Domino hydroformylation-Wittig olefination-hydrogenation

Article abstract of DOI:10.1016/j.tet.2005.03.112

Rhodium-catalyzed hydroformylation in the presence of stabilized phosphorus ylides initiates a domino hydroformylation-Wittig olefination process. When mono-substituted acceptor-stabilized phosphorus ylides were employed, a hydrogenation step succeeds the Wittig olefination to give a domino hydroformylation-Wittig olefination hydrogenation process. For the hydroformylation key step both, linear regioselective hydroformylation of terminal alkenes based on catalyst control as well as diastereoselective hydroformylation based on ortho-diphenylphosphanylbenzoate (o-DPPB)-directed active substrate control could be employed.

Full text of DOI:10.1016/j.tet.2005.03.112

Tetrahedron 61 (2005) 6171–6179
Domino hydroformylation–Wittig olefination–hydrogenation
b,†
*
Bernhard Breit and Stephan K. Zahn
a,
a
Albert-Ludwigs-Universit a¨ t Freiburg, Institut f u¨ r Organische Chemie und Biochemie, Albertstr. 21, 79104 Freiburg i. Brsg., Germany
b
Ruprecht-Karls-Universit a¨ t Heidelberg, Organisch-Chemisches Institut, Im Neuenheimer Feld 270, 69120 Heidelberg, Germany
Received 1 November 2004; revised 27 January 2005; accepted 4 March 2005
Available online 25 April 2005
Abstract—Rhodium-catalyzed hydroformylation in the presence of stabilized phosphorus ylides initiates a domino hydroformylation–
Wittig olefination process. When mono-substituted acceptor-stabilized phosphorus ylides were employed, a hydrogenation step succeeds the
Wittig olefination to give a domino hydroformylation–Wittig olefination hydrogenation process. For the hydroformylation key step both,
linear regioselective hydroformylation of terminal alkenes based on catalyst control as well as diastereoselective hydroformylation based on
ortho-diphenylphosphanylbenzoate (o-DPPB)-directed active substrate control could be employed.
q 2005 Elsevier Ltd. All rights reserved.
1. Introduction
2. Results and discussion
Key transformations in organic synthesis are those allowing
the coupling of two complex fragments in the course of a
convergent synthesis. Among the reactions, useful for this
purpose the Wittig olefination occupies a prominent
We recently, showed that attachment of the ortho-
diphenylphosphanylbenzoate function (o-DPPB) to a
methallylic alcohol enables a directed regio- and dia-
stereoselective hydroformylation to give the corresponding
syn-aldehydes 3 in good to excellent yield and diastereo-
1
position. One of the reaction partners required for the
7
Wittig olefination is a carbonyl derivative such as an
aldehyde. Because of the intrinsically high reactivity of the
aldehyde function it is typically generated just prior to use
employing either deprotection strategies or alternatively,
making use of redox processes. However, these reactions all
belong to the class of functional group interconversions,
which are not deemed synthetically efficient because they
do not contribute to an elaboration towards the target
selectivity. It was envisioned that hydroformylation of an
alkene in the presence of a carbon nucleophile compatible
with the hydroformylation conditions might allow for an
instantaneous trapping of the aldehyde with concomitant
carbon–carbon bond formation. As interesting carbon
nucleophiles stabilized phosphorus ylides were selected
for study.
2
skeleton. Thus, skeleton expanding operations such as C/C
bond formation which simultaneously generate the aldehyde
When o-DPPB esters 1 were subjected to hydroformylation
conditions (0.7 mol% [RhH(CO)(PPh ) ], 20 bar CO/H
3 3 2
(1:1), toluene, 90 8C) in the presence of the alkyl-substituted
stabilized ylides 5 and 7 the a,b-unsaturated carbonyl
3
in an atom economical fashion would be ideal. Syntheti-
cally even more useful would be skeleton expanding
reactions which simultaneously install new stereogenic
4
centers in a controllable and selective manner. Hence, a
reaction meeting all these requirements would be a merged
regio- and stereoselective hydroformylation–Wittig olefina-
5
tion process. We herein report in full detail on the
realization of the first, domino hydroformylation–Wittig
olefination as well as the first, domino hydroformylation–
6
Wittig olefination–hydrogenation reactions.
Keywords: Hydroformylation; Tandem catalysis; Wittig olefination;
Catalyst-directing group.
*
Corresponding author. Tel.: C49 761 203 6051; fax: C49 761 203 8715;
e-mail: bernhard.breit@organik.chemie.uni-freiburg.de
Present address: Boehringer Ingelheim, Vienna, Austria.
†
Scheme 1. Domino hydroformylation–Wittig olefination.
0040–4020/$ - see front matter q 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2005.03.112

6172
B. Breit, S. K. Zahn / Tetrahedron 61 (2005) 6171–6179
Table 1. Results of the o-DPPB-directed diastereoselective domino hydroformylation–Wittig olefination reaction
a
b
c
Entry
Substrate
Ylide
Ph
Major product
dr (syn/anti)
Yield %
1
3
PZCMeC(O)OEt
PZCMeC(O)Me
PZCMeC(O)OEt
96:4
75
(
5)
(
(
(
G)-4
G)-4
G)-9
(G)-6
(G)-8
2
3
Ph
(
3
93:7
92:8
78
60
7)
Ph
(
3
5)
(G)-10
a
Reaction conditions: 1.1 equiv ylide 5 or 7, 0.7 mol% [Rh(H)(CO)(PPh
Determined through NMR of the crude reaction mixture.
Isolated yield after chromatographic purification.
3
)
3
2
], toluene, 90 8C, 48 h, 20 bar H /CO (1:1).
b
c
derivatives 2 were formed in good yield and diastereo-
selectivity (Scheme 1, Table 1). Hence, these products arise
through a domino hydroformylation–Wittig olefination
sequence. Thus, a new carbon–carbon single bond as well
as a new carbon–carbon double bond were formed
concomitant with the installation of a new stereogenic
center based on acyclic stereocontrol. The syn-diastereo-
control is the result of a directed hydroformylation step
relying on the catalyst-directing ability of the o-DPPB
Presumably, due to less steric hindrance, the 1,2-disubsti-
tuted double bond of enone 14 undergoes a final
hydrogenation reaction to give the saturated ketone 12.
Thus, the same catalyst, that had catalyzed the initial
hydroformylation step, acted as a hydrogenation catalyst in
the final hydrogenation reaction of this three step domino
process.
In order to probe whether the directed hydroformylation
may be employed as the key step for a similar hydro-
formylation–Wittig olefination–hydrogenation sequence
methallylic-o-DPPB esters 1 were subjected to the reaction
conditions of the domino process (Scheme 3, Table 2).
Thus, using conditions similar to the hydroformylation–
Wittig olefination process but employing the mono-
substituted ylides 16 and 21 furnished the saturated
syn-1,6-oxygen functionalized ketones 15 in good yield and
with high levels of acyclic stereocontrol.
8
group. The E-selectivity of the olefination step stems from
the intrinsically high E-preference of stabilized phosphorus
1
ylides.
