literature report iv - dicp€¦ · education and employment: 2003–2007 b.s., university of...
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Palladium(0)-Catalyzed Directed syn-1,2-Carboboration and -Silylation
Literature Report IV
Engle, K. M. et al. Angew. Chem. Int. Ed. 2019, 58, 17068.
Reporter Checker
Date
: Yi-Xuan Ding : Zhou-Hao Zhu : 2019-11-18
CV of Prof. Keary M. Engle
Education and Employment: 2003–2007 B.S., University of Michigan
2008–2013 Ph.D., Chemistry, The Scripps Research Institute
2008–2013 D.Phil., Biochemistry, University of Oxford
2013–2015 Postdoc., California Institute of Technology
2015–Now Assistant Professor, The Scripps Research Institute
Research Interests: To advance the efficiency, effectiveness, and sustainability of organic small
molecules synthesis.
2
Contents
1
2
Introduction
3
syn-1,2-Carboboration and -Silylation Summary
3
Introduction
4
1,2-carboboration of alkenes
Cu-catalyzed
Ni-catalyzed
Pd-catalyzed
Coopera-tive
catalysis
Introduction
pinB Bpin+
R1 X SIMesCuCl
R4 R1
R4
(pin)BR2 R3
Cu(OAc)2 PCy3
R1
R3
pinB
R2
R1 = alkyl, benzyl, cinnamyl; R2, R3 = alkyl, aryl, H; R4 = boryl, phenyl, silyl
LCuOR
pinB Bpin(pin)BOR
LCu Bpin R R'
CuL
R'
pinB
R
CuL
R'
pinB
R
KOt-BuOt-Bu
K
LCuOt-Bu
R" X
R"
R'
pinB
R
pinB Bpin
(pin)BOt-Bu
A
Cu-catalyzed
Takaki, K. et al. Org. Lett. 2013, 15, 952.
5
Introduction
Ar + B2pin2[Cu]
Ar
[Cu]Bpin
Y
OP(OEt)2
O
Ar Bpin
Y
Ar = alkyl, heteroarylY = H, Me, Ph, Br 66-96% ee
L*
[Cu] + L*
L*Cu BpinpinBOMe
B2pin2
Ar
Ar
L*Cu
Bpin
LG
Cu∗
Ar
pinB
*L
LG
∗
Ar
pinB
L*Cu LG
B2pin2LiOMe
A
B
C
Yun, J. et al. Org. Lett. 2017, 19, 6144.
6
Introduction Ni-catalyzed
Ar1 R1Ar1 R1
Bpin
Ar2Ni
Ar2BrB2pin2KOEtDMA
Ni
Ar2BrB2pin2KOMetoluene Ar2 = 3,5-(Me)2C6H3
Ar1 R1
Ar2
Bpin
5 mol% NiCl2(DME)B2pin2 (2.0 equiv)PhBr (1.5 equiv)
NaOt-Bu, THF/DMA
R
pinBRPh
pinBR[Ni]via:
Brown, M. K. et al. Angew. Chem. Int. Ed. 2019, 58, 10956.
Brown, M. K. et al. J. Am. Chem. Soc. 2019, 141, 9391.
7
Introduction
NiCl2(DME)B2pin2KOR
2 KCl2 ROBpin
2 KCl2 ROBpin [Ni(II)]
[Ni(I)] XX = Cl, Br
pinBOEtLiX
LiOEtB2pin2
[Ni(I)] Bpin
Me
Ar1
[Ni(I)]
Bpin
Me
Ar1
[Ni(III)]
BpinAr2
Br
Comproportionation
Ar2Br
Ar1
Me
Bpin
Ar2
[Ni(0)]
[Ni(II)]Ar2
Br
Ar2Br
Me
Ar1
[Ni(II)]
Ar2
Br
Ar1
Me
Ar1
MepinBOMe
KBr
KOMeB2pin2
Me
Ar1
[Ni(II)]
Ar2
Bpin
Ar1
Me
Ar2
Bpin
DMAToluene
A
B
C
D
Brown, M. K. et al. Angew. Chem. Int. Ed. 2019, 58, 10956.
