A square-planar, iridium(I) carbene complex is shown to effect atom and group transfer from nitrous oxide and organic azides, releasing the corresponding formate or formimidate and an iridium(I)−dinitrogen adduct. The dinitrogen complex performs C−H activation upon photolysis or thermolysis, regenerating the carbene from tert-butyl methyl ether with loss of H_2. Taken together, these reactions represent a net catalytic cycle for C−H functionalization by double C−H activation to generate metal−carbon multiple bonds. Additionally, the unusual group transfer from diazo reagents underscores the unique nature of the reactivity observed for nucleophilic-at-metal carbene complexes

Grubbs, Robert H.

Whited, Matthew T.

English

Caltech Authors - Main

S1 
 
 
 
 
 
 
 
 
 
Supporting Information for 
 
A Catalytic Cycle for Oxidation of tert-Butyl Methyl Ether by a Double C–H Activation-
Group Transfer Process 
 
Matthew T. Whited and Robert H. Grubbs* 
 
Arnold and Mabel Beckman Laboratories of Chemical Synthesis, Division of Chemistry and Chemical Engineering 
California Institute of Technology, Pasadena, CA 91125 
 
 
 
Experimental Procedures .......................................................................................................... S2 
Figure S1. 1H NMR spectrum of (PNP)Ir=C(H)OtBu (1) before reaction with N2O .................. S7 
Figure S2. 1H NMR spectrum of crude mixture from reaction of 1 with N2O (15 min) ............. S8 
References and Notes .................................................................................................................. S9 
S2 
Experimental Section 
All manipulations were carried out using standard Schlenk or glove-box techniques under 
a dinitrogen atmosphere. Unless otherwise noted, solvents were deoxygenated and dried by 
thorough sparging with Ar gas followed by passage through an activated alumina column.1 
Hexamethyldisiloxane and tert-butyl methyl ether were distilled from CaH2 and degassed prior 
to use. (PNP)Ir=C(H)OtBu (1)2 and 2,6-diisopropylphenylazide3 were prepared according to 
literature procedures. Azidotrimethylsilane was purchased from Aldrich and degassed prior to 
use. Other reagents were purchased from commercial vendors and used without further 
purification. 
Elemental analyses were carried out at Desert Analytics, Tucson, Arizona. NMR spectra 
were recorded at ambient temperature on a Varian Mercury 300 MHz spectrometer. 1H and 13C 
NMR chemical shifts were referenced to residual solvent. 31P NMR chemical shifts are reported 
relative to an external standard of 85% H3PO4. Infrared spectra were recorded using a Perkin 
Elmer Spectrum BXII spectrometer. X-ray diffraction studies were carried out in the Beckman 
Institute Crystallographic Facility on a Bruker KAPPA APEX II diffractometer. 
Photolysis reactions were performed in pyrex vessels with 450W medium-pressure 
mercury arc lamp (Ace Glass) or a 120V/23W halogen bulb, which produced essentially 
identical results.  
 
X-ray Crystallography Procedures. X-ray quality crystals were grown as indicated in the 
experimental procedures for each complex. The crystals were mounted on a glass fiber with 
Paratone-N oil. Structures were determined using direct methods with standard Fourier 
S3 
techniques using the Bruker AXS software package. In some cases, Patterson maps were used in 
place of the direct methods procedure. 
 
(PNP)Ir–N2 (3). A 50 mL pressure tube was charged with (PNP)Ir=C(H)OtBu (1) (42.0 mg, 
0.0594 mmol) dissolved in toluene (15 mL). The solution was frozen and the headspace 
evacuated and backfilled with nitrous oxide (1 atm). Upon melting, the color of the solution 
changed from purple to orange over a period of 5 min. The solution was allowed to warm to 
ambient temperature, stirred for 15 min, and volatiles were removed in vacuo to afford an orange 
film. Lyophilization of the residues from benzene (5 mL) afforded 3 as a flocculent pale orange 
powder (37.9 mg, 98%). Orange crystals of 3 suitable for X-ray diffraction were obtained by 
slow evaporation of pentane from a concentrated solution. Due to its moderate light sensitivity, 
complex 3 was stored at –35 °C in the dark to prevent decomposition. 1H NMR (C6D6): δ 7.69 
(dt, J1 = 8.7 Hz, J2 = 2.1 Hz, 2H, Ar–H), 6.94 (m, 2H, Ar–H), 6.76 (dd, J1 = 8.4 Hz, J2 = 1.8 Hz, 
2H, Ar–H), 2.33 (m, 4H, –CH(CH3)2), 2.18 (s, 6H, Ar–CH3), 1.32 (dvt, 12H, –CH(CH3)2), 1.12 
(dvt, 12H, –CH(CH3)2. 13C{1H} NMR (C6D6): 164.1, 132.0, 131.6, 125.5, 121.7, 116.0, 26.4 
(m), 20.3, 19.1, 18.4. 31P{1H} NMR (C6D6): δ 46.9 (s). IR (THF, KBr, cm–1) υ(N2): 2067. Anal. 
Calcd. for C26H40IrN3P2: C, 48.13; H, 6.21; N, 6.48. Found: C, 48.57; H, 5.69; N, 6.15. 
 
