Catalytic enantioselective hydrophosphonylation of aldehydes using the iron complex of a camphor-based tridentate Schiff base [FeCl(SBAIB-d)]2

Article abstract of DOI:10.1002/adsc.201300653

An iron(III)-Schiff base-catalyzed, highly enantioselective hydrophosphonylation of various aldehydes is described. Under the optimized reaction conditions, 5 mol% of the iron/camphor-based tridentate Schiff base complex [FeCl(SBAIB-d)]₂ produces high yields (up to 99%) of α-hydroxy phosphonates in excellent enantioselectivities (up to 99%). The merits of this catalytic system are an easily synthesizable catalyst, inexpensive starting materials, practically simple aerobic reaction conditions, and low catalyst loading (5 mol%). Copyright

Full text of DOI:10.1002/adsc.201300653

FULL PAPERS
DOI: 10.1002/adsc.201300653
Catalytic Enantioselective Hydrophosphonylation of Aldehydes
Using the Iron Complex of a Camphor-Based Tridentate Schiff
Base [FeCl(SBAIB-d)]2
G
Ramalingam Boobalana and Chinpiao Chena,*
a
Department of Chemistry, National Dong Hwa University, Soufeng, Hualien 974, Taiwan, Republic of China
Fax : (+886)-3-836-0475; e-mail: chinpiao@mail.ndhu.edu.tw
Received: July 25, 2013; Revised: September 25, 2013; Published online: && &&, 0000
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/adsc.201300653.
Abstract: An ironACTHUNRTGNEUNG(III)-Schiff base-catalyzed, highly thesizable catalyst, inexpensive starting materials,
enantioselective hydrophosphonylation of various al- practically simple aerobic reaction conditions, and
dehydes is described. Under the optimized reaction low catalyst loading (5 mol%).
conditions, 5 mol% of the iron/camphor-based tri-
dentate Schiff base complex [FeClACTHNUTRGENUG(N SBAIB-d)]2 pro- Keywords: (1R)-camphor-based ligands; enantiose-
duces high yields (up to 99%) of a-hydroxy phospho- lective Pudovik reaction; hydrophosphonylation;
nates in excellent enantioselectivities (up to 99%). iron-Schiff base complexes; Schiff base of aminoiso-
The merits of this catalytic system are an easily syn- borneol
Introduction
by Shibasaskiꢀs group (although they were initiated
by Shibuya and Spilling independently),[3d,e] and
The enantioselective synthesis of chiral a-hydroxy Fengꢀs Al(BINOL-tert-amine);[3p] (ii) tri-/tetradentate
phosphonates is one of the rapidly growing research Schiff base catalysts, namely, Keeꢀs Al
(salcyen),[4a,b]
ACHTUNGTRENNUNG
fields in organic chemistry[1] because of the intriguing Katsukiꢀs Al(salalen),[4d,e,h] and Al(sal-binaphthyl-
AHCTUNGTRENNUNG
biological properties of these compounds and their en),[4f] as well as Fengꢀs tridentate Al-Schiff base ob-
derivatives, such as antibiotics, antivirals, anticancer tained from l-valinol;[4g] (iii) organocatalysts, namely
drugs, herbicides, insecticides, fungicides, and enzyme Wynbergꢀs quinine,[3a,b] and Ooiꢀs tetraaminophospho-
inhibitors.[2] Over the last two decades, considerable nium salt.[3q] Although the numerous catalytic systems
efforts were made to develop various methods for afford excellent yields and ee values of chiral a-hy-
synthesizing chiral a-hydroxy phosphonates, including droxy phosphonates, they are also highly moisture-
the asymmetric hydrogenation of a-keto phospho- sensitive, do not perform adequately under aerobic
nates, the enzymatic resolution of esters of a-hydroxy conditions, require a high amount of catalyst loading
phosphonates, the asymmetric a-hydroxylation of and an extended reaction time. We studied the enan-
alkyl phosphonates, the asymmetric Abramov reac- tioselective reactions by using camphor-based triden-
tion, and the asymmetric Pudovik reaction.[1] Among tate Schiff base SBAIB ligands (Figure 1).[6]
these methods, the Pudovik reaction, which is a base-
We hypothesized that this SBAIB ligand would
catalyzed enantioselective hydrophosphonylation of afford a high level of chiral induction in the hydro-
aldehydes, is the simplest reaction for forming a-hy-
droxy phosphonates. Substantial developments have
occurred in the design and use of numerous catalytic
À
systems for this critical enantioselective P C bond-
forming reaction.[3,4,5]
Highly enantioselective catalysts for the Pudovik
reaction of aldehydes are classified into three primary
types: (i) BINOL-based catalysts, namely, the tailor-
made heterobimetallic catalysts ALB (alumium lithi-
um binaphthoxide)[3f] and LLB (lathanam lithium bi-
Figure 1. Structures of the Schiff bases derived from amino-
ACHTUNGTRENUNiNG soborneol.