An interesting observation was made when mono-substi-
tuted ylide 16 was employed. Thus, subjection of the TBS–
ether functionalized terminal alkene 11 to the conditions of
a linear-regioselective hydroformylation with the Rh(I)/
9
BIPHEPHOS catalyst in the presence of ylide 16, a single
product was formed which was identified as the saturated
methylketone 12 (Scheme 2). Hence, a domino process
involving three separate steps had occurred. The initial step
is a linear selective hydroformylation to give aldehyde 13
followed by Wittig olefination to furnish enone 14.
However, the reaction does not stop at this stage as observed
for the disubstituted Wittig ylides (Scheme 1, Table 1).
Additionally, homomethallylic o-DPPB esters could be
employed. In this case 1,3-asymmetric induction trans-
mitted through the catalyst-directing o-DPPB group lead to
the formation of the anti-diastereomer 24 as the major
1
0
product (Scheme 4).
In these cases (Scheme 3 and 4) ‘active’ substrate control is
operative in which a suitable functional group (here, the
o-DPPB function) of the substrate generates attractive
interactions between the catalyst and the substrate causing
an intramolecular catalyst trajectory. Alternatively, if a
substrate passes a reactive conformation in which one of the
two diastereotopic alkene faces is more or less blocked
based on repulsive catalyst/substrate interactions, a
‘passive’ substrate control is operative. In both cases high
Scheme 2. Regioselective domino hydroformylation–Wittig olefination.
Scheme 3. Domino hydroformylation–Wittig olefination–hydrogenation.

B. Breit, S. K. Zahn / Tetrahedron 61 (2005) 6171–6179
6173
Table 2. Results of the o-DPPB-directed diastereoselective domino hydroformylation–Wittig olefination–hydrogenation reaction
a
b
c
Entry
Substrate
Ylide
Ph PZCHC(O)Me
Major product
dr (syn/anti)
Yield %
1
3
94:6
70
(
16)
(
(
G)-4
G)-9
(G)-17
(G)-18
(G)-20
2
3
4
Ph
(
3
PZCHC(O)Me
16)
96:4
94:6
94:6
68
60
36
Ph
(
3
PZCHC(O)Me
16)
(
G)-19
Ph
(
3
PZCHC(O)OEt
21)
(
G)-4
(G)-22
a
Reaction conditions: 1.5 equiv ylide 16 or 21, 0.7 mol% [Rh(H)(CO)(PPh
Determined through NMR of the crude reaction mixture.
Isolated yield after chromatographic purification.
3
)
3
2
], toluene, 90 8C, 48 h, 20 bar H /CO (1:1).
b
c
levels of diastereoselectivity may be obtained. An example
for passive substrate control is the hydroformylation of
alkene (G)-25. Subjection of 25 to the conditions of the
domino process furnished the all-anti-stereotriad building
block 26 with excellent acyclic stereocontrol (Scheme 5).
directed hydroformylation relative to a corresponding non-
8
directed hydroformylation was observed. In theory a
1
1
similar effect may be excerted by the o-DPPB group in
the course of the enone hydrogenation step to give saturated
ketones 15. In order to probe the role of the o-DPPB group
for the final hydrogenation step of the domino hydroformyl-
ation–Wittig olefination–hydrogenation processes, enone
derivative 33 was prepared. Thus, exchanging the phos-
phorus atom of the o-DPPB group through a CH increment
should suppress the ability of the benzoate function to bind
to the metal catalyst while keeping the steric influence
comparable. Thus, aldehyde 27 which stems from o-DPPB
directed diastereoselective hydroformylation of methallylic
o-DPPB ester 4 was protected as the dimethylacetal.
Alkaline hydrolysis allowed the removal and recovery of
the o-DPPB group as the corresponding carboxylic acid.
Alcohol 30 was esterified employing the Steglich conditions
In order to prove the relative configuration of the domino
7
,8
reaction products the known aldehyde 27 was transferred
via enone 28 to the saturated ketone 17 (Scheme 6) which
was identical in all respects (analytical and spectroscopical
data) with the product obtained through the domino process
(
Table 2, entry 1). Hence, the domino reaction conditions do
not influence the known stereochemical courses of the
hydroformylation step.
Previous research from these laboratories has established
the role of the o-DPPB group to act as a catalyst-directing
1
2
7
,8
to give CH-ester 31. Acetal deprotection followed by
Wittig olefination of the resulting aldehyde 32 with ylide 16
gave the desired enone substrate 33. Rhodium catalyzed
hydrogenation afforded the saturated CH-ketone 34
group which controls the reaction diastereoselectivity.
Additionally, a significant rate acceleration of the o-DPPB-
(
Scheme 7).
In order to probe the role of the o-DPPB group in the course
of the enone hydrogenation step a competition experiment
was initiated. Thus, a 1:1 mixture of enones 28 and 33 was
Scheme 4. 1,3-Asymmetric induction in the course of the domino
hydroformylation–Wittig olefination–hydrogenation.
Scheme 5. All-anti stereotriad synthesis through domino hydroformyla-
tion–Wittig olefination–hydrogenation.
Scheme 6. Synthesis of domino product 17 starting from the known
aldehyde (G)-27.

6174
B. Breit, S. K. Zahn / Tetrahedron 61 (2005) 6171–6179
Figure 1. Competition experiment. Concentration of enones 28 (%) and 33
2
(
(
0
&) versus time (for P-enone 28: yZK0.237xC60, R Z0.9987 gives kH2
K1 K1
2
28)ZK0.237 mmol l
.9815 gives kH2 (33)ZK0.180 mmol l
s
; for CH-enone 33: yZ0.1804xC53, R Z
K1 K1
s
).
small differences in rate constants suggests that the
hydrogenation step of the domino hydroformylation–Wittig
olefination–hydrogenation reaction does not involve active
participation of the o-DPPB function as a catalyst-directing
group.
Scheme 7. Preparation of CH-enoate 33.
subjected to the same reaction conditions which were used
in the domino process. Conversion was monitored as a
1
function of time employing H NMR spectroscopy (Table 3,
Fig. 1, for details see Section 4).
3. Conclusion
Stabilized Wittig ylides have proven as synthetically
interesting carbon nucleophiles which are compatible with
conditions of a rhodium-catalyzed hydroformylation. This
observation paved the way for the development of efficient
domino processes in which the hydroformylation as an atom
economic carbon–carbon bond forming process was
employed as the key step to generate the aldehyde
component of a succeeding Wittig olefination. With
disubstituted stabilized Wittig ylides the domino process
stops at the olefin stage. However, with mono-substituted
stabilized ylides the two step domino process was followed
by a hydrogenation reaction of the acceptor substituted
alkene. Thus, depending on the substitution pattern of the
ylide, domino hydroformylation–Wittig olefination and
domino hydroformylation–Wittig olefination–hydrogen-
ation processes could be realized. Both, regioselective
hydroformylation and diastereoselective hydroformylation
based on active and passive substrate control can be
employed as initial steps of these new domino processes.