Preparation of tert-butyl formate from complex (1). In a sealed NMR tube, a purple solution 
of 1 (ca. 15 mg) in C6D6 was frozen and the headspace evacuated and backfilled with nitrous 
oxide (1 atm). As the solution thawed, a gradual change in color from purple to pale yellow was 
observed. After 15 min, the disappearance of 1 was confirmed by NMR spectroscopy, and 
quantitative conversion to 3 and tert-butylformate was inferred as these were the only species 
S4 
observed in the 1H NMR spectrum (cf. Figures S1 and S2).  1H NMR (tert-butyl formate, C6D6): 
δ 7.64 (s, 1H, –C(O)H), 1.24 (s, 9H, –C(CH3)3). The identity of the tert-butylformate organic 
product was confirmed by comparison to an authentic sample obtained from Aldrich. 
 
Preparation of tert-butyl N-(2,6-diisopropylphenyl)formimidate from complex (1). 2,6-
diisopropylphenyl azide (6.1 mg, 0.030 mmol) was added in one portion to a solution of 1 (21.5 
mg, 0.0304 mmol) in C6D6 (800 μL), causing an immediate change in color from purple to 
golden. After 15 min, the disappearance of 1 was confirmed by NMR spectroscopy, and 
quantitative conversion to 3 and tert-butyl N-(2,6-diisopropylphenyl)formimidate was inferred as 
these were the only species observed in the 1H NMR spectrum. 1H NMR (tert-butyl N-(2,6-
diisopropylphenyl)formimidate, C6D6): δ 7.32 (s, 1H, –C(NDIPP)H), 7.25 – 7.10 (m, 3H, Ar–H), 
3.26 (septet, 3JHH = 6.9 Hz, 2H, –CH(CH3)2), 1.45 (s, 9H, –C(CH3)3), 1.23 (d, 3JHH = 6.9 Hz, 
12H, –CH(CH3)2). IR (C6D6, KBr, cm–1) υ(C=N): 1669. The tert-butyl N-(2,6-
diisopropylphenyl)formimidate organic product was identified by comparison of the distinctive 
spectral data, namely the 1H chemical shift of the formimidate proton and the energy of the 
medium-intensity C=N infrared stretch, to those of analogous formimidate complexes.2,4 
 
Preparation of tert-butyl N-adamantylformimidate from complex (1). 1-azidoadamantane 
(3.8 mg, 0.021 mmol) was added as a solid to a solution of 1 (13.1 mg, 0.0185 mmol) in C6D6 
(800 μL). Over a period of 15 min, the solution gradually lightened from purple to brown. 
Conversion to 3 and tert-butyl N-adamantylformimidate was complete in 2 h, and the yield of 
formimidate was judged to be quantitative by 1H NMR via integration versus an internal standard 
of hexamethyldisiloxane. 1H NMR (tert-butyl N-adamantylformimidate, C6D6): δ 7.46 (s, 1H, –
S5 
C(NAd)H), 1.96 (m, 3H, –CH (Ad)), 1.67 (d, 3JHH = 2.7 Hz, –NC(CH2)3 (Ad)), 1.58 (m, 6H, –
CH2 (Ad)), 1.49 (s, 9H, –C(CH3)3).  
 
Preparation of tert-butyl N-trimethylsilylformimidate from complex (1). Trimethylsilyl azide 
(2.5 μL, 0.019 mmol) was added in one portion to a solution of 1 (11.5 mg, 0.0163 mmol). No 
immediate color change was observed. After 10 h at ambient temperature, nitrene transfer to 
generate 3 and tert-butyl N-trimethylsilylformimidate was 25% complete, as judged by 1H and 
31P NMR. Extended heating (8 h, 70 °C) brought about the complete consumption of 1, though 
competitive degradation of 1 was noted at elevated temperatures (ca. 18% at 70 °C), as 
previously described.5 Addition of large excesses (> 10 equiv) of trimethylsilyl azide to solutions 
of 1 followed by 12 h of reaction at ambient temperature and 4 h at 70 °C also facilitated the 
complete consumption of 1 and formation of 3 and tert-butyl N-trimethylsilylformimidate 
without decomposition. 1H NMR (tert-butyl N-trimethylsilylformimidate, C6D6): δ 7.64 (s, 1H, –
C(NTMS)H), 1.38 (s, 9H, –C(CH3)3), 0.16 (s, 9H, –Si(CH3)3). 
 
