Pd-catalysed arylation of propan-1-ol and derivatives: Oxidative role of the arylating agent

Article abstract of DOI:10.1039/b005323f

With excess PhI under Pd catalysis, 1-PrOH was converted to a mixture of 3,3-diphenylpropenal and trans-2,3-diphenylpropenal by a concerted, oxidative sequence that involved two arylative couplings and an olefinic aldehyde that was generated in situ.

Full text of DOI:10.1039/b005323f

Pd-catalysed arylation of propan-1-ol and derivatives: oxidative role of the
arylating agent
Laurence Bagnell, Ulf Kreher and Christopher R. Strauss*
CSIRO Molecular Science, Private Bag 10, Clayton South, Victoria 3169, Australia.
E-mail: chris.strauss@molsci.csiro.au
Received (in Cambridge, UK) 3rd July 2000, Accepted 15th November 2000
First published as an Advance Article on the web
With excess PhI under Pd catalysis, 1-PrOH was converted
to a mixture of 3,3-diphenylpropenal and trans-2,3-di-
phenylpropenal by a concerted, oxidative sequence that
involved two arylative couplings and an olefinic aldehyde
that was generated in situ.
Mono-arylated products were not observed in the reaction of
1-PrOH, rendering as unlikely, a multi-step sequence involving
successive intermolecular Heck arylative couplings with an
olefin formed by dehydrogenation in situ.12 The absence of
detectable intermediates implies that the process was concerted
and may constitute a new reaction.
Recently in our laboratory, Pd on porous glass was developed as
a heterogeneous catalyst1 for promoting Glaser-type and Heck
arylative couplings2 without the need for solubilising or
activating ligands. Significantly, with excess allyl alcohol and
with PhI in air, Pd on porous glass gave trans-cinnamaldehyde
(1) along with 3-phenylpropanal (2; see entry 2, Table 1).1
Consistent with literature reports,3,4 in the absence of air, and
without the addition of Ag+ salts, 2 predominated and 1 was not
obtained (entry 1, Table 1).
With PhI in excess, the diarylated compounds 3 and 4
appeared as major products from allyl alcohol, along with 1 and
2 (entry 3, Table 1). This diarylation appeared to contrast with
a wealth of literature data on the Pd catalysed arylation of that
alcohol.3 Without Ag+ salts,4 one might expect that the first
arylation of allyl alcohol would be accompanied by rapid
migration of the olefinic bond to afford mainly 3-phenyl-
propanal (2), thereby removing the opportunity for a second
Heck arylation to occur.
Although air facilitated the dehydrogenation for the reaction
in entry 2 of Table 1,5 the results in entry 3 and co-formation of
biphenyl suggested that the arylating agent may have had an
additional role. To support this contention, we now report that
1-PrOH with excess PhI can afford a mixture of 3,3-di-
phenylpropenal (4) and trans-2,3-diphenylpropenal (5), even
under an inert gas atmosphere (see entry 9). This remarkable
transformation has been performed with either Pd(OAc)2 or Pd
on porous glass as catalyst6,7 (which was used for all entries in
Table 1) includes microwave heating8 in a reactor of our
design.9
A comparable stepwise process would require oxidation of
the hydroxy function of 1-PrOH, dehydrogenation of the
