Recent Developments in Rhodium Carbene and Nitrene Chemistry
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Recent Developments in Rhodium Carbene and Nitrene Chemistry Brian Ngo Laforteza MacMillan Group Meeting February 3, 2010 Metal carbenoid C-H functionalization "Traditional' C-H activation N 2 R 2 R 1 N 2 L n M L n M R 2 R 1 C H C ML n H X C X H L n M C H C R 2 H R 1
Transcript of Recent Developments in Rhodium Carbene and Nitrene Chemistry
Recent Developments in Rhodium Carbene and Nitrene Chemistry
Brian Ngo Laforteza
MacMillan Group Meeting
February 3, 2010
Metal carbenoid
C-H functionalization
"Traditional'
C-H activation
N2
R2
R1
N2
LnM
LnM
R2
R1
C H
C MLn
H
X
C X
H
LnM
C H
C
R2
H
R1
Rhodium Carbene and Nitrene ChemistryCatalysts
■Rhodium(II) acetate – prototypical structure of dirhodium carbene/nitrene catalysts
Rh Rh
O O
O O
Me
Me
OO
OO
Me
Me
Rh2(OAc)4 “Paddle wheel” catalyst
■Only one rhodium center functions as carbene binding site Second acts as electron sink to increase electrophilicity of carbene moiety – additional stabilization
open coordination site
Catalyst binds carbene through strong σ-acceptor interactions and weak π-back-donation M M
R
R
N2
R
R
N2
Rhodium Carbene and Nitrene ChemistryCatalysts
Symmetry may vary depending on orientation of ligand binding
Generally much more rigid than rhodium carboxylates
Optimal for enantioselective intramolecular C–H insertion
Very active at decomposing diazo compounds
Optimal for intermolecular C–H insertion reactions
Later generations possess rigid bridged structure
■Two widely utilized classes of catalysts
Rhodium(II) carboxamidates
XN
O
R
X = O, NCOR
Rh
Rh
4
Rhodium(II) carboxylates
N
SO2Ar
O
O Rh
Rh
4
Rh Rh
X Y
Y X
R
R
YX
YX
R
R
Rhodium Carbene ChemistryThe Metal Carbene
■Control carbene reactivity through substituents - “acceptors” and “donors”
H
N2
O
X
X = R, OR, NR2
N2
O
X
X, Y = R, OR, NR2
O
YY
N2
O
X
X = R, OR, NR2
Y = vinyl, aryl
Acceptor Acceptor/Acceptor Acceptor/Donor
Acceptor/acceptor and acceptor/donor groups stabilize diazo compound – more active catalyst needed for decomposition
Carbenoids formed from acceptor/acceptor diazo compounds very electrophilic
Donor substituent stabilizes carbenoid through resonance
Rhodium Carbene ChemistryTrends in C–H Activation
■Generally believed to occur through concerted (though asynchronous), three-centered transition state
H
A
D
B Rh2L4R
R+
HC
C
A
B
D
R
R
Rh2L4
A
D
B
R
H
R Rh2L4+
Build-up of positive charge at carbon undergoing C-H cleavage
C–H activation occurs preferentially at sites that can stabilize δ+
Reactivity of C–H bonds undergoing insertion
methine > methyelene >> methyl
Steric factors, however, can sometimes override this selectivity
α-hetero C–H, allylic C–H, benzylic C–H preferred sites of activation
Rhodium Carbene ChemistryRh2(DOSP)4
■Rhodium(II) carboxylate developed and heavily utilized by Huw M. L. Davies (Emory)
Rh
Rh
O
O
NH
SO2Ar
Ar = p-(C12H25)C6H4
O
O
N
SO2Ar
O
ON
SO2Ar
H
H
O
O
N
SO2ArH
■Stereochemical model
Esther considered sterically demanding group Davies et al. Chem. Rev. 2003, 103, 2861. Davies et al. J. Org. Chem. 2009, 74, 6555.