naphthoxide)[3h] that have been developed principally
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Figure 2. Metal complexes of tri-/tetradentate Schiff bases used for the catalytic enantioselective hydrophosphonylation of
aldehydes.
phosphonylation reactions of aldehydes because of the enantioselective Pudovik reaction except for 20.
the presence of high steric hindrances provided by Because we were inspired by the FeACTHNUGTRNEUNG(III)-Schiff base
both a camphor-backbone motif and electronically complex 20 and because one of our goals is to make
tunable alkyl groups in the phenol ring. Figure 2 stable and moisture-insensitive Schiff base SBAIB
shows the structure of various metal complexes of tri- metal complexs for asymmetric synthesis,[8] we synthe-
and tetradentate Schiff bases that, to date, are used in sized Fe
ACHTUNGTRENNUNG
the hydrophosphonylation of the aldehydes. Most of quently, we report a highly enantioselective FeACHTUNGTRENNUNG
the Schiff bases were used either as pre-prepared alu- tridentate Schiff base-catalyzed Pudovik reaction.
minium complexes or as in situ aluminium complexes
generated from Al
Al
(salalen) 15[4h] and Fengꢀs Al(Schiff base) 19[4g] are Results and Discussion
excellent catalysts for the Pudovik reaction of various
aldehydes. Al
(Salcyen) complexes 8–14[4a] were the Syntheses of Iron Complexes and Dialkyl Phosphites
ACHTUNGTRNE(NUNG III) salts. Among them, Katsukiꢀs
ACHTUNGTRENNUNG
ACHTUNGTRENNUNG
first Schiff base complexes that were tested for the
Pudovik reaction. Other than the aluminium-Schiff As shown in Scheme 1, seven iron complexes of the
bases, cobalt-Schiff base 16,[4f] and, more recently, an type [FeCl
ACHTUNGTRENNUNG
FeACHTUNGTRENNUNG
ACHTUNGTRENNUNG
AHCTUNGTRENNUNG
ACHTUNGTRENNUNG
ACHTUNGTRENNUNG
hydes. The iron complexes of 21 and 22 that were SBAIB complexes were confirmed by the paramag-
1
generated in situ through a reaction with FeCl3 were netic nature of H NMR and HR-MS results. Com-
demonstrated inferior results compared to complex pared to FeCl3, which became a paste or oil because
20.[4j]
HCl was released when exposed to atmospheric mois-
Furthermore, aluminium salts have disadvantages; ture, these Fe(III)-SBAIB complexes were highly
AHCTUNGTRENNUNG
for example, they need an inert atmosphere to con- stable under atmospheric conditions. The Schiff base
duct a reaction, and are highly sensitive to moisture, of aminoisoborneol, namely, (+)-SBAIB, could be ob-
difficult to handle, and considerably expensive. Con- tained easily from (1R)-camphor by following our
versely, iron salts have apparent advantages: they are previously reported procedure.[6a] We also synthesized
inexpensive, non-toxic, naturally abundant, environ- dialkyl phosphites from trialkyl phosphites by react-
mentally benign, have a mild Lewis acidity, and are ing them with an equimolar mixture of water and tet-
used as catalysts in many organic transformations.[7] rahydrofuran.[9]
However, their uses have rarely been investigated for
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Catalytic Enantioselective Hydrophosphonylation of Aldehydes
Scheme 1. Syntheses of FeACTHNUTRGNEUG(N III)-SBAIB complexes and dialkyl phosphites.