With the assumption that the hydrogenation rate is
independent from substrate concentration up to a conversion
of ca. 80% linear regression provides the corresponding rate
constants (Fig. 1). These results show that the hydrogen-
ation of the P-enone 28 proceeds about 1.3 times faster in
comparison to the CH-enone 33 hydrogenation. Hence, this
Table 3. Competition experiment
4. Experimental
4
.1. General
t (min)
Conversion of 28 (%)
Conversion of 33 (%)
Reactions were performed in flame-dried glassware either
under argon (purity O99.998%) or under nitrogen. The
solvents were dried by standard procedures, distilled and
0
0
0
6
27
64
3
9
1
0
0
80
10
35
72
1
13
stored under nitrogen. H, C NMR spectra: Bruker ARX-
00, Bruker AC-300, Bruker WH-400, Bruker AMX-500
with tetramethylsilane (TMS), chloroform (CHCl ) or
2
Results of hydrogenation of a 1:1 mixture of P-enone 28 and CH-enone 33.
3

B. Breit, S. K. Zahn / Tetrahedron 61 (2005) 6171–6179
6175
3
benzene (C H ) as internal standards. P NMR spectra:
1
1.0 mmol) and ylide 5 (399 mg, 1.1 mmol) was obtained
after 3 d 391 mg (75%) of enoate (G)-6 (dr (syn/anti)Z
6
6
Bruker WH 400 (161.978 MHz) with 85% H PO as
4
3
1
external standard. Elemental analyses: CHN-rapid analyzer
Heraeus). Flash chromatography: Silica gel Si 60, E. Merck
95:5). H NMR (300 MHz, CDCl ): dZ0.66–0.75 (m, 9H,
3
(
3!CH ), 1.14 (t, JZ7.1 Hz, 3H, CH CH ), 1.61 (s, 3H,
3
3
2
AG, Darmstadt, 40–63 mm. Hydroformylation reactions
were performed in 100 and 200 ml stainless-steel autoclaves
equipped with magnetical stirrers. Gases: Carbon monoxide
CH ), 1.73 –2.01 (m, 4H), 4.03 (q, JZ7.1 Hz, 2H, OCH ),
3
2
4.72 (dd, JZ7.6, 3.7 Hz, 1H), 6.58 (m , 1H, CH-olefin.),
c
6.79 (m , 1H, Ar-H), 7.11–7.16 (m, 10H, Ar-H), 7.23 (m ,
c
c
1
2H, Ar-H), 7.99 (m , 1H, Ar-H). C NMR (75.469 MHz,
3
2.0 (Messer-Griesheim), hydrogen 3.0 (Messer-Griesheim).
The following compounds were prepared according to
c
CDCl ): dZ12.2, 13.3, 13.9, 17.9, 18.8, 29.4, 32.7, 34.3,
3
7
literature procedures: Methallylic o-DPPB esters (G)-4 ,
3
60.0, 81.9, 127.8, 128.0 (d, JC,PZ7.1 Hz, 2C), 128.08 (d,
JC,PZ7.2 Hz, 2C), 128.25 (2C), 128.52, 130.10, 131.5
(2C), 133.5 (d, JC,PZ20.8 Hz, 2C), 133.7 (d, JC,PZ
7
G)-9 , (G)-19 , homomethallylic o-DPPB ester (G)-23 ,
7
10
3
(
benzylidene acetal (G)-25 , 2-diphenylmethyl benzoic
acid.
1
1
2
3
1
3
1
21.0 Hz, 2C), 133.93, 137.7 (d, JC,PZ12.5 Hz), 137.8 (d,
2
1
JC,PZ11.9 Hz), 139.8, 140.9 (d, JC,PZ28.2 Hz), 165.92,
3
167.60. P NMR (161.978 MHz, CDCl
1
4.1.1. Preparation of 1-tert-butyldimethylsilyloxy-5-
hexene (11). To a solution of 5-hexene-1-ol (1.50 g,
3
): dZK2.9 (s).
P (516.6). Calcd C 74.49, H 7.22; found C 74.61,
C H O
32 37 4
15.0 mmol) in DMF (25 ml) were added imidazol (1.12 g,
16.5 mmol) and tert-butyl dimethyl chlorosilane (2.37 g,
15.8 mmol). The reaction mixture was allowed to stir at rt
H 7.34.
4.2.2. (1R*,2R*,4E)-(G)-1-Isopropyl-2,5-dimethyl-6-
oxo-4-heptenyl-[2-(diphenylphosphanyl)]benzoate ((G)-
8). From o-DPPB ester (G)-7 (402 mg, 1.0 mmol) and ylide
7 (499 mg, 1.5 mmol) was obtained after 2 d 378 mg (78%)
for 30 h until TLC showed complete consumption of
starting material. Water (50 ml) and tert-butyl methyl
ether (100 ml) were added and the organic phase separated.
The organic phase was washed with water (3!50 ml), dried
1
of enone (G)-8 (dr (syn/anti)Z94:6). H NMR (300 MHz,
(
through flash chromatography gave 2.51 g (78%) of the
MgSO ) and the solvent removed in vacuo. Purification
CDCl ): dZ0.74–0.83 (m, 9H, 3!CH ), 1.60 (s, 3H, CH ),
1.81–2.08 (m, 5H), 4.79 (dd, JZ8.0, 3.7 Hz, 1H), 6.50 (mc,
4
3
3
3
1
TBDMS ether 11 as a colorless oil. H NMR (500.130 MHz,
1H, CH-olefin.), 6.85 (m , 1H, Ar-H), 7.18–7.24 (m, 10H,
c
1
3
CDCl ): dZ0.02 (s, 6H, Me Si), 0.87 (s, 9H, t-Bu), 1.38–
Ar-H), 7.32 (m , 2H, Ar-H), 8.05 (m , 1H, Ar-H). C NMR
c c
3
2
1
.44 (m, 2H), 1.48–1.55 (m, 2H), 2.04 (q, JZ7.0 Hz, 2H),
(75.469 MHz, CDCl ): dZ11.2, 13.7, 18.4, 19.0, 25.3, 26.9,
3
3
]
.59 (t, JZ6.7 Hz, 2H, CH O), 4.92 (d, JZ10.0 Hz, 1H,
33.3, 34.5, 81.6, 128.0 (2C), 128.1–128.4 (5 C), 128.8 (a-C-
2
3
2
CH ), 4.97 (d, JZ17.4 Hz, 1H, ]CH ), 5.77 (m , 1H).
olefin.), 130.2 (d, J Z2.0 Hz), 133.5 (d, J Z20.6 Hz,
C,P C,P
2 1
2
2
c
1
3
C NMR (125.758 MHz, CDCl ): dZK5.3 (2C), 18.3,
2C), 133.8 (d, J Z20.8 Hz, 2C), 134.2, 137.9 (d, JC,PZ
C,P
1 2
3
2
5.2, 26.0 (3C), 32.3, 33.5, 63.1, 114.3, 138.9. C H OSi
13.0 Hz), 138.0 (d, J Z12.3 Hz), 138.4, 141.0 (d, JC,PZ
1
2
26
C,P
2
(
214.4). Calcd C 67.22, H 12.22; found C 67.05, H 12.22.