Thermolysis of (PNP)Ir–N2 in MTBE. Complex 3 (ca. 10 mg) was dissolved in MTBE (800 
μL) and transferred to a resealable NMR tube under a nitrogen atmosphere. The solution was 
heated at 90 °C for 76 h, and the distribution of products was periodically monitored by 31P 
NMR (see chart below).6 After 7 d, the complete disappearance of (PNP)Ir–N2 and 
(PNP)Ir=C(H)OtBu and formation of trans-(PNP)Ir(CO)(H)2 were confirmed by 1H and 31P 
NMR spectroscopy. 
S6 
 
 
Stepwise synthesis of tert-butyl N-adamantylformimidate. A 30 mL resealable flask was 
charged with complex 1 (48.6 mg, 0.0687 mmol) and norbornene (31.9 mg, 0.339 mmol) in tert-
butyl methyl ether (15 mL). AdN3 (12.2 mg, 0.0688 mmol) was added and the reaction was 
stirred for 2 h, causing a color change to golden-brown. The solution was irradiated for 30 min, 
causing a darkening from golden to dark brown, and the reaction allowed to proceed at ambient 
temperature for 16 h, causing a color change to red-purple. A second equiv of AdN3 (12.2 mg, 
0.0688 mmol) was added and the solution was stirred for 2 h, causing the color to lighten to 
golden-brown. The sample was subjected to two additional cycles of photolysis and AdN3 
addition, as described above, and volatiles were removed in vacuo, leaving a brownish film. The 
residues were dissolved in C6D6 and the yield of tert-butyl N-adamantylformimidate (0.256 
mmol, 93% based on AdN3) determined by 1H NMR spectroscopy via integration relative to an 
internal standard of hexamethyldisiloxane. 
S7 
 
 
Figure S1. 1H NMR spectrum of (PNP)Ir=C(H)OtBu (1) before reaction with N2O 
S8 
 
 
Figure S2. 1H NMR spectrum of crude mixture from reaction of 1 with N2O (15 min) 
S9 
References and Notes 
 
(1) Pangborn, A. B.; Giardello, M. A.; Grubbs, R. H.; Rosen, R. K.; Timmers, F. J. Organometallics 1996, 15, 
1518. 
(2) Whited, M. T.; Grubbs, R. H. J. Am. Chem. Soc. 2008, 130, 5874. 
(3) Spencer, L. P.; Altwer, R.; Wei, P.; Gelmini, L.; Gauld, J.; Stephan, D. W. Organometallics 2003, 22, 3841. 
(4) (a) Aue, D. H.; Thomas, D. J. Org. Chem. 1974, 39, 3855. (b) Aue, D. H.; Thomas, D. J. Org. Chem. 1975, 40, 
2360. (c) Guzmán, A.; Muchowski, J. M.; Naal, N. T. J. Org. Chem. 1981, 46, 1224. 
(5) Romero, P. E.; Whited, M. T.; Grubbs, R. H. Organometallics 2008, 27, 3422. 
(6) For a related study on the thermolysis of (PNP)IrH2 in MTBE, see reference 5. 


A catalytic cycle for oxidation of tert-butyl methyl ether by a double C−H activation-group transfer process

A related but distinct tandem alkane dehydrogenation-olefin metathesis process has recently been reported for catalytic C-H functionalization via metal carbene intermediates:

For leading references regarding reactivity of organic azides, see:

For leading references, see: (a)

Hillhouse reports that pyridine N-oxide does not perform this transformation (ref 8b). We note the same behavior in our system, probably due to the poor electrophilicity of the reagent.

Nature 2002, 417, 507. (e) ActiVation and Functionalization

Organometallics

Related reactivity of Fischer carbenes with diazoalkanes: (a)

Stoichiometric generation of iridium carbenes by double C-H activation of ethers: (a)

http://authors.library.caltech.edu/14671/1/Whited2008p187J_Am_Chem_Soc.pdf

A catalytic cycle for oxidation of tert-butyl methyl ether by a double C−H activation-group transfer process

Abstract

Similar works

Full text

Available Versions

Caltech Authors - Main