Optimization of Reaction Conditions for the
Hydrophosphonylation of Benzaldehyde
corresponding diisopropyl a-hydroxy phosphonate in
24 h at room temperature. To date, this result is the
highest enantiomeric excess that has been provided
After producing seven FeACTHUNTGRNEUNG(III)-SBAIB complexes, the by any chiral iron complex. The exact reason behind
optimization commenced by implementing a catalyst the effect of substituents and its position in the
screening (Table 1). For this purpose benzaldehyde 28 phenyl ring of SBAIB is unclear. However, the size of
was reacted with diisopropyl phosphite 26 in the pres- the methyl substituent ortho to the hydroxy group in
ence of sodium carbonate and Fe
lysts in THF solution. Although in all cases 5 mol% ring of benzaldehyde in a certain distance and angle
of the Fe(III)-SBAIB complexes afforded a high yield for the formation of better p-p stacking (vide infra
for the base-catalyzed Pudovik reaction under aerobic for the proposed mechanism) than the other substitu-
conditions; as expected, the [FeCl
(SBAIB-d)]2 (4a) ents.[10] Subsequently, we systematically explored
(Table 1, entry 4) was found to be the optimal catalyst every criterion to identify the superior optimization
ACHTUNGERTN(NUNG III)-SBAIB cata- 4a might play a crucial role in keeping the phenyl
ACHTUNGTRENNUNG
AHCTUNGTRENNUNG
and displayed superior selectivity of 79% ee for the conditions for the [FeClACHTNUGTRENUNG(SBAIB-d)]2-catalyzed hydro-
phosphonylation.
Among the various solvents surveyed for this cata-
lytic system (Table 2, entries 1–6), THF was identified
as the most suitable solvent (Table 1, entry 4). The
alkyl group of the dialkyl phosphites played a vital
role regarding reactivity and enantioselectivity; for in-
stance, the reaction time of the hydrophosphonylation
of various aldehydes using a Yamamoto catalyst[3n] is
very short because of the use of highly reactive
bis(2,2,2-trifluroethyl) phosphites. Therefore, we sub-
sequently investigated the role of dialkyl phosphites
(Table 2, entries 7–10). Diethyl phosphite exhibits the
same chiral induction as diisopropyl phosphite; on the
other hand, dimethyl phosphite produced a corre-
sponding phosphonate with a slightly improved ee
(80%) but the yield was merely 50%. As anticipated,
the highly reactive bis(2,2,2-trifluoroethyl) phosphite
affords a high yield of the corresponding product
within 5 h reaction time, but with a lower enantiose-
lectivity (56%). We discovered that dibutyl phosphite
produced excellent yields (99%) of a-hydroxy phos-
phonate and the highest ee (83%) level (Table 2,
entry 9); thus, it was chosen as a suitable dialkyl phos-
phite for the catalytic system in this study.
Table 1. Catalyst screening and optimization.[a,b]
Entry
Catalyst [mol%]
Yield [%][c]
ee [%][d]
1
2
3
4
5
6
7
1a [5]
2a [5]
3a [5]
4a [5]
5a [5]
6a [5]
7a [5]
96
85
99
99
98
99
83
15
44
52
79
32
12
19
[a]
All reactions were done in 8-mL screw-capped vials
under aerobic conditions.
[b]
[c]
[d]
Reagents
1:1.1:1.
ratio:
PhCHO:HP(O)ACTHUNGRETNNU(G O-i-Pr)2:Na2CO3 =
Yields were for products purified by column chromatog-
raphy.
The chiral purity of the compound was checked by
HPLC using Chiralcel OD-H column.