hydrocarbon chain and two Heck-like arylative couplings of the
resultant olefin. However, for the one reaction, successive
intermolecular Heck arylative couplings onto the same olefin
are rare.10 Intramolecular examples usually have involved
mono-arylations of more than one carbon–carbon double
bond.11
Formation of biphenyl and benzene as by-products indicates
that PhI served as both an oxidant and a reactant. Buchwald and
Palucki observed similar behaviour of their arylating agent in
the ‘Pd’ catalysed reaction of cyclohexanol with 4-tert-
butylbromobenzene to produce the corresponding a-arylated
cyclohexanone and tert-butylbenzene.13 They surmised that
some of the haloarene was simultaneously reduced during
oxidation of the alcohol to cyclohexanone.
Although variations in the order of transformations and
alternative routes are possible for the present reaction, the
pathway in Scheme 1 appears to account for the products, by-
products and their relative proportions.
Preliminary investigations (see Table 1) into the process
utilised cinnamaldehyde (1),14 cinnamyl alcohol (6), 3-phenyl-
propanol (7) and 3-phenylpropanal (2). Cinnamyl alcohol (6)
afforded diarylenal 4 as a major product (along with 3 and the
2,3-diphenylpropenol isomer 8), irrespective of whether or not
the atmosphere contained air (entries 5 and 6). Under argon,
3-phenylpropanal (2) gave 2,3-diphenylpropanal (9) and prod-
ucts of higher oxidation state, including 1, 4 and 5 (entry 7).
3-Phenylpropanol (7) afforded 4 and 5 as major products, along
with traces of 1 and 2 (entry 8). The product distributions
obtained from Pd catalysed reactions of excess PhI with 6, 7 and
2 suggest that several competing processes were operating,
including a-arylation,13 Heck-like arylative coupling of olefinic
bonds2 as well as the new process described herein and
illustrated by Scheme 1.
These outcomes may have depended on whether or not
coordination of the olefin to Pd occurred in conjunction with the
establishment of a strong Pd–O bond, leading to a chelation
controlled reaction. Such bonds have been suggested for
palladium catalysed oxidation of alcohols.15 Scheme 1, pro-
posed for the reaction of 1-PrOH commences with Pd–O
chelation and proceeds preferably through metallaoxetane
intermediates,16 which account for the observed products and
their relative distribution. In the case of allyl alcohol (entry 3),
it appears that the double bond and the hydroxy group of the
Table 1 Example reactions and conditions
Major products
Entry
Starting material (mmol)
PhI/mmol
Ar or Air
(percentage of total detected)
Turnover Number
1
2
3
4
5
6
7
8
9
CH2NCH–CH2OH (13)
CH2NCH–CH2OH (13)
CH2NCH–CH2OH (14)
PhCHNCH–CHO, 1 (13)
PhCHNCHCH2OH, 6 (13)
PhCHNCHCH2OH, 6 (13)
PhCH2CH2CHO, 2 (6)
PhCH2CH2CH2OH, 7 (10)
CH3CH2CH2OH (20)
6
6
Ar
2 (59), CH3CH(Ph)CHO (23)
1 (60), 2 (40)
1 (16), 2 (7), 3 (24), 4 (26)
4 (99)
3 (36), 4 (18), 8 (15), 9 (10)
3 (6), 4 (62), 8 (13)
1 (5), 3 (16), 4 (39), 5 (6), 9 (18)
4 (60), 5 (18)
170
120
450
Air
Air
Ar or Air
Ar
Air
Ar
34
34
34
34
34
34
34
245 (Ar), 170 (Air)
700
560
270
50
Ar
Ar
4 (80), 5 (18)
30
DOI: 10.1039/b005323f
Chem. Commun., 2001, 29–30
This journal is © The Royal Society of Chemistry 2001
29

