Iridium-catalyzed isomerization of primary allylic
alcohols under mild reaction conditions
Luca Mantillia and Clément Mazeta*
a
Department of Organic Chemistry, University of Geneva, Quai Ernest Ansermet 30, 1211 Geneva,
Switzerland. Fax: (+41)22-379-3215; e-mail: clement.mazet@unige.ch
--------------------------------------------------------------------------------------------------------------------------------General Methods. All reactions were carried out under an inert atmosphere of argon or nitrogen using
either two-manifold vacuum / inert gas lines or a M.Braun glove-box, unless otherwise noted. Solvents
were dried over activated alumina columns and further degassed by three successive "freeze-pump-thaw"
cycles if necessary. NMR spectra were recorded on ARX-300, AMX-400 and AMX-500 Bruker Avance
spectrometers. 1H and 13C NMR chemical shifts are given in ppm relative to SiMe4, with the solvent
resonance used as internal reference. 31P NMR chemical shifts are reported in ppm relative to H3PO4. 19F
NMR chemical shifts are reported in ppm with absolute reference relative to 1H. Infrared spectra were
obtained on a Perkin-Elmer 1650 FT-IR spectrometer using neat samples on a diamond ATR Golden Gate
sampler. Optical rotations were measured on a Perkin-Elmer 241 polarimeter equipped with a Na-lamp.
The mass spectrometric data were obtained at the mass spectrometry facility of the University of Geneva
(http://www.ms.unige.ch/sms). Chiral GC analyses were performed on either a HP6890 or a HP6850 gas
chromatograph. Commercial reagents were purchased from Aldrich, Fluka, Acros or Strem and used
without further purification, unless otherwise noted. Liquid reagents were transferred with stainless steel
syringes or cannula. Flash chromatography was performed using silica gel 60 (230–400 mesh ASTM) from
Fluka.
IrCl3.(H2O)x was generously provided by Johnston-Matthey. [Ir(COD)Cl]2,1 [Ir(COD)2]BArF,2
[(Cy3P)(pyridine)Ir(COD)]PF6,3 [(Cy3P)(pyridine)Ir(COD)]BArF,4 [(pyridine)2Ir(COD)]BArF4 and catalyst
6,4 were prepared according to literature procedures. (E)-ethyl 4,4-dimethyl-3-phenylpent-2-enoate was
prepared according to the literature5 and reduced following the standard procedure described below.
General procedure for substrate synthesis.
To a stirred solution of triethylphosphonoacetate (67.5 mmol) in hexanes (67 mL) was added dropwise nBuLi (42 mmol, 1.6 M in hexanes) at 0°C. After stirring for 0.5 h at 0°C, the appropriate ketone (67.5
mmol) was added dropwise, and the reaction was refluxed overnight. The mixture was cooled to ambient
temperature, quenched with a saturated aqueous Na2CO3 solution and extracted with Et2O. The ethereal
organic phase was washed with water and dried over MgSO4. After filtration and removal of the volatiles,
the crude mixture was purified by flash chromatography (typically: cyclohexane / EtOAc = 20:1). The (E)
isomer always eluted first and the more polar (Z) isomer second. Both could be obtained pure as either
colorless oils or white solids.
The ester (6.9 mmol) was dissolved in Et2O (60 mL) and cooled down to -78°C. Dibal-H (15.1 mmol, 1.0
M in hexanes) was added dropwise. The reaction mixture was stirred at -78°C for 3h at which point the
cooling bath was removed until the reaction reached room temperature. The solution was quenched with a
saturated solution of NH4Cl at 0°C and stirred at room temperature for 1 h producing a white precipitate.
The precipitate was filtered through a pad of Celite® and the resulting solution dried over MgSO4. After
(1) Choudhury, J.; Podder, S.; and Roy. S. J. Am. Chem. Soc. 2005, 127, 6162−6163.
(2) Neumann, E.;Pfaltz A. Organometallics 2005, 24, 2008−2011.
(3) Crabtree, R. H.; Morehouse, S. M. Inorg. Synth. 1986, 24, 173−176.
(4) Wüstenberg, B.; Pfaltz A. Adv. Synth. Catal. 2008, 350, 174−178.
(5) Tanaka, K.; Fu, G. C. J. Org. Chem. 2001, 66, 8177−8186.
S-1
concentrating in vacuo, purification of the crude mixture by flash chromatography (typically: pentane /
Et2O = 2:1) yielded colorless oils or white solids. Configurations were assessed by 2DNMR experiments.
The vast majority of the allylic alcohols and aldehydes reported below have been previously reported. For
information, we give the 1H NMR analyses. Relevant references for supplementary analyses are provided in
each case. All new compounds have been fully characterized.
S-2
2-cyclohexylideneethanol. Colorless oil. 1H NMR (300 MHz, CDCl3, 298 K): δ =
5.37 (t, 3JHH = 7.2 Hz, 1H, CHCH2), 4.14 (dd, 3JHH = 7.2, Hz, 2JHH = 5.6 Hz, 2H,
CH2OH), 2.18 (m, 2H, CCH2 Cy), 2.11 (m, 2H, CCH2 Cy), 1.56 (m, 6H, CH2 Cy), 1.10
OH
(bs, 1H, OH).
Relevant reference for additional characterization, see: Kulkarni, G. H.; Arbale, A. A. Synth. Commun.
1988, 18, 2147−2159.
