.; Liang, J.; Dai, J. J.; Yang, C.-T.; Fu, Y.; Liu, L.
Adv. Synth. Catal. 2012, 354, 1685.
Fe catalyst: Atack, T. C.; Lecker, R. M.; Cook, S. P. J. Am. Chem. Soc. 2014.
Zn catalyst: Bose, S. K.; Fucke, K.; Liu, L.; Steel, P. G.; Marder, T. B.
Angew. Chem., Int. Edit. 2014, 53, 1799.
◼VerySimpleReaction,andCompetitive!
K. Kubota
Cu BO
OL
C C
C CC C
Cu Bor
C CH B
C CB
C CB
X
CuC C
BCu
X
C CB
n
Cu ORL(pin)B B(pin)
C CE B
H+orE
R X
Ar Xor
R BO
O
OC
R'R
NC
R'R
R''or
CR'R
OHBC
R'R
NHR"B
CatalysisDesign
allylic substitution
borylativecyclization
alkyl-, aryl-substitution
aldehyde, imineaddition
X
Cu BO
OL
C C
C CC C
Cu Bor
C CH B
C CB
C CB
X
CuC C
BCu
X
C CB
n
Cu ORL(pin)B B(pin)
C CE B
H+orE
R X
Ar Xor
R BO
O
OC
R'R
NC
R'R
R''or
CR'R
OHBC
R'R
NHR"B
CatalysisDesign
allylic substitution
borylativecyclization
alkyl-, aryl-substitution
aldehyde, imineaddition
■
Latitar, D. S.; Tsui, E. Y.; Sadighi, J. P. J. Am. Chem. Soc. 2006, 128, 11036.
O
H1.0 mol % ICyCu(O-t-Bu)
(pin)B−B(pin), toluene
86%
O
B(pin)
B(pin)
Catalyticdiboration
(pin)B−B(pin)MeOH, toluene
O
H
1.5 mol %ICyCu(O-t-Bu) OH
B(pin)
crude product
KHF2
MeOH/H2O
OH
BF3K
81%Molander, G. A.; Wisnieski, S. R. J. Am. Chem. Soc. 2012, 134, 16856.
■ Catalyticmonoborylation
N N
ICy
Copper(I)-CatalyzedCarbonylBorylation
Enantioselectiveborylation
L*M
B C
RH
B OM
Enantioenrichedα-alkoxyalkylboronates
O
C
RH
Borylnucleophile
EnantioselectivenucleophilicborylationofaC=Odoublebondhasnoteverbeenachieved.
■
Kubota, K.; Yamamoto, E.; Ito, H. J. Am. Chem. Soc. 2015, 137, 420.
EnantioselectiveBorylationofAldehydes
R
O
B(pin)
B(pin)
R
OH
BF3K
Lowstability Lowsolubility Sadighi, J. Am. Chem. Soc. 2006 Molander, J. Am. Chem. Soc. 2012
R
O
H
L*CuCl
K(O-t-Bu)THF
(pin)B−B(pin)
R H
BHO OO
unstable
R H
BPGO OOprotection
Ourapproachforisolation
HighstabilityHighsolubility
■ NotsuitableforHPLCanalysistodetermineeevalues
✓
cf. Moore, C. M.; Medina, C. R.; Cannameia, P. C.; Mclntosh, M. L.; Ferber, C. J.; Roering, A. J.; Clark, T. B. Org. Lett. 2014, 16, 6056.
alcohol
ProtectionforHPLCAnalysis
H
B(pin)BnO
Ph H
B(pin)MeO
Ph H
B(pin)O
Ph
Ph
O
H
B(pin)O
Ph
Me2N
O
H
B(pin)Me3SiO
Ph
BnBr, NaH26%
Me3OBF428%
(PhCO)2O, DMAP20%
Me2NCOCl, pyridinecomplex mixture
Me3SiCl, imidazole64%
Ph H
O
CuCl (2 mol %)ICy⋅HCl (2 mol %)(pin)B−B(pin) (1.0 equiv)
K(O-t-Bu) (10 mol %)MeOH (2.0 equiv), THF
R H
B(pin)HO
not isolated
protection
H
B(pin)PGO
isolated yield (%)Ph
then silica gel short column
ProtectionforHPLCAnalysisK. Kubota
Kubota, K.; Yamamoto, E.; Ito, H. J. Am. Chem. Soc. 2015, 137, 420.