Notes and references
1 J. Li, A. W.-H. Mau and C. R. Strauss, Chem. Commun., 1997, 1275.
2 A. de Meijere and F. E. Meyer, Angew. Chem., Int. Ed. Engl., 1994, 33,
2379; R. F. Heck in Comprehensive Organic Synthesis, series eds. B. M.
Trost, I. Fleming, vol. ed. M. F. Semmelhack, Pergamon, Oxford, 1993,
vol. 4, p. 833.
3 J. B. Melpolder and R. F. Heck, J. Org. Chem., 1976, 41, 265; A. J.
Chalk and S. A. Magennis, J. Org. Chem., 1976, 41, 273; A. J. Chalk
and S. A. Magennis, J. Org. Chem., 1976, 41, 1206; T. Jeffrey, J. Chem.
Soc., Chem. Commun., 1984, 1287; R. C. Larock, W.-Y. Leung and S.
Stolz-Dunn, Tetrahedron Lett., 1989, 30, 6629; S.-K. Kang, K.-Y. Jung,
C.-H. Park, E.-Y. Namkoong and T.-H. Kim, Tetrahedron Lett., 1995,
36, 6287; G. Dyker and P. Grundt, Tetrahedron Lett., 1996, 37, 619.
4 T. Jeffery, Tetrahedron Lett., 1991, 32, 2121.
5 C. R. Strauss, Aust. J. Chem., 1999, 52, 83.
6 A Into a dry, two-necked flask fitted with a reflux condenser and an inert
gas (Ar) bleed line was placed a solution of 1-PrOH (0.784 g; 13.06
mmol) and PhI (12.674 g; 62.12 mmol) in dry, deoxygenated N,N-
dimethyl acetamide (DMA; 50 mL). Anhydrous NaOAc (5.80 g; 70.70
mmol) and Pd(OAc)2 (0.564 g; 2.51 mmol) were added and the mixture
was heated at 125 °C for 16 h, then cooled, quenched with 80 mL H2O
and extracted with Et2O (1 3 80 mL, 2 3 50 mL). The ether extract was
washed thrice with water, dried with MgSO4 and the ether removed in
vacuo. Unconverted PhI was recovered by vacuum distillation at 40 °C
and 1 3 1022 mbar and biphenyl was removed by sublimation (80 °C
and 1 3 1022 mbar). Flash chromatography (silica gel 60, di-
chloromethane+pentane 1:1) afforded pure product 4 (395 mg). B Into
a dry, two-necked flask fitted with a reflux condenser and an inert gas
(Ar) bleed line was placed a solution of 1-PrOH (749 mg; 12.48 mmol)
and PhI (6.971 g; 34 mmol) in dry, deoxygenated N,N-dimethyl
acetamide (DMA; 50 mL). Anhydrous NaOAc (4.127 g; 50 mmol) and
Pd on porous glass (containing 19 mmol Pd)1 were added and the
mixture was heated at 125 °C for 16 h, then cooled. Work up as above
yielded pure product 4 (73 mg).
7 Although Pd(OAc)2 undergoes thermal decomposition to give finely
divided Pd metal and gases including CO2, methane and ethane (see
M. T. Reetz and M. Maase, Adv. Mat., 1999, 11, 773; M. T. Reetz and
G. Lohmer, Chem. Commun., 1996, 1921), no evidence was obtained to
associate that redox process with the present reaction.
8 Into a dry PTFE vessel under nitrogen was placed a solution of 1-PrOH
(0.803 g; 13.4 mmol) and PhI (6.853 g; 33.6 mmol) in dry,
deoxygenated N,N-dimethyl acetamide (DMA; 50 mL). Anhydrous
NaOAc (4.19 g; 51.0 mmol) and Pd(OAc)2 (50.4 mg; 0.22 mmol) were
added and the mixture was heated for 10 min at 220 °C in a microwave
batch reactor9 (MBR), then cooled. Work up as in footnote 6 yielded
pure product 4 (280 mg). For other examples of Pd catalysed reactions
under microwave heating, see M. Larhed and A. Hallberg, J. Org.
Chem., 1996, 61, 9582; U. Bremberg, M. Larhed, C. Moberg and A.
Hallberg, J. Org. Chem., 1999, 64, 1082; M. Larhed, M. Hoshino, S.
Hadida, D. P. Curran and A. Hallberg, J. Org. Chem., 1997, 62,
5583.
Scheme 1
9 C. R. Strauss and R. W. Trainor, Aust. J. Chem., 1995, 48, 1665; K. D.
Raner, C. R. Strauss, R. W. Trainor and J. S. Thorn, J. Org. Chem.,
1995, 60, 2456.
10 For examples see, T. Sugihara, M. Takebayashi and C. Kaneko,
Tetrahedron Lett., 1995, 36, 5547; B. M. Choudary, R. M. Sarma and
K. K. Rao, Tetrahedron, 1992, 48, 719.
11 L. F. Tietze, Chem. Rev., 1996, 96, 115; M. Lautens and S. Piguel,
Angew. Chem., Int. Ed., 2000, 39, 1045.
12 In water at high temperature, Pd(OAc)2 catalysed Heck arylations have
been reported with olefins generated in situ. However, at 400 °C, the
reaction between PhI and 1-PrOH gave 1-propylbenzene by
a
mechanism that was not determined. See E. J. Parsons, CHEMTECH,
1996, 26(7), 30.
13 M. Palucki and S. L. Buchwald, J. Am. Chem. Soc., 1997, 119,
11 108.
14 A. Amorese, A. Arcadi, E. Bernocchi, S. Cacchi, S. Cerrini, W. Fedeli
and G. Ortar, Tetrahedron, 1989, 45, 813.
15 S. Ait-Mohand, F. Henin and J. Muzart, Tetrahedron Lett., 1995, 36,
2473; V. Bellosta, R. Benhaddou and S. Czernecki, Synlett, 1993,
861.
16 E. Bernocchi, S. Cacchi, P. G. Ciattini, E. Morera and G. Ortar,
Tetrahedron Lett., 1992, 33, 3073.
alcohol compete for the Pd and products from both Heck-type
arylative coupling (2 and 3) as well as the sequence in Scheme
1 (diarylenal 4) result.
We thank Professor A. Hallberg and Dr M. Larhed of
Uppsala University, Sweden, and Dr H. Weigold of CSIRO for
reviewing drafts of the manuscript and for helpful discussion.
The work was supported by a postdoctoral fellowship (for U.K.)
from the German Academic Exchange Service (DAAD).
30
Chem. Commun., 2001, 29–30