Palladium-catalyzed formal hydroacylation of allenes employing carboxylic anhydrides and hydrosilanes

Article abstract of DOI:10.1016/j.tet.2015.01.066

The formal hydroacylation reaction of allenes has been developed employing carboxylic anhydrides as acyl sources and hydrosilanes as reducing reagents in the presence of a commercially available palladium complex as a catalyst. The reaction affords α,β-unsaturated ketones regio- and stereoselectively. The similar catalyst system is also effective for the reduction of carboxylic anhydrides to the corresponding aldehydes employing hydrosilanes.

Full text of DOI:10.1016/j.tet.2015.01.066

Tetrahedron 71 (2015) 4570e4574
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Tetrahedron
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Palladium-catalyzed formal hydroacylation of allenes employing
carboxylic anhydrides and hydrosilanes
*
Tetsuaki Fujihara , Takuro Hosomi, Cong Cong, Tomoya Hosoki, Jun Terao,
*
Yasushi Tsuji
Department of Energy and Hydrocarbon Chemistry, Graduate School of Engineering, Kyoto University, Kyoto 615-8510, Japan
a r t i c l e i n f o
a b s t r a c t
Article history:
The formal hydroacylation reaction of allenes has been developed employing carboxylic anhydrides as
acyl sources and hydrosilanes as reducing reagents in the presence of a commercially available palladium
Received 7 January 2015
Accepted 23 January 2015
Available online 10 February 2015
complex as a catalyst. The reaction affords
a,b-unsaturated ketones regio- and stereoselectively. The
similar catalyst system is also effective for the reduction of carboxylic anhydrides to the corresponding
aldehydes employing hydrosilanes.
Keywords:
Allene
Ó 2015 Elsevier Ltd. All rights reserved.
Carboxylic anhydride
Hydroacylation
Hydrosilane
Palladium
1. Introduction
cross-coupling reactions employing organoboronic acids8 and
organozinc reagents.9 Carboxylic anhydrides were also utilized in
Hydroacylation reaction involving the addition of aldehydes to
carbonecarbon multiple bonds is a useful synthetic method to
provide unsymmetrical ketones atom-economically.1 However,
intermolecular hydroacylation of alkenes and alkynes often suffers
from low selectivity and low yields. In order to ensure high effi-
ciency, i) intramolecular reaction,2 ii) substrates bearing suitable
directing groups,3 and/or iii) carbon monoxide pressure,4 were
often indispensable. An alternative method is a formal hydro-
acylation employing a suitable acyl source in place of an aldehyde.
The oxidative or reductive formal hydroacylation employing alco-
hols as acyl donors were reported.5 We recently found the
palladium-catalyzed formal hydroacylation of allenes employing
acid chlorides and hydrosilanes.6 The reaction afforded the corre-
the formal hydroacylation of styrene derivatives in the presence of
a rhodium catalyst.10
Herein, we report the palladium-catalyzed formal hydro-
acylation of allenes employing carboxylic anhydrides with stable
and easy-to-handle hydrosilanes as a reducing agent. As for the
hydroacylation of allenes using aldehydes,11 there have been only
two precedents to date, in which the aldehydes must bear
hydroxyl11a or thioether11b functionalities as directing groups.
Noteworthy is that no directing groups are necessary in the present
reaction.
2. Palladium-catalyzed reduction of carboxylic anhydrides
sponding a,b-unsaturated ketones regio- and stereoselectively.
Before investigating the formal hydroacylation of allenes, we
carried out reduction of carboxylic anhydrides to aldehydes
employing hydrosilanes as a reducing agent. Yamamoto and co-
workers reported the reduction of carboxylic anhydrides to the
corresponding aldehydes in the presence of palladium catalysts.12
However, the reaction required high pressure (3.0 MPa) of molec-
ular hydrogen. Based on our previous report that a palladium
complex efficiently catalyzes the reduction of carboxylic acids in
the presence of pivalic anhydride,13 Pd-catalyzed reduction of car-
boxylic anhydrides employing hydrosilanes to the corresponding
aldehydes was carried out. Thus, benzoyl anhydride (1a) was
treated with a mixture of Pd(dba)2 and P(p-MeOC6H4)3 as a catalyst
in the presence of H2SiMePh as a reducing agent in toluene at 50 ꢀC
Carboxylic anhydrides are stable, easy-to-handled, and easy-to-
prepare compounds from the corresponding carboxylic acids, and
are one of the most useful compounds in organic synthesis. Re-
garding the transition-metal catalyzed reactions, it is known that
the oxidative addition of the C(acyl)-O bond proceeds in the pres-
ence of suitable transition-metal complexes.7 Thus, carboxylic an-
hydrides were used as an acyl source in the palladium-catalyzed
* Corresponding authors. Tel.: þ81 75 383 2517; fax: þ81 75 383 2514 (T.F.); tel.:
þ81 75 383 2515; fax: þ81 75 383 2514 (Y.T.); e-mail addresses: tfuji@scl.kyoto-u.