Rh
RMeO2C
H
S
L
M
H
MeO2C R
Rh
RMeO2C
L
MSL
MS
L
MS
Combined C–H Insertion/Cope RearrangementSynthesis of 4-Substituted Indoles
■C–H insertion into 4-methyl-1,2-dihydronaphthalene proceeded with high diastereoselectivity
Me
CO2Me
N2
Ph
+
Rh2(S-DOSP)4 (0.5 mol%)
2,2-dimethylbutane, 0 °C
Me
H
Ph
CO2Me
95% yield
>98% de
>99% ee
Selectivity unusually high compared to what is known for C–H insertion into cycloalkenes
Mechanism more complex than appears?
■Proposed combined C–H activation/Cope rearrangement, followed by retro-Cope rearrangement
Me
Rh
PhCO2Me
H
H C-H/Cope
MePh
CO2Me
CopeMe
PhCO2Me
H
Fully conjugated product favored
Davies et al. J. Am. Chem. Soc. 2004, 126, 10862.
Combined C–H Insertion/Cope RearrangementRetro-Cope
■Mechanistic analysis
Davies et al. J. Am. Chem. Soc. 2004, 126, 10862.
■Preliminary scope
X
R2
R1
X = CH2, O
R1 = H, m-/p-OMe
R2 = OAc, OSiR3
CO2MeEt
Me
C-H/Cope
>98% de
98% ee
Me
CO2Me
N2
Et
+
Rh2(S-DOSP)4 (2 mol%)
2,2-dimethylbutane, 23 °C
Me
H
Et
CO2Me
//
110 °C
92%, 98% ee
Combined C–H Insertion/Cope RearrangementSynthesis of 4-Substituted Indoles
■C–H insertion into dihydroindoles followed by Cope rearrangement and aromatization
Davies et al. J. Am. Chem. Soc. 2006, 128, 1060.
NBoc
OAc
R
N2
CO2Me+
DMB, rtNBoc
R CO2Me
Rh2(S-DOSP)4
NBoc
OAc
R
CO2Me
NBoc
H
AcO
RR
Cope
Combined C–H Insertion/Cope RearrangementSynthesis of 4-Substituted Indoles
Davies et al. J. Am. Chem. Soc. 2006, 128, 1060.
NBoc
OAc
R
N2
CO2Me+
DMB, rtNBoc
R CO2Me
Rh2(S-DOSP)4
■C–H insertion into dihydroindoles followed by Cope rearrangement and aromatization
MeO Br Cl
Cl
NBoc
H3C
65%, 98% ee 52%, 98% ee 53%, 99% ee 45%, 98% ee
56%, 98% ee 64%, 98% ee 65%, 99% ee 61%, 99% ee
Combined C–H Insertion/Cope RearrangementApplication Towards Natural Product Synthesis
Davies et al. Angew. Chem. Int. Ed. 2005, 44, 1733.
■(+)-erogorgiaene: kinetic enantiodifferentiation
Me
Me
Me
H
Me
Me
(+)-erogorgiaene
Me
(±)
N2
MeMe
+
Me2 mol%
Rh2(R-DOSP)4
Me
Me
MeO2C
H
Me
48%, 90% ee
2 mol%
Rh2(R-DOSP)4
Me
MeH
H
MeO2C
Me
48%
Combined C–H Insertion/Cope RearrangementApplication Towards Natural Product Synthesis
Davies et al. J. Am. Chem. Soc. 2006, 128, 2485. Davies et al. Tetrahedron 2006, 62, 10477.
■Similar enantiodifferentiating step used in analogous syntheses
Me
Me
Me
H
Me
Me
O
O
Me
MeH
Me
O
O
Me MeOH
(+)-elisabethadione (+)-p-benzoquinone
Me
Me
O
OMeH
H
HOHO HO
Me
Me
OH
HO
H
Me
H
Me
O
(–)-colombiasin A (–)-elisapterosin B
Me
Tandem Cyclopropanation/Cope RearrangementFormal [4+3] Cycloadditions
Davies et al. J. Am. Chem. Soc. 2003, 125, 15902.