(E)-3,4-dimethylpent-2-en-1-ol. Colorless oil. 1H NMR (300 MHz, CDCl3, 298 K):
δ = 5.41 (t, 3JHH = 6.9 Hz, 1H, CHCH2), 4.14 (apt, 3JHH = 6.0 Hz, 2H, CH2OH), 2.25
3
3
i-Pr
OH (hept, JHH = 6.9 Hz, 1H, CHiPr), 1.64 (s, 3H, CCH3), 1.16 (bs, 1H, OH), 1.01 (d, JHH
= 6.9 Hz, 6H, CH3 iPr).
Relevant reference for complete characterization: Bhatnagar, S. C.; Caruso, A. J.; Polonsky, J.; Rodriguez,
B. S. Tetrahedron 1987, 43, 3471−3480.
Me
(E)-3-cyclohexylbut-2-en-1-ol. Colorless oil. 1H NMR (400 MHz, CDCl3, 298 K): δ
= 5.38 (t, 3JHH = 6.8 Hz, 1H, CHCH2), 4.16 (apt, 3JHH = 6.0 Hz, 2H, CH2OH), 1.841.66 (m, 6H, CH2 Cy), 1.66 (s, 3H, CH3), 1.35-1.16 (m, 5H, CH2 Cy), 1.18 (bs, 1H, OH).
Cy
OH
Relevant reference for complete characterization: Morrill, C.; Beutner, G. L.; Grubbs,
R. H. J. Org. Chem. 2006, 71, 7813−7825.
Me
(Z)-3-cyclohexylbut-2-en-1-ol. Colorless oil. 1H NMR (400 MHz, CDCl3, 298 K): δ
= 5.33 (t, 3JHH = 7.1 Hz, 1H, CHCH2), 4.13 (d, 3JHH = 6.8 Hz, 2H, CH2OH), 2.42 (m,
Me
OH 1H, OH), 1.79-1.18 (m, 6H, CHCy), 1.65 (s, 3H, CH3).
Relevant reference, see: Bellucci, C.; Gualtieri, F.; Scapecchi, S.; Teodori, E.
Farmaco 1989, 44, 1167−1191.
Cy
(E)-3,4,4-trimethylpent-2-en-1-ol. Colorless oil. 1H NMR (400 MHz, CDCl3, 298
K): δ = 5.45 (t, 3JHH = 6.9 Hz, 1H, CHCH2), 4.19 (apt, 3JHH = 6.0 Hz, 2H, CH2OH),
t-Bu
OH 1.66 (s, 3H, CCH3), 1.18 (bs, 1H, OH), 1.05 (s, 9H, CH3 tBu).
Relevant reference for complete characterization: Morrill, C.; Grubbs, R. H. J. Am.
Chem. Soc. 2005, 127(9), 2842−2843.
Me
(E)-3-phenylbut-2-en-1-ol. Colorless oil. 1H NMR (400 MHz, CDCl3, 298 K): δ =
7.41 (m, 2H, HmPh), 7.34 (m, 2H, HpPh), 7.28 (m, 1H, HoPh), 5.98 (t, 3JHH = 7.3 Hz, 1H,
Ph
OH CHCH2), 4.16 (apt, 3JHH = 5.8 Hz, 2H, CH2OH), 2.09 (s, 3H, CH3), 1.42 (bs, 1H, OH).
Relevant reference for complete characterization: Carruthers, W.; Evans, N.; Pooranamoorthy, R. J. Chem.
Soc., Perkin Trans 1 1975, 76−79.
Me
(Z)-3-phenylbut-2-en-1-ol. Colorless oil. 1H NMR (400 MHz, CDCl3, 298 K): δ =
7.37-7.25 (m, 3H, HPh), 7.17 (m, 2H, HPh), 5.72 (m, 1H, CHCH2), 4.08 (apt, 3JHH = 6.0
Me
OH Hz, 2H, CH2OH), 2.09 (s, 3H, CH3), 1.28 (bs, 1H, OH).
Relevant reference for complete characterization: Carruthers, W.; Evans, N.;
Pooranamoorthy, R. J. Chem. Soc., Perkin Trans 1 1975, 76−79.
Ph
(E)-3-phenylpent-2-en-1-ol. Colorless oil. 1H NMR (400 MHz, CDCl3, 298 K): δ =
7.28 (m, 3H, Ho,pPh), 7.21 (m, 2H, HmPh), 5.84 (t, 3JHH = 6.7 Hz, 1H, CHCH2), 4.36
3
Hz, 2H, CH2OH), 2.54 (q, 3JHH = 7.3 Hz, 1H, CH2 Et), 1.51 (m, 1H,
Ph
OH (apt, JHH = 5.6
3
OH), 1.00 (t, JHH = 7.3 Hz, 3H, CH3 Et).
Relevant reference for complete characterization: Morrill, C.; Beutner, G. L.; Grubbs, R. H. J. Org. Chem.
2006, 71, 7813−7825.
Et
i-Pr
Ph
OH
(E)-4-methyl-3-phenylpent-2-en-1-ol. Colorless oil. 1H NMR (400 MHz, CDCl3,
298 K): δ = 7.28 (m, 3H, Ho,pPh), 7.18 (m, 2H, HmPh), 5.49 (t, 3JHH = 6.7 Hz, 1H,
CHCH2), 4.16 (dd, 3JHH = 6.7 Hz, 3JHH = 5.6 Hz, 2H, CH2OH), 3.03 (hept, 3JHH = 7.1
Hz, 1H, CHiPr), 1.31 (t, 3JHH = 5.6 Hz, 1H, OH), 1.05 (d, 3JHH = 7.1 Hz, 6H, CH3 iPr).