Ph
O
1. CuCl / L* (5 mol %) K(O-t-Bu) (10 mol %) MeOH (2.0 equiv) THF, 30 °C, 6 h
2. BnMe2SiCl, imidazole CH2Cl2, 3 h
Ph HH
BnMe2SiO B
(S)NMR yield (%)
B BO
O O
O+
1.0 equiv
OO
ChiralLigandScreening
Kubota, K.; Yamamoto, E.; Ito, H. J. Am. Chem. Soc. 2015, 137, 420.
Ph
O
1. CuCl / L* (5 mol %) K(O-t-Bu) (10 mol %) MeOH (2.0 equiv) THF, 30 °C, 6 h
2. BnMe2SiCl, imidazole CH2Cl2, 3 h
Ph HH
BnMe2SiO B
(S)NMR yield (%)
B BO
O O
O+
1.0 equiv
OO
O
O
O
O
PP
tBuOMe
tButBu
OMetBu
2
2
(R)-DTBM-SEGPHOS72%, 96% ee
O
O
O
O
PP
Me
MeMe
Me
2
2(R)-DM-SEGPHOS
71%, 32% ee(R)-SEGPHOS74%, 24% ee
O
O
O
O
PP
2
2
largersterichinderance
higherenantioselectivity
ChiralLigandScreening
Kubota, K.; Yamamoto, E.; Ito, H. J. Am. Chem. Soc. 2015, 137, 420.
coordination
σ-bondmetathesis
protonation
enantioselectiveinsertion
P
P= (R)-DTBM-SEGPHOS
DFT: Kubota, K.; Jin, M.; Ito, H. Organometallics, under revision.cf. Zhao, H.; Dang, L.; Marder, T. B.; Lin, Z. J. Am. Chem. Soc. 2008, 130, 5586.
Cu B(pin)PP
CuB(pin)
PP
O CHR
O CCu
R
B(pin)
H
PP
Cu ORPP R = OMe or
O-t-Bu
O CHR
(pin)B−B(pin)
MeOH
(pin)B−OR
A
B
C
DO CR
B(pin)
HH
Pointsnotelucidated
1.Mechanismofenantioselection
2.Effectofprotonsource
ProposedReactionMechanism
M. Jing
K. Kubota
Kubota, K.; Yamamoto, E.; Ito, H. J. Am. Chem. Soc. 2015, 137, 420.
Cu
B
P PO
HHH
Cu
B
P PO
H
HH
Ph Ph
Ph Ph
Ph
Ph Ph
Ph
Si-faceTS(favored) Re-faceTS(disfavored)
0kcal/mol +1.04kcal/mol
<
B3PW91/cc-PVDZ,RelativeGvalue(kcal/mol)at298K,1.0atm,gasphase.
Observedresult24%ee
DFT: Kubota, K.; Jin, M.; Ito, H. Organometallics, under revision.
EnantioselectionModels[(R)-SEGPHOS]
Cu
B
P PO
HHH
Cu
B
P PO
H
HH
Ar Ar
Ar Ar
Ar
Ar Ar
Ar
Si-faceTS(favored) Re-faceTS(disfavored)
0kcal/mol +1.97kcal/mol
<observedresult96%ee
Modelsfor[(R)-DTBM-SEGPHOS]
DFT: Kubota, K.; Jin, M.; Ito, H. Organometallics, under revision.B3PW91/cc-PVDZ,RelativeGvalue(kcal/mol)at298K,1.0atm,gasphase.