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Table 2. Optimization of other criteria for the hydrophosphonylation of benzaldehyde.[a]
FULL PAPERS
Entry
4a [mol%]
R’
Base [equiv.][b]
Solvent [volume][b]
Temp. [8C]
Time [h]
Yield [%][c]
ee [%][d]
1
2
3
4
5
6
7
8
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
7.5
2.5
1
5
5
5
5
5
5
5
5
5
i-Pr
i-Pr
i-Pr
i-Pr
i-Pr
i-Pr
Me
Et
Na2CO3 [1]
Na2CO3 [1]
Na2CO3 [1]
Na2CO3 [1]
Na2CO3 [1]
Na2CO3 [1]
Na2CO3 [1]
Na2CO3 [1]
Na2CO3 [1]
Na2CO3 [1]
K2CO3[1]
NaOMe
KO-t-Bu [1]
pyridine [1]
DBU [1]
DABCO [1]
lutidine[1]
TEA [1]
DCM [40]
DCE [40]
hexane [40]
toluene [40]
dioxane [40]
Et2O [40]
THF [40]
THF [40]
THF [40]
THF [40]
THF [40]
THF [40]
THF [40]
THF [40]
THF [40]
THF [40]
THF [40]
THF [40]
THF [40]
THF [40]
THF [40]
THF [40]
THF [40]
THF [40]
THF [40]
THF [40]
THF [40]
THF [20]
none (neat)
THF [60]
THF [80]
THF [100]
THF [40]
THF [40]
THF [40]
THF [60]
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
45–50
4
24
24
24
24
24
24
24
24
24
5
24
24
24
24
24
24
24
24
24
24
18
24
24
30
20
30
36
18
2
90
30
88
71
57
95
50
87
99
96
88
trace
trace
45
82
95
99
99
99
95
90
85
87
99
99
96
99
91
99
99
98
95
97
99
99
99
65
72
33
52
73
60
80
79
83
56
56
NA
NA
37
2
67
63
87
84
86
87
80
82
57
87
79
71
84
68
89
88
86
86
91
92
93
9
Bu
CF3CH2
Bu
Bu
Bu
Bu
Bu
Bu
Bu
Bu
Bu
Bu
Bu
Bu
Bu
Bu
Bu
Bu
Bu
Bu
Bu
Bu
Bu
Bu
Bu
Bu
Bu
Bu
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
TBA [1]
DIPEA [1]
TEA [1.5]
TEA [0.75]
TEA [0.5]
none
TEA [1]
TEA [1]
TEA [1]
TEA [1]
TEA [1]
TEA [1]
TEA [1]
TEA [1]
TEA [1]
TEA [1]
TEA [1]
TEA [1]
24
24
24
14
24
35
35
À25
À25
[a]
All reactions were done in 8-mL screw-capped vials.
Abbreviations: 1,8-diazabicycloACTHNUGTRENNUG[5.4.0]undec-7-ene (DBU), 1,4-diazabicycloAHCTUNGTRNE[NUGN 2.2.2]octane (DABCO), triethylamine (TEA),
[b]
tributylamine (TBA), diisopropylethylamine (DIPEA), dichloromethane (DCM), 1,2-dichloroethane (DCE), tetrahydro-
furan (THF).
Yields were for products purified by column chromatography.
[c]
[d]
The chiral purity of the compound was checked by HPLC using a Chiralcel OD-H column.
Subsequently, we focused on optimizing the base
ACHTUNGTRENaNGNU mine, produced a phosphonate product with a higher
for our base-catalyzed hydrophosphonylation. Inor- ee (87%, and 86%, respectively) than did inorganic
ganic bases have been considered to facilitate the hy- bases, such as Na2CO3 and K2CO3. A similar charac-
drophosphonylation reaction without eroding the teristic of the organic bases was identified using
enantioselectivity because they exhibit a relatively Fengꢀs YbACTHUNRTGNE(GNU III) complex-catalyzed hydrophosphonyla-
weak basicity and a low solubility in THF.[4k] Howev- tion,[3r] where pyridine was determined as the superior
er, the results of the base screening (Table 2, en- base. The inorganic bases NaOMe and KO-t-Bu
tries 11–20) showed that 1 equivalent of an organic afford only traces of product, and the non-nucleophil-
base, such as triethylamine and diisopropylethyl- ic organic base DBU affords almost racemic phospho-
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Catalytic Enantioselective Hydrophosphonylation of Aldehydes
nate (2% ee). One equivalent of TEA was necessary Thus, 60 volume of THF was chosen as the optimal
and this was confirmed by using various amount of solvent volume. Simultaneously, the optimal tempera-
TEA (Table 2, entries 21–23). The higher and lower ture of the reaction was determined. When the reac-
equivalents of TEA did not improve the ee. A high tion temperature was increased to 45–508C (Table 2,
yield of phosphonate product was also obtained in entry 33) from room temperature (Table 2, entry 18),
a reaction time that was a slightly longer when no the ee change in a short reaction time was insignifi-
base was used (Table 2, entry 24); however, low enan- cant (86% ee). However, when the reaction tempera-
tioselectivity (57% ee) was observed.