28.4 Hz), 141.0 (d, JC,PZ28.4 Hz), 141.3 (b-C-olefin.),
3
1
1
66.1, 199.5. P NMR (81.015 MHz, CDCl ): dZK3.2 (s).
3
4
.2. General procedure for the domino hydroformyl-
C H O P (486.6). Calcd C 76.52, H 7.52; found C 76.65,
31 35 3
ation–Wittig olefination and domino hydroformylation–
Wittig olefination–hydrogenation reaction
H 7.56.
4
.2.3. (1R*,2S*,4E)-(G)-1-[(1R*)-2-tert-Butylcarbonyl-
To a solution of [RhH(CO)(PPh ) ] (6.4 mg, 0.007 mmol)
3
in toluene (3 ml) was added at rt the alkene (1.0 mmol,
oxy)-1-methylethyl]-5-(ethyloxycarbonyl)-2-methyl-4-
hexenyl-[2-(diphenylphosphanyl)]benzoate ((G)-10).
From o-DPPB ester (G)-9 (352 mg, 0.7 mmol), (380 mg,
3
1
5
1
.0 equiv) and the reaction mixture was stirred for further,
min. Subsequently, the corresponding ylide (1.0–
.5 mmol, 1.0–1.5 equiv) was added and the reaction
1.05 mmol)
[RhH(CO)(PPh ) ] (4.5 mg, 0.0049 mmol) was obtained
ylide
5
(380 mg,
1.05 mmol),
3
3
mixture was transferred with additional toluene (2 ml) into
a stainless steel autoclave. The pressure was adjusted to
after 26 h 250 mg (60%) of enoate (G)-10 (dr (syn/anti)Z
1
92:8). H NMR (300 MHz, CDCl ): dZ0.87–0.89 (m, 6H,
3
2
0 bar synthesis gas (CO/H 1:1) and heated to 90 8C until
2
2!CH ), 1.17 (s, 9H, 3!CH ), 1.30 (t, JZ7.0 Hz, 3H),
3
3
TLC showed complete consumption of starting material
1–3 d). After cooling to rt the autoclave was depressurized
1.76 (s, 3H, CH ), 1.92–2.19 (m, 4H), 3.80–3.92 (m, 2H,
CH OPiv), 4.16 (q, JZ7.1 Hz, 2H, CH O), 5.10 (m , 1H),
3
(
2
2
c
and an appropriate amount of silica gel was added. The
solvent was removed in vacuo to dryness. The residue was
added onto a silica column (3!1.5 cm) and eluted with tert-
butyl-methyl ether (50–100 ml). After removal of solvent in
vacuo the crude product was analyzed by NMR to determine
the diastereoselectivity of the reaction. The crude products
were purified by flash chromatography with petroleum ether
6.67 (m , 1H, ]CH), 6.93 (m , 1H, Ar-H), 7.22–7.36 (m,
c c
13
10H, Ar-H), 7.39 (m , 2H, Ar-H), 8.10 (m ,1H, Ar-H).
C
c
c
NMR (75.469 MHz, CDCl ): dZ12.4, 14.1, 14.4, 27.0 (3!
3
CH ), 32.6, 34.5, 34.8, 38.6, 49.2, 60.3, 65.9, 77.6, 128.0,
3
3
3
128.3 (d, J Z12.2 Hz, 4C), 128.4, 129.0 (d, JC,PZ
C,P
14.0 Hz), 130.4, 131.7–131.9 (6 Ar-C), 133.2, 133.7 (d,
2
2
JC,PZ20.8 Hz), 133.8 (d, JC,PZ21.0 Hz), 134.2, 137.9,
139.4, 165.9, 167.7, 178.1. P NMR (81.015 MHz, CDCl3):
3
1
(
40–60)/tert-butyl methyl ether (9:1) or petroleum ether
40–60)/ethyl actetate (8:2), depending on the polarity of the
(
dZK3.2 (s). C H O P (616.7). Calcd C 72.06, H 7.35;
3
7 45 6
product, to give the products as highly viscous colorless to
yellowish oils.
found C 71.90, H 6.91.
4.2.4. (1R*,2R*)-(G)-1-Isopropyl-2-methyl-6-oxoheptyl-
4.2.1. (1R*,2R*,4E)-(G)-5-(Ethyloxycarbonyl)-1-iso-
propyl-2-methyl-4-hexenyl-[2-(diphenylphosphanyl)]-
benzoate ((G)-6). From o-DPPB ester (G)-4 (402 mg,
[2-(diphenylphosphanyl)]benzoate ((G)-17). From
o-DPPB ester (G)-4 (402 mg, 1.0 mmol), ylide 16
(478 mg, 1.5 mmol), [RhH(CO)(PPh ) ] (6.4 mg,
3
3

6176
B. Breit, S. K. Zahn / Tetrahedron 61 (2005) 6171–6179
0
.007 mmol) was obtained after 24 h 328 mg (70%) of
CDCl ): dZ0.66 – 0.80 (m, 9H, 3!CH ), 0.97 (m , 1H),
3 3 c
1
ketone (G)-17 (dr (syn/anti)Z94:6). H NMR (300 MHz,
CDCl ): dZ0.67–0.82 (m, 9H, 3!CH ), 0.97 (m , 1H),
1.13 (t, JZ7.1 Hz, 3H), 1.50 (m , 2H), 1.68 (m , 1H), 1.82
c c
(m , 1H), 2.00–2.09 (m, 3H), 4.00 (q, JZ7.1 Hz, 2H,
3
3
c
c
1
.08 (m , 1H), 1.43 (m , 2H), 1.65 (m , 1H), 1.80 (m , 1H),
CH O), 4.71 (dd, JZ7.5, 4.4 Hz, 1H), 6.82 (m , 1H, Ar-H),
c
c
c
c
2
c
1
.97 (s, 3H, CH C(O)), 2.10–2.20 (m, 2H, CH ), 4.72 (dd,
3
7.14–7.22 (m, 10H, Ar-H), 7.28 (m , 2H, Ar-H), 8.00 (m ,
2
c c
1
3
JZ7.8, 4.1 Hz, 1H), 6.82 (m , 1H, Ar-H), 7.10–7.20 (m,
1H, Ar-H). C NMR (75.469 MHz, CDCl ): dZ3.5, 13.9,
c
3
1
3
1
0H, Ar-H), 7.26 (m , 2H, Ar-H), 8.01 (m , 1H, Ar-H).
