Oxidative Pd(II)-Catalyzed C-H Bond Amination to Carbazoles at Ambient Temperature

Transcription

1 xidative Pd(II)-Catalyzed C- Bond Amination to Carbazoles at Ambient Temperature Supplementary Information ( Pages) James A. Jordan-ore, Carin C. C. Johansson, Moises Guilias Costa, Elizabeth M. Beck and Matthew J. Gaunt* Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge, UK, CB EW

2 General methods: MR spectra were recorded on a Bruker DPX 00 spectrometer in deuterated chloroform, benzene, toluene or DMS, operating at 00 Mz. C MR and 9 F MR were recorded on a Bruker DPX 00 spectrometer operating at 00 Mz and Mz respectively. Chemical shifts are quoted relative to residual solvent (e.g.,. ppm for and.0 ppm for C in CDCl,.0 ppm for and.0 ppm for C in d -benzene,.0 ppm,.00 ppm,. ppm for and. ppm and 0. ppm for C in d -toluene,. ppm for and 9. ppm for C in d -DMS) and coupling constants (J) are given in z. For convenience, the following abbreviations are used to indicate the multiplicity of the signals: s singlet; d doublet; t triplet; q quartet; qu quintet; hex hextet; sept septet; dd doublet of doublets; dt doublet of triplets; m multiplet; br broad; app is used where absolute multiplicity assignment is uncertain. The temperature of acquisition of the MR spectra was 9 ± K, unless otherwise indicated. DEPT and -dimensional experiments (CSY, MBC, MQC, SEY) were used to support assignments where appropriate. igh resolution mass spectral (RMS) analyses were measured on a Micromass Q-TF spectrometer using EI (electron impact) or ES (electrospray ionisation) techniques at the Department of Chemistry, University of Cambridge or at EPSRC RMS services, University of Wales Swansea. Compounds with Br or Cl isotopes were quoted as M.9 and M.99 respectively. Infrared spectra were recorded on a Perkin Elmer Polarimeter. Melting points are quoted as an average of two runs and were recorded using a Gallenkamp melting point apparatus and are reported uncorrected. All slow additions were performed using a World Precision Instruments AL 000 syringe pump. All anhydrous solvents were dried by standard techniques and freshly distilled before use. Pet ether 0-0 o C refers to the fraction collected between 0-0 o C from the distillation of crude petrol ether. All flash column chromatography was carried out using dry-packed Merck 9 Kieselgel 0 silica gel. Reactions were monitored by thin layer chromatography (TLC) carried out on Kieselgel 0 PF (Merck) 0. mm plates. Palladium(II) acetate (Pd(Ac) ) was purchased from Sigma Aldrich and given by a generous donation from Johnson Matthey. Phenyliodonium diacetate (PIDA) was purchased from the Sigma-Aldrich Chemical Company and all other chemicals were purchased from Sigma-Aldrich, Fluka, Lancaster, Avocado, Afla Aesar or Strem and used without further purification. R R Ar Ar R mol% Pd(Ac),. eq PIDA, PhMe R R Ar Ar R General procedure A - carbazole formation: The biarylamine ( mmol) and Pd(Ac) ( mol%) were stirred, unless otherwise stated, in toluene (0.0 M) at room temperature for h. Phenyliodonium diacetate (PIDA,. mmol, in one portion or by slow addition) was then added and the reaction mixture was stirred at room temperature unless otherwise stated. The reaction was monitored by LC/MS and TLC until completion. The solvent was removed under reduced pressure and the resulting residue absorbed onto silica and purified by flash column chromatography (with a gradient from 00:0 to 0: to 0:, pet ether C : diethyl ether). R R Ar Ar R mol% Pd(Ac),. eq PIDA, PhMe Ac R R Ar Ar R General procedure B - acid assisted carbazole formation: The biarylamine ( mmol) and Pd(Ac) ( mol%) were stirred, unless otherwise stated, in toluene (0.0 M) at room temperature for h. Phenyliodonium diacetate (PIDA,. mmol, in one portion or by slow addition) and acetic acid were then added and the reaction mixture was stirred at room temperature unless otherwise stated. The reaction was monitored by LC/MS and TLC until completion. The solvent was removed under reduced pressure and the resulting residue absorbed onto silica and purified by flash column chromatography (with a gradient from 00:0 to 0: to 0:, pet ether C : diethyl ether). SI

