Supporting information Rhodium(II)-Catalyzed C–H Aminations using N-Mesyloxycarbamates

86 Pages·2017·1.63 MB·English

Electronic Supplementary Material (ESI) for Chemical Science.
This journal is © The Royal Society of Chemistry 2018
Supporting information

Rhodium(II)-Catalyzed C–H Aminations using N-Mesyloxycarbamates:
Reaction Pathway and By-Product Formation

Emna Azek, Maroua Khalifa, Johan Bartholoméüs, Matthias Ernzerhof and Hélène Lebel

Département de Chimie, Université de Montréal, C.P. 6128,
Succursale Centre-ville, Montréal, Québec, Canada H3C 3J7.

[email protected]

S-1
Table of Content

S1. Computational Methods…………………………………………………………………………………………………… S4
S2. Tables, Schemes and Figures…………………………………………………………………………………………….. S5
Table S2-1. The Singlet and Triplet Energy Split (E =E -E ) in kcal/mol of the
st singlet triplet
((OAc) Rh =NH Complex with Different Computational Methods and Basis-Set Levels…. S5
4 2
Table S2-2. Calculated Free Energy Profile for the Singlet and Triplet Pathways with
Rhodium Nitrene Species of A at the B3LYP/BS2 Level of theory (the relative free
energies (DG , kcal/mol in ethyl acetate are provided).…………………………………..…………. S5
sol
Table S2-3. Spin Densities for Selected Atoms in 3NR, 3TS, 3INT and TSr for A and C at the
PBE/BS1 Level of Theory……………………………………………..………………………………………………… S5
Table S2-4. Calculated Activation Barrier for the Reaction of 3NR with Various Hydrogen
A
Sources at the PBE/BS2 Level of Theory (DG , kcal/mol in ethyl acetate)…………………… S6
sol
Table S2-5. Calculated Activation Barrier for the Reaction of 3NR with Various Hydrogen
E
Sources at the PBE/BS2 Level of Theory (DG , kcal/mol in ethyl acetate)…………………….. S6
sol
Scheme S2-1. Calculated Activation Barrier for the a-C-H insertion for 1NR at the
A
PBE/BS2 Level of Theory (DG , kcal/mol in ethyl acetate)…………………………………………… S6
sol
Scheme S2-2. Intermolecular Hydride transfer from Salt-K to 1NR affording 2-phenyl-
A A
acetaldehyde…………………………………………………………………………………………………………………. S7
Figure S2-1. Calculated Free Energy Profile of the Formation of 2-Phenylacetaldehyde
from 1NR at the PBE/BS2 Level of theory……………………………………………………………………… S7
A
Figure S2-2. Rate Comparison for the C-H vs C-D Amination with N-Mesyloxycarbamate
A……………………………………………………………………………………………………………………………………. S8
Figure S2-3. Rate Comparison for the C-H vs C-D Amination with N-Mesyloxycarbamate
B………….………………………………………………………………………………………………………………………... S8
Figure S2-4. Rate Comparison for the Amination of Ethyl Benzene and Deuterated Ethyl
Benzene with N-Mesyloxycarbamate C ………………………………………………………………………… S9
S3. Procedures for the kinetic isotope effect study……………………………………………………………….. S9
S4. Synthesis of the primary carbamate from 2-iodophenetyl-N-mesyloxycarbamate……….. S11
S5. Cartesian coordinates, total energies (a.u), vibrational zero-point energies (a.u) free
energies and solvation free enthalpies (a.u, at 298.15 K, and 1 atm) for the stationary
structures……………………………………………………………………………………………………………………………… S12
S5-1. Deprotonation step of A, B & C with KOAc (Figure 1)………………………………………….. S12
S5-2. Deprotonation step of A with NaOAc (Figure 2)…………………………………………………… S18
S5-3. Deprotonation step of A with LiOAc (Figure 2)…………………………………………………….. S19
S-2
S5-4. Rhodium-Nitrene species formation of A, B & C with KOAc (Figure 3)…………………. S21
S5-5. Triplet Rh-Nitrenes species of A, B & C (Table 2)…………………………………………………. S35
S5-6. Rh-Nitrenes C-H insertion mechanisms for A & C (Figure 6)………………………………… S37
S5-7. Rh-Nitrenes C-H insertion mechanisms for B (Figure 3)……………………………………….. S46
S5-8. Ketone Formation from D (Figure 10)………………………………………………………………….. S48
S5-9. By-products formation for Substrate E (Figure 12)…………………………………………….… S56
S5-10. Hydrogen transfer to 3NR (Table S2-3)…………………………………………………………….. S68
A
S5-11. Hydrogen transfer to 3NR (Table S2-4)……………………………………………………………… S73
E
S5-12. By-products formation for Substrate A (Scheme S2-1, S2-2 & Figure S2-1)………… S78