ture was decreased to 48C, the ee was considerably
When the catalyst loading was increased to improved (91%, Table 2, entry 34). When the reaction
7.5 mol%, instead of 5 mol%, no change was ob- temperature was further reduced to À258C (Table 2,
served in the ee (Table 2, entry 25); however, when it entry 35), the ee improved by merely 1% with an ex-
was decreased to 2.5 mol% and 1 mol% (Table 2, en- tended reaction time (35 h). Without further decreas-
tries 26 and 27), a substantial decrease in the ee was ing the reaction temperature, À258C was chosen to
observed. Subsequently, the volume of the solvent be the optimal temperature of the reaction.
was examined to determine the source of improve-
ment in the ee. In cases of lower volume (20 volumes (1 equiv.) reacted with [FeClAHCNUTGTRENNUNG
At this optimal temperature, benzaldehyde
(SBAIB-d)]2 (5 mol%),
with respect to benzaldehyde) and a neat reaction, de- TEA (1 equiv.) and dibutyl phosphite (1.1 equiv.) in
spite the production of high yields in short reaction THF (60 volume) under aerobic conditions to afford
time, the ee decreased considerably (Table 2, en- dibutyl hydroxyACTHNUGRTNEUNG(phenyl)methanephosphonate in an
tries 28 and 29). When it was increased to 60 volumes, excellent ee (93%) and yield (99%) in 35 h (Table 2,
the ee improved from 87% to 89% (Table 2, entry 36). Thus, this was selected as the optimal set of
entry 30); however, further dilution to 80 and 100 vol- reaction conditions to explore the [FeClACTHNUTRGEN(UNG SBAIB-d)]2-
umes, did not increase the ee; rather, it decreased to catalyzed enantioselective hydrophosphonylation of
88% and 86%, respectively(Table 2, entry 31 and 32). various aldehydes.
Table 3. Enantioselective hydrophosphonylation of various aldehydes using [FeClACHTUNGTRNEUNG
(SBAIB-d)]2.[a]
Entry
Aldehyde
Product
Time [h]
Yield [%][b,d]
ee [%][c,d]
Sign/Configuration[g]
1
2
3
4
5
6
7
8
PhCHO 28
28a
29a
30a
31a
32a
33a
34a
35a
36a
37a
38a
39a
40a
41a
42a
43a
44a
45a
35
72
55
72
50
72
60
60
60
48
48
55
72
72
73
72
96
90
86 (99)
81 (90)
99[e]
96 (93)
>99 (95)
91
+/R
+/R
+/R
+/R
+/R
+/R
+/R
+/R
+/R
+/R
+/R
+/R
+/R
+/R
+/R
+/R
À/R
À/R
4-MeOC6H4CHO 29
3-MeOC6H4CHO 30
2-MeOC6H4CHO 31
4-PhC6H4CHO 32
4-Me2NC6H4CHO 33
4-MeC6H4CHO 34
3-MeC6H4CHO 35
2-MeC6H4CHO 36
4-FC6H4CHO 37
83 (92)
85 (97)
77 (87)
86 (99)
83(99)
88 (99)
80(90)
90[e]
95 (85)
99 (88)
>99 (94)
93 (88)
92 (85)
92 (83)
91 (83)
85
9
10
11
12
13
14
15
16
17
18
4-BrC6H4CHO 38
2-naphthaldehyde 39
pyrrole-2-carboxaldehyde 40
furfural 41
thiophene-2-carboxaldehyde 42
a-methyl-trans-cinnamaldehyde 43
butyraldehyde 44
79 (93)
>99 (88)
87
84
86[e]
91[e]
92[e]
89
70 (80)
>99 (89)
90[e]
83[f]
valeraldehyde 45
94[e]
79[f]
[a]
The reactions were carried out with reagent ratio of RCHO:HP(O)
Yields obtained after a single recrystallization from hexane/ether.
The chiral purity of the compound after a single recrystallization from ether/hexane that checked by HPLC using Chiral-
cel OD-H and Chiralpak AD columns.
Values in parenthesis are before recrystallization.
Physical state of the product is an oil.
