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Hydroamination
Literature Seminar 2016. 5. 14
Akinori Yamaguchi1
Amines in Biologically Amines in Biologically Amines in Biologically Amines in Biologically AAAActive ctive ctive ctive MMMMoleculesoleculesoleculesolecules
2
Strategies for Amine SynthesisStrategies for Amine SynthesisStrategies for Amine SynthesisStrategies for Amine Synthesis
31) Kan, T.; Fukuyama, T. Chem. Commun. 2004, 353.
The Challenge for The Challenge for The Challenge for The Challenge for HydroaminationHydroaminationHydroaminationHydroamination
41) Brunet, J. J.; Neibecker, D.; Niedercorn, F. J. Mol. Catal. 1989, 49, 235.
Late Transition Metal CatalystsLate Transition Metal CatalystsLate Transition Metal CatalystsLate Transition Metal Catalysts
PdN
R1 R2+ PdH N
R1
R2
H
calatyst deactibationamine catalyst
Calatyst deactibation
With Brønsted acid cocatalyst
coordination
Ar+
Ar Me
RNAr'
HN
Ar' R
H+
25-100 °C
arylamine vinylarene
+ Pd
catalyst
51) Kawatsura, M.; Hartwig, J. F. J. Am. Chem. Soc. 2000, 122, 9546.
Intermolecular, Markovnikov Intermolecular, Markovnikov Intermolecular, Markovnikov Intermolecular, Markovnikov HydroaminationHydroaminationHydroaminationHydroamination
NHR
X +
Pd(PPh3)4 (2 mol %)TFA (10 mol%)
toluene25 °C, 24 h
RN
X
N
R1 R2H
aliphatic amine
Ar+
Pd(OCOCF3)2 (5 mol %)DPPF (10 mol %)TfOH (20 mol %)
1,4-dioxane120 °C, 24 h Ar Me
NR1R2
Fe
PPh2
PPh2
DPPF =
NHR
X Ar+
Pd(OCOCF3)2 (2 mol %)DPPF (3 mol %)TfOH (20 mol %)
toluene100 °C, 7-12 h Ar Me
RN
X
6
1) Kawatsura, M.; Hartwig, J. F. J. Am. Chem. Soc. 2000, 122, 9546.
2) Lober, O.; Kawatsura, M.; Hartwig, J. F. J. Am. Chem. Soc. 2001, 123, 4366.
3) Pawlas, J.; Nakao, Y.; Kawatsura, M.; Hartwig, J. F. J. Am. Chem. Soc. 2002, 124, 3669.
Mechanistic StudyMechanistic StudyMechanistic StudyMechanistic Study
71) Nettekoven, U.; Hartwig, J. F. J. Am. Chem. Soc. 2002, 124, 1166.
Proposed MechanismProposed MechanismProposed MechanismProposed Mechanism
81) Nettekoven, U.; Hartwig, J. F. J. Am. Chem. Soc. 2002, 124, 1166.
Discovery Discovery Discovery Discovery of Antiof Antiof Antiof Anti----Markovnikov Markovnikov Markovnikov Markovnikov HydroaminationHydroaminationHydroaminationHydroamination
91) Utsunomiya, M.; Hartwig, J. F. J. Am. Chem. Soc. 2003, 126, 5608.
Mechanistic StudyMechanistic StudyMechanistic StudyMechanistic Study
RuPh2P PPh2
H
(cod)Ru
Ru(cod)(2-methylallyl)2
DPPPentTfOH
THF, rt
Ph
THF, 80 °C
isolated ( 6-styrene)Ru complex
OTf
RuPh2P PPh2
H
OTf
Stichometric reaction
O
HN
(20 eq.)
+
dioxane-NMP20 °C
RuPh2P PPh2
H
OTf
NO
RuPh2P PPh2
H
OTf
NO
dioxane-NMP100 °C
(40 eq.)