S-3
S1. Computational Methods
The Gaussian ’09 software package1 was used for all calculations reported in this paper. Reaction
and activation energies were calculated using Kohn-Sham density functional theory (DFT) with
the PBE approximation for the exchange-correlation energy. Geometry optimization, harmonic
vibrational frequency calculations, intrinsic reaction coordinate (IRC) calculations, Kohn-Sham
orbital analysis, and Mulliken spin-density analysis were carried out in the gas phase with the 6-
31G(d) basis set for H, C, N, O, S, Cl, K, Na and Li atoms, LANL2DZ augmented with p and d
functions for I and the 1997 Stuttgart relativistic small-core potential (Stuttgart RSC 1997 ECP)2
for Rh, augmented with a 4f function (!f(Rh)=1.350).3 This composite basis set (denoted as BS1)
was found to be effective for the assessment of activation free energies of Rh-centered
complexes. Heavy-atom basis set definitions and corresponding pseudopotential parameters
were obtained from the EMSL basis set exchange library. Energetics of the reported structures
(PBE/BS1 optimized geometries) were improved by performing single-point energy calculations
at the PBE level of theory in conjunction with the 6- 311++G(d,p) set for C, H, N, O, Cl, K, Li, Na
and S and the same basis set as in BS1 for the I and Rh atoms (denoted as BS2). Free energies are
reported in kcal/mol and were calculated at 1 atm and 298.15 K. Solvent effects in ethyl acetate
were included by means of the PCM method.4 In these calculations, the free energy of solvation
was computed as G = E + ΔG . E refers to the solvation single point energy and
solv solv corr_gas solv
ΔG refers to the thermal correction to the free energy of the solute in the gas phase. The
corr_gas
charge analysis has been performed by the natural bond orbital method5 at PBE/BS2 level of
theory using natural bond orbital (NBO) program under Gaussian 09 program package. According
to the calculated energy Hessians, the stationary points, minima or transition states, are defined
by having 0 and 1 imaginary frequency, respectively. Graphical analysis of the imaginary
vibrational normal modes as well as the performed IRC calculations confirmed the nature of the
located transition states. Explicit relativistic effects treatments were performed using LANL2DZ
basis set augmented with p and f functions for Rh denoted as BS36
Cartesian coordinates, total energies (a.u), vibrational zero-point energies (a.u) and free energies
(a.u, at 298.15 K, and 1 atm) for the stationary structures Rh-nitrene species, amination TS for
substrate A, B and C as well as by-products TS formation for substrates A, D and E are provided.
The order of the stationary point is based on the number of imaginary frequencies.

1 M. J. Frisch, G. W. Trucks, H. B. Schlegel, G. E. Scuseria, M. A. Robb, J. R. Cheeseman, G. Scalmani, V. Barone, B.
Mennucci, G. A. Petersson, H. Nakatsuji, M. Caricato, X. Li, H. P. Hratchian, A. F. Izmaylov, J. Bloino, G. Zheng, J. L.
Sonnenberg, M. Hada, M. Ehara, K. Toyota, R. Fukuda, J. Hasegawa, M. Ishida, T. Nakajima, Y. Honda, O. Kitao, H.
Nakai, T. Vreven, J. A. Montgomery Jr., J. E. Peralta, F. Ogliaro, M. Bearpark, J. J. Heyd, E. Brothers, K. N. Kudin, V.
N. Staroverov, R. Kobayashi, J. Normand, K. Raghavachari, A. Rendell, J. C. Burant, S. S. Iyengar, J. Tomasi, M. Cossi,
N. Rega, J. M. Millam, M. Klene, J. E. Knox, J. B. Cross, V. Bakken, C. Adamo, J. Jaramillo, R. Gomperts, R. E.
Stratmann, O. Yazyev, A. J. Austin, R. Cammi, C. Pomelli, J. W. Ochterski, R. L. Martin, K. Morokuma, V. G.
Zakrzewski, G. A. Voth, P. Salvador, J. J. Dannenberg, S. Dapprich, A. D. Daniels, Ö. Farkas, J. B. Foresman, J. V.
Ortiz, J. Cioslowski, D. J. Fox, Gaussian 09, revision A.01; Gaussian, Inc.: Wallingford, CT, 2009.
2 (a) U. Steinbrenner, A. Bergner, M. Dolg and H. Stoll, Mol. Phys., 1994, 82, 3. (b) A. Henglein, J. Phys. Chem., 1993,
97, 5457. (c) M. Kaupp, P. v. R. Schleyer, H. Stoll and H. Preuss, J. Chem. Phys., 1991, 94, 1360.
3 W. H. Lam, K. C. Lam, Z. Lin, S. Shimada, R. N. Perutz and T. B. Marder, Dalton Trans., 2004, 1556.
4 J. Tomasi, B. Mennucci and R. Cammi, Chem. Rev., 2005, 105, 2999.
5 A. E. Reed, L. A. Curtiss and F. Weinhold, Chem. Rev., 1988, 88, 899.
6 O. M. Roscioni, E. P. Lee, J. M. Dyke, J. Comput. Chem., 2012, 33, 2049.
S-4
S2. Tables, Schemes & Figures