ac.jp (T. Fujihara), ytsuji@scl.kyoto-u.ac.jp (Y. Tsuji).
http://dx.doi.org/10.1016/j.tet.2015.01.066
0040-4020/Ó 2015 Elsevier Ltd. All rights reserved.

T. Fujihara et al. / Tetrahedron 71 (2015) 4570e4574
Table 2 (continued )
4571
(Table 1). As a result, benzaldehyde (2a) was obtained in 85% yield
(entry 1). Without the ligand, 1a did not convert at all (entry 2). As
the ligand, PPh3, P(p-MeC6H4)3 and PCy3 also afforded 2a in good
yields (entries 3e5). As for hydrosilanes, HSiEt3 afforded 2a in 67%
yield, while more bulky HSiiPr3 was not efficient (entries 6 and 7).
H2SiEt2 and H2SiPh2 provided 2a in 74% and 9% yields, respectively
(entries 8 and 9). MeCN was also a good solvent in the reaction
(entry 10).
Entry
Carboxylic anhydride (1)
Temp (oC)
50
Yield (%)b
6
2g:88d
2h:93d
1g
1h
7
8
50
60
2i:82
Table 1
1i
Effect of ligands and hydrosilanes on the palladium-catalyzed reduction of benzoic
anhydride (1a)a
9
120
2j:73d
1j
a
Reaction conditions: carboxylic anhydride (1: 0.50 mmol), H2SiMePh
(0.55 mmol), Pd(dba)2 (0.025 mmol, 5.0 mol %), P(p-MeOC6H4)3 (0.050 mmol,
10 mol %, P/Pd¼2) in toluene (1.0 mL), for 20 h.
Entry
Ligand
Hydrosilane
Yield (%)b
b
Isolated yield.
1
2
3
4
5
6
7
8
P(p-MeOC6H4)3
None
PPh3
P(p-MeC6H4)3
PCy3
P(p-MeOC6H4)3
P(p-MeOC6H4)3
P(p-MeOC6H4)3
P(p-MeOC6H4)3
P(p-MeOC6H4)3
H2SiMePh
H2SiMePh
H2SiMePh
H2SiMePh
H2SiMePh
HSiEt3
85
Trace
68
74
66
67
14
74
9
c
Pd(dba)2 (0.05 mmol, 10 mol %), P(p-MeOC6H4)3 (0.10 mmol, 20 mol %, P/Pd¼2).
d
Yield based on the GC internal standard technique.
reaction temperature to 120 ꢀC (entry 9). Unfortunately, pivalic
anhydride could not be employed as the substrate in the present
catalytic system possibly because of its steric hindrance.
HSiiPr3
H2SiEt2
H2SiPh2
H2SiMePh
9
10c
81
3. Palladium-catalyzed formal hydroacylation of allenes
a
Reaction conditions: benzoic anhydride (1a: 0.50 mmol), hydrosilane
(0.55 mmol), Pd(dba)2 (0.025 mmol, 5.0 mol %), ligand (0.05 mmol, 10 mol %, P/
Pd¼2) in toluene (1.0 mL) at 50 ꢀC for 20 h.
As mentioned above, a hydrosilane is an excellent reducing re-
agent for the reduction of carboxylic anhydrides. Thus, the formal
hydroacylation of cyclohexylallene (3a) with 1a was carried out
using HSiiPr3 as a reducing agent in the presence of a catalytic
amount of PdCl2(MeCN)2 in MeCN at 50 ꢀC (Table 3). Under the
reaction conditions, an E/Z mixture of hydroacylated product (4a)
was obtained in 96% total yield with good E-selectivity (E/Z¼88/12,
entry 1). By column chromatography, pure (E)-4a was isolated in
71% yield. In this reaction, the addition of auxiliary ligands such as
PPh3 inhibited the formation of 4a (entry 2). As for hydrosilane,
HSiEt3, HSiPh3 and HSi(OEt)3 were not effective (entries 3e5). PhCN
as a solvent provided 4a in 72%, while DMF and THF were not
suitable for this reaction (entries 6e8).
b
Yield based on the GC internal standard technique.
c
MeCN (1.0 mL) was used as the solvent.