■Stereochemical model for cyclopropanation: based on “end-on” approach of olefin
R5
R6R7
R4
R3
N2
MeO2C
R2
R1
+Rh(II)
R4MeO2C
R3
R1
R2 R5
R6R7
MeO2C
R2
R4
R5
R3
R7R6R1
Cope
■General idea
Rh
R2MeO2C
HH
H R1
Rh
R2MeO2C
HH
R1
MeO2C
R2
HH
R1
Tandem Cyclopropanation/Cope RearrangementFormal [4+3] Cycloadditions
Davies et al. J. Am. Chem. Soc. 2009, 131, 8329.
■Scope of dienes
CO2Me
OTBS
Me
CO2Me
OTBS
Ph
CO2Me
OTBS
Me
TBSO
CO2Me
OTBS
MeO
TBSOCO2Me
OTBS
CO2Me
OTBS
MeMe
80% yield
87% ee
82% yield
95% ee
70% yield
99% ee
63% yield
95% ee
86% yield
92% ee
57% yield
R3R2
R1
R4N2
CO2Me
OTBS+
1 mol% Rh2(S-PTAD)4
hexanes, –26 °CR3
CO2Me
OTBS
R4
R1R2
O
OH
N
O
ORh
Rh
4
Rh2(S-PTAD)4
Tandem Cyclopropanation/Cope RearrangementFormal [4+3] Cycloadditions
■Total synthesis of (–)-5-epi-vibsanin E
R3R2
R1
R4N2
CO2Me
OTBS+
1 mol% Rh2(S-PTAD)4
hexanes, –26 °CR3
CO2Me
OTBS
R4
R1R2
Davies et al. J. Am. Chem. Soc. 2009, 131, 8329.
CO2Me
OTBS
Me
Me
Me
N2
CO2Me
OTBS
0.5 mol%
Rh2(S-PTAD)4
Me Me
Me+
O
O
Me
Me
Me
Me
O
OMe
Me
65% yield
90% ee
(–)-5-epi-vibsanin E
Nucleophilic Attack on Rhodium CarbenesFormal [3+2] Annulation of Indoles
■Two isomers of annulated product initially observed
Davies et al. J. Am. Chem. Soc. 2010, 132, 440.
NMe
N2
MeO2C Ph
+Rh2(R-DOSP)4
CH2Cl2, –45 °CNMe
H
H
CO2Me
Ph
+
NMe
H
H
Ph
72% yield
80% ee
CO2Me
exo
17%
>99% ee
endo
■Competition between C2- and C3-nucleophilic attack?
NMe
N2
MeO2C Ph
toluene, –45 °CNMe
H
Me
CO2Me
Ph
68% yield
97% ee
exo
MeRh2(S-DOSP)4
NMe
N2
MeO2C Ph
toluene, –45 °CNMe
Me
H
Ph
CO2Me
74% yield
99% ee
endo
Rh2(S-DOSP)4
Me
Nucleophilic Attack on Rhodium CarbenesFormal [3+2] Annulation of Indoles
■Proposed mechanism
Davies et al. J. Am. Chem. Soc. 2010, 132, 440.
■Stereochemical rationale: configuration of carbene and olefin govern diastereoselectivity
NMe
Rh2L4
MeO2C Ph
NMe
CO2Me
L4Rh2
Ph
NMe
H
H
CO2Me
Ph
Zwitterionic intermediate
Rh
MeO2C Ph
s-cis
NMe
Me
exo
Rh
MeO2C
s-trans
Ph
MeN
Me
endo
Nucleophilic Attack on Rhodium CarbenesImines As Nucleophiles
■Bicyclic pyrrolidines are formed when excess diazo compound is used
Doyle et al. J. Am. Chem. Soc. 2003, 125, 4692.
■Proposed mechanism
Rh2L4
CO2MePh
N
R
Ar
CO2Me
NAr
R
Ph
N Ar
CO2Me
Ph
R
N
NO2
N2
MeO2C Ph+
1 mol% Rh2(OAc)4
CH2Cl2, refluxR
N
NO2
CO2Me
Ph
Ar
R = H, Cl, Me, OMe
47-66% yield
up to 98:2 dr
Nucleophilic Attack on Rhodium CarbenesImines As Nucleophiles
■Bicyclic pyrrolidines are formed when excess diazo compound is used
Doyle et al. J. Am. Chem. Soc. 2003, 125, 4692.
