Unravelling Nucleophilic Aromatic Substitution Pathways with Bimetallic Nucleophiles

81 Pages·2017·2.87 MB·English

by  Microsoft Office User

Electronic Supplementary Material (ESI) for ChemComm.
This journal is © The Royal Society of Chemistry 2019
Supporting Information for:
Unravelling Nucleophilic Aromatic Substitution Pathways with
Bimetallic Nucleophiles
Martí Garçon,‡ Clare Bakewell,‡ Andrew J. P. White and Mark R. Crimmin*
S-1
Contents
1. General Experimental Section..............................................................................................S-3
2. Synthetic Procedures.............................................................................................................S-4
2.1. Preparation of Fe–Mg heterobimetallics........................................................................S-4
2.2. Preparative Reaction of a Fe–Mg nucleophile with 2-(pentafluorophenyl)pyridine.......S-5
2.3. NMR scale reactions of a Fe–Mg nucleophile with fluoroarenes....................................S-6
2.4. Additional NMR experiments with polar additives........................................................S-10
2.5. Diffusion NMR spectroscopy..........................................................................................S-11
3. Multinuclear NMR Data.....................................................................................................S-12
4. X-Ray Crystallographic Data.............................................................................................S-22
5. Computational Details.........................................................................................................S-25
5.1 Methods..........................................................................................................................S-25
5.2 Impact of solvation in the reaction profiles...................................................................S-25
5.3 Bonding analysis of Fe–Mg heterobimetallics...............................................................S-27
5.4 Insight and orbital analysis of the S Ar pathway..........................................................S-29
N
5.5 Reactions with fluoroarenes...........................................................................................S-30
5.6 XYZ coordinates.............................................................................................................S-32
6. References............................................................................................................................S-81
S-2
1. General Experimental Section
All manipulations were carried out using standard Schlenk-line and glovebox techniques under an inert atmosphere
of argon or dinitrogen. The preparation of all metal complexes and their reactions with fluoroarenes were carried
out in a glovebox. A MBraun Labmaster glovebox was employed, operating at < 0.1 ppm O2 and < 0.1 ppm H2O.
Solvents were dried over activated alumina from an SPS (solvent purification system) based upon the Grubbs design
and degassed before use. Glassware was dried for 12 h at 120 °C prior to use. Benzene-d6 and toluene-d8 were stored
over 3Å molecular sieves and distilled prior to use. NMR-scale reactions were conducted in J. Young’s tap tubes and
prepared in a glovebox. All heating mentioned was done using silicone oil baths. 1H, 13C and 19F NMR spectra were
obtained on BRUKER 400 MHz or 500 MHz machines unless otherwise stated; all peak intensities are derived
internal standard peak with values quoted in ppm. Data was processed using the MestReNova or Topspin software.
Carbon-13 NMR data for fluoroaryl complexes has been assigned to the highest reasonable standard, given the

resolution of the data obtained for 13C{1H} nuclei coupling to multiple 19F nuclei (I=1/2). CIVrefers to quaternary
carbons.
Fluorocarbons, where liquids at 25 °C were dried over activated 3Å molecular sieves and freeze-pump-thaw
degassed before use. All other chemicals were purchased from Fluorochem, Sigma Aldrich or Alfa Aesar and used

without purification unless stated. The β-diketiminate ligands BDIH (mes and dipp)1 andBDIMg–MgBDI (dipp (2)
and mes)2,3 were prepared by literature procedures.
S-3
2. Synthetic Procedures
2.1. Preparation of Fe–Mg heterobimetallics
Synthesis of 1: To a 20 mL scintillation vial was added dippBDIMg–MgBDIdipp (2, 100 mg, 0.11 mmol) and
cyclopentadienyliron dicarbonyl dimer (Fp ) (40.0 mg, 0.11 mmol) in toluene (10 mL) and the reaction was stirred
2
at 298 K for 2 h. The solvent was concentrated in vacuo and n-hexane (5 mL) was added and the resulting solution
was filtered and left to stand at 238 K. The product crystallised as a yellow solid (90 mg, 64%).