Cu
B
P PO
HHH
Cu
B
P PO
H
HH
Ar Ar
Ar Ar
Ar
Ar Ar
Ar
Si-faceTS(favored) Re-faceTS(disfavored)
0kcal/mol +1.97kcal/mol
<observedresult96%ee
Modelsfor[(R)-DTBM-SEGPHOS]
DFT: Kubota, K.; Jin, M.; Ito, H. Organometallics, under revision.B3PW91/cc-PVDZ,RelativeGvalue(kcal/mol)at298K,1.0atm,gasphase.
R
O
1. 5 mol % CuCl/ (R)-DTBM-SEGPHOS K(O-t-Bu) (10 mol %) MeOH (2.0 equiv) THF, 30 °C, 6 h
2. R3SiCl, imidazole CH2Cl2, 3 h
HB B
O
O O
O+
1.0 equiv
R H
R3SiO B
(S)isolated yield (%)
OO
B(pin)Me3SiO
H
B(pin)Me3SiO
H
B(pin)Me3SiO
H
51%, 96% ee 61%, 95% ee 84%, 95% ee 61%, 96% ee
B(pin)HO
H
B(pin)BnMe2SiO
HN
B(pin)Me3SiO
HNBoc Ts
81%, 95% ee 52%, 91% ee
B(pin)BnMe2SiO
H
69%, 90% ee
BzO
B(pin)BnMe2SiO
H
69%, 95% ee
BnO
BorylationofVariousAldehydes
Kubota, K.; Yamamoto, E.; Ito, H. J. Am. Chem. Soc. 2015, 137, 420.
H
O
H
B(pin)HOCuCl / L* (5 mol %)(pin)B−B(pin) (1.0 equiv)
K(O-t-Bu) (10 mol %)MeOH (2.0 equiv)THF (0.5 M), 30 °C, 6 h
Ph2MeSiClimidazole
CH2Cl2, 3 h
>99% conversionL* = (R)-DTBM-SEGPHOS
H
B(pin)Ph2MeSiO
22% yield99% ee
H
BF3KHOKHF2 (4.0 equiv)
MeOH/H2O, 30 min
71% yield
■ Poorstabilityoftheproducttowardsilicagelcolumn
Goodisolatedyield(71%)byconvertingintotri]luoroborate■
AromaticAldehydeCase:Unstable
CuCl / ligand (5 mol %)(pin)B−B(pin) (1.0 equiv)K(O-t-Bu) (10 mol %)MeOH (2.0 equiv)
solvent, 30 °C, 18 hthen Me3SiClimidazole, 3 h (R,S)
H
O
Me
TBSO
B(pin)
OSiMe3
Me
TBSO
(R,R)
B(pin)
OSiMe3
Me
TBSO
+
(R)
α-Stereocenter
ICy⋅HCl (2 mol %), toluene: 69%, (R,S):(R,R) = 30:70
(R)-DTBM-SEGPHOS, THF: 73%, (R,S):(R,R) = 89:11(S)-DTBM-SEGPHOS, THF: 77%, (R,S):(R,R) = 5:>95
■ Catalyst-controlledselectivityoversubstratevias
CatalystControlledReaction
For a review of Matteson homologation chemistry: Matteson, D. S. Tetrahedron 1998, 54, 10555.
cf. Sadhu, K. M.; Matteson, D. S. Organometallics 1985, 4, 1687.
Stereospeci@icC(sp3)-C(sp3)bondformation;One-carbonhomologation
Larouche-Gauthier, R.; Elfold, T. G.; Aggarval, V. K. J. Am. Chem. Soc. 2011, 133, 16794.