8
Introduction Pd-catalyzed
N2BF4
Ar1
Ar2
+Pd(0)
Ar1
Ar2PdLn B2pin2
Ar1
Ar2Bpin
R1NH
O
R2 N
+ H [C] + B2pin2
5-10 mol% Pd(OAc)21-2 equiv KF
10-20 mol% BQHFIP, O2 (1 atm), 60 oC(AQ)
[C]
O
R2R1
Bpin
AQ
Song, Q. et al. Org. Lett. 2016, 18, 5460.
Engle, K. M. et al. J. Am. Chem. Soc. 2018, 140, 3223.
9
Introduction
LnPd(0) N2BF4Ar2
PdLnAr2
Ar1
Ar1
Ar2PdLn
Ar1
Ar2PdLn
B2pin2
Ar1
Ar2Bpin
oxidativeaddition
insertionπ-allylformation
Ar1
Ar2
Ar1LnPd H
Ar1
PdLn B2pin2
LnPd(0)
Ar1
Bpin
AC
B
D
E F G
Song, Q. et al. Org. Lett. 2016, 18, 5460.
10
Introduction
PdIIXm
NH
O
N
N
O
NPdII
X
Pd(OAC)2
Nu H KX
HX
N
OK
NPdII
XNu
pinB Bpinbase
X BpinN
OK
NPdII
B(pin)Nu
Pd0Lm
HX
OBpin
AQNu
[O]
catalystreoxidation
ligandexchange
nucleo-palladation
trans-metalation
reductiveelimination
Engle, K. M. et al. J. Am. Chem. Soc. 2018, 140, 3223.
11
Introduction
GR
G Bpin
R
Ar2
cat. Pd/CuAr2 X B2pin2+ +
NaOMeG = Ar1 or CO2MeR = H or Me
Pd Cycle Cu CycleLPd0
Bpin
LPdII Ar1
Ar2
XLPdII
Ar2
Ar1
CuL'
Bpin
L'Cu X L'Cu OR
L'Cu BpinAr2 X
Ar1
Bpin
Ar2
M OR M X
pinB Bpin
pinB OR
Ar1
A
B
C
D
cooperative catalysis (Pd/Cu)
Nakao, Y. et al. J. Am. Chem. Soc. 2014, 136, 7567.
12
Introduction cooperative catalysis (Ni/Cu)
Ar1 RAr1 R
Bpin
Ar2Ni
Ar2 X B2pin2+ +Cu
X = Cl or OTs
Ni Cycle Cu CycleLNi0
ClLNiII
Ar2
Ar1
CuLR
LCu Cl LCu Ot-Bu
LCu BpinAr2 Cl
Ar1
Bpin
Ar2
LiOt-Bu
pinB Bpin
pinB Ot-Bu
Ar1
R
Ar1
Bpin
LNi
R
Ar2
LiCl
R
BpinA
B
C
D
Nakao, Y. et al. Org. Lett. 2016, 18, 3956.
13
Background and project synopsis
RNH
O
N(AQ)
B2pin2+ +cat. PdII
KF, HFIP, O2
RO
n
[C]
Bpin
AQ
n = 1 or 2 (indole)
n [C]-H
previous work: anti-carboboration via Wacker-type nucleopalladation (PdII/Pd0 cycle)
this work: syn-carboboration/silylation via Heck-type migratory insertion (Pd0/PdII cycle)
RNH
O
N(AQ)
[M]-Bpin+ +cat. Pd0/L R
O
n
[C]
[M]
AQ[C]-OTfn
n = 1 or 2
[C] = Aryl, Alkenyl, [M] = Bpin, SiMe2Ph
14
Optimization of 1,2-arylboration reaction
RNH
O
N(AQ)
OTf
B2pin2+ +
Pd2dba3 (10 mol%)Ligand (20 mol%)
base (2 equiv)100 oC
RO
n
Ph
Bpin
AQ
R = H, 1aR = Et, 1c 2a 3a 4a or 4c
Entry[a] Substrate Solvent Base Ligand Yield [%][b]
1 1a DMPU K2CO3 Cy-JohnPhos 61
2 1a DMPU KF Cy-JohnPhos 70
3 1a DMPU K2HPO4 Cy-JohnPhos 89
4 1a DMPU i-Pr2NEt Cy-JohnPhos 90
5 1a t-AmylOH KF Cy-JohnPhos 95
6 1a DMSO KF Cy-JohnPhos 15
7 1a toluene KF Cy-JohnPhos 89
8[c] 1a t-AmylOH i-Pr2NEt Cy-JohnPhos (98)
15
Optimization of 1,2-arylboration reaction
Entry[a] Substrate Solvent Base Ligand Yield [%][b]
9[c] 1c t-AmylOH i-Pr2NEt PPh3 trace
10[c] 1c t-AmylOH i-Pr2NEt CyPPh2 12
11[c] 1c t-AmylOH i-Pr2NEt RuPhos >99
12[c] 1c t-AmylOH i-Pr2NEt XPhos 98
[a] Reaction conditions: 1a or 1c (0.1 mmol), 2a (1.5 equiv), 3a (2 equiv), Pd2dba3 (10 mol%), Ligand (20 mol%), base (2 equiv), 4Å MS (15-30 mg), 100 ºC, N2, 16-20 h. [b] Yields were determined by 1H NMR analysis of the crude reaction mixture using CH2Br2 as internal standard. Values in parentheses represent isolated yields. [c] Pd2dba3 (3 mol%), Ligand (6 mol%), 90 ºC.