S-3
Relevant reference for complete characterization: Tanaka, K.; Qiao, S.; Tobisu, M.; Lo, M. M.-C.; Fu, G.
C. J. Am. Chem. Soc. 2000, 122, 9870−9871.
(Z)-4-methyl-3-phenylpent-2-en-1-ol. Colorless oil. 1H NMR (400 MHz, CDCl3,
298 K): δ = 7.35-7.25 (m, 3H, HPh), 7.05 (d, 3JHH = 6.2 Hz, 2H, HoPh), 5.65 (t, 3JHH =
i-Pr
OH 6.9 Hz, 1H, CHCH2), 3.96 (bt, 3JHH = 6.2 Hz, 2H, CH2OH), 2.59 (hept, 3JHH = 9.0 Hz,
1H, CHiPr), 1.56 (bs, 1H, OH), 1.03 (d, 3JHH = 9.0 Hz, 6H, CH3 iPr).
Relevant reference for complete characterization: Tanaka, K.; Qiao, S.; Tobisu, M.; Lo, M. M.-C.; Fu, G.
C. J. Am. Chem. Soc. 2000, 122, 9870−9871.
Ph
(E)-4,4-dimethyl-3-phenylpent-2-en-1-ol. colorless oil. 1H NMR (400 MHz, CDCl3,
298 K): δ = 7.27-7.22 (m, 3H, Ho,pPh), 7.09-7.07 (m, 2H, HmPh), 5.34 (t, 3JHH = 6.3 Hz,
3
2), 4.50 (apt, JHH = 5.6 Hz, 2H, CH2OH), 1.48 (bs, 1H, OH), 1.14 (s, 9H,
Ph
OH 1H, CHCH
13
1
CH3 tBu). C{ H}NMR (101 MHz, CDCl3, 298 K): δ = 151.7 (s, CCPh), 145.6 (CipsoPh),
129.9 (CHCH2), 128.5 (s, CmPh), 127.5 (s, CoPh), 126.1 (s, CpPh), 58.5 (s, CH2OH), 35.8 (s, CH3 tBu), 31.5 (s,
CH3tBu). IR: ν (cm-1) = 3308, 3055, 2961, 2905, 2869, 2045, 1943, 1599, 1490, 1463, 1441, 1396, 1363,
1212, 1071, 1038, 1021, 908, 833, 810,767, 702, 668. HR-MS (ESI+) calculated for C13H17 [M-OH]+:
173.1324, found 173.1314.
t-Bu
(E)-3-o-tolylbut-2-en-1-ol. Colorless oil. 1H NMR (400 MHz, CDCl3, 298 K): δ
= 7.18-7.14 (m, 3H, HAr), 7.08 (m, 1H, HAr), 5.54 (dt, 3JHH = 6.4 Hz, 4JHH = 1.5
OH Hz, 1H, CHCH2), 4.35 (ap.t, 3JHH = 6.4 Hz, 2H, CH2OH), 2.29 (s, 3H, CH3 Mes),
1.99 (s, 3H, CCH3), 1.49 (m, 1H, OH). 13C NMR (CDCl3, 101 MHz, 298 K): δ
(ppm) = 144.7 (Cquat Ar), 139.8 (Cquat), 134.6 (Cquat Ar), 130.2 (CAr) 128.1 (CAr)
127.0 (CAr) 125.7 (CAr), 59.7 (CH2), 19.9(CH3 Ar), 18.4 (CH3). IR (neat): ν (cm-1) = 3322, 3059, 3015,
2921, 2868, 1659, 1486, 1437, 1377, 1098, 1064, 996, 757, 727. LRMS (ESI+) calculated for C11H13 [M –
OH]+: 145.1 ; found 145.4.
Me
Me
(E)-2,3-diphenylprop-2-en-1-ol. White solid. 1H NMR (300 MHz, CDCl3, 298 K): δ
= 7.33 (m, 3H, HAr), 7.25 (m, 2H, HAr), 7.10 (m, 3H, HAr), 6.99 (m, 1H, HAr), 6.70 (s,
Ph
CH), 4.48 (d, 3JHH = 6.0 Hz, 2H, CH2OH), 1.38 (t, 3JHH = 6.0 Hz, 1H, OH).
Relevant reference for complete characterization: Kang, Y. H.; Lee, C. J.; Kim, K. J. Org. Chem. 2001, 66,
2149−2153.
Ph
OH
OH
N
(E)-3-(1-methyl-1H-pyrrol-2-yl)prop-2-en-1-ol. Yellow oil. 1H NMR (300 MHz,
CDCl3, 298 K): δ = 6.59 (bt, 3JHH = 2.1 Hz, 1H, HAr), 6.50 (d, 3JHH = 15.7 Hz, 1H,
CHCH2), 6.34 (dd, 3JHH = 2.7 Hz, 3JHH = 1.6 Hz, 1H, HAr), 6.17-6.08 (m, 2H,
CHCH2 and HAr), 4.28 (apt, 3JHH = 4.5 Hz, 2H, CH2OH), 3.62 (s, 3H, NCH3), 1.38
Me
(m, 1H, OH).