■Proposed mechanism
N
Y
N2
MeO2C Ph+
1 mol% Rh2(OAc)4
CH2Cl2, reflux
X = H, Cl, Me, NO2
up to 84% yield
~ 1:1 dr
2 eq
Y = H, OMe, NO2
X
N
Y
X
Ph H CO2Me
CO2MePh
CHO2MeN
Ph
Ar2
Ar1
N
Ar2
Ar1
Ph Rh2L4
CO2MeRh2L4
CO2MePh CO2MePh
N
Ar2
Ar1
Ph H CO2Me
E Ph
Rhodium(II) Carbenoid Cyclization/Cycloaddition CascadeCycloadditions with Carbonyl Ylides
■Carbonyl oxygen can also act as nucleophile
Padwa et al. Tetrahedron 2008, 64, 988.
■Albert Padwa (Emory) – amide cyclization followed by [3+2] cycloaddition
R1
O
O
R2
N2
( )n
Rh(II) O R2R1
On( )
A B
O
A B
R2R1
n( )O
Carbonyl ylide
NN
O O
Me
O
CO2Me
N2
Rh2(OAc)4
A B
benzenereflux
NN
O
Me
A
B
OO
CO2Me
O
O
O
O
OMe
CO2Me
O
H
75% 77% 78% 85%
Rhodium(II) Carbenoid Cyclization/Cycloaddition CascadeCycloadditions with Carbonyl Ylides
■Reactions highly regio- and stereoselective
Padwa et al. Tetrahedron 2008, 64, 988.
NN
O O
Me
O
CO2Me
N2
Rh2(OAc)4
A B
benzenereflux
NN
O
Me
A
B
OO
CO2Me
Regioselectivity governed by FMO interactions – HOMO of carbonyl ylide, LUMO of dipolarophile
Predominant exo-selectivity result of steric interactions
NN
O O
Me
O
CO2Me
O
OMe!"
!+
Carbonyl Ylides Three-Component Cycloaddition
■Joe Fox (Delaware): Coupling between aldehydes, diazo compounds, and dipolarophiles
Fox et al. J. Am. Chem. Soc. 2009, 131, 1101.
CO2Me CO2Et
Me
O MeO
O
O
O
O
N
N
EtO2C
CO2EtMe CO2Me
R
CN
R1
O
H+ +
CO2R3
N2
R2Rh2(Piv)4 (0.5 mol%)
CH2Cl2, –78 °C
R1 = aryl, alkynyl R2 = alkyl, benzyl R3 = Et, t-Bu
A B
A B
OR1 CO2R3
R2
up to 99% yield
up to >95:5 dr
Carbonyl Ylides Three-Component Cycloaddition
■Joe Fox (Delaware): Coupling between aldehydes, diazo compounds, and dipolarophiles
Fox et al. J. Am. Chem. Soc. 2009, 131, 1101.
R1
O
H+ +
CO2R3
N2
R2Rh2(Piv)4 (0.5 mol%)
CH2Cl2, –78 °C
R1 = aryl, alkynyl R2 = alkyl, benzyl R3 = Et, t-Bu
A B
A B
OR1 CO2R3
R2
up to 99% yield
up to >95:5 dr
■High diastereoselectivity result of endo approach of dipolarophile
O
R2
CHO2R3
H
R1
R4
R5
OR1 CO2R
3
R2
R5R4
endo
O
R2
CHO2R3
H
R1
R4
R5
OR1 CO2R
3
R2
R5R4
exo
Carbonyl Ylides Three-Component Cycloaddition
■Joe Fox (Delaware): Coupling between aldehydes, diazo compounds, and dipolarophiles
Fox et al. J. Am. Chem. Soc. 2009, 131, 1101.