+ Ph RuPh2P PPh2
H
OTf
PhN
O
+
ligand exchange
nucleophilic attack
101) Takaya, J.; Hartwig, J. F. J. Am. Chem. Soc. 2005, 127, 5756.
Proposed Reaction MechanismProposed Reaction MechanismProposed Reaction MechanismProposed Reaction Mechanism
111) Takaya, J.; Hartwig, J. F. J. Am. Chem. Soc. 2005, 127, 5756.
Limitation: Narrow Substrate ScopeLimitation: Narrow Substrate ScopeLimitation: Narrow Substrate ScopeLimitation: Narrow Substrate Scope
121) Hannedouche, J.; Schulz, E. Chem. Eur. J. 2013, 19, 4972.
Initial Discovery of Initial Discovery of Initial Discovery of Initial Discovery of CuHCuHCuHCuH----Catalyzed Catalyzed Catalyzed Catalyzed HydroaminationHydroaminationHydroaminationHydroamination
13
Novel Mechanistic Novel Mechanistic Novel Mechanistic Novel Mechanistic Approach to Approach to Approach to Approach to HydroaminationHydroaminationHydroaminationHydroamination
141) Zhu, S.; NiljianSkul, N.; Buchwald, S. L. J. Am. Chem. Soc. 2013, 135, 15746.
Proposed Reaction MechanismProposed Reaction MechanismProposed Reaction MechanismProposed Reaction Mechanism
151) Zhu, S.; NiljianSkul, N.; Buchwald, S. L. J. Am. Chem. Soc. 2013, 135, 15746.
CuHCuHCuHCuH----Catalyzed Catalyzed Catalyzed Catalyzed HydroaminationHydroaminationHydroaminationHydroamination (1)(1)(1)(1)
161) Zhu, S.; NiljianSkul, N.; Buchwald, S. L. J. Am. Chem. Soc. 2013, 135, 15746.
CuHCuHCuHCuH----Catalyzed Catalyzed Catalyzed Catalyzed HydroaminationHydroaminationHydroaminationHydroamination (2)(2)(2)(2)
171) Zhu, S.; NiljianSkul, N.; Buchwald, S. L. J. Am. Chem. Soc. 2013, 135, 15746.
CuHCuHCuHCuH----Catalyzed Catalyzed Catalyzed Catalyzed HydroaminationHydroaminationHydroaminationHydroamination (3)(3)(3)(3)
R1
NR2
OBz
+
Cu(OAc)2 (2 mol %)(R)-DTBM-SEGPHOS
(2.2 mol %)
(EtO)2MeSiH (2 eq.)THF, 40 °C, 36 h
(1 eq.) (1.2 eq.)
88%, 60% ee
R
R'
R
R'
NR2
R1
-chiral amine
BnNBn2
Me
i-PrNBn2
Me
t-BuNBn2
Me
Me2PhSiNBn2
NC
90%, 83% ee 86%, 92% ee 58%, 92% ee
NBn2
MeO
91%, 80% ee
TrON
D
86%, 12:1 d.r.
Ph
OTBS
Me
Bn
NBn2
HMe
H
HH
MeO87%, >50:1 d.r.
estronederivative
(R)-DTBM-SEGPHOS
Ar = 3,5-(t-Bu)2-4-OMeC6H2
O
O
O
O
PAr2
PAr2
181) Zhu, S.; Buchwald, S. L. J. Am. Chem. Soc. 2014, 136, 15913.
Synthesis of Chiral Secondary AminesSynthesis of Chiral Secondary AminesSynthesis of Chiral Secondary AminesSynthesis of Chiral Secondary Amines
191) Niu, D.; Buchwald, S. L. J. Am. Chem. Soc. 2015, 137, 9716.