Various carboxylic anhydrides were smoothly converted to the
corresponding aldehydes in good to high yields (Table 2). Among
them, the reaction of an aromatic acid anhydride having an electron
donating group (-OMe) proceeded smoothly, giving the corre-
sponding aldehyde in 83% yield (entry 1). In the reaction of 1c
bearing an electron withdrawing group (-CF3), 2c was isolated in
52% yield (entry 2). 3-Pyridinecarboxylic anhydride 1d gave 2d in
good yield (entry 3). With 3-arylpropionic acid anhydrides (1e and
1f), the desired aldehydes (2e and 2f) were obtained in good yields
(entries 4e5). Other aliphatic acid anhydrides such as 1g, 1h, and 1i
also converted to the corresponding aldehydes in 88%, 93%, and 82%
yields, respectively (entries 6e8). In addition, cyclohexane-car-
boxylic anhydride 1j also afforded 2j in 73% yield by elevating the
Table 3
Optimization of reaction conditions on the palladium-catalyzed formal hydro-
acylation of cyclohexylallene (3a) with 1aa
Table 2
The palladium-catalyzed reduction of carboxylic anhydrides to the corresponding
aldehydesa
Entry
Hydrosilane
Solvent
Total yield (4a) (%)b
96 (71)d
Selectivity (E/Z)c
Entry
1
Carboxylic anhydride (1)
Temp (oC)
50
Yield (%)b
1
2e
3
4
5
6
7
8
HSiiPr3
HSiiPr3
HSiEt3
HSiPh3
HSi(OEt)3
HSiiPr3
HSiiPr3
HSiiPr3
MeCN
MeCN
MeCN
MeCN
MeCN
PhCN
DMF
88/12
d
0
37
20
39
81
29
7
88/12
86/14
78/22
89/11
86/14
d
2b:83
1b
2c
40
2c:52
THF
1c
a
Reaction conditions: 1a (0.50 mmol), cyclohexylallene (3a: 1.0 mmol), hydro-
silane (0.65 mmol), PdCl2(MeCN)2 (0.025 mmol, 5.0 mol %), solvent (1.0 mL) at 50 ꢀ
for 20 h.
C
b
3
4
5
40
60
40
2d:75
2e:76
2f:70
Based on the GC internal standard technique.
Determined by GC and GCeMS analysis.
Isolated yield of (E)-4a.
PPh3 (0.050 mol) was added.
c
1d
d
e
1e
Next, the formal hydroacylation of several allenes (3) with car-
boxylic anhydrides (1) was carried out under the same reaction
conditions as in entry 1, Table 3 (Table 4). The reaction of 3a with an
aromatic carboxylic anhydride bearing electron withdrawing
1f

4572
T. Fujihara et al. / Tetrahedron 71 (2015) 4570e4574
Table 4
The palladium-catalyzed formal hydroacylation of allenesa
Entry
Carboxylic
anhydride (1)
Allene (3)
Yield of (E)-4 (%)b
(E/Z ratio in crude)c
1
1c
3a
4b: 81 (93/7)
4c: 41 (84/16)
4d: 81 (94/6)
2
1b
1e
1a
3a
3a
3d
Scheme 1. Proposed mechanism.
4
3b
anhydrides as an acyl source in the presence of a commercially
available palladium complex as a catalyst. The reactions afforded
4e: 40 (91/9)
a,b-unsaturated ketones regio- and stereoselectively. In the pres-
ence of the similar catalyst system, the reduction of carboxylic
anhydrides to the corresponding aldehydes proceeded effectively.
5
1a
3c
4f: 73
5. Experimental section
5.1. General
a
Reaction conditions: anhydride (1, 0.50 mmol), allene (3, 1.0 mmol), triisopro-
pylsilane (0.65 mmol), PdCl2(MeCN)2 (0.025 mmol, 5.0 mol %), MeCN (1.0 mL) at
50 ꢀC for 20 h.
b
Isolate yield of (E)-4.