16
RNH
O
N(AQ)
OTf
B2pin2+ +
Pd2dba3 (10 mol%)Ligand (20 mol%)
base (2 equiv)100 oC
RO
n
Ph
Bpin
AQ
R = H, 1aR = Et, 1c 2a 3a 4a or 4c
Alkene scope of 1,2-arylboration
RNH
O
Nn = 1 or 2n
(AQ)
OTf
B2pin2+ +
Pd2dba3 (3 mol%)L (6 mol%)
i-Pr2NEt (2 equiv)90 oC, t-AmylOH, 4 Å MS
(then [O])
RO
n
Ph
Bpin
AQPCy2
L
1a-q 2a 3a 4a-q
MeO
Ph
Bpin
AQPhOBpin
AQ
O
Ph
Bpin
AQMePh
OBpin
AQ
Me
O
Ph
Bpin
AQPhthN
O
Ph
Bpin
AQTsHN 4Ph
O
Ph
Bpin
AQ
BocHN
PhBpin
O
AQ
PhO
AQ
MepinB PhOBpin
AQMe Me
PhO
AQ
MepinB
Me Me
4a, 98% (±)-4b, 99% (±)-4c, 99%(from E-alkene)
(±)-4d, 97%(from Z-alkene)
(±)-4e, 87%(from E-alkene)
(±)-4f, 98%(from E-alkene)
4g, 96%(from E-alkene)
(±)-4h, 92%dr = 16:1
[b]
4i, 99% 4j, 92%[c] 4k, 61%[c]
17
Alkene scope of 1,2-arylboration
RNH
O
Nn = 1 or 2n
(AQ)
OTf
B2pin2+ +
Pd2dba3 (3 mol%)L (6 mol%)
i-Pr2NEt (2 equiv)90 oC, t-AmylOH, 4 Å MS
(then [O])
RO
n
Ph
Bpin
AQPCy2
L
1a-q 2a 3a 4a-q
O
AQPh
Bpin
Me O
AQPh
Bpin
Me
O
AQPh
Bpin NPhth
HN
Ph
OH O
N
(PA)
AQ
O
OH
Ph
(±)-4m, 85%(from Z-alkene)
4n, 99%dr = 1.2:1
4o, 99%dr = 2:1
4p, 70%[c,d] 4q, 54%[d]
[a] Reaction conditions: 1a-q (0.05 mmol or 0.1 mmol), 2a (1.5 equiv), 3a (2 equiv), Pd2dba3 (3 mol%), L (6mol%), i-Pr2NEt (2 equiv), 4 Å MS (15-30 mg), N2, 38-44 h. Percentages refer to isolated yields. Unlessotherwise noted, diastereomeric ratio (dr) was found to be > 30:1 in all cases. [b] 2a (3 equiv), 3a (3 equiv),Pd2dba3 (5 mol%), L (10 mol%), i-Pr2NEt (3 equiv). [c] 2a (2 equiv), 3a (3 equiv), Pd2dba3 (4.5 mol%), L (9mol%), i-Pr2NEt (3 equiv). [d] The final product was oxidized to the corresponding alcohol with NaBO3•4H2O (5 equiv) for ease of isolation.