3 S -Substituted Amination a - 9-benzyl-9-carbazole a 9 0 Following the general procedure A: Biarylamine a (0 mg, 0.9 mmol); Pd(Ac) (. mg, mol%); PIDA (. mg, 0. mmol); toluene (. ml); for h. The compound was purified by flash column chromatography to give carbazole a (. mg, 9 %) as a white solid;! max (thin film)/cm - 00, 00, 9,, 9, 9,, 0,,,, 9,,, 0,,,, 9; " (00 Mz; CDCl ) (, dt, J =.,.0, Ar-),.-.9 (, m, Ar-),.9-.0 (, m, Ar-),.-.0 (, m, Ar-), (, m, Ar-),.-. (, s, -); " C (00 Mz; CDCl ).,., 9.,.9,.9,.,., 0., 9., 09.,.0; RMS found ES [M+] +., requires [C 9 +] +.. d - 9-isopropyl-9-carbazole d Following the general procedure A: Biarylamine d (00 mg, 0. mmol); Pd(Ac) (. mg, mol%); PIDA ( mg, 0. mmol); toluene (9. ml); h. The compound was purified by flash column chromatography to give carbazole d (9 mg, 0 %) as a white solid;! max (thin film)/cm - 0, 0, 90, 9,, 9,,, 0,,, 9, 09,,, 9,,,, 0, 0, 999, 90, 9, 0; " (00 Mz; CDCl ).9-. (, d, J =. z, -, -),.-. (, m, -, -),.-. (, app dt, J =.,., -, -0),.-. (, m, -9, - ), (, heptet, J =.0, -),.-. (, d, J =.0, -); " C (00 Mz; CDCl ) 9.,.,., 0.,., 09.9,., 0.; RMS found ES [M+] + 0., requires [C +] e - 9-methyl-9-carbazole Me e Following the general procedure A: Biarylamine e (0 mg, 0. mmol); Pd(Ac) (. mg, mol%); PIDA (09 mg, 0. mmol); toluene (. ml); for h. The compound was purified by flash column chromatography to give carbazole e (9 mg, 9 %) as a yellow solid;! max (thin film)/cm - 0, 9, 9, 9,,,,,,,,, 0,,, 0, 00, 9,,, 0; " (00 Mz; CDCl ).0 (d,, J =. z, -),.9 (ddd,, J =.,.,. z, -),. (d,, J =. z, -),. (app. t,, J =. z, -),. (s,, - SI

4 ); " C (00 Mz; CDCl).0,.,., 0.,., 0., 9.0; RMS found ES [M-] +.09, requires [C +] f - 9-allyl-9-carbazole f t 9 c Following the general procedure A: Biarylamine f ( mg, 0. mmol); Pd(Ac) (. mg, 0 mol%); PIDA (9 mg, 0.0 mmol); toluene ( ml); for h. The compound was purified by flash column chromatography to give carbazole f (. mg, 9 %) as a yellow solid;! max (thin film)/cm - 0, 9, 9, 9,,,,,,, 00, 00, 9,,, 9,, 0, ; " (00 Mz; CDCl ).0 (d,, J =. z, -),. (ddd,, J =.,.,. z, -),.9 (d,, J =. z, -),. (ddd,, J =.9,.,.0 z, -),.9 (tdd,, J =., 0.,.9 z, -),.0 (ddd,, J = 0.,.9,. z, t -9),.9 (ddd,, J =.0,.9,. z, c -9),. (td,, J =.9,. z, -); " C (00 Mz; CDCl) 0.,.,.,.9, 0., 9.0,., 0.,.; RMS found EI [M-] , requires [C -] g - 9-tert-butyl-9-carbazole g Following the general procedure A: Biarylamine g ( mg, 0.0 mmol); Pd(Ac) (. mg, 0 mol%); PIDA (0 mg, 0. mmol); toluene ( ml); for.h. The compound was purified by flash column chromatography to give carbazole g ( mg, %) as an oil;! max (thin film)/cm - 9, 99, 9,,, 99, 0,,, 90, 0, 9,,, 0,, ; " (00 Mz; CDCl ).0 (ddd,, J =.,., 0. z, -),. (d,, J =. z, -),. (ddd,, J =.,.,. z, Ar-),.0 (ddd,, J =.,., 0. z, Ar-),.0 (s, 9, -); " C (00 Mz; CDCl) 0.,.0,., 9.,.,., 9.0,.0; Anal (%) C.0,.,,.. v - (R,S,S,R)--(9-carbazol-9-yl)--(ethanoyloxymethyl)tetrahydro--pyran-,,-triyl triethanoate v Following the general procedure A: Biarylamine v (0 mg, 0.0 mmol); Pd(Ac) (. mg, 0 mol%); PIDA (.0 mg, 0. mmol); toluene ( ml); for h at 0 o C. The compound was purified by flash column chromatography to give carbazole v (0 mg, %) as a white crystalline solid after recrystallization from pet ether;! max (thin film)/cm -, 9, 9,,, 0,,, SI