Ph H
B(pin)BnMe2SiO
96% ee
ClCH2Br n-BuLi
THF−78 °C→rt3 h
Ph H
BnMe2SiO B(pin)
92%, 96% ee
H2O2NaOH Ph H
HO OH
77%, 96% ee
chiral1,2-diol
chiral1,2-haloalcohol
Ph H
R3SiO Br
80%, 96% ee3,5-(CF3)2C6H3Lithen NBS, −78 °C
Usefulintermediatechiralβ-alkoxyboron
Stereospeci]icFunctionalization
Kubota, K.; Yamamoto, E.; Ito, H. J. Am. Chem. Soc. 2015, 137, 420.
H
(pin)B OSiMe3
95% ee
(S)
Benzofuran (1.2 equiv)n-BuLi (1.2 equiv)
THF, −78 °C, 1 h
NBS (1.2 equiv)
−78 °C, 1 hthen TBAF, 2 hH
Li
H
52%, 95% ee
(pin)B OSiMe3
OOH
O
(R)
Bonet, A.; Odachowski, M.; Leonori, D.; Essafi, S.; Aggarwal, V. K. Nature. Chem. 2014, 6, 584.
Stereospeci@icC(sp3)-C(sp2)bondformation;Cross-couplingwithaheteroaromaticcompound
AggarwalArylation
ChiralNHC/copper(I)complexcatalyst
HO B OO
Ph *
59%, 9% ee
HO B OO
*Ph
62%, 9% ee
HO B OO
*
no reaction
Unsuccessfulsubstrates
OB B
O
O O
O+
1.0 equiv
5 mol % CuCl / L*
NNL* =
BF4
HO B OO
*
47%, 98% ee
10 mol % K(O-t-Bu)MeOH (2.0 equiv)toluene/THF, rt, 4 h
EnantioselectiveBorylationofKetones
NH
F
O
OO
(− )-paroxetine N
N N
N
N
OPh
NH2
O ibrutinib
WAY-163909
N
NH
N
OH
(− )-preclamol
NN
Me
HMe
Me
OHN
OMe
(−)-Physostigmine
NovelBoronReagentsforAlkaloidSynthesis
N OH
(– )-preclamol
NO
Ph
PhO
O zamifenacine
ibrutinib
PyridineanditsDerivativesinHeterocyclesinNaturalProductSynthesis,Majumdar,K.C.;Chattopadhyay,S.K.,Ed.;Wiley-VCH,Weinheim,2011,Chap.8,pp.267.
NH
F
O
OO
(− )-paroxetine N
N N
N
N
OPh
NH2
O ibrutinib
WAY-163909
N
NH
N
OH
(− )-preclamol
NN
Me
HMe
Me
OHN
OMe
(−)-Physostigmine
NovelBoronReagentsforAlkaloidSynthesis
N OH
(– )-preclamol
NO
Ph
PhO
O zamifenacine
ibrutinib
PyridineanditsDerivativesinHeterocyclesinNaturalProductSynthesis,Majumdar,K.C.;Chattopadhyay,S.K.,Ed.;Wiley-VCH,Weinheim,2011,Chap.8,pp.267.
N-Heterocyclic borons
NH
BR
NH
R1
B
R
NH
F
O
OO
(− )-paroxetine N
N N
N
N
OPh
NH2
O ibrutinib
WAY-163909
N
NH
N
OH
(− )-preclamol
NN
Me
HMe
Me
OHN
OMe
(−)-Physostigmine
NovelBoronReagentsforAlkaloidSynthesis
*LCu B
N
R3
R1
R2
NR1
R2
Novel enantioselectiveborylation
Abundant, cheap andreadily available
N OH
(– )-preclamol
NO
Ph
PhO
O zamifenacine
ibrutinib
PyridineanditsDerivativesinHeterocyclesinNaturalProductSynthesis,Majumdar,K.C.;Chattopadhyay,S.K.,Ed.;Wiley-VCH,Weinheim,2011,Chap.8,pp.267.