O
AQPh
Bpin
4l, 98%
18
Electrophile scope
R1
O
n = 1 or 2n R2OTf B2pin2+ +
Pd2dba3 (3 mol%)L (6 mol%)
i-Pr2NEt (2 equiv)
90 oC, t-AmylOH, 4 Å MS(then [O])
R2
O
n
R1
Bpin
AQ
1a, 1c, 1l 2b-i 3a 4r-z
AQ
R2 = Aryl or Alkenyl
OBpin
AQ
Me
(±)-4r, 98%(from E-alkene)
OBpin
AQ
Me
(±)-4s, 99%(from E-alkene)
MeO OOH
AQ
Me
(±)-4t, 83%(from E-alkene)
F3C
OBpin
AQ
Me
(±)-4u, 98%(from E-alkene)
[X-ray]
O2N
OBpin
AQ
4v, 70%
NOBpin
AQ
N OOH
AQ
4x, 61%[c]
BocNOBpin
AQ
Me
(±)-4y, 86%(from E-alkene)
[b,c]
4w, 62%
[a] Unless otherwise specified, reaction conditions were as in Table 1. dr values were found to be >30:1 in all cases. [b] 2d (2 equiv), 3a (3 equiv). [c] The final product was oxidized to the corresponding alcohol with NaBO3•4H2O (5 equiv) for ease of isolation.
19
Dearomative aryl/alkenylboration
ROTf B2pin2+ +
Pd2dba3 (5 mol%)L (10 mol%)
i-Pr2NEt (3 equiv)
100 oC, t-AmylOH, 4 Å MS
1t-v 2a-c, 2i 3a 5a-f
X
AQ
O
X H
R
pinB
AQO
NMe
H
Ph
pinB
AQO
NAc
H
Ph
pinB
AQO
O H
Ph
pinB
AQO
O H
pinB
AQOOMe
O H
pinB
AQO
O H
pinB
AQO
[b](±)-5a, 63% (±)-5b, 66% (±)-5c, 86%
(±)-5d, 73%[c] (±)-5e, 87% (±)-5f, 72%
[a] Reaction conditions: 1t-v (0.05 mmol or 0.1 mmol), 2a-c, or 2i (3 equiv), 3a (3 equiv), Pd2dba3 (5 mol%), L (10 mol%), i-Pr2NEt (3 equiv), 4 Å MS (20-30 mg), N2, 38-44 h. Percentages refer to isolated yields. The diastereomeric ratio (dr) wasfound to be > 30:1 in all cases. [b] Reaction time of 96 h. [c] 1v (0.1 mmol), 2c (2 equiv), Pd2dba3 (4.5 mol%), L (9 mol%).
20
Scope of alkene aryl/alkenylsilylation
R1
O
R2OTf+ +
Pd2dba3 (5 mol%)L (10 mol%)
i-Pr2NEt (2 equiv)100 oC, DMF, 4 Å MS R1
O
R2
Si
AQ
1a, 1c, 1z 2a-d, 2g, 2i 3b 6a-i
AQ
R2 = Aryl or Alkenyl
Si BpinPh
MeMe
PhMeMe
O
Ph
Si
AQ
PhMeMe
PhOSi
AQ
PhMeMe
MePh
OSi
AQ
PhMeMe
n-Pr
OSi
AQ
PhMe
MeMeO
OSi
AQ
PhMeMe
Me
OMe
OSi
AQ
PhMe
MeOSi
AQ
PhMe
Me
F3C
OSi
AQ
PhMe
N
Me
6a, 79% (±)-6b, 71%(from E-alkene)
(±)-6c, 71%(from Z-alkene)
6d, 81%
(±)-6e, 72%(from E-alkene)
6f, 87% 6g, 68% 6h, 47%
[a] Reaction conditions: 1a, 1c, 1z (0.1 mmol), 2a-d, 2g, 2i (1.5 equiv), 3b (3 equiv), Pd2dba3 (5 mol%), L (10 mol%), i-Pr2NEt (2 equiv), 4 Å MS (20-30 mg), N2, 38-44 h. Percentages refer to isolated yields.