1: 1H NMR (400 MHz, benzene-d , 298 K): 1.15 (d, 12H, CH(CH ) , 3J = 6.8 Hz), 1.36 (d, 12H, CH(CH ) , 3J = 6.8
6 3 2 HH 3 2 HH
Hz), 1.68 (s, 6H, C(CH )CHC(CH )), 3.28 (sept, 4H, CH(CH ) , 3J = 6.8 Hz), 3.96 (s, 5H, CpCH), 4.98 (s, 1H,
3 3 3 2 HH
C(CH )CHC(CH )), 7.13 (m, 6H, CH); 13C{1H} NMR (100 MHz, benzene-d , 298 K): 23.8 (CH(CH ) ), 23.9
3 3 6 3 2
(C(CH )CHC(CH )), 24.1 (CH(CH ) ), 28.6 (CH(CH ) ), 77.7 (CpCH), 95.8 (C(CH )CHC(CH )), 124.0 (CH), 126.0 (CH),
3 3 3 2 3 2 3 3
141.9 (CIV), 144.5 (CIV), 169.6 (C(CH )CHC(CH )), 218.3 (CO); ATIR, (CO), cm-1: 1948 (s), 1871 (s); Anal. Calc.
3 3
(C H FeMgN O ): C, 69.86; H, 7.49; N, 4.53. Found: C, 69.79; H, 7.60; N, 4.72.
36 46 2 2
Synthesis of S1: To a 20 mL scintillation vial was added mesBDIMg–MgBDImes (100 mg, 0.13 mmol) and
cyclopentadienyliron dicarbonyl dimer (Fp ) (49.5 mg, 0.13 mmol) in toluene (10 mL) and the reaction was stirred
2
at 298 K for 1 h. The precipitate was isolated by centrifugation and washed with n-hexane (5 mL), yielding the
product as a pale-yellow powder (100 mg, 69%).
S1: 1H NMR (400 MHz, benzene-d , 298 K): 1.62 (s, 6H, C(CH )CHC(CH )), 2.25 (s, 6H, p-CH mes), 2.35 (s, 12H, o-
6 3 3 3
CH mes), 4.07 (s, 5H, CpCH), 4.93 (s, 1H, C(CH )CHC(CH )), 7.01 (s, 4H, CH); 13C{1H} NMR (100 MHz, benzene-d , 298
3 3 3 6
K): 19.2 (o-CH mes), 20.7 (p-CH mes), 23.3 (C(CH )CHC(CH )), 78.9 (CpCH), 95.6 (C(CH )CHC(CH )), 129.2 (CH), 131.7
3 3 3 3 3 3
(CIV), 133.2 (CIV), 146.0 (CIV), 167.9 ((C(CH )CHC(CH ))), 221.5 (CO); IR (KBr disc): (CO), cm-1: 1949 (bs), 1800 (bs);
3 3
Repeated attempts to obtain satisfactory elemental analysis on this compound failed.
S-4
Synthesis of S1•THF: S1 was recrystallised from tetrahydrofuran/hexane solution.
S1•THF: 1H NMR (400 MHz, benzene-d , 298 K): 1.31 (m, 4H, O(CH ) (CH ) ), 1.68 (s, 6H, C(CH )CHC(CH )), 2.19 (s,
6 2 2 2 2 3 3
6H, p-CH mes), 2.31 (s, 12H, o-CH mes), 3.97 (m, 4H, O(CH ) (CH ) ), 4.02 (s, 5H, CpCH), 4.95 (s, 1H, C(CH )CHC(CH )),
3 3 2 2 2 2 3 3
6.92 (s, 4H, CH); 13C{1H} NMR (100 MHz, benzene-d , 298 K): 18.3 (o-CH mes), 20.6 (p-CH mes), 23.2
6 3 3
(C(CH )CHC(CH )), 24.9 (O(CH ) (CH ) ), 70.3 (O(CH ) (CH ) ), 77.9 (CpCH), 95.0 (C(CH )CHC(CH )), 129.3 (CH),
3 3 2 2 2 2 2 2 2 2 3 3
131.4 (CIV), 133.0 (CIV), 145.7 (CIV), 167.5 ((C(CH )CHC(CH ))), 221.3 (CO); ATIR, (CO), cm-1: 1921 (s), 1853 (s);
3 3
Repeated attempts to obtain satisfactory elemental analysis on this compound failed.