N-Heterocyclic borons
NH
BR
NH
R1
B
R
Hydrogenation
Electrophilicallylicsubstitution
Kuwano, R.; Sato, K.; Kurokawa, T.; Karube, D.; Ito, Y. J. Am. Chem. Soc. 2000, 122, 7614.
Trost, B. M.; Quancard, J. J. Am. Chem. Soc. 2006, 128, 6314.
Trost ligand
(S,S)-(R,R)-PhTRAP
FeFe
PPh2PPh2
O NH
HN O
Ph2PPPh2
2.5 mol % Pd2(dba)3CHCl37.5 mol % chiral ligand
9-BBN-C6H13 (1.05 equiv)CH2Cl2, 4 °C
NH
N+
HO
MeO
MeO
3 equiv92%, 85% ee
1.0 mol % [Rh(nbd)2]SbF61.05 mol % PhTRAP10 mol % Cs2CO3
i-PrOH, H2 (5.0 MPa)60 °C, 2 h
NAc
NAc
91%, 91% ee
AsymmetricDearomatizations
Kubota,K.;Hayama,K.;Iwamoto,H.;Ito,H.Angew.Chem.,Int.Ed.2015,30,8809.
The first enantioselective carbon-boron bond forming dearomatization by copper(I) catalysis✓Direct synthesis of chiral boryl-indolines from readily available indoles✓
N
O
OMeCbz
+ B B
2.0 equiv
O
OO
O
10 mol % Cu(O-t-Bu) / L*10 mol % Na(O-t-Bu)
t-BuOH (2.0 equiv)THF, 30 °C, 20 h
NCbz
B(pin)
OMe
O
98%, d.r. 97:393% ee
P P
Me
Me
MeMe
Me
Me
Me
Me
L* = (R,R)-xyl-BDPP
EnantioselectiveBorylativeDearomatization
Coordinationσ-Bondmetathesis
Diastereoselectiveprotonation
3,4-Additionandtoutomerization
Stericrepulsion
Cu BP
P
P
P= (R,R)-xyl-BDPP
(pin)B−(O-t-Bu)
NCbz
OOMe
Cu BPP
NCbz
O
OMeBPP
NCbz
O
OMeB
HO
HO
Cu(O-t-Bu)P
P
diboron
substrate
HO
disfavored
favored
Cu
CuP
P
A
BC
D
E
NCbz
B(pin)
OMe
OH
Kubota,K.;Hayama,K.;Iwamoto,H.;Ito,H.Angew.Chem.,Int.Ed.2015,30,8809.
ProposedReactionMechanism
Coordinationσ-Bondmetathesis
Diastereoselectiveprotonation
3,4-Additionandtoutomerization
Stericrepulsion
Cu BP
P
P
P= (R,R)-xyl-BDPP
(pin)B−(O-t-Bu)
NCbz
OOMe
Cu BPP
NCbz
O
OMeBPP
NCbz
O
OMeB
HO
HO
Cu(O-t-Bu)P
P
diboron
substrate
HO
disfavored
favored
Cu
CuP
P
A
BC
D
E
NCbz
B(pin)
OMe
OH
Kubota,K.;Hayama,K.;Iwamoto,H.;Ito,H.Angew.Chem.,Int.Ed.2015,30,8809.
MeOH: 94%, 94% ee d.r. 75:25
t-BuOH: 98%, 93% ee d.r. 97:3
ProposedReactionMechanism
10 mol % Cu(O-t-Bu) 10 mol % chiral ligand10 mol % Na(O-t-Bu)
N
O
OMeCbz
N
O
OMeCbz
B(pin)
0.5 mmol
+OB
OB
O
O
2.0 equiv
t-BuOH (2.0 equiv) THF, 30 °C, 18−48 h
NMR yield (%)
PP
Me
Me
Me
Me
Me
Me
Me
Me PP
P
P
MeMe
Me
Me
(R,R)-BenzP*77%, d.r. 91:9
61% ee
(R,R)-Me-Duphos71%, d.r. 97:3
37% ee
P
P
Me
tBu
tBu
MeN
N P
P
Me
tBu
tBu
Me
(R,R)-3,5-xyl-BDPP98%, d.r. 97:3
93% ee
(R,R)-BDPP98%, d.r. 89:11
74% ee
(R,R)-QuinoxP*93%, d.r. 90:10
27% ee
LigandScreening
Kubota, K.; Hayama, K. Ito, H. Angew. Chem., Int. Ed. 2015, 54, 8809.