21
Diversification of arylborylated products
n = 1 or 2
1) Boc2O, DMAP, 60 oC, MeCN
2) pyrrolidine, tolueneR
O
n
Bpin
AQ
8a-c4c, 4j, 4l
R
O
n
Bpin
N
OBpin
N
PhMe
OBpin
NPh
O
N
Bpin
PhMe Me
(±)-8a, 93% 8b, 79%
8c
Ph
OBpin
AQ
(±)-4c (0.1 mmol)
Me100 oC, MeOH
Ni(tmhd)2
Ph
OBpin
OMe
(±)-9, 78%
Me
A
B
C
SelectfluorTHF
cat. AgNO3MgBr
2) I2/NaOMe
1)
8c, 84%
O
N
F
Ph
11, 37%
O
NPh
10, 87%
22
Summary
RNH
O
N(AQ)
B2pin2+ +cat. Pd0/L
i-Pr2NEt, t-AmylOH
RO
n
[C]
Bpin
AQ[C]-OTfn
n = 1 or 2[C] = Aryl, Alkenyl 54-99% yield
23
RNH
O
N(AQ)
PhMe2Si-Bpin+ +cat. Pd0/L R
O
[C]
PhMe2Si
AQ
[C] = Aryl
[C]-OTf
47-87% yield
Carboboration
Carbosilylation
24
The first paragraph
写作思路
阐述金属催化的 碳硼化反应的重要性
总结前人的工作 (催化体系、底物范围等)
The first paragraph
Metal-catalyzed 1,2-carboboration of alkenes is a powerful means of
simultaneously forming a C(sp3)-C and a C(sp3)-B bond in a single step
with multiple levels of selectivity control. Indeed, successful examples of
catalytic 1,2-carboboration have been developed with copper, palladium,
nickel, and dual catalyst systems. Of the various coupling
partners that can be engaged in 1,2-carboboration, organohalides and
pseudohalides are particularly important, given the structural diversity and
widespread availability of these electrophiles. In this area, classical
limitations have included the scope of compatible alkenes and associated
issues with regiocontrol; indeed, the vast majority of successful examples
involve activated alkenes, such as styrenes or norbornenes.
25
The first paragraph
Previously, Xiao and Fu developed a Cu-catalyzed regiodivergent 1,2-
alkylboration of non-conjugated terminal alkenes containing a proximal
heteroatom. Recently, Brown has developed an elegant series of nickel-
catalyzed 1,2-arylboration methods capable of functionalizing mono-, di-
and tri-substituted nonconjugated alkenes without formation of
competitive chain-walking products. These reactions are believed to
proceed via a NiI-Bpin intermediate, which generally delivers the Bpin
group to the less substituted carbon atom. With trisubstituted alkenes, the
reactions are highly regioselective, whereas with non-symmetric 1,2-
disubstituted alkenes and terminal alkenes, regiomeric ratios (r.r.) are
variable and controlled by a combination of steric and electronic factors.
26
27
The last paragraph
总结工作(完成烯烃的碳硼化和碳硅化)
底物范围广
反应可放大量
产物实用性强
可以合成手性产物
The last paragraph In conclusion, we have developed highly regio- and diastereoselective
carboboration and carbosilylation reactions of alkenyl carbonyl
compounds using a substrate directivity strategy. Compatible substrates
include alkenes with various substitution patterns and benzo-fused
heteroaromatics that react through five- and six-membered palladacycle
intermediates. These methods allow direct access to carbonyl products
containing boron and silicon groups at the β and γ positions. Furthermore,
an array of aryl and alkenyl triflates are suitable carbon electrophiles. The
reactions are scalable and operationally simple. Diversification of
arylborylated products was also demonstrated, showcasing the synthetic
versatility of the products. Finally, examples of diastereoselective 1,2-
arylboration using a chiral directing group were shown.
28
Representative examples
These methods allow direct access to carbonyl products containing
boron and silicon groups at the β and γ positions.
Furthermore, an array of aryl and alkenyl triflates are suitable carbon
electrophiles.
Previously, Xiao and Fu developed a Cu-catalyzed regiodivergent 1,2-
alkylboration of non-conjugated terminal alkenes containing a proximal
heteroatom.
Recently, Brown has developed an elegant series of nickel-catalyzed
1,2-arylboration methods capable of ……
Though useful in its own right, this method is limited in terms of the
carbogenic groups that can be introduced (indole-type nucleophiles) and
the alkene scope (terminal and 1,2-disubstituted alkenes).
29