C
17.9, 19.2, 22.2, 29.3, 32.8, 33.9, 34.0, 59.8, 81.7, 127.7,
c
c
3
NMR (75.469 MHz, CDCl ): dZ13.6, 18.3, 19.1, 21.3,
128.0–128.2 (7 C), 130.4 (d, J Z1.8 Hz), 131.4, 133.5
3
C,P
2
2
2
1
1
9.1, 29.4, 33.1, 34.2, 43.6, 81.8, 128.0, 128.1–128.5 (5C),
28.9, 130.2, 131.7, 133.3 (d, J Z21.5 Hz, 2C), 133.9,
34.0 (d, J Z25.8 Hz, 2C), 134.2, 138.0 (d, JC,PZ
(d, JC,PZ19.4 Hz, 2C), 133.8 (d, JC,PZ21.2 Hz, 2C),
2
1 1
133.9, 137.9 (d, J Z12.6 Hz), 138.0 (d, JC,PZ12.1 Hz),
C,P
2 3
C,P
2
1
140.9 (d, J Z28.1 Hz), 166.0 (d, JC,PZ2.9 Hz), 173.2
C,P
C,P
1
31
1
0.3 Hz), 138.2 (d,
JC,P27.9 Hz), 166.3, 208.7. P NMR (81.015 MHz,
JC,PZ11.8 Hz), 141.0 (d,
(CO Et). P NMR (81.015 MHz, CDCl ): dZK3.0 (s).
2
3
2
31
C H O P (504.6). Calcd C 73.79, H 7.39; found C 73.60,
H 7.54.
31 37 4
CDCl ): dZK2.9 (s). C H O P (474.58). Calcd C
3
30 35 3
7
5.93, H 7.43; found C 75.91, H 7.72.
4
.2.8. (1R*,3S*)-(G)-1-Isopropyl-2-methyl-7-oxooctyl-
4
1
.2.5. (1R*,2S*)-(G)-1-[(1R*)-2-tert-Butylcarbonyloxy)-
-methyl-ethyl]-2-methyl-6-oxoheptyl-[2-(diphenyl-
[2-(diphenylphosphanyl)]benzoate ((G)-24). From
o-DPPB ester (G)-23 (458 mg, 1.1 mmol), ylide 16
(525 mg, 1.65 mmol), [RhH(CO)(PPh ) ] (7.1 mg,
phosphanyl)]benzoate ((G)-18). From o-DPPB ester (G)-
(352 mg, 0.7 mmol), ylide 16 (334 mg, 1.05 mmol),
RhH(CO)(PPh ) ] (4.5 mg, 0.0049 mmol) was obtained
3
3
9
[
0.0077 mmol) was obtained after 48 h at 50 8C and 48 h at
70 8C 441 mg (82%) of ketone (G)-24 (dr (anti/syn)Z
3
3
1
after 28 h 274 mg (68%) of ketone (G)-18 (dr (syn/anti)Z
91:9). H NMR (300 MHz, CDCl ): dZ0.76 (d, JZ6.4 Hz,
3
1
9
6:4). H NMR (300 MHz, CDCl ): dZ0.84 (d, JZ6.8 Hz,
3H, CH ), 0.82 (d, JZ6.8 Hz, 6H, 2!CH ), 1.08–1.79 (m,
3
3
3
3
CH, C(CH ) ), 1.44–1.77 (m, 3H), 2.09 (s, 3H, CH ), 2.14
H, CH ), 0.88 (d, JZ6.8 Hz, 3H, CH ), 1.14–1.26 (m, 10H,
8H), 2.08 (s, 3H, CH ), 2.36 (pt, JZ7.5 Hz, 2H), 4.98 (m ,
3
3
3
c
1H), 6.90 (m , 1H, Ar-H), 7.24–7.33 (m, 10H, Ar-H), 7.39
c
3
3
3
1
3
(
OCH ), 5.04 (m , 1H), 6.90 (m , 1H, Ar-H), 7.21–7.32 (m,
m , 1H, CH), 2.26–2.35 (m, 3H), 3.77–3.91 (m, 2H,
(m , 2H, Ar-H), 8.06 (m , 1H, Ar-H).
c
C NMR
(75.469 MHz, CDCl ): dZ17.9, 18.4, 19.2, 21.2, 29.1,
c
c
2
c
c
3
1
3
1
0H, Ar-H), 7.40 (m , 2H, Ar-H), 8.06 (m ,1H, Ar-H).
c
C
29.8, 32.2, 37.2, 38.1, 44.0, 77.4, 128.1, 128.4–128.5 (8
c
2
NMR (75.469 MHz, CDCl ): dZ12.7, 14.3, 21.2, 27.2 (3!
Ar-C), 130.5, 131.7, 133.9 (d, J Z20.8 Hz, 2C), 134.1
3
C,P
2
1
CH ), 33.0, 34.5, 34.7, 38.7, 43.7, 49.4, 66.2, 77.8, 128.0,
1
(d, J Z20.8 Hz, 2C), 134.3, 138.3 (d, J Z12.1 Hz,
C,P C,P
3 31
2C), 167.8 (d, JC,PZ3.0 Hz), 208.9.
3
2
28.1–128.5 (7 Ar-C), 128.6, 130.5, 131.9, 133.9 (d, JC,PZ
0.6 Hz, 4C), 134.3, 137.9 (d, J Z12.0 Hz), 141.0 (d,
JC,PZ28.0 Hz), 166.0 (d, JC,PZ2.7 Hz), 178.2, 208.7.
P NMR
1
2
(81.015 MHz, CDCl ): dZK3.3 (s). C H O P (488.6).
C,P
3
31 37 3
2
3
31
P
Calcd C 76.20, H 7.63; found C 75.96, H 7.42.
NMR (81.015 MHz, CDCl ): dZK3.1 (s). C H O P
3
35 43 5
(
574.7). Calcd C 73.15, H 7.54; found C 73.02, H 7.60.
4.2.9. (6S*)-(G)-6-[(2R*,4S*,5R*)-5-Methyl-2-phenyl-
1,3]-dioxan-4-yl]-heptan-2-one ((G)-26). From benzyl-
idene acetal (G)-25 (218 mg, 1.0 mmol), ylide 16 (478 mg,
1.5 mmol), [RhH(CO)(PPh ] (6.4 mg, 0.007 mmol) was
[
4.2.6. (1R*,2S*)-(G)-1-[(1R*)-1-(Ethyloxycarbonyl)-
ethyl]-2-methyl-6-oxoheptyl-[2-(diphenylphosphanyl)]-
)
3 3
benzoate ((G)-20). From o-DPPB ester (G)-12 (461 mg,
1
obtained after 48 h at 50 8C and 48 h at 70 8C 174 mg (78%,
based on 77% conversion) of ketone (G)-26 (dr (anti/
.0 mmol),
RhH(CO)(PPh ) ] (6.4 mg, 0.007 mmol) was obtained
ylide
16
(414 mg,
1.3 mmol),
1
[
after 23 h 316 mg (59%) of ketone (G)-20 (dr (syn/
syn)ZO98:2). H NMR (300 MHz, CDCl
3
): dZ0.76 (d,
), 1.08 (d, JZ6.9 Hz, 3H, CH ), 1.26–
1.59 (m, 3H), 1.66–1.84 (m, 3H), 2.00–210 (m, 1H), 2.13 (s,
3H, CH C(O)), 2.43 (pt, JZ7.1 Hz, 2H), 3.35 (dd, JZ
10.0 Hz, 1H), 3.48 (pt, JZ11.0 Hz, 1H), 5.45 (s, 1H), 7.31–
3
3
JZ6.7 Hz, 3H, CH
3
3
1
anti)Z94:6). H NMR (300 MHz, CDCl ): dZ0.82 (d,
3
JZ6.8 Hz, 3H, CH ), 1.07–1.13 (m, 8H), 1.55 (pseudo
3
3
quint., JZ7.9 Hz, 2H), 1.75 (m , 1H), 2.10 (s, 3H,
c
1
3
CH C(O)), 2.29 (m , 2H), 2.83 (m , 1H), 3.97 (m , 2H),
5
7.38 (3H, Ar-H), 7.46–7.49 (2H, Ar-H). C NMR
(75.469 MHz, CDCl ): dZ12.2, 17.0, 22.1, 29.2, 29.8,
30.6, 33.8, 44.0, 73.2, 87.7, 101.2, 126.0 (2C), 128.1 (2C),
128.5, 139.0, 209.4. C18 (290.4). Calcd C 74.45, H
9.02; found C 74.40, H 8.92.