NCbz
B(pin)
OMe
OF
93% yieldd.r. 97:3, 95% ee
NCbz
B(pin)
OMe
OCl
93% yieldd.r. 93:7, 95% ee
NCbz
B(pin)
OMe
OBr
96% yieldd.r. 97:3, 92% ee
NCbz
B(pin)
OMe
OMeO
99% yieldd.r. 97:3, 97% ee
NCbz
B(pin)
OMe
O
88% yieldd.r. 97:3, 93% ee
MeO NCbz
B(pin)
OMe
O
99% yieldd.r. 93:7, 86% ee
Br NCbz
B(pin)
OMe
O
82% yieldd.r. 83:17, 89% ee
N
O
OMeCbz
10 mol % Cu(O-t-Bu)10 mol % (R,R)-xyl-BDPPB2(pin)2 (2.0 equiv)
10 mol % Na(O-t-Bu)t-BuOH (2.0 equiv)THF, 30 °C, 4−18 h
NCbz
B(pin)
OMe
OR1
R2
R1
R2
Kubota,K.;Hayama,K.;Iwamoto,H.;Ito,H.Angew.Chem.,Int.Ed.2015,30,8809.
BorylativeDearomatizationofVariousIndoles
CuCl (5 mol %)Xantphos (5 mol %)ClCO2Me (1.0 equiv)
K(O-t-Bu)/THF (1.0 equiv)MeOH (2.0 equiv), rt,
N + B B
1.2 equiv
O
OO
ON
MeO
O
BO O
detected by GC-Massdecomposed during purification
predicted structures
N
MeO
O
B O
O+Possible intermediate
NO
MeO
Cl
O
P
P
Ph Ph
Ph Ph
CuBvia
Kubota,K.;Watanabe,Y.;Hayama,K.;Ito,H.Submitted.
InitialAttemptforChiralBoryl-Piperidine
cat. Cu/L*B2(pin)2
alkoxide basealcohol
N N
RO
OClCO2R
hydridesource
N
RO
O
N
RO
O
B(pin)
B(pin)
N
RO
O
(pin)B
N
RO
O
B(pin)
*
*
*
*
Regioselective? Enantioselective?
No examples of selective borylationof conjugated dienamines
ClCO2R
NaBH4 orLiBH4
✓
✓
cat. Cu(I)/L*B2(pin)2
alkoxide basealcohol
Kubota,K.;Watanabe,Y.;Hayama,K.;Ito,H.Submitted.
AlternativeStrategy:SequencialMethod
cat. Cu/L*B2(pin)2
alkoxide basealcohol
N N
RO
OClCO2R
hydridesource
N
RO
O
N
RO
O
B(pin)
B(pin)
N
RO
O
(pin)B
N
RO
O
B(pin)
*
*
*
*
Regioselective? Enantioselective?
No examples of selective borylationof conjugated dienamines
ClCO2R
NaBH4 orLiBH4
✓
✓
cat. Cu(I)/L*B2(pin)2
alkoxide basealcohol
Kubota,K.;Watanabe,Y.;Hayama,K.;Ito,H.Submitted.
Sasaki,Y.;Zhong,C.;Sawamura,M.;Ito,H.J.Am.Chem.Soc.2010,132,1226.