All manipulations were performed under an argon atmosphere
using standard Schlenk-type glassware on a dual-manifold Schlenk
line. Solvents were dried and purified before use by usual
methods.15 1H NMR and 13C NMR spectra were measured with
a JEOL ECX-400P spectrometer. The 1H NMR chemical shifts are
reported relative to tetramethylsilane (TMS, 0.00 ppm). The 13C
NMR chemical shifts are reported relative to CDCl3 (77.0 ppm). GC
analysis was carried out using Shimadzu GC-17A equipped with an
integrator (C-R8A) with a capillary column (CBP-1, 0.25 mm
i.d.ꢁ25 m). Medium-pressure column chromatography (MPLC) was
performed with a Biotage IsoleraOne (SNAP Ultra 25 g). Column
chromatography was carried out on silica gel (Kanto N60, spherical,
c
E/Z ratio of crude reaction mixture by GC and GCeMS analysis.
d
10 mol % catalyst was used.
groups (-CF3) gave (E)-4b in high yield (entry 1). On the other hand,
an aromatic carboxylic anhydride with electron donating groups
(-OMe) afforded the a,b-unsaturated ketones (4c) in moderate yield
with lower E/Z selectivity (entry 2). The reaction of 3-
phenylpropionic anhydride (1e) gave the corresponding product
(4d) in 81% yield in the presence of 10 mol % palladium catalyst
(entry 3). The reaction of 1-(2-phenylethyl)allene (3b) with 1a
afforded the corresponding a,b-unsaturated ketone (E)-4e in 40%
yield (entry 4). Gratifyingly, 1,1-disubstituted allene (3c) also pro-
vided the desired product (4f) in good yield (entry 5). Un-
fortunately, the formal hydroacylation of 1-phenylallene only
afforded the corresponding product in poor yields.
As for reaction mechanism, the reduction of 1 employing
hydrosilanes would share several catalytic steps with the formal
hydroacylation of 3 with 1 (Scheme 1). The oxidative addition of the
Pd(0) active catalyst species to a carboneoxygen bond of 1 affords
an acyl palladium species A (step a).14 In the formal hydroacylation
of 3, the insertion of 3 to the palladiumecarbon bond of A gives an
allyl palladium intermediate B (step b). Then, reaction of B with
hydrosilane affords an allylhydrido intermediate C (step c). Finally,
neutral, 63e210 mm). TLC analyses were performed on commercial
glass plates bearing a 0.25-mm layer of Merck Silica gel 60F254.
Unless otherwise noted, materials obtained from the commercial
suppliers were used without further purification.
5.2. General procedure for the palladium-catalyzed reduction
of carboxylic anhydrides (Tables 1 and 2)
To a 10 mL Schlenk flask with a magnetic stir bar, a carboxylic
anhydride (1, 0.50 mmol), Pd(dba)2 (0.025 mmol) and P(p-
OMeC6H4)3 (0.050 mmol) were added. The flask was evacuated and
backfilled with argon three times. Then, toluene (1.0 mL) was added
to the flask and the resultant solution was stirred at room tem-
perature for 10 min. After H2SiMePh (0.55 mmol) was added to the
flask, the reaction mixture was stirred at 40e120 ꢀC for 20 h under
an argon atmosphere. The reaction mixture was cooled to room
temperature, the yield of aldehyde (2) was determined by GC
analysis or the product was isolated with silica gel column chro-
matography. The yields of 2a, 2g, 2h, and 2j were determined by GC
analysis based on the internal standard technique. 1H and 13C NMR
spectra of isolated 2b, 2c, 2d, 2e, 2f, and 2i were good agreement
with reported data.13,16
the reductive elimination affords a,b-unsaturated ketone (4) as the
product, and the Pd(0) catalyst species regenerates (step d). In the
reduction of 1, A reacts with hydrosilane directly, giving an acyl-
hydrido intermediate D (step e). The reductive elimination of D
affords aldehyde (2) as the product and the Pd(0) species re-
generates (step f).
4. Conclusions
We found that hydrosilanes are versatile reducing reagents in
the formal hydroacylation reaction of allenes using carboxylic

T. Fujihara et al. / Tetrahedron 71 (2015) 4570e4574
4573
5.2.1. 4-Methoxybenzaldehyde (2b). Pale yellow oil (57 mg, 83%), 1H
NMR (400 MHz, CDCl3):
7.01 (d, J¼8.8 Hz, 2H), 3.90 (s, 3H).