Table S2-1. The Singlet and Triplet Energy Split (E =E -E ) in kcal/mol of the ((OAc) Rh =NH
st singlet triplet 4 2
Complex with Different Computational Methods and Basis-Set Levels.
Model LDA/ PBE PBE- BPW91/ PBEh/ PBEh- B3PW91 B3PW91- B3LYP B3LYP- CCSD(T)//
BS1 /BS1 DKH7/BS3 BS8 BS1 DKH7/BS3 /BS8 DKH7/BS3 /BS1 DKH7/BS BPW918
DE -1.7 1.2 0.8 2.9 13.2 12.1 13.2 10.9 10.8 10.4 1.4
st

Table S2-2. Calculated Free Energy Profile for the Singlet and Triplet Pathways with Rhodium
Nitrene Species of A at the B3LYP/BS2 Level of theory (the relative free energies (DG , kcal/mol
sol
in ethyl acetate are provided).
Singlet Triplet
B3LYP/BS2 pathway pathway
NR 0.0 -6.3
A
TS 5.5 6.2
A
3INT --- -13.1
A
DDG‡ 0.7
k /k 3.2
singlet triplet

Table S2-3. Spin Densities for Selected Atoms in 3NR, 3TS, 3INT and TSr for A and C at the PBE/BS1
Level of Theory.
Rh N C Total
2
3NR 0.840 1.104 0.008 1.952
A
3TS 0.816 0.827 0.418 2.061
A
3INT 0.852 0.280 0.705 1.837
A
TSr 0.923 0.254 0.671 1,857
A
3NR 0.933 1.013 0.000 1.946
C
3TS 0.708 0.535 0.624 1.867
C
INT 0.715 0.367 0.778 1.860
C
TSr 0.718 0.299 0.766 1.783
C

7 G. Jansen and B. A. Hess, Phys. Rev. A, 1989, 39, 6016.
8 Values from : X. F. Lin, C. Y. Zhao, C. M. Che, Z. F. Ke and D. L. Phillips, Chem. Asian J., 2007, 2, 1101.
S-5
Table S2-4. Calculated Activation Barrier for the Reaction of 3NR with Various Hydrogen Sources
A
at the PBE/BS2 Level of Theory (DG , kcal/mol in ethyl acetate).
sol
O
O hydrogene source
Ph [Rh]
Ph [Rh] O N
O N
H
3NR
A
hydrogen ΔG
source kcal/mol
H2O 43.6
CH Cl 38.4
2 2
41.6a
HOAc
35.4b
Salt-K 32.4
A
aAcetic acid coordinated to the catalyst.
bAcetic acid not coordinated to the catalyst.

Table S2-5. Calculated Activation Barrier for the Reaction of 3NR with Various Hydrogen Sources
E
at the PBE/BS2 Level of Theory (DG , kcal/mol in ethyl acetate).
sol
O
O
[Rh] hydrogene source
O N [Rh]
O N
I
3NR I H
E
hydrogen ΔG
source kcal/mol
H2O 45.9
CH2Cl2 40.7
39.8a
HOAc 37.2b
aAcetic acid coordinated to the catalyst.
bAcetic acid not coordinated to the catalyst.