2.2. Preparative Reaction of a Fe–Mg nucleophile with 2-(pentafluorophenyl)pyridine
Isolation of compounds 3c and 4:
Compound 1 (35 mg, 0.06 mmol) and 2-(pentafluorophenyl)pyridine (7 mg, 0.03 mmol) were dissolved in benzene-
d (0.6 mL) and transferred into a YT-NMR tube. The reaction was left at 298 K overnight, after which time full
6
conversion to the products was confirmed by 1H and 19F NMR spectroscopy. The solvent was removed in vacuo and
n-hexane (1 mL) was added. Compound 3c remained insoluble in hexane and could be cleanly separated from
compound 4 by filtration. Compound 4 was then obtained by crystallisation from the n-hexane filtrate at -35 C.
3c: 1H NMR (400 MHz, benzene-d , 298 K): 3.95 (s, 5H, CHCp), 6.60 (ddd, 1H, Py-CBH, 3J = 7.8 Hz, 3J = 4.8 Hz, 4J
6 BC AB HH
= 1.1 Hz), 7.07 (td, 1H, Py-CCH, 3J = 7.8 Hz, 4J = 1.8 Hz), 7.28 (dm, 1H, Py-CDH, 3J = 7.8 Hz), 8.60 (ddd, 1H, Py-
HH HH HH
CAH, 3J = 4.8 Hz, 4J = 1.8 Hz, 5J = 1.0 Hz); 19F NMR (376.5 MHz, benzene-d , 298 K): -145.8 (dd, 3J = 29.0 Hz, 4J
AB AC AD 6 FF FF
= 12.4 Hz), -108.0 (dd, 3J = 29.0 Hz, 4J = 12.4 Hz); 13C{1H} NMR (100 MHz, benzene-d , 298 K): 84.9 (CHCp), 117.2
FF FF 6
S-5
(t, CIV, 3J = 16.4 Hz), 121.1 (tm, CIV, 3J = 46.6 Hz), 122.7 (CBH), 125.8 (CDH), 135.8 (CCH), 143.8 (dm, CIV, 1J = 250.0
CF CF CF
Hz), 150.1 (CIV), 150.3 (CAH), 152.3 (dm, CIV, 1J = 220.0 Hz), 214.0 (CO); ATIR, (CO), cm-1: 2034 (s), 1979 (s). Anal.
CF
Calc. (C H F FeNO ): C, 53.63; H, 2.25; N, 3.47. Found: C, 50.06; H, 2.27; N, 3.37. The CHN analysis are inaccurate,
18 9 4 2
and low in carbon possibly due to incomplete combustion (iron carbide formation).
4: 1H NMR (400 MHz, benzene-d , 298 K): 0.52 (d, 6H, CH(CH ) , 3J = 6.8 Hz), 1.07 (d, 6H, CH(CH ) , 3J = 6.8 Hz),
6 3 2 HH 3 2 HH
1.18 (d, 6H, CH(CH ) , 3J = 6.8 Hz), 1.21 (d, 6H, CH(CH ) , 3J = 6.8 Hz), 1.35 (d, 6H, CH(CH ) , 3J = 6.8 Hz), 1.39
3 2 HH 3 2 HH 3 2 HH
(d, 6H, CH(CH ) , 3J = 6.8 Hz), 1.45 (d, 6H, CH(CH ) , 3J = 6.8 Hz), 1.50 (d, 6H, CH(CH ) , 3J = 6.8 Hz), 1.54 (s, 6H,
3 2 HH 3 2 HH 3 2 HH
CH ), 1.59 (s, 6H, CH ), 2.78 (sept, 2H, CH(CH ) , 3J = 6.8 Hz), 3.22 (m, 4H, CH(CH ) ), 3.39 (sept, 2H, CH(CH ) , 3J
3 3 3 2 HH 3 2 3 2 HH
= 6.8 Hz), 4.26 (s, 5H, CpCH), 4.79 (s, 2H, C(CH )CHC(CH )), 6.99-7.22 (m, 12H, CH); 19F NMR (376.5 MHz, benzene-d ,
3 3 6
298 K): -193.6 (s, Mg-F-Mg); 13C{1H} NMR (100 MHz, benzene-d , 298 K): 23.3 (CH ), 23.6 (CH ), 23.9 (CH ), 24.2
6 3 3 3
(CH ), 24.4 (CH ), 24.6 (CH ), 24.7 (CH ), 24.9 (CH ), 25.7 (CH ), 27.8 (CH(CH ) ), 28.3 (CH(CH ) ), 28.6 (CH(CH ) ),
3 3 3 3 3 3 3 2 3 2 3 2
28.6 (CH(CH ) ), 80.8 (CpCH), 95.4 (C(CH )CHC(CH )), 123.6 (CH), 123.8 (CH), 124.3 (CH), 125.5 (CH), 125.9 (CH),
3 2 3 3