MeOH (2.0 equiv)THF,−20 °C, 22 h
5 mol% Cu(O-t-Bu)/(R,R)-Me-Duphos
90%, 95% ee
B(pin)
P
PMeMe
Me
Me
(R,R)-Me-Duphos
+ B B
1.5 equivO
OO
O
cf. Enantioselective monoborylation of carbocyclic dienes
10 mol %Cu(O-t-Bu)/(R,R)-Me-Duphos
MeOH (1.0 equiv)THF, –20 °C, 22 h
90%, 95% ee
P
PMeMe
Me
Me
(R,R)-Me-Duphos
AlternativeStrategy:SequencialMethod
Pyridinesto3-SubstitutedPiperidinesCuCl (5 mol %)chiral ligand (5 mol %)3 (1.2 equiv)
K(O-t-Bu) (20 mol %)MeOH (2 equiv)THF, temp., 2-4 h2a (R)-4a
NaBH4ClCO2Me
MeOH−78 °C1 h, 71%1a
NNO
MeO
NO
MeOB(pin)
P
P
Me tBu
tBu Me(R,R)-BenzP*92%, 98% ee
N
N P
P
Me tBu
tBu Me(R,R)-QuinoxP*93%, 99% ee
O
O
O
O
PPh2PPh2
(R)-SEGPHOS, <5%
P
PMeMe
Me
Me
(R,R)-Me-Duphos83%, 93% ee
PPh2PPh2
(R)-SEGPHOS, <5%
N
R1R2
NaBH4 orLiBH4
ClCO2R3
MeOH−78 °C
N
R3O
O
R1R2 5 mol % CuCl/
(R,R)-QuinoxP*B2(pin)2 (1.2 equiv)
K(O-t-Bu) (20 mol %)MeOH (2.0 equiv)THF, –10 °C, 2 h
N
R3O
O
R1R2
B(pin)
76%, 97% ee
N
BnO
OB(pin)
N
MeO
OB(pin)
93%, 99% ee
N
O
OB(pin)
88%, 98% ee
N
O
OB(pin)
90%, 97% ee
N
PhO
OB(pin)
84%, 93% ee
N
O
OB(pin)
91%, 97% ee
N
MeO
OB(pin)
86%, 92% ee
N
MeO
OB(pin)
67%, 96% ee
Me Me
N
MeO
OB(pin)
Me
no reaction
76%, 97% ee
N
N P
P
Me tBu
tBu Me
(R,R)-QuinoxP*
93%, 99% ee 88%, 98% ee 90%, 97% ee 76%, 97% ee 84%, 93% ee
91%, 97% ee 86%, 92% ee 67%, 96% ee
Kubota,K.;Watanabe,Y.;Hayama,K.;Ito,H.Submitted.
UnprecedentedRegio-andEnantioselective
N ClCO2MeMeOH−78 °C
N
MeO
OAr NaBH4
Ar
5 mol % CuCl/(S)-SEGPHOSB2(pin)2 (1.2 equiv)
K(O-t-Bu) (20 mol %)t-BuOH (2.0 equiv)toluene/DME0 °C, 2 h
N
MeO
O
Ar
B(pin)
(R)-SEGPHOSO
O
O
O
PPh2PPh2
(R)-SEGPHOS
5 mol % CuCl/(R)-SEGPHOSB2(pin)2 (1.2 equiv)
K(O-t-Bu) (20 mol %)t-BuOH (2.0 equiv)toluene/DME/THF(6:6:1), 0 °C, 2 h
N
MeO
OBO
O
Me
91%, d.r. 98:295% ee
N
MeO
OBO
O
OMe
82%, d.r. 96:496% ee
90%, d.r. 97:392% ee
N
MeO
OB
93%, d.r. 99:139% ee*(R,R)-QuinoxP* was used.
O
O N
MeO
OBO
O
F
91%, d.r. 96:496% ee*(S)-SEGPHOS was used.
Kubota, K.; Watanabe, Y.; Hayama, K.; Ito, H. Submitted.