Relevant reference, see: Lu, K.; Luo, T.; Xiang, Z.; You, Z.; Fathi, R.; Chen, J.; Yang, Z. J. Comb. Chem.
2005, 7, 958−967.
OH
N
Me
(E)-3-(1-methyl-1H-indol-3-yl)prop-2-en-1-ol. Yellow oil. 1H NMR (400
MHz, CDCl3, 298 K): δ = 7.86 (d, 3JHH = 8.1 Hz, 1H, HAr), 7.29 (tr, 3JHH = 8.9
Hz, 1H, HAr), 7.25 (d, 3JHH = 8.9 Hz, 1H, HAr), 7.18 (t, 3JHH = 8.1 Hz, 1H, HAr),
6.33 (dt, 3JHH = 16.2 Hz, 3JHH = 6.0 Hz, 2H, CHCH2), 4.32 (d, 3JHH = 6.0 Hz,
2H, CH2OH), 3.71 (s, 3H, NCH3), 1.79 (m, 1H, OH).
Relevant reference, see: Pindur, U.; Adam, R. Chemiker-Zeitung 1988, 112,
175−176.
(E)-2-methyl-3-phenylbut-2-en-1-ol. Colorless oil. 1H NMR (400 MHz, CDCl3, 298
K): δ = 7.31 (t, 3JHH = 7.1 Hz, 2H, HmPh), 7.23 (t, 3JHH = 7.1 Hz, 2H, HpPh), 7.13 (d, 3JHH
Ph
OH = 7.1 Hz, 1H, HoPh), 4.31 (s, 2H, CH2OH), 2.03 (s, 3H, PhCCH3), 1.68 (s, 3H,
CH2CCH3), 1.40 (bs, 1H, OH).
Me
Relevant reference for complete characterization: Hülskämper, L.; Weyerstahl, P.
Chem. Ber. 1981, 114, 746−756.
Me
S-4
(E)-1,1-dideuterium-4-methyl-3-phenyl-2-penten-1-ol. C12H14D2O. Colorless
oil. SiO2 (C5H12 / Et2O = 2 :1) Rf = 0.25 (UV). 1H NMR (CDCl3, 400 MHz, 298
K): δ (ppm) = 7.33-7.25 (m, 3H, Ho,pPh), 7.19-7.17 (m, 2H, HmPh), 5.47 (s, 1H,
OH
CHCD2), 3.03 (hept, 3JHH = 7.2 Hz, 1H, CHiPr), 1.22 (bs, 1H, OH), 1.06 (d, 3JHH =
7.2 Hz, 6H, CH3 iPr). 13C NMR (CDCl3, 101 MHz, 298 K): δ (ppm) = 150.4
(CCPh), 142.4 (CipsoPh), 128.6 (CmPh), 127.8 (CoPh), 127.4 (CHCD2), 126.8 (CpPh),
58.5 (t, 1JCD = 21.7 Hz, CH2OH), 30.0 (CH iPr), 22.2 (CH3 iPr). IR (neat): ν (cm-1) = 3306, 3079, 3055, 3021,
2963, 2930, 2872, 2172, 2093, 1600, 1491, 1460, 1442, 1384, 1263, 1142, 1113, 1079, 1010, 957, 912,
757, 700, 654. HRMS (ESI+) calculated for C12H13D2 [M – OH]+: 161.1299 ; found 161.1294.
D D
2-cyclohexylacetaldehyde. Colorless oil. 1H NMR (400 MHz, CDCl3, 298 K): δ =
9.75 (t, 3JHH = 2.3 Hz, 1H, CHO), 2.29 (dd, 3JHH = 7.1, Hz, 3JHH = 2.5 Hz, 2H,
CH2CHO), 1.86 (m, 1H, CHCy), 1.69 (bm, 5H, CCH2 Cy), 1.30-098 (m, 5H, CH2 Cy).
O Relevant reference for complete characterization: Rao, C. G.; Kulkarni, S. U.; Brown,
H. C. J. Organomet. Chem. 1979, 172, C20–C22.
Me
Cy
O
3-cyclohexylbutanal. Colorless oil. 1H NMR (400 MHz, CDCl3, 298 K): δ = 9.73 (apt,
3
JHH = 0.8 Hz, 1H, CHO), 2.43 (ddd, 2JHH = 15.9 Hz, 3JHH = 4.8 Hz, 3JHH = 1.8 Hz, 1H,
CH2CHO), 2.16 (ddd, 2JHH = 15.9, Hz, 3JHH = 8.9 Hz, 3JHH = 3.0 Hz, 1H,
CH2CHO),1.96-0.96 (m, 12H, CH2 Cy and CH Cy and CHCH3), 0.89 (d, 3JHH = 8.9 Hz,
3H, CH3).
Relevant reference for complete characterization: Ollivier, C.; Renaud, P. Chem. Eur. J. 1999, 5,
1468−1473.
3-phenylbutanal. Colorless oil. 1H NMR (400 MHz, CDCl3, 298 K): δ = 9.72 (s, 1H,
CHO), 7.32-7.22 (m, 5H, HPh), 3.37 (m, 1H, CHCH2), 2.71 (m, 2H, CH2CHO), 2.09 (d,
3
JHH = 6.8 Hz, 3H, CH3).
Ph
O
Relevant reference for complete characterization: Lee, T.; Jones, J. B. J. Am. Chem. Soc.