Unproductive Reduction of NUnproductive Reduction of NUnproductive Reduction of NUnproductive Reduction of N----O BondO BondO BondO Bond
LCuHN O
O
ArR
H
+ N
R
H
H
O
O
Ar
LCu
+
NMR competition experiment
BnN
O
OH
BnN
O
OBn Cu(OAc)2 (5 mol %), PPh3 (11 mol %)(R)-DTBM-SEGPHOS (5.5 mol %)
(EtO)2MeSiH (5 eq.)d8-THF, 40 °C, 1 h
+
(1 eq.) (1 eq.)
>80% redused <5% redused
BnN
O
OH
BnN
O
OH Cu(OAc)2 (5 mol %), PPh3 (11 mol %)(R)-DTBM-SEGPHOS (5.5 mol %)
(EtO)2MeSiH (5 eq.)d8-THF, 40 °C, 1 h
+
(1 eq.) (1 eq.)
~80% redused ~20% redused
H NMe2
reagent
reduction
201) Niu, D.; Buchwald, S. L. J. Am. Chem. Soc. 2015, 137, 9716.
DFT Calculation for the DFT Calculation for the DFT Calculation for the DFT Calculation for the HHHHydrocuprationydrocuprationydrocuprationydrocupration of Olefinsof Olefinsof Olefinsof Olefins
211) Yang, Y.; Shi, S.; Niu, D.; Liu, P.; Buchwald, S. L. Science 2015, 349, 62.
Proposed Catalytic CycleProposed Catalytic CycleProposed Catalytic CycleProposed Catalytic Cycle
221) Yang, Y.; Shi, S.; Niu, D.; Liu, P.; Buchwald, S. L. Science 2015, 349, 62.
HydrocuprationHydrocuprationHydrocuprationHydrocupration of of of of UnactivatedUnactivatedUnactivatedUnactivated Internal Internal Internal Internal OlefonsOlefonsOlefonsOlefons
R4N
O
OR3
(1 eq.)NEt2
RR
(3 eq.)
+
Cu(OAc)2 (5 mol %)(S)-DTBM-SEGPHOS (5.5 mol %)
(MeO)2MeSiH (3 eq.)THF, 45 °C, 36 h
R1 R2
NR4R3
Et Pr
NBnBn
83%, 98% ee
NBnBn
HOOH
61%, 97% ee
Me Et
NBn
76%, 97% ee
N
Me
Me Et
NBn
70%, 97% ee
OMe
Me Et
NBn
85%, 98% ee
OMeMeO
NMeCF3
EtMe
NMeCF3
EtMe
80%, >95:5 d.r.
with (R)-DTBM-SEGPHOS
81%, >95:5 d.r.
with (S)-DTBM-SEGPHOS
derivatization ofCinacalect
(calcimimetic)
231) Yang, Y.; Shi, S.; Niu, D.; Liu, P.; Buchwald, S. L. Science 2015, 349, 62.
Outlook Outlook Outlook Outlook
Ph Me
krel 6.6 x 105 1.2 x 102 1.1 x 102 1
more challenginghydrocupration
>1 >>1
Tri- and tertasubstituted alkenes
Aminating agents to transfer aromatic amines or ammonia
N OR
R
N OR
H
H
or
?
aromatic amine ammonia
241) Pirnot, M. T.; Wang, Y.; Buchwald, S. L. Angew. Chem. Int. Ed. 2016, 55, 48.
SummarySummarySummarySummary
25
AppendixAppendixAppendixAppendix
26
Classification of Classification of Classification of Classification of HydroaminationHydroaminationHydroaminationHydroamination: : : : RRRRegiochemicalegiochemicalegiochemicalegiochemical outcomeoutcomeoutcomeoutcome
271) Yang, Y.; Shi, S.; Niu, D.; Liu, P.; Buchwald, S. L. Science 2015, 349, 62.
28
1) Kawatsura, M.; Hartwig, J. F. J. Am. Chem. Soc. 2000, 122, 9546.
PdPdPdPd----CatalizedCatalizedCatalizedCatalized Markovnikov Markovnikov Markovnikov Markovnikov HydroaminationHydroaminationHydroaminationHydroamination
291) Lober, O.; Kawatsura, M.; Hartwig, J. F. J. Am. Chem. Soc. 2001, 123, 4366.