5 ,,,, 9, 0, 09, 0, 0; " (00 Mz; toluene) (, d, J =., -, -),.0-. (, t, J =., -, 0-),.0-. (, d, J =., -, 9-),.0-.0 (, m, -, -),.0-.9 (, t, J = 9., -),.-.9 (, m, -, -, -),.0-. (, dd, J =.,.0, -),.0-.9 (, dd, J =.,., -),.-.0 (, m, -),. (, s, C C ),. (, s, C C ),.9 (, s, C C ),.0 (, s, C C ); " C (00 Mz; DMS) 0., 9., 9.,., 0.0,.0,.0,.0,.,., 0., 0., 0., 9.9,., 09.,.,.,.,.,.,., 0., 0., 0., 9.; RMS found ES [M++a] + 0., requires [C 9 a] SI

6 S Amination into Ar C- h - 9-benzyl--methyl-9-carbazole Ar 9 Me 0 h Following the general procedure A: Biarylamine h (0 mg, 0. mmol); Pd(Ac) (.0 mg, mol%); PIDA (0. mg, 0. mmol); toluene (. ml); for h. The compound was purified by flash column chromatography to give carbazole h (. mg, 9 %) as a white solid;! max (thin film)/cm - 00, 09, 9,, 90, 9, 0,, 09, 0,, 0, 0, 0, 09, 90,, 9,, 9, 9; " (00 Mz; CDCl ).0-.9 (, d, J =., -),.9-. (, m, -),.-. (, m, Ar-),.0-.0 (, m, Ar-),.0-.0 (, m, Ar-),.9-.9 (, m, Ar-),. (, s, -),. (, s, -); " C (00 Mz; CDCl ) 0.,.,.,.0,.,.,.,.,.,., 9., 9.0,,,.,., 0.9,.,.; RMS found [M+] +.9, requires [C 0 ] +.. i - 9-benzyl--methoxy-9-carbazole Ar 9 0 i Me Following the general procedure A: Biarylamine i (0 mg, 0. mmol); Pd(Ac) (.9 mg, mol%); PIDA (. mg, 0. mmol); toluene (. ml); for h. The compound was purified by flash column chromatography to give carbazole i (. mg, %) as a white solid;! max (thin film)/cm - 9,, 0, 9,,, 9, 9, 9,, 0, 999,,, ; " (00 Mz; CDCl ).0-.0 (, app. dt, J =., 0.9, -), (, d, J =., -),.-. (, m, Ar-),.-. (, m, Ar-),.-. (, m, Ar-),.9-.9 (, m, J =.,., Ar-),.-. (, d, J =., Ar-),. (, s, -),.9 ( s, -); " C (00 Mz; CDCl ).,.,.,., 9.,.9,.9,.0,.,., 0.0, 9.,., 09., 0.0, 9.9,.,.0; RMS found ES [M+] +., requires [C 0 ] +.. j - 9-benzyl--(trifluoromethyl)-9-carbazole Ar 9 0 j CF SI

7 Following the general procedure B: Biarylamine j ( mg, 0. mmol); Pd(Ac) (. mg, 0mol%); PIDA ( mg, 0.0 mmol); Ac (9 µl, equiv); toluene (. ml); for.h. The compound was purified by flash column chromatography to carbazole j (mg, %) as a white solid;! max (thin film)/cm - 9,,, 0,,,,, 9,,,,, 0, 0, 0, 9,,,, 0,, 9; " (00 Mz; CDCl ). (, d, J., -),. (, d, J., -),.9 (, s, -),.-. (, m, -, -9),. (, d, J., -),.-.0 (, -, -, -), (, m, -),. (, s, -); " C (00 Mz; CDCl )., 9.,.,.9,.9-0. ( J C-F., CF ).-. ( J C-F., C-0),.,.,.,.,.,.0, 0., 0., 9.9,.0-.9 ( J C-F., C-), 09., ( J C-F., C-9),.; " F ( Mz; CDCl ).; RMS found ES [M+] +. ([C 0 F +] + requires.). k - 9-benzyl--chloro-9-carbazole Ar 9 Cl 0 k Following the general procedure A: Biarylamine k (0 mg, 0. mmol); Pd(Ac) (.9 mg, mol%); PIDA (. mg, 0.0 mmol); toluene (. ml); for h. The compound was purified by flash column chromatography to give carbazole k (. mg, 9 %) as a white solid;! max (thin film)/cm - 0, 9,, 99, 90,, 0,,,,,, 0,, 0, 0, 0, 0, 00,,,, 9,,, 9; " (00 Mz; CDCl ) (, m, -, - ),.9-. (, m, Ar-),.0-. (, m, Ar-),.0-.0 (, m, Ar-),.0-.9 (, m, Ar-),. (, s, -); " C (00 Mz; CDCl ) 9.,.0,.,.9,.,.,.,.0,.,., 0.,.,.,., 0.0, 0.,.; RMS found ES [M+] + 9.0, requires [C 9 Cl] l - 9-benzyl--methyl-9-carbazole Ar Me 9 0 l Following the general procedure B: Biarylamine l (00 mg, 0. mmol); Pd(Ac) (. mg, mol%); PIDA ( mg, 0. mmol), Ac (. mg, 0. mmol); toluene (. ml); h. The compound was purified by flash column chromatography to give carbazole l ( mg, 0 %) as a white solid;! max (thin film)/cm - 0, 9,, 0,,,, 9,, 9,,,, 90, 0, 9,, ; " (00 Mz; CDCl ).0-. (, dt, J =., 0.9, -Ar),.0-.0 (, app. quartet, J = 0.9, -Ar),.0-. (, m, -Ar),.-.9 (, app. d, J =., -Ar),.-.9 (, m, -Ar),.-. (, m, -Ar);. (, s, -),. (, s, -); " C (00 Mz; CDCl ) 0.9,.9,.,.,.,.,.,.,.,.,., 0., 0.,.9, 0., 0.,.,.; RMS found ES [M+] +.9, requires [C 0 +] +.. SI