1996, 118, 502–508.
Me
3-phenylpentanal. Colorless oil. 1H NMR (400 MHz, CDCl3, 298 K): δ = 9.67 (apt,
3
JHH = 2.0 Hz, 1H, CHO), 7.35-7.15 (m, 5H, HPh), 3.08 (m, 1H, CHCH2), 2.72 (dd, 3JHH
3
3
Ph
O = 5.3 Hz, JHH = 2.0 Hz, 2H, CH2CHO), 1.69 (m, 2H, CH2 Et), 0.81 (t, JHH = 7.3 Hz, 3H,
CH3 Et).
Relevant reference for complete characterization: Mukaiyama, T.; Hayashi, H.; Miwa, T.; Narasaka, K.
Chem. Lett. 1982,1637–1640.
Et
4-methyl-3-phenylpentanal. 1H NMR (400 MHz, CDCl3, 298 K): δ = 9.59 (apt, 3JHH =
1.7 Hz, 1H, CHO), 7.31-7.12 (m, 5H, HPh), 2.95 (m, 1H, CHCH2), 2.71 (m, 2H,
3
3
CH
2CHO), 1.88 (m, 1H, CHiPr), 0.94 (d, JHH = 6.8 Hz, 3H, CH3 iPr), 0.77 (d, JHH = 6.8
Ph
O
Hz, 3H, CH3 iPr).
Relevant reference for complete characterization: Tanaka, K.; Qiao, S.; Tobisu, M.; Lo, M. M.-C., Fu, G.
C. J. Am. Chem. Soc. 2000, 122, 9870−9871.
i-Pr
4,4-dimethyl-3-phenylpentanal. Colorless oil. 1H NMR (400 MHz, CDCl3, 298 K): δ =
9.52 (apt, 3JHH = 1.7 Hz, 1H, CHO), 7.29-7.14 (m, 5H, HPh), 3.01 (dd, 3JHH = 10.6 Hz,
3
JHH = 4.7 Hz, 1H, CHCH2), 2.82 (m, 2H, CH2CHO), 0.90 (s, 9H, CH3 tBu).
Ph
O
Relevant reference for complete characterization: Tanaka, K.; Fu, G. C. J. Org. Chem.
2001, 66, 8177−8186.
t-Bu
Me
Me
O
3-o-tolylbutanal. Colorless oil. 1H NMR (400 MHz, CDCl3, 298 K): δ = 9.72 (s,
1H, CHO), 7.19-7.10 (m, 4H, HAr), 3.60 (m, 1H, CHCH2), 2.72 (m, 2H, CH2CHO),
2.38 (s, 3H, CH3 Tol), 1.28 (d, 3JHH = 7.1 Hz, 3H, CH3). 13C NMR (CDCl3, 101 MHz,
298 K): δ (ppm) = 201.9 (CHO), 143.6 (Cquat Ar), 135.4 (Cquat Ar), 130.6 (CAr) 126.5
(CAr) 126.3 (CAr) 125.3 (CAr), 51.2 (CH2), 29.3 (CH), 21.6 (CH3 Tol), 19.5 (CH3 Ar).
S-5
IR (neat): ν (cm-1) = 3020, 2963, 2927, 2872, 2720, 1722, 1490, 1455, 1377, 1083, 1035, 1003, 757, 727.
LRMS (ESI+) calculated for C11H13 [M – OH]+: 145.1 ; found 145.4.
2,3-diphenylpropanal. White solid. 1H NMR (400 MHz, CDCl3, 298 K): δ = 9.52 (bs,
Ph
O 1H, CHO), 7.38 (m, 8H, HPh), 7.07 (d, 2JHH = 7.3 Hz, 2H, Hph), 3.86 (bt, 3JHH = 7.1 Hz,
Ph
1H, CH), 3.49 (dd, 3JHH = 13.9 Hz, 3JHH = 6.8 Hz, 1H, CH2), 2.99 (bt, 3JHH = 14.1 Hz,
3
JHH = 7.8 Hz, 1H, CH2).
Relevant reference for complete characterization: Gensler, W. J.; Dheer, S. K. J. Org. Chem. 1981, 46,
4051–4057.
O
N
Me
3-(1-methyl-1H-pyrrol-2-yl)propanal. Yellow oil. 1H NMR (400 MHz, CDCl3,
298 K): δ = 9.86 (bs, 1H, CHO), 6.58 (bt, 3JHH = 2.0 Hz, 1H, HAr), 6.00 (bt, 3JHH = 3.0
Hz, 1H, HAr), 5.87 (m, 1H, HAr), 3.56 (s, 3H, NCH3), 2.90-2.82 (m, 4H, CH2).
O
N
Me
3-(1-methyl-1H-indol-3-yl)propanal. Yellow oil. 1H NMR (400 MHz, CDCl3,
298 K): δ = 9.85 (bt, 3JHH = 1.8 Hz, 1H, CHO), 7.59 (d, 3JHH = 8.0 Hz, 1H, HAr),
7.32-7.24 (m, 4H, HAr), 6.86 (s, 1H, NCH), 3.75 (s, 3H, NCH3), 3.12 (t, 3JHH =
7.3 Hz, 2H, CH2) , 2.85 (td, 3JHH = 7.3 Hz, 3JHH = 1.8 Hz, 2H, CH2CHO).
Relevant reference for complete characterization: Brown, S. P.; Brochu, M. P.;
Sinz, C. J.; MacMillan, D. W. C. J. Am. Chem. Soc. 2003, 125, 10808−10809.