2H), 7.47 (tt, J¼7.2,1.4 Hz,1H), 7.36 (t, J¼7.5 Hz, 2H), 7.29 (t, J¼7.2 Hz,
2H), 7.23e7.15 (m, 3H), 6.28 (tq, J¼7.2, 1.4 Hz, 1H), 2.75 (t, J¼7.5 Hz,
2H), 2.60 (td, J¼7.5, 7.2 Hz, 2H), 1.91 (s, 3H). 13C NMR (100 MHz,
d
9.89 (s, 1H), 7.85e7.83 (d, J¼8.8 Hz, 2H),
CDCl3):
d 198.8, 145.0, 141.0, 138.5, 136.9, 131.3, 129.2, 128.4, 128.3,
5.2.2. 4-Trifluoromethylbenzaldehyde (2c). Pale yellow oil (45 mg,
127.9,126.1, 34.6, 30.7,12.4. HRMS (m/z): [MþH]þ calcd for C18H18O:
52%), 1H NMR (400 MHz, CDCl3):
2H), 7.81 (d, J¼8.0 Hz, 2H).
d
10.11 (s, 1H), 8.01 (d, J¼8.4 Hz,
250.1358. Found: 250.1360.
5.3.6. 2-Cyclohexylidene-1-phenylpropan-1-one (4f). Colorless oil
5.2.3. 3-Pyridinecarboaldehyde (2d). Colorless solid (42 mg, 75%),
1H NMR (400 MHz, CDCl3):
10.14 (s,1H), 9.11 (s,1H), 8.87e8.85 (m,
(73 mg, 73%),1H NMR (400 MHz, CDCl3):
d
7.92 (dt, J¼6.6,1.6 Hz, 2H),
d
7.54 (tt, J¼7.2,1.6 Hz,1H), 7.45 (t, J¼7.5 Hz, 2H), 2.30 (t, J¼6.1 Hz, 2H),
1H), 8.21e8.17 (m, 1H), 7.53e7.50 (m, 1H).
1.98 (t, J¼5.7 Hz, 2H), 1.87 (s, 3H), 1.69e1.62 (m, 2H), 1.59e1.52 (m,
2H), 1.47e1.39 (m, 2H). 13C NMR (100 MHz, CDCl3):
d 201.9, 140.2,
5.2.4. 3-Phenyl-1-propanal (2e). Pale yellow oil (51 mg, 76%), 1H
136.9,133.0,129.3,128.6,126.2, 32.8, 29.9, 27.7, 27.6, 26.4,15.7. HRMS
NMR (400 MHz, CDCl3):
J¼8.0 Hz, 3H), 2.96 (t, J¼8.0 Hz, 2H), 2.78 (t, J¼7.6 Hz, 2H).
d
9.82 (s, 1H), 7.29 (t, J¼7.6 Hz, 2H), 7.21 (t,
(m/z): [MþH]þ calcd for C15H18O: 214.1358. Found: 214.1358.
Acknowledgements
5.2.5. 3-(4-Chlorophenyl)-1-propanal (2f). Pale yellow oil (119 mg,
70%), 1H NMR (400 MHz, CDCl3):
2H), 7.12 (d, J¼8.8 Hz, 2H), 2.92 (t, J¼7.6 Hz, 2H), 2.78e2.74 (m, 2H).
d
9.80 (m, 1H), 7.25 (d, J¼8.4 Hz,
This work was supported by Grant-in-Aid for Scientific Research
(A) and also by Grant-in-Aid for Scientific Research on Innovative
Areas (“Molecular activation directed toward straightforward syn-
thesis”) from MEXT, Japan.
5.2.6. Tetradecanal (2i). White solid (90 mg, 82%), 1H NMR
(400 MHz, CDCl3):
2H), 1.66e1.59 (m, 2H), 1.34e1.23 (m, 20H), 0.88 (t, J¼6.8 Hz, 3H).
d
9.76 (t, J¼1.4 Hz, 1H), 2.42 (td, J¼7.6, 2.0 Hz,
Supplementary data
5.3. General procedure for the palladium-catalyzed formal
hydroacylation of allenes (Tables 3 and 4)
Supplementary data related to this article can be found at http://
dx.doi.org/10.1016/j.tet.2015.01.066.