Scheme S2-1. Calculated Activation Barrier for the a-C-H insertion for 1NR at the PBE/BS2 Level
A
of Theory (DG , kcal/mol in ethyl acetate).
sol
H
H O O
Ph [Rh] α-C-H insertion N [Rh]
O N O
1NRA ΔG‡ : 32.1 kcal/mol AZA Ph

S-6
Scheme S2-2. Intermolecular Hydride transfer from Salt-K to 1NR affording 2-phenyl-
A A
acetaldehyde.
O
Ph [Rh]
O N O
1NRA Ph [Rh]
O N
+
K H K
H O
Ph
Ph O O O=C=NOMs
O N S
Salt-KA O O INT’A
n
egeneratio -[Rh] ProtonatioHA
R n
O
Salt-K + Ph Ph
A O O NH2
+ O=C=NH + Ph
O
+O=C=NOMs + KA
ΔGsol (kcal/mol)
4.5 Hydride transfer TS
0.0
-2.7 Protonation TS
2.8
1NRA β-C-H TS
O
Ph
INT’ O NH
A 2
-19.9 [Rh] + Ph
O
+O=C=NOMs + KA
-41.2
-50.4 Salt-KA Ph
+ O
O O=C=NH [Rh]
-55.0
HN
O
Ph

Figure S2-1. Calculated Free Energy Profile of the Formation of 2-Phenylacetaldehyde from 1NR
A
at the PBE/BS2 Level of theory (the relative free energies (DG , kcal/mol in ethyl acetate are
sol
provided). (Different atom styles are used for clarity purposes).

S-7
Rh (tpa) (3 mol %)
H H 2 4 O
H K CO aq. sat. (3.0 equiv)
O N 2 3 HN
Ph OMs
EtOAc (0.1 M), 25 °C O
A O Ph
H
Rh (tpa) (3 mol %)
D D H K CO2 aq. s4at. (3.0 equiv.) O
O N 2 3 HN
Ph OMs
EtOAc (0.1 M), 25 °C O
O Ph
D

Figure S2-2. Rate Comparison for the C-H vs C-D Amination with N-Mesyloxycarbamate A.

Rh (tpa) (3 mol %)
O K CO2 aq. s4at. (1.5 equiv) H
2 3
OMs
O N O
H H H EtOAc (0.1 M), t.a. HN
B
O
Rh (tpa) (3 mol %)
D DD D O K CO2 aq. s4at. (1.5 equiv) D DD DD
2 3 D
D OMs
D D D DD D O NH EtOAc (0.1 M), t.a. D D D D HN O
O

Figure S2-3. Rate Comparison for the C-H vs C-D Amination with N-Mesyloxycarbamate B.

S-8
O Ph
O Ph
MsO
N O CCl
3
HH H (1.2 equiv) HN O CCl3
Rh [(S)-Br-nttl] (5 mol %)
2 4
KOAc, AcOEt (0.2 M)
O Ph
O Ph
MsO
N O CCl
3
D D D H (1.2 equiv) D HND O CCl3
D D Rh [(S)-Br-nttl] (5 mol %) D D
2 4
D D
D KOAc, AcOEt (0.2 M) D
D D D D
D D

Figure S2-4. Rate Comparison for the Amination of Ethyl Benzene and Deuterated Ethyl Benzene
with N-Mesyloxycarbamate C.

S3. Procedures for the kinetic isotope effect study

Rh (tpa) (3 mol %)
H H 2 4 O
H K CO aq. sat. (3.0 equiv)
O N 2 3 HN
Ph OMs
EtOAc (0.1 M), 25 °C O
A O Ph
H
(±)-4-Phenyloxazolidin-2-one. N-mesyloxycarbamate A (0.130 g, 0.500 mmol) was dissolved in
non-anhydrous EtOAc (5.00 mL). Green Rh (tpa) (20.3 mg, 0.015 mmol, 3.00 mol %) was added
2 4
and the resulting mixture was stirred. After complete dissolution of the rhodium dimer, a
saturated aqueous K CO solution (0.187 mL, 3.00 equiv) was added. The resulting turquoise
2 3
heterogeneous mixture was stirred at room temperature. The reaction was quenched by adding
a drop of pyridine to the reaction mixture at given times. The crude mixture was filtered through
Celite, and the later was thoroughly washed with EtOAc. The solvent was evaporated under
reduced pressure. The residue was chromatographed on silica gel eluting with 20% then 40%
EtOAc/hexanes to afford the desired oxazolidinone as a white solid. R 0.17 (40%
f
EtOAc/Hexanes); mp 135-136 °C (lit. 135-136 °C);9 1H NMR (500 MHz, CDCl ) δ 7.43-7.33 (m, 5H),
3
5.73 (s (br), 1H), 4.96 (dd, J = 8.0, 1H), 4.74 (t, J = 8.7 Hz, 1H,), 4.19 (dd, J = 8.6, 7.0 Hz, 1H); 13C
NMR (125 MHz, CDCl ) δ 159.5, 139.4, 129.2, 128.9, 126.0, 72.5, 56.4.
3