142.4 (CIV), 142.8 (CIV), 143.1 (CIV), 143.2 (CIV), 144.3 (CIV), 144.7 (CIV), 169.3 (C(CH )CHC(CH )), 170.2
3 3
(C(CH )CHC(CH )), 235.5 (CO); IR (KBr disc), cm-1: 1789 (s), 1685 (s); It was not possible to obtain elemental
3 3
analysis on this compound.
2.3. NMR scale reactions of a Fe–Mg nucleophile with fluoroarenes
NMR scale reactions: 1 (7 mg, 0.011 mmol) was dissolved in benzene-d (0.6 mL) and the solution transferred into
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a Young’s tap NMR tube equipped with a capillary tube containing a ferrocene standard solution; a t=0 1H NMR
spectrum was recorded. The fluoroarene (0.11 mmol, 10 equiv.) was added using a micropipette (or as a solid) and
the reaction mixture was monitored by 1H and 19F NMR spectroscopy. NMR yields were recorded by comparison
against the ferrocene internal standard,  = 4.00 ppm.
S-6
Table S1: The reactivity of 1 with a range of fluorinated arenes.
Product 19F
Reaction
Substrate Yield vs Fc standard NMR shifts
Time
(C D )
6 6
-162.9 (m), 2F
10 days @
-160.2 (t), 1F
353 K
-106.7 (m), 2F
-143.7 (m), 2F
4 days -105.7 (m), 2F
-55.58 (t), 3F
-145.8 (dd), 2F
< 1 hour
-108.0 (dd), 2F
S-7
Figure S1: Stack plot of the reaction of 1 with hexafluorobenzene. Bottom: starting material Top: products.
Internal ferrocene standard marked with an asterisk.
Figure S2: Stack plot of the reaction of 1 with perfluorotoluene. Bottom: starting material Top: products. Internal
ferrocene standard marked with an asterisk.
S-8
Figure S3: Stack plot of the reaction of 1 with 2-(pentafluorophenyl)pyridine. Bottom: starting material Top:
products. Internal ferrocene standard marked with an asterisk.
S-9
2.4. Additional NMR experiments with polar additives
The effect of polar additives, i.e. pyridine or THF, in the reaction of 1 with fluoroarenes was investigated. The
reaction of 1 with C F in THF or in benzene-d with 1 equiv. of pyridine led to improved yields and significantly
6 6 6
milder reaction conditions than those for solely benzene-d . The formation of complex 4 was greatly reduced and
6
the yields of C–F activation products increased accordingly. For 2-(pentafluorophenyl)pyridine the effect was less
pronounced, and the same regioselectivity and similar reaction yields were obtained in benzene-d (Table S1) and
6
THF-d (Table S2). The higher yields reported in Table S2 compared to Table S1 are consistent with the polar
8
additive breaking up the coordination complex 4 liberating a further ½ equiv. of 1 to participate in nucleophilic
attack.
Table S2: Additional reactivity of 1 with fluoroarenes.
Reaction
Substrate Yield vs Fc standard Reaction conditions
Time
C D , pyridine (1 equiv.),
6 6
1 day
298 K
1 day THF-d , 298 K
8
2 hours THF-d , 298 K
8
S-10