3
c
c
c
.23 (dd, JZ8.3, 3.9 Hz, 1H), 6.90 (m , 1H, Ar-H), 7.19–
3
c
7
.32 (m, 10H, Ar-H), 7.37 (m , 2H, Ar-H), 8.08 (m , 1H,
c
c
1
3
Ar-H). C NMR (75.469 MHz, CDCl ): dZ13.5, 13.9,
H O
26 3
3
1
1
2
4.0, 21.4, 27.0, 32.9, 34.3, 42.3, 43.7, 60.6, 77.7, 128.0,
Z
2
28.2–128.4 (8 Ar-C), 130.5, 131.8, 133.7 (d, JC,P
2
0.7 Hz, 2C), 133.9 (d, J Z21.0 Hz, 2C), 134.2, 138.0
4.3. Regioselective domino hydroformylation–Wittig
olefination–hydrogentation of silylether 11
C,P
1
1
(
d, JC,PZ12.4 Hz), 138.2 (d, JC,PZ12.7 Hz), 165.5,
3
1
1
73.6, 208.8. P NMR (81.015 MHz, CDCl ): dZK3.7
3
(
7
s). C H O P (532.6). Calcd C 72.16, H 7.00; found C
1.99, H 6.91.
4.3.1. Preparation of 10-(tert-butyldimethylsilyloxy)-
decane-2-one (12). To a solution of [Rh(CO) acac]
3
2 37 5
2
(1.3 mg, 0.005 mmol) in THF (2 ml) was added at rt
4
2
2
2
0
.2.7. (1R*,2R*)-(G)-5-(Ethyloxycarbonyl)-1-isopropyl-
-methylpentyl-[2-(diphenylphosphanyl)]benzoate ((G)-
2). From o-DPPB ester (G)-4 (402 mg, 1.0 mmol), ylide
1 (523 mg, 1.5 mmol), [RhH(CO)(PPh ) ] (6.4 mg,
BIPHEPHOS (15.7 mg, 0.002 mmol). Subsequently alkene
11 (106 mg, 0.5 mmol) and ylide 16 (191 mg, 0.6 mmol)
was added. The resulting solution was transferred with
additional THF (2 ml) into the autoclave. Hydroformylation
was performed during 4 d at 60 8C to give after the usual
workup 103 mg (72%) of the methylketone 12 (rsR98:2) as
3
3
.007 mmol) was obtained after 24 h 328 mg (36%) of
1
ester (G)-22 (dr (syn/anti)Z95:5). H NMR (300 MHz,

B. Breit, S. K. Zahn / Tetrahedron 61 (2005) 6171–6179
6177
1
13
Ar-H), 8.11 (m , 1H, Ar-H). C NMR (125.758 MHz,
a colorless oil. H NMR (500.130 MHz, CDCl ): dZ0.02 (s,
3
c
6
1
H, Me Si), 0.87 (s, 9H, t-Bu), 1.25–1.27 (m, 8H), 1.45–
.57 (m, 4H), 2.11 (s, 3H, CH CO), 2.40 (t, JZ7.4 Hz, 2H,
CDCl ): dZ13.8, 18.4, 19.2, 29.4, 30.5, 36.4, 53.0, 53.1,
2
3
82.1, 102.7, 128.1, 128.3–128.5 (6 Ar-C), 130.5, 131.9,
3
1
3
2
2
CH CO), 3.57 (t, JZ6.6 Hz, 2H, CH O). C NMR
133.8 (d, J Z20.8 Hz, 2C), 134.0 (d, J Z21.0 Hz,
C,P C,P
2 1
2
2
(
125.758 MHz, CDCl ): dZK5.3 (2C), 23.8, 25.7, 26.0
2C), 134.1 (d, J Z17.0 Hz), 134.3, 138.1 (d, JC,PZ
11.6 Hz), 138.2 (d, JC,PZ12.3 Hz), 141.1 (d, JC,P
28.0 Hz), 166.3 (d,
3
C,P
2
2
(3C), 28.7, 29.1, 29.2, 29.4, 29.8, 32.8, 43.8, 63.2, 209.3.
C H O Si (286.5). Calcd C 67.07, H 11.96; found C
Z
NMR
3
31
JC,PZ2.8 Hz).
P
1
6 34 2
6
6.86, H 12.11.
(202.456 MHz, CDCl ): dZK4.5 (s). C H O P (478.6).
3 29 35 4
Calcd C 72.78, H 7.37; found C 72.53, H 7.30.
4
.3.2. (1R*,2R*,4E)-(G)-1-Isopropyl-2-methyl-6-oxo-4-
heptenyl-[2-benzhydryl]benzoate ((G)-28). To a solution
of aldehyde (G)-27 (162 mg, 0.39 mmol) in dichloro-
methane (4 ml) was added ylide 16 (186 mg, 0.59 mmol).
The reaction mixture was heated during 12 h to 40 8C in a
Schlenk pressure vessel. Removal of the solvent in vacuo
and purification through flash chromatography with
petroleum ether (40–60)/tert-butyl methyl ether (4:1) gave
4.4.2. (3R*,4R*)-(G)-6,6-Dimethoxy-2,4-dimethyl-
hexan-3-ol ((G)-30). Dimethylacetal ester (G)-29
(2.25 g, 4.7 mmol) was dissolved in ethanolic KOH (sat.)
and heated to reflux for 12 h. Water (50 ml) was added and
the mixture was extracted with tert-butyl methyl ether (3!
30 ml). The combined organic phases were dried (MgSO4)
and the solvent removed in vacuo. Flash chromatography of
the residue with petroleum ether (40–60)/tert-butyl methyl
ether (4:1) furnished 810 mg (90%) of alcohol (G)-30 as a
pale yellow oil.