To a 10 mL Schlenk flask with a magnetic stir bar, a carboxylic
anhydride (1, 0.50 mmol), PdCl2(MeCN)2 (0.025 mmol, 5.0 mol %)
were added. The flask was evacuated and backfilled with argon
three times. Then, MeCN (1.0 mL) and an allene (3, 1.0 mmol)
were added to the flask and the resultant solution was stirred at
room temperature for 10 min. After tri-isopropylsilane
(0.65 mmol) was added, the reaction mixture was stirred at
50 ꢀC for 20 h under an argon atmosphere. After the reaction
mixture was cooled to room temperature, the products were
isolated either by silica gel column chromatography or MPLC. 1H
and 13C NMR spectra of isolated 4aed were good agreement with
reported data.6
References and notes
1. For reviews, see: (a) Willis, M. C. Chem. Rev. 2010, 110, 725e748; (b) Leung, J. C.;
Krische, M. J. Chem. Sci. 2012, 3, 2202e2209; (c) Park, Y. J.; Park, J.-W.; Jun, C.-H.
Acc. Chem. Res. 2008, 41, 222e234; (d) Jun, C.-H.; Jo, E.-A.; Park, J.-W. Eur. J. Org.
Chem. 2007, 1869e1881; (e) Fu, G. C. In Modern Rhodium-Catalyzed Organic
Reactions; Evans, A., Ed.; Wiley-VCH: Weinheim, Germany, 2005; pp 79e91.
2. Selected examples for intramolecular hydroacylations, see: (a) Hoshimoto, Y.;
Hayashi, Y.; Suzuki, H.; Ohashi, M.; Ogoshi, S. Angew. Chem., Int. Ed. 2012, 51,
10812e10815; (b) Coulter, M. M.; Dornan, P. K.; Dong, V. M. J. Am. Chem. Soc.
2009, 131, 6932e6933; (c) Kundu, K.; McCullagh, J. V.; Morehead, A. T., Jr. J. Am.
Chem. Soc. 2005, 127, 16042e16043; (d) Sato, Y.; Ohnishi, Y.; Mori, M. Angew.
Chem., Int. Ed. 2002, 41, 1218e1221; (e) Tanaka, K.; Fu, G. C. J. Am. Chem. Soc.
2003, 125, 8078e8079; (f) Tanaka, K.; Fu, G. C. J. Am. Chem. Soc. 2001, 123,
11492e11493; (g) Larock, R. C.; Oertle, K.; Potter, G. F. J. Am. Chem. Soc. 1980,
102, 190e197.
3. Selected examples for chelation-assisted hydroacylations, see: (a) von Delius,
M.; Le, C. M.; Dong, V. M. J. Am. Chem. Soc. 2012, 134, 15022e15032; (b) Coulter,
M. M.; Kou, K. G. M.; Galligan, B.; Dong, V. M. J. Am. Chem. Soc. 2010, 132,
16330e16333; (c) Murphy, S. K.; Petrone, D. A.; Coulter, M. M.; Dong, V. M. Org.
Lett. 2011, 13, 6216e6219; (d) Zhang, H.-J.; Bolm, C. Org. Lett. 2011, 13,
3900e3903; (e) Chaplin, A. B.; Hooper, J. F.; Weller, A. S.; Wills, M. C. J. Am.
Chem. Soc. 2012, 134, 4885e4897; (f) Moxham, G. L.; Randell-Sly, H. E.; Bray-
shaw, S. K.; Weller, A. S.; Willis, M. C. Chem.dEur. J. 2008, 14, 8383e8397; (g)
Osborne, J. D.; Willis, M. C. Chem. Commun. 2008, 5025e5027; (h) Moxham, G.
L.; Randell-Sly, H. E.; Brayshaw, S. K.; Woodward, R. L.; Weller, A. S.; Willis, M. C.
Angew. Chem., Int. Ed. 2006, 45, 7618e7622; (i) Jun, C.-H.; Lee, H.; Hong, J.-B. J.