8 m - 9-benzyl--fluoro-9-carbazole Ar 9 F 0 m Following the general procedure A: Biarylamine m (0 mg, 0. mmol); Pd(Ac) (.00 mg, mol%); PIDA (9. mg, 0. mmol); toluene (. ml); for h. The compound was purified by flash column chromatography to give carbazole m ( mg, %) as a white solid;! max (thin film)/cm - 0, 9, 0, 0,,,,,,,,, 0, 0,, 99,,,, 9; " (00 Mz; CDCl ) (, app. dt, J =.9, 0., Ar-),.-. (, dd, J =.,., Ar-),.-. (, m, Ar-),.9-. (, app. d, J =., Ar-),.0-. (, m, Ar- ), (, dd, J = 9.0,., Ar-), (, m, Ar-),.9 (, s, -); " C (00 Mz; CDCl ).-. (d, J C-F =.9, C-F),.,.0,.0 (overlapping),.,.,.,.,.-. (d, J C-F =.),.-. (d, J C-F =.), 0., 9.,.-. (d, J C-F = 9.), (d, J C-F =.), 09., (d, J C-F = 9.0),.; " F ( Mz; CDCl ) -.; RMS found ES [M+] +.9, requires [C 9 F+] +.9. n - methyl 9-benzyl-9-carbazole--carboxylate 9 Ar Me C 9 0 n Following the general procedure B: Biarylamine n (0 mg, 0. mmol); Pd(Ac) (.0 mg, 0 mol%); PIDA ( mg, 0.9 mmol); CCl (. ml); PIDA was added over h, the reaction mixture was stirred for a further h at rt; the compound was purified by flash column chromatography to give carbazole n (0 mg, 0 %) as a white solid;! max (thin film)/cm - 90, 0,, 00, 9,,, 9, 0,, 0, 0,,,, 9; " (00 Mz; CDCl ).0-. (, dt, J =., 0.9, -Ar),.0-.0 (, app. quartet, J = 0.9, -Ar),.0-. (, m, -Ar),.-.9 (, app. d, J =., -Ar),.-.9 (, m, -Ar),.-. (, m, -Ar);. (, s, -),. (, s, -); " C (00 Mz; CDCl ).,.,.,.9, 9.,.,.,.9,.,.,.,.,., 0., 09., 0.9,.,.; RMS found ES [M+] +., requires [C +] +.. o - -iodo-9-isopropyl-9-carbazole Ar I 9 0 o SI

9 Following the general procedure A: Biarylamine o (0 mg, 0. mmol); Pd(Ac) (. mg, 0 mol%); PIDA (. mg, 0. mmol); toluene ( ml); for h. The compound was purified by flash column chromatography to give carbazole o (. mg, %) as a white solid;! max (thin film)/cm - 9, 9,, 9,,,,, 00, 0, 0,,,,,, 00,, 00,,,, ; " (00 Mz; C D ).-. (, d, J =., -),.0-.0 (, d, J =., -),.-. (, dd, J =.,., 0-),.-.9 (, d, J =., -),.-. (, m, -),.-. (, d, J =., -),.-.9 (, m, -),.0-. (, septet, J =.0, - ),.-. (, d, J =.9, -); " C (00 Mz; CDCl ) 9.9, 9.0,.9, 9.,.,.,., 0.9, 9.,., 0.,.,.,.; RMS found ES [M+] +.0, requires [C I] p - 9-benzyl--methyl-9-carbazole Ar p Me 9 0 Following the general procedure A: Biarylamine p (0 mg, 0. mmol); Pd(Ac) (.0 mg, mol%); PIDA (0. mg, 0. mmol); toluene (. ml); for h. The compound was purified by flash column chromatography to give carbazole p (. mg, %) as a white solid;! max (thin film)/cm - 0, 9,,, 9, 9,,,,,,, 0, 0, 99, 9, 0, 9,,,, 9; " (00 Mz; CDCl ).-. (, d, J =., -),.-.0 (, m, Ar-),.0-. (, m, Ar-),.-. (, m, Ar-),.-.0 (, m, Ar-),.0-.0 (, m, Ar-),.9-.9 (, d, J =., Ar-),. (, s, -),. (, s, -); " C (00 Mz; CDCl ) 9., 9.,.9,.,.,.,.,.,.9,.,., 0., 9.,.9, 0., 0.,., 9.; RMS found ES [M+] +., requires [C 0 ] +.. SI 9