R1
O
H+ +
CO2R3
N2
R2Rh2(Piv)4 (0.5 mol%)
CH2Cl2, –78 °C
R1 = aryl, alkynyl R2 = alkyl, benzyl R3 = Et, t-Bu
A B
A B
OR1 CO2R3
R2
up to 99% yield
up to >95:5 dr
■Suppression of β-hydride elimination of alkyldiazoacetates has been a continuing challenge
CO2t-Bu
N2
Me Rh2(OAc)4CO2Me
Me
O
+Me
Ph
O
+
Carbonyl Ylides Three-Component Cycloaddition
■Joe Fox (Delaware): Coupling between aldehydes, diazo compounds, and dipolarophiles
Fox et al. J. Am. Chem. Soc. 2009, 131, 1101.
R1
O
H+ +
CO2R3
N2
R2Rh2(Piv)4 (0.5 mol%)
CH2Cl2, –78 °C
R1 = aryl, alkynyl R2 = alkyl, benzyl R3 = Et, t-Bu
A B
A B
OR1 CO2R3
R2
up to 99% yield
up to >95:5 dr
■β-hydride elimination can be completely suppressed through appropriate conditions
Rh2(Piv)4
-78 °C
O CO2t-BuPh
MeO
Me
CO2t-Bu
N2
Me
O
+Me
Ph
O
+
77%
Sterically encumbering catalysts and low temperatures are critical!
Rhodium(II) Nitrene-Mediated C–H InsertionAzide Precursors to Nitrenes
■Carbazole synthesis via bisaryl azides
Stokes et al. J. Org. Chem. 2009, 74, 3225.
m-substituted pendant arenes lead to mixtures of regioisomers
■Intermediacy of free nitrene, or completely catalyst-mediated?
N3
OMe
toluene
NH
OMe
NH
OMe
+
Rh2(O2CC7H15)4
heat (250 °C)
94 6:
31 : 69
reversal in thermal selectivity argues against presence of free nitrene
R1
N3
NH
R1
Rh2(O2CC3F7)4
toluene, 60 °C
R1-R2 = H, Me, Et, t-Bu, Cl, F, OMe, CF3, NO2, vinyl, CO2Et
41-98% yield
R2
R2
Rhodium(II) Nitrene-Mediated C–H InsertionAzide Precursors to Nitrenes
■Proposed mechanism
Stokes et al. J. Org. Chem. 2009, 74, 6442.
[Rh]
N
R
[Rh]
N
R
[Rh]
4-electron-5-atomelectrocyclization
N
[Rh]
H
R
NH
R
Primary KIE 1.01
Linear correleation with σp Hammet values (negative ρ values)
Nonlinear correlation with σm Hammet values (not electrophilic aromatic substitution on nitrene)
Mechanistic EvidenceN3
R
N
R
[Rh]
N2
Rhodium(II) Nitrene-Mediated C–H InsertionAzide Precursors to Nitrenes
■Proposed mechanism
Stokes et al. J. Org. Chem. 2009, 74, 6442.
[Rh]
N
R
[Rh]
N
R
[Rh]
4-electron-5-atomelectrocyclization
N
[Rh]
H
R
NH
R
N3
R
N
R
[Rh]
N2
N3NH
Rh(II)//
Contiguous array of π-orbitals necessary
Rhodium(II) Nitrene-Mediated C–H InsertionAzide Precursors to Nitrenes
■Synthesis of indoles and N-heteroarenes via vinyl azides
Stokes et al. J. Am. Chem. Soc. 2007, 129, 7500.
R1
R2
R3N3
CO2Me Rh2(O2CC3F7)4
toluene
R1
R2
R3 NH
CO2Me
R1-R3 = H, Me, i-Pr, t-Bu, l, Br, OMe, CF3
71-98% yield
N3
CO2Me
N3
CO2Me
O
N3
CO2Me E
N3
CO2Me
E = O, S, N(PG)
Rhodium(II)-Catalyzed C–H Amination Iminoiodanes
■Traditionally, iminoidanes were treated with metal complexes to generate nitrenes
Dauban et al. Synlett 2003, 1571.
IN
SO2Ar LnMLnM N
SO2Ar RR
RR
N
SO2Ar
Isolated material
I(OAc)2
+H2N
SAr
O O
Rhodium(II)-Catalyzed C–H Amination Iminoiodanes
■Traditionally, iminoidanes were treated with metal complexes to generate nitrenes
Du Bois et al. J. Am. Chem. Soc. 2001, 123, 6935.