Org. Chem. 1997, 62, 1200e1201; (j) Kokubo, K.; Matsumasa, K.; Miura, M.;
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5.3.1. (E)-3-Cyclohexyl-2-methyl-1-phenylprop-2-en-1-one
(4a). Colorless oil (81 mg, 71%), 1H NMR (400 MHz, CDCl3):
d 7.62
(dt, J¼6.8, 1.4 Hz, 2H), 7.48 (tt, J¼7.5, 1.4 Hz, 1H), 7.40 (t, J¼7.5 Hz,
2H), 6.11 (dd, J¼9.5, 1.4 Hz, 1H), 2.46 (tdt, J¼10.9, 9.5, 3.6 Hz, 1H),
1.98 (d, J¼1.4 Hz, 3H), 1.77e1.63 (m, 5H), 1.39e1.04 (m, 5H).
5.3.2. (E)-3-Cyclohexyl-2-methyl-1-[4-(trifluoromethyl)phenyl]prop-
2-en-1-one (4b). Pale yellow oil (121 mg, 81%), 1H NMR (400 MHz,
CDCl3):
d
7.72e7.64 (m, 4H), 6.10 (dd, J¼9.5, 1.4 Hz, 1H), 2.48 (tdt,
J¼11.1, 9.5, 3.4 Hz, 1H), 1.99 (d, J¼1.4 Hz, 3H), 1.79e1.64 (m, 5H),
1.41e1.02 (m, 5H).
4. (a) Kondo, T.; Akazome, M.; Tsuji, Y.; Watanabe, Y. J. Org. Chem. 1990, 55,
1286e1291; (b) Kondo, T.; Tsuji, Y.; Watanabe, Y. Tetrahedron Lett. 1987, 28,
6229e6230.
5.3.3. (E)-3-Cyclohexyl-1-(4-methoxyphenyl)-2-methylprop-2-en-1-
one (4c). Pale yellow oil (54 mg, 41%), 1H NMR (400 MHz, CDCl3):
5. Selected examples for oxidative and reductive formal hydroacylations, see: (a)
Han, S. B.; Kim, I.-S.; Han, H.; Krische, M. J. J. Am. Chem. Soc. 2009, 131,
6916e6917; (b) Bower, J.; Skucas, E.; Patman, R. L.; Krische, M. J. J. Am. Chem.
Soc. 2007, 129, 15134e15135; (c) Skucas, E.; Bower, J.; Krische, M. J. J. Am. Chem.
Soc. 2007, 129, 12678e12679; (d) Shibahara, F.; Bower, J. F.; Krische, M. J. J. Am.
Chem. Soc. 2008, 130, 14120e14122; (e) Shibahara, F.; Bower, J. F.; Krische, M. J. J.
Am. Chem. Soc. 2008, 130, 6338e6339; (f) Patman, R. L.; Chaulagain, M. R.;
Williams, V. M.; Krische, M. J. J. Am. Chem. Soc. 2009, 131, 2066e2067; (g)
Omura, S.; Fukuyama, T.; Horiguchi, J.; Murakami, Y.; Ryu, I. J. Am. Chem. Soc.
2008, 130, 14094e14095; (h) Hatanaka, S.; Obora, Y.; Ishii, Y. Chem.dEur. J. 2010,
16, 1883e1888.
d
7.67 (dt, J¼9.2, 2.5 Hz, 2H), 6.91 (dt, J¼9.4, 2.5 Hz, 2H), 6.04 (dd,
J¼9.5, 1.4 Hz, 1H), 3.86 (s, 3H), 2.45 (tdt, J¼11.1, 9.5, 3.6 Hz, 1H), 1.96
(d, J¼1.4 Hz, 3H), 1.78e1.62 (m, 5H), 1.40e1.04 (m, 5H).
5.3.4. (E)-1-Cyclohexyl-2-methyl-5-phenylpent-1-en-3-one
(4d). Pale yellow oil (105 mg, 81%), 1H NMR (CDCl3):
d 7.31e7.25 (m,
2H), 7.22e7.16 (m, 3H), 6.39 (dd, J¼9.1, 1.4 Hz, 1H), 3.00e2.89 (m,
4H), 2.36 (tdt, J¼11.1, 9.5, 3.8 Hz, 1H), 1.79 (d, J¼1.4 Hz, 3H),
1.77e1.61 (m, 5H), 1.37e1.01 (m, 5H).
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3100e3120.
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Gooßen, L. J.; Ghosh, K. d Eur. J. Org. Chem. 2002, 3254e3267.
5.3.5. (E)-2-Methyl-1,5-diphenylhept-2-en-1-one (4e). Colorless oil
(51 mg, 40%), 1H NMR (400 MHz, CDCl3):
d
7.53 (dt, J¼8.1, 1.1 Hz,

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