10 S Amination into Ar C- i - 9-benzyl--methoxy-9-carbazole Ar 9 0 i Me Following the general procedure A: Biarylamine i (0 mg, 0. mmol); Pd(Ac) (. mg, 0 mol%); PIDA (. mg, 0. mmol); toluene (. ml); for h. The compound was purified by flash column chromatography to give carbazole i (9. mg, %) as a white solid;! max (thin film)/cm - 9,, 0, 9,,, 9, 9, 9,, 0, 999,,, ; " (00 Mz; CDCl ).0-.0 (, app. dt, J =., 0.9, -), (, d, J =., -),.-. (, m, Ar-),.-. (, m, Ar-),.-. (, m, Ar-),.9-.9 (, m, J =.,., Ar-),.-. (, d, J =., Ar-),. (, s, -),.9 ( s, -); " C (00 Mz; CDCl ).,.,.,., 9.,.9,.9,.0,.,., 0.0, 9.,., 09., 0.0, 9.9,.,.0; RMS found ES [M+] +., requires [C 0 ] +.. k - 9-benzyl--chloro-9-carbazole 0 9 Cl Ar k Following the general procedure B: Biarylamine k (9 mg, 0.0 mmol); Pd(Ac) (. mg, 0 mol%); PIDA ( mg, 0. mmol); Ac ( µl, eq) toluene ( ml); for h. The compound was purified by flash column chromatography to give carbazole k ( mg, 0 %) as a white solid;! max (thin film)/cm - 0, 9,, 99, 90,, 0,,,,,, 0,, 0, 0, 0, 0, 00,,,, 9,,, 9; " (00 Mz; CDCl ) (, m, -, -),.9-. (, m, Ar-),.0-. (, m, Ar-),.0-.0 (, m, Ar-),.0-.9 (, m, Ar-),. (, s, -); " C (00 Mz; CDCl ) 9.,.0,.,.9,.,.,.,.0,.,., 0.,.,.,., 0.0, 0.,.; RMS found ES [M+] + 9.0, requires [C 9 Cl] l - 9-benzyl--methyl-9-carbazole Me Ar 9 0 l SI 0

11 Following the general procedure B: Biarylamine l (00 mg, 0. mmol); Pd(Ac) (. mg, mol%); PIDA ( mg, 0. mmol); toluene (. ml); h. The compound was purified by flash column chromatography to give carbazole l ( mg, %) as a mixture of inseparable regioisomers.! max (thin film)/cm - 0, 9,, 0,,,, 9,, 9,,,, 90, 0, 9,, ; " (00 Mz; CDCl ).0-. (, dt, J =., 0.9, -Ar),.0-.0 (, app. quartet, J = 0.9, -Ar),.0-. (, m, -Ar),.-.9 (, app. d, J =., -Ar),.-.9 (, m, -Ar),.-. (, m, -Ar);. (, s, -),. (, s, -); " C (00 Mz; CDCl ) 0.9,.9,.,.,.,.,.,.,.,.,., 0., 0.,.9, 0., 0.,.,.; RMS found ES [M+] +.9, requires [C 0 +] +.. m - 9-benzyl--fluoro-9-carbazole 0 9 F Ar m Following the general procedure A: Biarylamine m (0 mg, 0. mmol); Pd(Ac) (. mg, 0 mol%); PIDA ( mg, 0. mmol); toluene (. ml); for.h. The compound was purified by flash column chromatography to give major carbazole m ( mg, % of a : mixture) as a white solid;! max (thin film)/cm - 0, 9, 0, 0,,,,,,,,, 0, 0,, 99,,,, 9; " (00 Mz; CDCl ) (, app. dt, J =.9, 0., Ar-),.-. (, dd, J =.,., Ar-),.-. (, m, Ar-),.9-. (, app. d, J =., Ar-),.0-. (, m, Ar-), (, dd, J = 9.0,., Ar-), (, m, Ar-),.9 (, s, -); " C (00 Mz; CDCl ).-. (d, J C-F =.9, C-F),.,.0,.0 (overlapping),.,.,.,.,.-. (d, J C-F =.),.-. (d, J C-F =.), 0., 9.,.-. (d, J C-F = 9.), (d, J C-F =.), 09., (d, J C-F = 9.0),.; " F ( Mz; CDCl ) -.; RMS found ES [M+] +.9, requires [C 9 F+] +.9. n - methyl 9-benzyl-9-carbazole--carboxylate 9 Me C Ar 9 0 n Following the general procedure B: Biarylamine n (0 mg, 0. mmol); Pd(Ac) (. mg, 0 mol%); PIDA (.00 mg,.9 mmol); toluene (. ml); for h. The compound was purified by flash column chromatography to give carbazole n (. mg, 9 %) as a white solid;! max (thin film)/cm - 90, 0,, 00, 9,,, 9, 0,, 0, 0,,,, 9; " (00 Mz; CDCl ).0-. (, dt, J =., 0.9, -Ar),.0-.0 (, app. quartet, J = 0.9, -Ar),.0-. (, m, -Ar),.-.9 (, app. d, J =., -Ar),.-.9 (, m, -Ar),.-. (, m, -Ar);. (, s, -),. (, s, -); " C (00 Mz; CDCl ).,.,.,.9, 9.,.,.,.9,.,.,.,.,., 0., 09., 0.9,.,.; RMS found ES [M+] +., requires [C +] +.. SI