2-methyl-3-phenylbutanal. Trans: 1H NMR (400 MHz, CDCl3, 298 K): δ = 9.68 (bs,
1H, CHO), 7.43-7.15 (m, 5H, HPh), 3.16 (m, 1H, CHPh), 2.60 (m, 1H, CHPh), 1.31 (d,
3
3
1
Ph
O JHH = 6.8 Hz, 3H, CH3), 0.88 (d, JHH = 6.8 Hz,3H, CH3). Cis: H NMR (400 MHz,
CDCl3, 298 K): δ = 9.58 (bs, 1H, CHO), 7.43-7.15 (m, 5H, HPh), 3.02 (m, 1H, CHPh),
Me
2.51 (m, 1H, CHPh), 1.26 (d, 3JHH = 6.8 Hz, 3H, CH3), 1.10 (d, 3JHH = 6.8 Hz,3H, CH3).
Relevant reference for complete characterization: Fleming, I.; Lewis, J. J. J. Chem Soc., Perkin Trans I
1992, 24, 3257−3266.
Me
Synthesis of [(Ph3P)(pyridine)Ir(COD)]BArF.
According to modified literature procedures: (a) O'Connor, J. M. Science of Synthesis 2002, 1, 617−744.
(b) Faller J. W.; Milheiro, S. C.; Parr J. J. Organomet. Chem. 2006, 691, 4945−4955.
Triphenylphosphine (35 mg, 132 mmol) was added to a solution of [Ir(COD)Cl]2 (44 mg, 66 mmol) in a
mixture of n-hexanes (1.5 mL) and CH2Cl2 (0.5 mL). The reaction was stirred at room temperature for 2 h.
After concentration to one-third of the original volume the orange precipitate formed was collected and
recrystallized with a 1:1 mixture of n-hexanes / CH2Cl2 (0.6 mL) to give [Ir(COD)(PPh3)Cl] (48 mg, 80
mmol, 61% yield) which was used whithout any further purification.
Ir(COD)(PPh3)Cl (36 mg, 60 mmol) was dissolved in CH2Cl2 (6 mL) and NaBArF (53 mg, 60 mmol) was
added in one portion. After 15 minutes, 4.9 µL of pyridine (60 mmol) were added. The mixture was stirred
at room temperature for 1 hour. The volatiles were removed under vacuum and the resulting orange solid
was washed with n-hexanes. (77 mg, 85% yield).
Catalyst 3: C63H44BF24IrNP. Orange solid. 1H NMR (CDCl3, 400 MHz, 298
K): δ (ppm) = 8.09 (bs, 2H, Hm Py), 7.71 (s, 8H, HoBArF), 7.51 (s, 4H, HpBArF),
BArF 7.50-7.32 (m, 16H, Py, PPh ) 6.98 (t, 3J = 6.5 Hz, 2H, Py) 4.29 (bs, 2H,
3
HH
N
Ph3P
CHCOD), 3.70 (bs, 2H, CHCOD), 2.42-2.28 (m, 4H, CH2 COD), 2.07-1.90, (m,
Ir
4H, CH2 COD). 13C{1H} NMR (CDCl3, 101 MHz, 298 K): δ (ppm) = 161.8 (q,
1
(COD)
JCB = 49.4 Hz, CipsoBArF), 150.1 (s, CmPy), 138.1 (s, CpPy), 134.9 (s, CoBArF),
133.8
(d, 3JCP = 8.0 Hz, CmPh), 131.8 (s, CpPh), 129.3 (d, 2JCP = 11.1 Hz, CoPh),
3
128.8 (q, 2JCF = 29.6 Hz, CCF3), 128.0 (d, 1JCP = 51.7 Hz, Cipso Ph), 124.6 (q,
1
JCF = 274.1 Hz, CF3), 117.6 (s, Cp BArF), 92.8 (d, 2JCP = 12.0 Hz, CHCOD), 67.3 (s, CHCOD), 32.4 (s, CH2
31
1
COD), 32.3 (s, CH2 COD), 30.0 (s, CH2 COD), 29.9 (s, CH2 COD). P{ H} NMR (CDCl3, 161 MHz, 298 K): δ
S-6
(ppm) = 18.4 (s). 19F{1H} NMR (CDCl3, 376 MHz, 298 K): δ (ppm) = -61.6. IR (neat) ν (cm-1) = 2925,
2025, 1609, 1484, 1450, 1436, 1353, 1272, 1119, 1001, 929, 886, 838,744, 715,693, 681, 668. LRMS
(ESI+): calculated for C23H20IrNNaP+ [M – BArF + Na]+: 556.59 ; found 557. Mp = 126-127 ˚C
Synthesis of [(SIMes) (pyridine) Ir(COD)]BArF.
According to a modified literature procedure: Lee, H. M.; Jiang, T. J.; Stevens, E. D.; Nolan, S. P.
Organometallics 2001, 20, 1255−1258.
SIMes•HCl (57 mg, 166 mmol) and KOtBu (19 mg, 166 mmol) were dissolved in THF (10 mL) and stirred
at room temperature for 1 h. The solvent was removed under vacuum. The residue was extracted with
toluene (3×3 mL) using a filtering cannula. 147 mg of [(pyridine)2Ir(COD)]BArF (111 mmol) were added
in one portion. The suspension was stirred at room temperature for 2 days. The solvent was removed and
the resulting red solid was purified by flash chromatography (cyclohexane / CH2Cl2 = 3:1). [(SIMes)
(Pyridine) Ir(COD)]BArF was obtained as an orange solid (105 mg, yield 61%).