PdPdPdPd----CatalizedCatalizedCatalizedCatalized Markovnikov Markovnikov Markovnikov Markovnikov HydroaminationHydroaminationHydroaminationHydroamination
30
1) Pawlas, J.; Nakao, Y.; Kawatsura, M.; Hartwig, J. F. J. Am. Chem. Soc. 2002, 124, 3669.
PdPdPdPd----CatalizedCatalizedCatalizedCatalized Markovnikov Markovnikov Markovnikov Markovnikov HydroaminationHydroaminationHydroaminationHydroamination
Competition ExperimentCompetition ExperimentCompetition ExperimentCompetition Experiment
311) Nettekoven, U.; Hartwig, J. F. J. Am. Chem. Soc. 2002, 124, 1166.
O
HN
+
5 mol%
[Rh(cod)(DPEphos)]BF4
toluene (1 M)70 °C, 48 h
(1 eq.) (4 eq.)
N
O
N
O
53%
18%
DPEphos =O
PPh2PPh2
cod =
RhodiumRhodiumRhodiumRhodium----Catalyzed AntiCatalyzed AntiCatalyzed AntiCatalyzed Anti----Markovnikov Markovnikov Markovnikov Markovnikov HydroaminationHydroaminationHydroaminationHydroamination
32
33
RuRuRuRu----CatalizedCatalizedCatalizedCatalized AntiAntiAntiAnti----Markovnikov Markovnikov Markovnikov Markovnikov HydroaminationHydroaminationHydroaminationHydroamination
1) Utsunomiya, M.; Hartwig, J. F. J. Am. Chem. Soc.
2003, 126, 5608.
34
RuRuRuRu----CatalizedCatalizedCatalizedCatalized AntiAntiAntiAnti----Markovnikov Markovnikov Markovnikov Markovnikov HydroaminationHydroaminationHydroaminationHydroamination
1) Utsunomiya, M.; Hartwig, J. F. J. Am. Chem. Soc. 2003, 126, 5608.
35
Synthesis of Amine Transfer Reagents Synthesis of Amine Transfer Reagents Synthesis of Amine Transfer Reagents Synthesis of Amine Transfer Reagents
1) Niu, D.; Buchwald, S. L. J. Am. Chem. Soc. 2015, 137, 9716.
CuHCuHCuHCuH----Catalyzed Catalyzed Catalyzed Catalyzed HydroaminationHydroaminationHydroaminationHydroamination by Miura et al. by Miura et al. by Miura et al. by Miura et al.
36
1) Miki, Y.; Hirano, K.; Sato, T.; Miura, M. Angew. Chem. Int. Ed. 2013, 52, 10830.
371) Zhu, S.; NiljianSkul, N.; Buchwald, S. L. J. Am. Chem. Soc. 2013, 135, 15746.
CuHCuHCuHCuH----Catalyzed Catalyzed Catalyzed Catalyzed HydroaminationHydroaminationHydroaminationHydroamination
38
HydroaminationHydroaminationHydroaminationHydroamination Using Using Using Using MMMModified odified odified odified AAAAmine Transfer Reagents mine Transfer Reagents mine Transfer Reagents mine Transfer Reagents
1) Niu, D.; Buchwald, S. L. J. Am. Chem. Soc. 2015, 137, 9716.
39
Unproductive Reduction of NUnproductive Reduction of NUnproductive Reduction of NUnproductive Reduction of N----O BondO BondO BondO Bond
1) Niu, D.; Buchwald, S. L. J. Am. Chem. Soc. 2015, 137, 9716.
TransitionTransitionTransitionTransition----State Structures of the State Structures of the State Structures of the State Structures of the HydrocuprationHydrocuprationHydrocuprationHydrocupration
401) Yang, Y.; Shi, S.; Niu, D.; Liu, P.; Buchwald, S. L. Science 2015, 349, 62.