12 o - 9-benzyl--methyl-9-carbazole o Me Ar 9 0 Following the general procedure B: Biarylamine o (0 mg, 0. mmol); Pd(Ac) (. mg, 0 mol%); PIDA ( mg, 0. mmol); Ac (0 µl, 0. mmol); toluene (. ml); hrs. The compound was purified by flash column chromatography to yield carbazole o (mg, %) as a white solid;! max (thin film)/cm - 0, 9,,, 9, 9,,,,,,, 0, 0, 99, 9, 0, 9,,,, 9; " (00 Mz; CDCl ).-. (, d, J =., -),.-.0 (, m, Ar-),.0-. (, m, Ar-),.-. (, m, Ar-),.-.0 (, m, Ar-),.0-.0 (, m, Ar-),.9-.9 (, d, J =., Ar-),. (, s, -),. (, s, -); " C (00 Mz; CDCl ) 9., 9.,.9,.,.,.,.,.,.9,.,., 0., 9.,.9, 0., 0.,., 9.; RMS found ES [M+] +., requires [C 0 ] +.. q - 9-benzyl--methoxy-9-carbazole Me Ar q 9 0 Following the general procedures A: Biarylamine q (0 mg, 0. mmol); Pd(Ac) (.9 mg, mol%); PIDA (. mg, 0. mmol); toluene (. ml); for h. The compound was purified by flash column chromatography to give the major regioisomer, carbazole q (. mg, %) as a white solid;! max (thin film)/cm - 09, 9,,, 0, 9,,,, 9,,,,, 00, 09, 90, 0, 99,,, 9; " (00 Mz; CDCl ) (, app. dt, J =., 0.9, -),.-.9 (, d, J =., -),.-. (, m, Ar-),.-.9 (, app. d, J =., Ar- ),.-.0 (, m, Ar-),.0-.9 (, m, Ar-),.9-.9 (, dd, J =.9,., Ar-),. (, s, -),.0 (, s, -); " C (00 Mz; CDCl ).,.,.,., 9.,.9,.,.,.,., 0., 9.,., 0., 09., 0.9,.,.; RMS found ES [M+] +.9, requires [C 0 ] +.. r - 9-benzyl--nitro-9-carbazole 9 0 Ar r Following the general procedure A: Biarylamine r (9 mg, 0. mmol); Pd(Ac) (0. mg, 0 mol%); PIDA (. mg, 0. mmol, equiv); toluene (. ml); for h at 00 o C. The compound was purified by flash column chromatography to give carbazole r (0 mg, %) as a yellow solid;! max (thin film)/cm - 0, 9, 0, 0, 9,, 9,,,,,, 9,, SI

