Angewandte
Chemie
Table 2: Reduction of a,b-unsaturated acids.[a]
ate activity for the hydrogenation of the carbon–carbon
double bond of 2 was observed, whereas no aldehyde product
could be detected. Competing hydrogenation presents the
major limitation during hydroformylation of a,b-unsaturated
aldehydes, ketones, or esters.[11,12] However, changing to
ligand 1 completely switched the course of the reaction.
Surprisingly, oct-2-enoic acid (2) was selectively transformed
to octanal (4) (Scheme 2).
Entry
1
Product
Yield [%][b]
91
2
74, 97[c]
47, 98[c]
92[c]
Then, we investigated the influence of various reaction
parameters in more detail (Table 1). Under relatively mild
conditions (10 bar CO/H2, 2 58C; Table 1, entry 1), complete
conversion of 2 had occurred after 24 hours and nearly perfect
selectivity for the formation of 4 (94% yield; GC) was
observed.[13] Reactions conducted in THF or toluene also
proceeded selectively, but the catalyst activity was lower
(Table 1, entries 2and 3). When a lower ligand loading was
used, a small amount of the undesired hydrogenation product
3 appeared (Table 1, entry 4). The optimal ratio of rhodium to
ligand to substrate was identified to be [Rh(CO)2(acac)]/1/2 =
1:10:200. Increasing the synthesis gas pressure led to an
increased reaction rate, but this was accompanied by the
formation of the undesired “over-hydrogenated” alcohol
product 5. In one experiment the partial pressure of hydrogen
was further increased and octanol 5 was obtained in 23.5%
yield after 48 hours (Table 1, entry 7).
3
4
5
6
94
97
7
8
9
94
87
91
10
11
74
75
12
13
96
95
With the optimal reaction conditions in hand, we focused
on the functional group compatibility and generality of this
reduction process for various 3-substituted alk-2-enoic acids.
In general, a slightly higher synthesis gas pressure (13 bar)
was applied to make sure that full conversion was reached
after 24 hours.
Thus, linear unfunctionalized alk-2-enoic acids (Table 2,
entry 1) as well as substrates with an alkyl substitution in 4-
and 5-positions (Table 2, entries 2, 3, 4) gave excellent results.
Interestingly, other internal double bonds included in the
substrate molecule are not affected at all (Table 2, entries 5
and 6). A wide range of functional groups including hydroxy,
ketone, dialkylsulfide, ether, ester, and acetal functions
(Table 2, entries 7–14) were found to be compatible with the
optimized reaction conditions. Slightly lower reactivity under
standard conditions was observed for substrates equipped
14
68[d]
15[e]
16
77
50[f]
[a] Conditions: [Rh(CO)2(acac)]/1/substrate=1:10:200, c0(substrate)=
0.2m, CH2Cl2 (8 mL), 13 bar CO/H2 (1:1), 258C, 24 h; Bn=benzyl, Bz=
benzoyl, TBS=tert-butyldimethylsilyl. [b] Yields of isolated products.
[c] Yield determined by NMR spectroscopy. [d] 93% conversion.
[e] [Rh(CO)2(acac)]/1/substrate=1:10:100, 20 bar CO/H2 (1:1),
c0(substrate)=0.1m, 20 h. [f] 75% conversion (low solubility of the
substrate in CH2Cl2).
with carbamate (Table 2, entry 15)
and carboxylate (Table 2, entry 16)
functions, but also in these cases
practical yields of aldehyde could
be obtained. A number of standard
protecting groups for alcohols and
aldehydes (Table 2, entries 11–14)
displayed complete compatibility.
However, more importantly, unpro-
tected alcohol, oxo, or carboxylic
acid functions were also tolerated
(Table 2, entries 8, 9, 16).
Table 1: Influence of reaction conditions on the reduction of 2.[a]
Entry Solvent Pressure [Rh(CO)2(acac)]/1/2 t [h]
3 [%][b] 4 [%][c] 5 [%][c] TOF [hÀ1 [d]
]
(CO/H2)
1
CH2Cl2
THF
toluene 5/5
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
5/5
5/5
1:10:200
1:10:200
1:10:200
1:5:200
1:10:200
1:10:200
1:10:200
24
20
20
20.5
23
<1
<1
<1
94
17
14
91
91.5
89
67
0.3
–
–
0.8
2.8
3.1
23.5
8.8
1.9
1.9
2[e]
3[e]
4
5/5
4.5
9.2
5
6
7
7.5/7.5
10/10
5/35
<1
<1
<1
15.8
23.6
42
To clarify the role of ligand 1 in
18.7
48
the course of this reaction,
a
number of control experiments
were undertaken. Unmodified rho-
dium catalyst (Table 3, entry 2)
[a] Conditions: c0(2)=0.2m, solvent (4 or 8 mL), 258C. [b] Determined by NMR spectroscopy.
[c] Determined by GC analysis. [d] Turnover frequency (mol 4 per mol catalyst) hÀ1 determined by GC
analysis. [e] Reaction performed at 408C.
Angew. Chem. Int. Ed. 2008, 47, 3946 –3949
ꢀ 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
3947