Catalyst 4: C66H55BF24IrN3. Orange solid. SiO2 (CH2Cl2 / C6H12 = 4:1) Rf
= 0.74 (UV). 1H NMR (CDCl3, 400 MHz, 298 K): δ (ppm) = 7.71 (s, 8H,
BArF HoBArF), 7.70 (m, 2H, HmPh), 7.53 (m, 1H, HpPh), 7.51 (s, 4H, HpBArF), 7.07
(m, 2H, HpPh, 2H, HmMes), 6.86 (m, 2H, HmMes), 3.92 (m, 2H, NCH2), 3.78
N
N
Ir
(m,
2H, CHCOD), 3.72 (m, 2H, NCH2), 3.10 (m, 2H, CHCOD), 2.41 (s, 6H,
Mes
CH3 oMes), 2.35 (s, 6H, CH3 o’Mes), 1.87 (s, 6H, CH3 pMes), 1.86 (m, 4H, CH2
(COD)
13
1
COD), 1.53 (m, 4H, CH2 COD). C{ H} NMR (CDCl3, 101 MHz, 298 K): δ
4
(ppm) = 201.3 (s, NCN), 161.8 (q, 1JCB = 49.6 Hz, CipsoBArF), 151.0 (s,
CmPy), 139.6 (s, CipsoMes), 1387.6 (s, CpPy), 136.3 (s, CoMes), 135.7 (s, Co’Mes), 135.6 (s, CpMes), 134.9 (s,
CoBArF), 130.2 (s, CmMes), 130.0 (s, Cm’Mes), 128.8 (q, 2JCF = 29.6 Hz, CCF3), 125.7 (s, CoPy), 124.6 (q, 1JCF =
274.1 Hz, CF3), 117.6 (s, CpBArF), 84.2 (s CHCOD), 65.7 (s, CHCOD), 52.6 (s, NCH2), 32.4 (s, CH2 COD), 29.1
(s, CH2 COD), 21.1 (s, CH3 pMes), 18.3 (s,CH3 oMes), 18.1 (s, CH3 o’Mes). 19F{1H} NMR (CDCl3, 376 MHz, 298
K): δ (ppm) = - 62.4. IR (neat): ν (cm-1) = 2925, 1608, 1482, 1418, 1353, 1273, 1159, 1116, 949, 929, 885,
855, 839, 757, 714, 681, 668. HRMS (ESI+): calculated for C26H31IrN3Na [M – BArF – COD + Na]+:
603.2162 ; found 603.2170. Mp = 194-195 ˚C.
Mes
N
S-7
Representative procedure for the catalytic isomerization of allylic alcohols using 2.
A 25 mL Schlenk containing 3.0 mg of catalyst 2 (0.2 mmol, 1.0 mol%) was purged by three successive
vaccum/N2 sequences and finally refilled with N2. Distilled THF (4 mL) was added next and H2 gas was
gently bubbled directly through the solution via a stainless-steel needle at room temperature. The orange
solution rapidly discolored and after 1 minute bubbling, the rubber septum was replaced with a
polyethylene stopper and the solution was degassed by two successive freeze-pump-thaw cycles. After the
second cycle, 35 µL of (E)-3-phenylpent-2-en-1-ol (0.2 mmol) were added by micro-syringe and the
reaction stirred at room temperature for the specified amount of time (see Full Text for details).[#] Volatiles
were removed under vacuum, the yellow residue was dissolved in CDCl3 and conversions were assessed by
either 1H NMR spectroscopy or GC analysis using an internal standard.
For purification, the residue was dissolved in cyclohexane/ethyl acetate (5:1) and filtered through a short
plug of silica or Celite® (pasteur pipette) to remove the deactivated catalyst. The aldehyde was obtained
nearly quantitatively.
Table 1, Entry 18: A 10 mL Young® valve Schlenk was used instead. After the second degassing cycle,
32 µL of (E)-2-methyl-3-phenylbut-2-en-1-ol (0.2 mmol) were added by micro-syringe, the reaction vessel
tightly closed with the Young® valve and directly placed in a preheated oil bath (65°C, 22h).
[#]
Solvent screen using catalyst 2.
Reactions were run on a 0.2 mmol scale according to the general procedure.
i-Pr
Ph
Entry
1
2
3
4
Solvent
THF
MeOH
Hexanes
CH3CN
i-Pr
2 (1 mol%), solvent
OH
1 min H2
degassed, 23°C, 6 h
Conversion (%)
> 99
< 5
< 5
< 5
Entry
5
6
7
8
Ph
O
Solvent
C6H6
CH2Cl2
Acetone
EtOAc
Comparative study between Crabtree catalyst 1 and Crabtree analogue 2.
S-8
Conversion (%)
17
94
49
78
Competitive hydrogenation / isomerization reactions with cinnamyl alcohol and catalyst 2.
The isomerization of cinnamyl alcohol was run following the general procedure for the catalytic
isomerization of allylic alcohols. The hydrogenation reaction (1 bar H2) was conducted similarly, but the
stainless-steel needle was maintained in solution for 2 hours. The high-pressure hydrogenation was
conducted in a High-Pressure ‘Vivor’ Premex autoclave. Work up and purification were identical to the
isomerization reaction.