IN
SO2Ar LnMLnM N
SO2Ar RR
RR
N
SO2Ar
■Du Bois (Stanford): generation of iminoiodanes in situ
H2NS
X
O O
R
NS
X
O O
R
PhIN
SX
O O
R
L4Rh2HN
SX
O O
R
PhI(OAc)2 Rh2L4 "C-H"
Rhodium(II)-Catalyzed C–H Amination Understanding the Mechanism
■General reactivity trends parallel those of rhodium(II) carbenes
Du Bois et al. Tetrahedron 2009, 65, 3042.
■Six-membered oxathiazinanes favored
Reactivity of C–H bonds undergoing insertion
methine > ethereal ~ benzylic > methyelene >> methyl
NS
X
O O
R
L4Rh2HN
SX
O O
R
"C-H"
Elongated S–X, S–N bonds
Obtuse N–S–X bond angle
■Concerted C–H insertion
NH2
SO
OO
Ph
H D KIE of 1.9 ± 0.2
HNS
X
O O
H
Ph
No opening of radical clock (not C–H abstraction/radical-rebound
Rhodium(II)-Catalyzed C–H Amination Understanding the Mechanism
■Proposed mechanism of rhodium-nitrene formation
Du Bois et al. Tetrahedron 2009, 65, 3042.
ROS
NH2
O O PhI(OAc)2
ROS
NH
O O
IPh
OAc–AcOH
ROS
N
O O
IPh
Rh2L4
fast
ROS
N
O O
IPh
Rh2L4–IPh
ROS
N!Rh2L4
O O"C–H"HNS
O
O O
R
First-order dependence on sulfamate and oxidant
Zero-order dependence on catalyst (during initial reaction burst)
Rhodium(II)-Catalyzed C–H Amination Rh2(esp)2
■Very efficient catalyst for C–H aminations
Du Bois et al. J. Am. Chem. Soc. 2004,126, 15378.
Rh
Rh
O
O
O
O
O
O O
O
Me MeMeMe
MeMe Me Me
Rh2(esp)2
■Dinuclear rhodium catalysts known to undergo structural changes within minutes of initiating the reaction
Catalyst degradation believed to proceed through ligand exchange
Appropriately spaced linker in (esp) ligand adds stability to dirhodium complex
Rhodium(II)-Catalyzed C–H Amination Rh2(esp)2
■Interesting results obtained in intermolecular C–H amination experiments
Du Bois et al. J. Am. Chem. Soc. 2007,129, 562. Du Bois et al. J. Am. Chem. Soc. 2009, 131, 7558.
From oxidant?
■If C–H bond is slow to intercept reactive Rh-nitrene intermediate, catalyst degradation occurs
Formation mixed-valence Rh2+/Rh3+ species observed by UV/vis spectroscopy
Could this mixed-valence dimer interact with oxidant in reaction mixture?
Me2 mol % Rh2(esp)2
TcesNH2, benzene
Me
NHTces
+N
Me
Me
Tces
72% 15%
PhI(CO2t-Bu)2
Tces =Cl3C O
S
O O
Rhodium(II)-Catalyzed C–H Amination Rh2(esp)2
■Interesting results obtained in intermolecular C–H amination experiments
Du Bois et al. J. Am. Chem. Soc. 2007,129, 562. Du Bois et al. J. Am. Chem. Soc. 2009, 131, 7558.
Me2 mol % Rh2(esp)2
TcesNH2, benzene
Me
NHTces
+N
Me
Me
Tces
72% 15%
PhI(CO2t-Bu)2
Radical decarboxylation
[Rh2(esp)2]+
Rh2(esp)2
t-Bu
O
O
CO2, H•
Me
Me
t-BuCO2H
Ph Me
1 mol% Rh(II)