1
60 mg (90%) of the unsaturated ketone (G)-28 as a
colorless highly viscous oil. H NMR (500.130 MHz,
1
CDCl ): dZ0.76 (d, JZ6.7 Hz, 3H, CH ), 0.82 (d, JZ
3
3
6
.8 Hz, 3H, CH ), 0.86 (d, JZ6.9 Hz, 3H, CH ), 1.76 (m ,
3 3 c
1
H), 1.90 (m , 1H), 2.03 (m , 1H), 2.21 (s, 3H, CH ), 4.79
Recovery of the ortho-diphenylphosphanylbenzoic acid. The
above obtained aqueous phase was acidified to pH 1 with
sulphuric acid (1 N) and subsequently extracted with
dichloromethane (3!30 ml). The combined organic phases
c
c
3
(dd, JZ8.1, 3.8 Hz, 1H), 5.96 (d, JZ16.0 Hz, 1H, a-olefin.-
H), 6.67 (m , 1H, b-olefin.-H), 6.81 (s, 1H, CHPh ), 7.00–
7
5
c
2
.15 (m, 5H, Ar-H), 7.14–7.19 (m, 2H, Ar-H), 7.20–7.26 (m,
H, Ar-H), 7.31 (m , 1H, Ar-H), 7.40 (m , 1H, Ar-H), 7.88
c
c
were dried (MgSO ) and the solvent was removed in vacuo.
4
1
3
(
d, JZ7.5 Hz, 1H, Ar-H). C NMR (125.758 MHz,
Filtration through a plug of silica with tert-butyl methyl
ether and removal of the solvent in vacuo gave 1.22 g (85%)
of the acid as pale yellow crystals.
CDCl ): dZ13.3, 18.4, 19.1, 26.9, 29.7, 34.2, 36.8, 51.7,
3
8
1
1
1.1, 126.2 (2C), 128.18 (2C), 128.20 (2C), 129.7 (2C),
29.8 (2C), 130.2, 130.6, 131.1, 131.5, 132.7 (2C), 143.7,
43.8, 148.1, 146.1, 167.2, 198.4. C H O P (472.6). Calcd
1
Spectroscopic data of alcohol (G)-30. H NMR
3
0
33
3
C 76.25, H 7.04; found C 76.02, H 7.26.
.4. Hydrogenation of enone (G)-28
To a solution of [RhH(CO)(PPh ) ] (29.3 mg, 0.032 mmol)
(500.130 MHz, CDCl ): dZ0.87 (d, JZ7.2 Hz, 3H, CH ),
3
3
0
.89 (d, JZ7.1 Hz, 3H, CH ), 0.89 (d, JZ7.0 Hz, 3H, CH ),
3
3
4
1.54–1.60 (m, 1H), 1.68–1.76 (m, 3H), 1.85 (m
(
c
, 1H), 3.10
m , 1H), 3.33 (s, 3H, OMe), 3.34 (s, 3H, OMe), 4.48 (dd,
c
1
3
JZ6.6, 4.8 Hz, 1H, CH(OMe) ). C NMR (125.758 MHz,
3
3
2
in toluene (3 ml) was added enone (G)-28. This solution
was transferred with further, toluene (1 ml) into a stainless
steel autoclave. The autoclave was pressurized with
hydrogen gas (20 bar) and warmed to 70 8C. After 48 h
under these conditions the autoclave was cooled, depressur-
ized, and the solvent removed in vacuo. Purification through
flash chromatography with petroleum ether (40–60)/ethyl
acetate (7:3) gave 938 mg (62%) of the saturated ketone
CDCl
79.7, 103.3.
): dZ12.7, 19.2, 19.3, 30.9, 31.5, 37.1, 52.4, 53.0,
3
4.4.3. (1R*,2R*)-(G)-1-Isopropyl-4,4-dimethoxy-2-
methyl-butyl-2-benzhydryl benzoate ((G)-31). To a
solution of alcohol (G)-30 (390 mg, 2.0 mmol) in dichloro-
methane (25 ml) was added successively 2-diphenylmethyl
benzoic acid (577 mg, 2.0 mmol), DMAP (244 mg,
2.0 mmol) and DCC (412 mg, 2.0 mmol). After stirring
for 48 h at rt the reaction mixture was filtered with
(G)-17. Spectroscopical and analytical data were identical
to those obtained from the ketone product (G)-17 of the
domino process.
w
additional dichloromethane (50 ml) through celite . All
volatile components were removed in vacuo and the residue
was purified through flash chromatography with petroleum
ether (40–60)/tert-butyl ethyl ether (9:1) to give 650 mg
4.4.1. (1R*,2R*)-(G)-1-Isopropyl-4,4-dimethoxy-2-
methyl-butyl-[2-(diphenylphosphanyl)]benzoate ((G)-
1
2
9). To a solution of aldehyde (G)-27 (2.27 g,
.25 mmol) in methanol (40 ml) was added sodium sulfate
(71%) of ester (G)-31 as a colorless highly viscous oil. H
NMR (500.130 MHz, CDCl ): dZ0.66 (d, JZ6.6 Hz, 3H,
5
3
w
3 g), acidic ion exchange resin Lewatit S100 (740 mg).
(
CH ), 0.84 (d, JZ6.8 Hz, 6H, 2!CH ), 1.30 (m , 1H), 1.60
3
3
c
The reaction was stirred for 3 d at rt and subsequently
filtered through basic aluminium oxide. Removal of all
volatile components in vacuo gave 2.4 g (96%) of the
(m , 1H), 1.89 (m , 1H), 1.96 (m , 1H), 3.26 (s, 3H, OCH ),
3.29 (s, 3H, OCH ), 3.26 (pt, JZ5.7 Hz, 1H), 4.78 (dd, JZ
7.8, 4.1 Hz, 1H), 6.77 (s, 1H), 7.04 (m , 1H, Ar-H), 7.14–
c
c c c 3
3
1
dimethylacetal (G)-29 as a colorless, highly viscous oil. H
NMR (500.130 MHz, CDCl ): dZ0.77 (d, JZ6.6 Hz, 3H,
7.29 (m, 7H, Ar-H), 7.39 (m , 1H, Ar-H), 7.88 (d, JZ
c
1
3
7.7 Hz, 1H, Ar-H). C NMR (125.758 MHz, CDCl ): dZ
3
3
CH ), 0.84 (d, JZ6.8 Hz, 3H, CH ), 0.89 (d, JZ7.0 Hz, 3H,
13.8, 18.2, 19.2, 29.5, 30.5, 36.4, 51.7, 52.6, 52.9, 81.6,
102.8, 126.1 (2C), 126.2, 128.1 (2C), 128.2 (2C), 129.7
(4C), 130.3, 130.8, 131.2, 131.4, 143.89, 143.90, 144.9,
167.4. C H O (460.6). Calcd C 78.27, H 7.88; found C
3
3
CH ), 1.30 (m , 1H), 1.60 (m , 1H), 1.87–2.00 (m, 2H), 3.21
(
3
c
c
s, 3H, OCH ), 3.29 (s, 3H, OCH ), 4.44 (pt, JZ5.9 Hz, 1H,
3 3
CH(OMe) ), 4.80 (dd, JZ7.9 Hz, 4.1 Hz, 1H), 6.92 (m ,
2
c
30 36 4
1
H, Ar-H), 7.23–7.30 (m, 10H, Ar-H), 7.35–7.41 (m, 2H,
78.31, H 7.81.