Isomerization
2 (5 mol%)
OH
1 min H2
O
degassed
THF, 2 h, 23°C
> 99% conv.
Hydrogenation
2 (5 mol%)
OH
OH
H2 (1 bar)
THF, 2 h, 23°C
70% conv.
2 (5 mol%)
OH
OH
H2 (60 bar)
THF, 2 h, 23°C
93% conv.
S-9
Identification of the dihydride active species by low temperature NMR experiments.
1
H NMR (500 MHz; THF-d8; 223K)
1 min H2
Cy3P
Ir
Py
THF-d8
Cy3P
degassed
- 50°C
2
H
H
Ir
H
Py
THF
THF
cis-2-(H)2
+
Cy3P
THF
Ir
H
Py
THF
trans-2-(H)2
X = BArF
ROESY (1H; 1H)
31
P{1H}NMR (THF-d8; 223K)
A 10 mL Schlenk containing 20.0 mg of catalyst 2 (0.013 mmol) was purged by three successive
vaccum/N2 sequences and finally refilled with N2. Dry THF-d8 (0.8 mL) was added next and H2 gas was
gently bubbled directly through the solution via a stainless-steel needle at room temperature. The orange
solution rapidly discolored and after 5 minutes bubbling, the rubber septum was replaced with a
polyethylene stopper and the solution was degassed by two successive freeze-pump-thaw cycles. By means
of a stainless-steel syringe, 0.45 mL of the colorless solution was transferred in a Young® valve NMR tube,
previously conditioned by successive ‘vacuum/N2 refill’ cycles. The sample was rapidly injected in a
AMX-500 MHz Bruker NMR spectrometer pre-cooled to 223K and analyzed.
Relevant references for similar studies using iridium complexes: (a) Crabtree, R. H.; Felkin, H.; FillbeenKahn, T.; Morris, G. E. J. Organomet. Chem. 1979, 168, 183−195. (b) Crabtree, R. H.; Demou, P. C.;
Eden, D.; Mihelic, J. M.; Parnell, C. A.; Quirk, J. M.; Morris, G. E. J. Am. Chem. Soc. 1982, 104,
6994−7001. (c) Crabtree, R. H.; Uriarte, R. J. Inorg. Chem. 1983, 22, 4152−4154. (d) Crabtree, R. H.;
Hlatky, G. G.; Parnell, C. A.; Segmueller, B. E.; Uriarte, R. J. Inorg. Chem. 1984, 23, 354−358. (e)
Kimmich, B. F. M.; Soomsook, E.; Landis, C. R. J. Am. Chem. Soc. 1998, 120, 10115-10125. (f) Mazet, C.;
Smidt, S. P.; Meuwly, M.; Pfaltz, A. J. Am. Chem. Soc. 2004, 126, 14176−14181.
Relevant references for similar studies using rhodium complexes: (a) Gridnev, I. D.; Higashi, N.; Asakura,
K.; Imamoto, T. J. Am. Chem.. Soc. 2000, 122, 7183−7194. (b) Heinrich, H.; Giernoth, R.; Bargon, J.;
Brown, J. M. Chem Commun. 2001, 1296−1297.
S-10
Labeling experiments: representative procedure for the catalytic isomerization of allylic alcohols
using 2 and (E)-1,1-dideuterium-4-methyl-3-phenyl-2-penten-1-ol.
Following the general procedure for the catalytic isomerization reaction using variable loadings of 2 (vide
supra). After TLC indicated complete conversion to the products, volatiles were removed under vacuum,
the yellow residue was dissolved in CDCl3 and conversions were assessed by 1H NMR spectroscopy.
i-Pr D D
Ph
3
2
1 min H2
Cy3P
Ir
Py
THF
H
Cy3P
H
degassed
RT
2
Ir
1
C3H
C2H2
OH
Py
THF
THF
2-(H)2
5 mol% [Ir]: ~ 10% H
10 mol% [Ir]: ~ 20% H
Ph
H/D
15 mol% [Ir]: ~ 30% H
D
i-Pr
3
20 mol% [Ir]: ~ 40% H
2
1
O
1
EI-HRMS
H NMR (CDCl3; 400 MHz)
Crossover experiment.
Carried out following the general procedure for the catalytic isomerization reaction using 15 mg of 2 (5
mol%, 0.010 mmol) and a 1:1 mixture of (E)-1,1-dideuterium-4-methyl-3-phenyl-2-penten-1-ol and (E)-3phenylpent-2-en-1-ol (0.2 mmol each), these two substrates exhibiting very similar reaction rates. After
TLC indicated complete conversion to the products, volatiles were removed under vacuum; the yellow
residue was dissolved in CDCl3 and analyzed by 1H NMR spectroscopy.
i-Pr D D
Ph
OH
Et H H
Ph
Ph
D
2 (5 mol%)
1 min H2, THF
degassed, 23°C
i-Pr
Ph
H
OH
Et
D
O
Ph
H
O
Ph
D
H
i-Pr
D
O
Et
H
O
The two possible isotopomers were observed by 1H NMR (CDCl3, 400 MHz, 298 K) for each substrate,
indicating an intramolecular process is at play. The four compounds were also clearly detected by EILRMS (Electronic Impact Low Resolution Mass Spectrometry).
S-11