TcesNH2
PhI(CO2R)2
Ph Me
NHTcesR = Me
n-Pr
t-Bu
CMe2Ph
12%
17%
27%
62%
More reducing carboxylic acid – higher yields
Evidence that Rh2(esp)2 is active catalyst
Rhodium(II)-Catalyzed C–H Amination Justin Du Bois
■Rich variety of rhodium-catalyzed aminations
intermolecular amination oxathiazinanes 1,3-diamines 1,2-diamines
■Amines are readily deprotected
J. Am. Chem. Soc. 2001,123, 6935. J. Am. Chem. Soc. 2007, 129, 562.
J. Am. Chem. Soc. 2008, 130, 11248. Angew. Chem. Int. Ed. 2009, 48, 2777.
NHTces
R2
R1HN
SNBoc
O O
R1 R2
HNS
O
O O
NR1 R2
HNS
O
O O
R1 R2
HNS
NBoc
O O
Ph
DMAP
Cl3CCH2OH
dioxane, 80 °C
TcesHN NHBoc
Ph89%
Rhodium(II)-Catalyzed C–H Amination Justin Du Bois
■Products can act as iminium ion equivalents
J. Am. Chem. Soc. 2003,125, 2028. Angew. Chem. Int. Ed. 2004, 43, 4349.
■Diastereoselectivity governed by combination of twist Felkin-Ahn transition state model
Nu =R
Li
SiMe3
R
OSiR3
HNS
O
O O
LG R2
HNS
O
O O
R2
–LG Nu-HN
SO
O O
Nu R2
R1 R1 R1
S
O
NH
O
OR1
R1
H
N HO
S
O
O
Nu
Felkin-Ahn T.S.
O
SNO
O NuH
R1
HNS
O
O O
Nu
R1
H
no destabilizing
interactions
Rhodium(II)-Catalyzed C–H Amination Justin Du Bois
■Products can act as iminium ion equivalents
J. Am. Chem. Soc. 2003,125, 2028. Angew. Chem. Int. Ed. 2004, 43, 4349.
■Diastereoselectivity governed by combination of twist Felkin-Ahn transition state model
Nu =R
Li
SiMe3
R
OSiR3
HNS
O
O O
LG R2
HNS
O
O O
R2
–LG Nu-HN
SO
O O
Nu R2
R1 R1 R1
Introduction of R2 can have a dramatic impact on selectivity!
S
O
NH
O
OR1
R2
S
O
NR1
R2
O
O H
destabilizing
Leads to Felkin-Ahn-disfavored T.S.
Erosion of diastereoselectivity
Rhodium(II)-Catalyzed C–H Amination Justin Du Bois
■Application towards natural product synthesis
J. Am. Chem. Soc. 2002,124, 12950. J. Am. Chem. Soc. 2006,128, 3926.
Angew. Chem. Int. Ed. 2009, 48, 3802.
HN N
O
O
NH
Br
CO2HMe
manzacidin A
N NH
NHHN
H2N
HO
HO
NH2
O NH2
O
(+)-saxitoxin
N
NH
Br
O
NH
NHO
Me
O
(–)-agelastatin A
C–H Amination with N-Tosyloxycarbamates Rhodium Nitrene Formation without Iminoiodanes
■Substitute in situ-generated iminoiodanes with alternative leaving group?
Lebel et al. Chem. Eur. J. 2008, 14, 6222.
R1O
O
NH
OTsRh2L4
R1O
O
NOTs
Rh2L4
K2CO3
K+
–KOTs
R1O
O
N!Rh2L4
R2 R3
R2 R3
NHCO2R1
■Lebel (Montréal) utilized the tosyl leaving group
R2
R1
OHN
O
OTs
Rh2(tpa)4 (6 mol%)
K2CO3, CH2Cl2, 25 °C
OHN
O
R2R1
41-92% yield
R1 R2Cl3C O N
H
O
OTs+Rh(II)
R1 R2
NHTroc
50-87% yield
(R1-R3 = alkyl, Ar)
Ph3C
O
O Rh
Rh
4
Rh2(tpa)4 =
Up to 15 eq of alkane required (Du Bois requires only 1 eq)
Amination of Alkynes and Allenes π-Nucleophilic Attack onto Rhodium Nitrenes
■Electrophilic rhodium(II) nitrene analogous to rhodium carbenes
Blakey et al. J. Am. Chem. Soc. 2008, 130, 5020.