Diastereo-andEnantioselectiveBorylation
(−)-ParoxetineAntidepressant drug
3. MsCl (1.5 equiv) Et3N (3.0 equiv) CH2Cl2, 0 °C→rt
1. LiCH2Cl (1.5 equiv) −78 °C→rt, 3 h2. NaBO3•4H2O (4.0 equiv), rt, 1 h
N
MeO
OBO
O
d.r. 95:596% ee
F
N
MeO
O
F
OMs
77% (3 steps)d.r. 95:5
O
O
HO
(2 equiv)
Cs2CO3 (4.0 equiv)MeCN, 90 °C, 2 hthen Pd/C, H2, 12 h
N
MeO
O
F
O
67% (2 steps)d.r. >95:5, 94% ee
O
OKOH (30 equiv)
EtOH/H2O (4:1)100 °C, 42 h
HN
F
O
61% O
O
d.r. 96:496% ee
77% (3 steps)d.r. 96:4
67% (2 steps)d.r. >95:5, 94% ee
61%
Hynes, P. S.; Stupple, P. A.; Dixon, D. J. Org. Lett. 2008, 10, 1389.
Krautwald, S.; Schafroth, M. A.; Sarlah, D.; Carreira, E. M. J. Am. Chem. Soc. 2014, 136, 3020.
KOH (30 equiv)
EtOH/H2O (4:1)reflux, 42 h
d.r. 96:496% ee
77% (3 steps)d.r. 96:4
67% (2 steps)d.r. >95:5, 94% ee
61%
Kubota, K.; Watanabe, Y.; Hayama, K.; Ito, H. Submitted.
Diastereo-andEnantioselectiveBorylation
Cu-CatalyzedBorylationfromOurGroup
CuX/PR3: Ito, H.; Yamanaka, H.; Tateiwa, J.; Hosomi, A. Tetrahedron Lett. 2000, 41, 6821.
+
cat. CuX PR3
DMI, rt
H3O+
OO
BB B
O
OO
O
OO
87%
Cu-CatalyzedBorylationfromOurGroup
R
BOO
J. Am. Chem. Soc. 2005J. Am. Chem. Soc. 2007
B
OR
OO
Angew. Chem., Int. Ed. 2010
BR OO
J. Am. Chem. Soc. 2010
(rac)-
R
BO
O
Angew. Chem., Int. Ed. 2008J. Am. Chem. Soc. 2010
C C CB
BuMe
H
OO
J. Am. Chem. Soc. 2008
BO
O
J. Am. Chem. Soc. 2010
BO
O
or
B
B
O
O
O
O
J. Am. Chem. Soc. 2015
B(pin)
Org. Lett. 2012
RB
O
O
Nature Chem. 2010
Bu
BO
O
Angew. Chem., Int. Ed. 2011
RO
BOO
J. Am. Chem. Soc. 2014
B
RSi
OO
Ph Ph
Org. Lett. 2010
B(pin)HO
H
J. Am. Chem. Soc. 2013
N
B(pin)
CO2R
Angew. Chem., Int. Ed. 2015
¥Funding¥MEXT
PRESTONEXTMMCFCC
Dr. Tatsuo IshiyamaDr. Yasunori Yamamoto
Dr. Tomohiro SekiDr. Ikuo Sasaki
Dr. Eiji Yamamoto
Prof. Akira HosomiProf. Tsuneo Imamoto
Prof. Masaya Sawamura Prof. Tetsuya Taketsugu
Prof. Satoshi Maeda
Tomoko IshizukaChika KawakamiYuki KosakaShin-ichiro ItoKou MtsuuraKosuke NonoyaamTakashi Toyoda
Dr. Chongmin ZhongDr. Yusuke SasakiTakuma OkuraShun KuniiKoji KubotaTaichi OzakiYuta Takenouchi
Yuko HoritaKiyotaka IzumiRyoto KojimaHiroaki IwamotoSatoshi UkigaiDr. Ryohei Uematsu
Acknowledgements