13 090, 0, 90,, 9, 0, 0, 9, ; " (00 Mz; CDCl ) (, d, J =., -),.0-. (, dd, J = 9.,., -),.-.0 (, dt, J =., 0., -),.9-. (, m, Ar-),.9-. (, d, J =., Ar-),.-. (, m, Ar-),.-. (, m, Ar-),.0-.0 (, m, Ar-).0 (, s, -); " C (00 Mz; CDCl ).,.9,.0,., 9.0,.0,.,.,.0,.,...,.0,., 09.9, 0.,.0; RMS found ES [M+] + 0., requires [C 9 ] s - methyl 9-benzyl-9-carbazole--carboxylate Ar Me s Following the general procedure A: Biarylamine s (0 mg, 0. mmol); Pd(Ac) (. mg, mol%); PIDA (.00 mg,.9 mmol); toluene (. ml); for h. The compound was purified by flash column chromatography to give carbazole s (.9 mg, 9 %) as a white solid;! max (thin film)/cm - 00, 90, 0,, 99, 9, 0,,,,,, 0,, 0,, 0, 00, 90,,,, 9; " (00 Mz; CDCl ) (, m, -, 9-, -),.-. (, dd, J =.,., -),.9-. (, m, Ar-),.-. (, d, J =., Ar-),.0-.0 (, m, Ar-),.0-.9 (, m, Ar-),. (, s, -),. (, s, 9-); " C (00 Mz; CDCl )., 0.,.,.,.,.,.,.,.,.9, 0.9, 9., 9.,.,., 09., 0.0, 0.,.; RMS found ES [M+] +., requires [C ] +.. t - 9-benzyl--methoxy-9-carbazole Me 0 9 t Following the general procedure A: Biarylamine t (0 mg, 0. mmol); Pd(Ac) (.9 mg, mol%); PIDA (. mg, 0. mmol); toluene (. ml); for h. The compound was purified by flash column chromatography to give carbazole t (. mg, %) as a white solid;! max (thin film)/cm - 90,, 99,, 0,,,,,,,,,, 0, 999,,,, 9; " (00 Mz; CDCl ).-. (, d, J =., -),.-. (, m, Ar-),.0-. (, m, Ar-),.-.0 (, m, Ar-),.0-.9 (, d, J =., -),.-. (, d, J =.0, -),.9 (, s, -),.0 (, s, -); " C (00 Mz; CDCl ).,., 0.,., 9.,.,.0,.,.,.,., 9.9,., 0., 0., 00.,.9,.; RMS found ES [M+] +., requires [C 0 ] +.. SI

14 u - -benzyl--azatetracyclo[..0.0,.0, ]heptadeca--(0),(),,,,(),,-octene 9 0 Ar 9 0 ne u Following the general procedure A: Biarylamine u (0 mg, 0. mmol); Pd(Ac) (.9 mg, 0 mol%); PIDA (0 mg, 0. mmol); toluene (. ml); for h. The compound was purified by flash column chromatography to give carbazole u ( mg, %) as a white solid;! max (thin film)/cm - 0, 9,,,, 9, 9,,,,,,, 09, 99, 0,, 9, 9; " (00 Mz; CDCl ). (d,, J =. z, -),. (d,, J =. z, -),.9 (d,, J =. z, Ar-),.9 (d,, J =. z, Ar-),. (d,, J =.9 z, Ar-),. (ddd,, J =.,.9,. z, Ar-),. (d,, J =.9 z, Ar-),. (d,, J =. z, Ar-),.-. (m, ),. (ddd,, J =.,.,. z, Ar-),.-. (m,, Ar-),.0-.0 (m,, Ar-),. (s,, - ); " C (00 Mz; CDCl) 9.,.,., 9.9, 9., 9.,.,.,.,.0,.,.,.,.,.9,., 0.,., 0., 09.,.; RMS found ES [M+] + 0., requires [C +] SI

15 S Structural Assignment Example of Complete Structural Assignment of -Iodo-9-isopropylcarbazole o MR with expansion of the aromatic region. I D CSY Verifying the structural assignment.9 -. region of the -MR. CDCl i Pr I SI

16 ne differences Justifying the structural assignment Ar ne = ne =. ne =. I ne =.0 ne =. ne =. ne between isopropyl protons omitted for clarity ne =. (C irradiated) and. (CC irradiated) SI

17 S Kinetic Isotope Effect Following the general procedure A: Biarylamine d-d (00 mg, 0. mmol); Pd(Ac) (. mg, 0 mol%); PIDA (. mg, 0. mmol,. equiv); toluene (. ml); for h. The compound was purified by flash column chromatography (pet ether) to give carbazoles d & d-d as an inseparable mixture (90 mg, 9 %) as a white solid. D Bn D Bn Bn Case Case d-d d-d d Determining the distribution of products was achieved using the benzylic protons as an internal standard. In both reaction outcomes the integral of the benzylic position will always be two. owever, the peak corresponding to - (IUPAC Carbazole umbering) will be in extreme cases: o o Case - integrate to one (amination occurring exclusively via the proton, generating carbazole d-d) or, Case - integrate to two (amination occurring exclusively via the deuterium, generating carbazole d). Therefore, the minimum integral of position - is one, this corresponds to case. Any integral higher than one will denote the percentage insertion via the deuterium. SI

18 Kinetic Isotope Effect Experiment at o C, (Room Temperature) MR This corresponds to a KIE (k / k D ) of.9 D Bn d-d mol% Pd(Ac) PhI(Ac), PhMe, r.t. D Bn d-d.: Bn d SI