LnMN
R
Nu-
N R
LnM
N R
LnM
Nu
MLn
N RNu
O
OSO2NH2
Rh2L4
OS
N
O O
O
L4Rh2
OS
N
O O
O
L4Rh2
OS
N
O O
O
NaBH4O
SHN
O O
O
■Blakey (Emory) utilized oxygen for nucleophilic attack onto carbocation
Amination of Alkynes and Allenes π-Nucleophilic Attack onto Rhodium Nitrenes
■Scope
Blakey et al. J. Am. Chem. Soc. 2008, 130, 5020.
OSO2NH2
( )n2 mol % Rh2(esp)2
PhI(OAc)2
CH2Cl2, RT
then NaBH4
ROO
SHN
O O
O R
( )n
OS
HN
O O
O
Ph
56%
OS
HN
O O
O
Ph
71%
OS
HN
O O
O
76%
OS
HN
O O
O
85%
OS
HN
O O
O
98%
OS
HN
O O
O
81%
(quenched with allyl-MgBr)
NHS
O
O O
O
Ph
R
R = H, 55%
Me, 48%
Amination of Alkynes and Allenes π-Nucleophilic Attack onto Rhodium Nitrenes
■Scope
OSO2NH2
( )n2 mol % Rh2(esp)2
PhI(OAc)2
CH2Cl2, RT
then NaBH4
ROO
SHN
O O
O R
( )n
Blakey et al. J. Am. Chem. Soc. 2009, 131, 2434.
■Other nucleophilic traps – arenes and olefins
R = Ph R =
R'
OSO2NH2
R
OS
HN
O O
Friedel-Crafts termination
OS
HN
O O
R'
cyclopropanation
Amination of Alkynes and Allenes π-Nucleophilic Attack onto Rhodium Nitrenes
■Mechanistic insight – what is the active intermediate?
Blakey et al. J. Am. Chem. Soc. 2009, 131, 2434.
OS
N
O OL4Rh2
OS
N
O O
L4Rh2
1,3-shift
R R
vinyl cation iminocarbenoid
■Control experiment
OSO2NH2O
SN
O O
L4Rh2
Rh(II)
OS
N
O Obenzylic "C–H"
Rh(II)
OS
N
O OL4Rh2
OS
HN
O OFriedel-Crafts
72% Not observed
Amination of Alkynes and Allenes π-Nucleophilic Attack onto Rhodium Nitrenes
■Allene amination - amidoallylcations
Blakey et al. J. Am. Chem. Soc. 2010, ASAP.
■Aminocyclopropanes
OS
N
O O
Me
OS
N
O OL4Rh2
•
OSO2NH2
Me
OS
HN
O O
Me
O
t-BuO
73%
t-BuCO2H
5 mol% Rh2(esp)2
t-BuCO2H
C6H5CF3, 45 °C
PhI(CO2t-Bu)2
R
•
LnMN
R'
N
R'
R
LnM
Amination of Alkynes and Allenes π-Nucleophilic Attack onto Rhodium Nitrenes
■Allene amination - amidoallylcations
Blakey et al. J. Am. Chem. Soc. 2010, ASAP.
•
OSO2NH2
R
5 mol% Rh2(esp)2
PhI(CO2t-Bu)2
then R'MgX
OS
HN
O O
R
R'52-85% yield
single isomers
R = Me, allyl, benzyl
R' = Me, i-Pr, Ar, vinyl
•
OSO2NH2
R
OS
HN
O O
Me
H
Me
Ar
96% ee 53%, 82% ee
Chirality transfer Cycloadditions
OS
N
O OL4Rh2
Ph
O
O
O
SHN
Ph
O
O
40%
![Reactivity of Rhodium(II) amido/Rhodium(I) aminyl complexesN-C coupling Radical Nitrene ABSTRACT Reaction of the Rh(II) dimer [LRh] 2(μ-Br) 2 (L=([2,6-Me 2C 6H 3NCMe] 2CH) with the](https://static.fdocuments.net/doc/165x107/5f0f57bf7e708231d443affb/reactivity-of-rhodiumii-amidorhodiumi-aminyl-complexes-n-c-coupling-radical.jpg)
