Catalytic conjunctive cross-coupling enabled by metal-induced metallate rearrangement

TLDR: It is demonstrated that vinyl boronic ester ate complexes, prepared by combining organoboronates and organolithium reagents, engage in palladium-induced metallate rearrangement wherein 1,2-migration of an alkyl or aryl group from boron to the vinyl α-carbon occurs concomitantly with C–Pd σ-bond formation.

Abstract: Transition metal catalysis plays a central role in contemporary organic synthesis. Considering the tremendously broad array of transition metal-catalyzed transformations, it is remarkable that the underlying elementary reaction steps are relatively few in number. Here, we describe an alternative to the organometallic transmetallation step that is common in many metal-catalyzed reactions, such as Suzuki-Miyaura coupling. Specifically, we demonstrate that vinyl boronic ester ate complexes, prepared by combining organoboronates and organolithium reagents, engage in palladium-induced metallate rearrangement wherein 1,2-migration of an alkyl or aryl group from boron to the vinyl α-carbon occurs concomitantly with C-Pd σ-bond formation. This elementary reaction enables a powerful cross-coupling reaction in which a chiral Pd catalyst merges three simple starting materials-an organolithium, an organoboronic ester, and an organotriflate-into chiral organoboronic esters with high enantioselectivity.

Full text

Catalytic Conjunctive Cross-Coupling
enabled by Metal-Induced Metallate
Rearrangement
L. Zhang, G. J. Lovinger, E. K. Edelstein, A. A.
Szymaniak, M. P. Chierchia, J. P. Morken
Science 2016, 351, 70-74.
O
B
O
R
1
Li
+
Pd(OAc)
2
L1,
R
2
OTf
THF, 60
o
C, 14 h
then NaOH, H
2
O
2
R
1
OH
R
2
Mike Frasso @ Wipf Group
Page 1 of 16
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1,2-Metallate Shifts with Boron
B
R
AL
L
X
A = C
X = Cl
A = O
X = OH
A = N
X =OBz
A = P
X = Cl
A = S
X = Cl
R OH
R NH
2
R CR'
3
BL
2
R'
2
P R
R'S R
Mike Frasso @ Wipf Group
Page 2 of 16
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Recent 1,2-Metallate Shifts from Boron to Carbon
Nature Chem.
2014, 6, 584-589.
J. AM. Chem. Soc. 2015, 137, 10958-10961.
O
Li
R
1
R
2
B(pin)
R
1
R
2
O
B(pin)
R
1
R
2
O
NBS
R
1
R
2
O
B(pin)
Br
THF, -78
o
C, then NBS
O
Br
1,2 shift
B(pin)
R
1
R
2
N
Li
R
1
R
2
B(pin)
THF, -78
o
C
Nu
-
R
1
R
2
B(pin)N
R
1
R
2
N
TrocCl,
then H
2
O
2
,NaOH
Mike Frasso @ Wipf Group
Page 3 of 16
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Alkyl-Metal Regents Generated from Alkenes
L
n
M
BL
n
R
R
CuCl, (Bpin)
2
,
Ligand
LiOtBu, DMA, 60
o
C
Alkyl I
R
Alkyl
B(pin)
R
B(pin)
Alkyl
or
Ar
CuOAc, (Bpin)
2
,
Ligand, Pd(dppf)Cl
2
KOH,tBuOMe, 0
o
C
BocO
R
Ar
(pin)B
R
Ar
CuSIMesCl, (Bpin)
2
,
Pd-XPhos precat.
NaOtBu,tBuOMe
Ar
R
B(pin)
R Br
CuBr, (Bpin)
2
,
Ligand
NaOtBu,PhMe, 120
o
C
B(pin)
O
O
Ar
J. Am. Chem. Soc. 2015, 137, 14578-14581.
Chem. Eur. J. 2014, 20, 12032-12036.
Angew. Chem. Int. Ed. 2015, 54, 12957-12961.
J. Am. Chem. Soc. 2015, 137, 13760-13764.
Mike Frasso @ Wipf Group
Page 4 of 16
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Stereoinvertive vs. Stereoretentive Transmetallation
Ph
Tol-Br
CuSIMesCl, (Bpin)
2
,
Pd-RuPhos precat.
NaOtBu, THF
Ar
Tol
Ph
Ph
B(pin)
Ph
H
Ph
(pin)B
Cu
Pd
Br
L
PCy
2
Ar
Tol
Tol-Br
CuSIMesCl, (Bpin)
2
,
Pd-PiBu
3
precat.
NaOtAmyl, PhMe
Ph B(pin)
Ph
H
L
n
Cu Pd
Br
PR
3
Tol
Ar
Tol
Ph
B(pin)
Angew. Chem. Int. Ed. 2015, 54, 5228-5231.
Mike Frasso @ Wipf Group
Page 5 of 16
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