6178
B. Breit, S. K. Zahn / Tetrahedron 61 (2005) 6171–6179
4
.4.4. (1R*,2R*)-(G)-3-Formyl-1-isopropyl-2-methyl-
NMR (500.130 MHz, CDCl ): dZ0.61 (d, JZ6.7 Hz, 3H,
3
propyl-[2-benzhydryl]benzoate ((K)-32). To a solution
of dimethylacetal (G)-31 (152 mg, 0.33 mmol) in THF
CH ), 0.72 (d, JZ6.8 Hz, 3H, CH ), 0.75 (d, JZ6.8 Hz, 3H,
3
3
CH ), 0.89–0.95 (m, 1H), 1.07–1.12 (m, 1H), 1.43–1.51 (m,
2H), 1.67 (m , 1H), 1.80 (m , 1H), 2.03 (s, 3H, CH ), 2.23
3
(
(
3 ml) was added water (1 ml) and trifluoro acetic acid
1 ml) and the reaction mixture was allowed to stir for 12 h
c
c
3
(m , 2H), 4.71 (dd, JZ7.8, 4.2 Hz, 1H), 6.71 (s, 1H,
c
at rt. Subsequently, the mixture was added to aqueous. sat.
NaHCO (20 ml). The aqueous phase was extracted with
CHPh ), 6.94–6.98 (m, 5H, Ar-H), 7.07–7.12 (m, 2H,
Ar-H), 7.15–7.23 (m, 5H, Ar-H), 7.31 (m , 1H, Ar-H), 7.81
(d, JZ7.5 Hz, 1H, Ar-H). C NMR (125.758 MHz,
2
3
c
1
3
tert-butyl methyl ether (2!30 ml) and the combined
organic phases were dried (MgSO ). Removal of the solvent
CDCl ): dZ13.6, 18.2, 19.2, 21.4, 29.5, 29.8, 33.2, 34.3,
4
3
in vacuo and flash chromatography with petroleum ether
(
43.8, 51.7, 81.6, 126.1, 126.2, 128.17 (2C), 128.18 (2C),
129.72 (2C), 129.76 (2C), 130.3, 130.6, 131.0, 131.1, 131.3,
143.9, 144.0, 144.9, 167.4, 208.9. HRMS (FAB) Calcd for
40–60)/tert-butyl methyl ether (4:1) furnished 127 mg
93%) of aldehyde (G)-32 as a colorless highly viscous oil.
(
1
C
H NMR (500.130 MHz, CDCl ): dZ0.78 (d, JZ6.6 Hz,
C H O (M CH): 457.2743; found 457.2747.
31 37 5
3
3
3
1
H, CH ), 0.80 (d, JZ6.8 Hz, 3H, CH ), 0.90 (d, JZ6.9 Hz,
3
3
H, CH ), 1.81 (ddd, JZ17.8, 8.1, 1.4 Hz, 1H), 1.90 (m ,
3
c
4.5. Competition experiment: hydrogenation of a 1:1
mixture of (G)-28 and (G)-33
H), 2.05 (dd, JZ17.8, 5.4 Hz, 1H), 2.41 (m , 1H), 4.74 (dd,
c
JZ8.9, 3.1 Hz, 1H), 6.84 (s, 1H), 6.98 (d, JZ7.7 Hz, 1H,
Ar-H), 7.04 (m , 4H, Ar-H), 7.13–7.18 (m, 2H, Ar-H), 7.21–
c
To a solution of [RhH(CO)(PPh ) ] (2.3 mg, 0.0025 mmol)
3
3
7
7
.30 (m, 5H, Ar-H), 7.37 (m , 1H, Ar-H), 7.87 (d, JZ
c
13
in toluene (2 ml) was added (G)-28 (118 mg, 0.25 mmol),
G)-33 (116 mg, 0.25 mmol) and 1,3,5-trimethoxybenzene
(16 mg, 10 mol%) as internal standard. The reaction
solution was transferred with additional toluene (2 ml)
into a stainless steel autoclave. The autoclave was heated to
.7 Hz, 1H, Ar-H), 9.51 (s, 1H, CHO).
C NMR
(
(
125.758 MHz, CDCl ): dZ13.2, 18.8, 18.9, 28.6, 29.6,
3
4
1
1
7.8, 51.7, 81.1, 126.16, 126.17, 126.20, 128.17 (2C),
28.20 (2C), 129.7 (2C), 129.8 (2C), 130.2, 130.5, 131.0,
31.5, 143.8, 144.0, 145.1, 167.3, 201.3. HRMS (FAB )
C
9
synthesis gas (CO/H 1:1, 20 bar). Aliquots (0.5 ml) were
0 8C and the reaction was started upon addition of
C
Calcd for C H O (M CH) 415.2273; found 415.2275.
30
2
8
5
2
taken at tZ0, 30, 90 and 180 min, filtrated through silica,
evaporated and analyzed by NMR to determine conversion.
4
.4.5. (1R*,2R*,4E)-(G)-1-Isopropyl-2-methyl-6-oxo-4-
heptenyl-[2-benzhydryl]benzoate ((G)-33). To a solution
of aldehyde (G)-32 (162 mg, 0.39 mmol) in dichloro-
methane (4 ml) was added ylide 16 (186 mg, 0.59 mmol).
After heating the reaction mixture for 12 h at 40 8C in a
Schlenk pressure vessel, silica gel (1 g) was added and all
volatile components were removed in vacuo. Flash
chromatography with petroleum ether (40–60)/tert-butyl
methyl ether (4:1) furnished 160 mg (90%) of unsaturated
Acknowledgements
We thank the Fonds of the Chemical Industry, the Deutsche
Forschungsgemeinschaft and the Krupp Foundation (Krupp
Award for young university teachers to B.B.) for financial
support.
1
ketone (G)-33 as a colorless highly viscous oil. H NMR
(
500.130 MHz, CDCl ): dZ0.76 (d, JZ6.7 Hz, 3H, CH ),
3
3
0
1
.82 (d, JZ6.8 Hz, 3H, CH ), 0.86 (d, JZ6.9 Hz, 3H, CH ),
3 3
.76 (m , 1H), 1.90 (m , 1H), 2.03 (m , 1H), 2.21 (s, 3H,
c
c
c
CH ), 4.79 (dd, JZ8.1, 3.8 Hz, 1H), 5.96 (d, JZ16.0 Hz,
References and notes
3
1
CHPh ), 7.00–7.15 (m, 5H, Ar-H), 7.14–7.19 (m, 2H,
H, a-olefin.-H), 6.67 (m , 1H, b-olefin.-H), 6.81 (s, 1H,
c
2
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1
3
(
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3
3
1
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(
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3
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9:1) gave 25 mg (55%) of the saturated ketone (G)-34. H

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1
4
1
2