19 S - Competition Experiments X Me C Me Bn n/q mol% Pd(Ac) eq. PhI(Ac) Bn Bn PhMe, r.t. eq. n and eq. q n : q The following four competition experiments have been conducted in order to determine how ring electronics effect substrate consumption. E E Electron rich vs. Electron neutral E Electron deficient vs. Electron neutral E Electron rich vs. Electron deficient E Electron rich vs. Electron deficient PIDA as a limiting reagent Electron Rich vs. Electron eutral Following general procedure A: Biarylamine d (0 mg, 0.9 mmol, equiv); Biarylamine q (. mg, 0.9 mmol, equiv) and Pd(Ac) (. mg, mol%) were added sequentially to d -Benzene (. ml) and stirred for hr. PIDA (. mg, 0. mmol,. equiv) was then added and the resultant mixture was stirred for hrs. Me Me vs. Aliquots were taken at regular intervals until the reaction was deemed to have reached a satisfactory comparison by MR. SI 9

20 Expansion of the..0 ppm region SI 0

21 Details from the MR E Biarylamine d and q benzylic positions overlap therefore the Me was used as the diagnostic peak Biarylamine q reacts preferentially Ca. min carbazole q product is apparent (Product Me ~.ppm). Electronically rich substrates react in preference over electronically neutral substrates. Electron Deficient vs. Electron eutral Following general procedure A: Biarylamine d (0 mg, 0.9 mmol, equiv); Biarylamine n (. mg, 0.9 mmol, equiv) and Pd(Ac) (. mg, mol%) were added sequentially to d -Benzene (. ml) and stirred for hr. PIDA (. mg, 0. mmol,. equiv) was then added and the resultant mixture was stirred for hrs. Me C Me C vs. Aliquots were taken at regular intervals until the reaction was deemed to have reached a satisfactory comparison by MR. SI

22 Expansion of the..0 ppm region Details from the MR E Biarylamine d reacts preferentially Ca. min carbazole d product is apparent (benzyl C ~.0ppm). At ca. min carbazole d product is apparent (benzyl C ~.ppm) Again, electronically rich systems react in preference. Electron Rich vs. Electron Deficient Following general procedure A: Biarylamine q (0 mg, 0.9 mmol, equiv); Biarylamine n (. mg, 0.9 mmol, equiv) and Pd(Ac) (. mg, mol%) were added sequentially to d -Benzene (. ml) and stirred for hr. PIDA (. mg, 0. mmol,. equiv) was then added and the resultant mixture was stirred for hrs. Me C Me Me C Me vs. Aliquots were taken at regular intervals until the reaction was deemed to have reached a satisfactory comparison by MR. SI

23 Expansion of the diagnostic regions Details from the MR Biarylamine q reacts preferentially SI

24 Ca. min carbazole q product is apparent At ca. 0min carbazole n product is apparent From the benzylic region (.0.00 ppm) it is clear that q appears first Again, electronically rich systems react in preference E Electron rich vs. Electron deficient PIDA as a limiting reagent Following general procedure A: Biarylamine q (0 mg, 0.9 mmol, equiv); Biarylamine n (. mg, 0.9 mmol, equiv) and Pd(Ac) (. mg, mol%) were added sequentially to d -Benzene (. ml) and stirred for hr. PIDA (. mg,. mmol,. equiv) was then added and the resultant mixture was stirred for hrs. Me C Me Me C Me vs. 0mol% PIDA equiv equiv Aliquots were taken at regular intervals until the reaction was deemed to have reached a satisfactory comparison by MR. SI

25 Expansion of the diagnostic region Details from the MR Biarylamine q reacts almost exclusively nly after 0min does biarylamine n begin to react Under oxidant-limiting conditions electronically rich systems react almost exclusively. SI

26 S Palladacycle Formation Pd (Ac),. equiv Ph Toluene, h Me Pd Ph Me Pd Me Ph Pd Me Formation of Palladacycle IId To a stirred solution of d (g,.mmol) in toluene was added Pd (Ac) (.g,. equiv), the resultant deep red solution was stirred at room temperature for h. ver time the deep red solution became clear and a beige precipitate was visible, this precipitate was filtered, washed with diethyl ether and petrol and dried in vacuo to give palladacycle IId as an off beige solid. Crystallization of IId Crystals suitable for X-ray diffraction were grown by slow diffusion of DCM into petrol ether (0-0 o C). Palladacycle IId (0mgs) was stirred in DCM ( ml) for 0 min, the resultant slurry was filtered through cotton wool, the filtrate was collected and placed into a vial which was in turn placed into a larger vial containing petrol ether (0-0 o C) and then sealed. The vial was stored at ~ C for days, palladacycle IId crystallized as microscopic colourless plates. SI