9 H. Lebel, K. Huard and S. Lectard, J. Am. Chem. Soc., 2005, 127, 14198.
S-9
Rh (tpa) (3 mol %)
D D H K CO2 aq. s4at. (3.0 equiv.) O
O N 2 3 HN
Ph OMs
EtOAc (0.1 M), 25 °C O
O Ph
D
(±)-4-Phenyloxazolidin-2-one-4-d. The title compound was prepared according to the procedure
using N-mesyloxycarbamate A. R 0.17 (40% EtOAc/Hexanes); mp 121.4-123.2 °C; 1H NMR (500
f
MHz, CDCl ) δ 7.41-7.33 (m, 5 H), 5.62 (s (br), 1H), 4.73 (d, J = 8.6 Hz, 1H), 4.19 (d, 8.6 Hz, 1H); 13C
3
NMR (125 MHz, CDCl ) δ 159.6, 139.5, 129.4, 129.0, 126.2, 72.6, 56.2 (t, J = 21.9 Hz).
3

Rh (tpa) (3 mol %)
O K CO2 aq. s4at. (1.5 equiv) H
2 3
OMs
O N O
H H H EtOAc (0.1 M), t.a. HN
B
O
(±)-4-Butyloxazolidin-2-one. The title compound was prepared according to the procedure using
N-mesyloxycarbamate A. 1H NMR (500 MHz, CDCl ) δ 6.35 (s (br), 1H), 4.47 (t, J = 8.5 Hz, 1H), 4.00
3
(dd, J = 8.5, 6.0 Hz, 1H), 3.89-3.82 (m, 1H), 1.63-1.50 (m, 2H), 1.36-1.23 (m, 4H), 0.90 (t, J = 7.0
Hz, 3H); 13C NMR (125 MHz, CDCl ) δ 160.1, 70.3, 52.6, 35.0, 27.3, 22.4, 13.8.
3

Rh (tpa) (3 mol %)
D DD D O K CO2 aq. s4at. (1.5 equiv) D DD DD
2 3 D
D OMs
D D D DD D O NH EtOAc (0.1 M), t.a. D D D D HN O
O
4-(Butyl-d )oxazolidin-2-one-4-d. The title compound was prepared according to the procedure
9
using N-mesyloxycarbamate A. R 0.16 (40% EtOAc/Hexanes); 1H NMR (500 MHz, CDCl ) δ 5.62
f 3
(br s, 1H), 4.73 (d, J = 8.6 Hz, 1H), 4.19 (d, J = 8.6 Hz, 1H); 13C NMR (125 MHz, CDCl ) δ 159.7, 70.3,
3
53.5, 52.4, 33.9, 29.8, 21.3; IR (neat) 3284, 2921, 2873, 2212, 1749, 1447, 1287, 1178, 1037, 700
cm-1; HRMS (ESI-TOF) m/z: [M+H]+ calcd for C H D NO 154.16467; found 154.16407.
7 4 10 2

O Ph
MsO O Ph
N O CCl
3
H (1.2 equiv)
HN O CCl
3
Rh [(S)-Br-nttl] (5 mol %)
2 4
KOAc, AcOEt (0.2 M)

(R)-2,2,2-trichloro-1-phenylethyl ((R)-1-phenylethyl)carbamate. In a 4-mL vial equipped with a
magnetic stirrer, ethylbenzene (16 mg, 0.15 mmol, 1.00 equiv) was dissolved in EtOAc (0.5 mL).
Rh [(S)-Br-nttl] (13 mg, 0.0075 mmol, 5 mol %), potassium acetate (44 mg, 0.45 mmol, 3.00
2 4
equiv) and N-mesyloxycarbamate (47 mg, 0.18 mmol, 1.2 equiv) were successively added to the
solution. The resulting green solution was stirred at room temperature. The reaction was
quenched by adding a drop of pyridine to the reaction mixture at given times. The solution was
then diluted with EtOAc (2 mL). Celite was added to the solution and the resulting heterogeneous
mixture was filtered over a short pad of celite, and the residue was washed with EtOAc (2 x 2
mL). A short amount of silica was then added to the solution and the resulting mixture was
evaporated to dryness. The crude adsorbed on silica was then purified by flash chromatography
(10% Et O/Hexanes) to afford the desired product. R 0.22 (20% Et O/Hexanes); 1H NMR (500
2 f 2
MHz, DMSO-d6, 100 °C) d 7.88 (br, 1H), 7.64-7.62 (m, 2H), 7.42-7.39 (m, 3H), 7.30-7.24 (m, 4H),
S-10