ACHTUGNRTEN(UNNG OBu)2:ACHTUNTRGEG[NNUN FeClACHTNUGRTEN(NUGN SBAIB-d)]2:TEA=1:1.1:0.05:1
[b]
[c]
[d]
[e]
[f]
The chiral purity was determined for the corresponding benzoates.
Configuration was assigned on the basis of a thorough literature survey.
[g]
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Scope of this Catalytic System for Other Aldehydes
of which afforded 40a, 41a, and 42a in high ee (84–
89%, Table 3, entries 13–15). In addition, N-non-pro-
Table 3 shows the result of the hydrophosphonylation tected pyrrole-2-carboxaldehyde (40) was a new sub-
of various aldehydes under our optimal conditions. strate for the hydrophosphonylation reaction. The
All of the aldehydes rendered adequate to excellent a,b-unsaturated aldehyde, trans-a-methylcinnamalde-
yields (up to 99%) of a-hydroxy phosphonates and an hyde (43), was also examined, found to be a suitable
excellent ee (up to 99%). The aromatic aldehydes substrate for this reaction, and produced highly enan-
possessing a strong electron-donating group at the tioselective (>99% ee) phosphonate 43a. Good to ex-
para-position showed a high enantioselectivity; for in- cellent enantioselectivities were also observed for the
stance, 4-methoxybenzaldehyde (29) and 4-N,N-dime- aliphatic aldehydes 44 and 45.
thylaminobenzaldehyde (33) showed a 95% ee for
29a, and a 94% ee for 33a, respectively (Table 3, en-
tries 2 and 6). Electron-withdrawing halogen substitu- Proposed Mechanism for Chiral Induction
ents slightly reduce the enantioselectivity (Table 3, en-
tries 10 and 11). However, most of the obtained aro- The configuration of obtained phosphonates was as-
matic phosphonates 28a–38a were solids or low-melt- signed as R by conducting a detailed comparison
ing point solids except for 30a and 38a; an excellent study with the corresponding analogues.[11] The most
enantioselectivity was induced by recrystallization probable mechanism is proposed for the 4a-catalyzed
from the ether-hexane solvent mixture at either room enantioselective hydrophosphonylation of benzalde-
temperature or low temperature. A polycyclic aro- hyde in Scheme 2. It was suspected to be a bimetallic
matic aldehyde, (i.e., 2-naphthaldehyde 39) is also process, which was supported by the study of non-
a suitable substrate that renders 39a in high ee (88%), linear effect (NLE) with various % ee of 4a.
and its recrystallization produced the highest ee (>
This catalytic system found to have a (À) NLE (see
99%) without substantially reducing the yield. The the Supporting Information). The catalytic cycle
heteroaromatic aldehydes 40, 41, and 42 were also ad- begins by substituting one of the chloride ions on 4a
equate substrates for the present catalytic system, all by a phosphite anion 46, which could be easily gener-
Scheme 2. Proposed mechanism for 4a-catalyzed asymmetric hydrophosphonylation.
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Catalytic Enantioselective Hydrophosphonylation of Aldehydes
ated through a reaction of TEA with the highly reac- posed. The applications of this catalytic system to
tive phosphite form of the equilibrium mixture of other substrates, such as ketones and imines, is cur-
phosphonate and phosphite to produce an intermedi- rently under study.
ate 47. Subsequently, the benzaldehyde coordinates to
another Lewis acidic iron in the manner shown in 48.
Presumably, 48 is a favorable intermediate because of Experimental Section
the presence of p-p stacking between the phenyl rings
of benzaldehyde and one of the Schiff base phenyl General Procedure for Synthesis of IronACTHNUTRGENUG(N III)
rings. In addition, 48 displays less substantial steric Complexes [FeClACTHNUTRGENUN(G SBAIB)]2
hindrance between the phenyl ring of the benzalde-
A mixture of anhydrous FeCl3 (1.2 equiv.) and (+)-SBAIB
(1 equiv,) in THF (75 volumes) was stirred under an argon
atmosphere for 1 h at room temperature. Subsequently, to
this mixture the triethylamine (2.5 equiv) was added, and
stirred for 12 h at room temperature. The THF was evapo-
rated; water was added and extracted with DCM (5 times).
The combined DCM layer was dried over anhydrous
Na2SO4 and concentrated to afford a brownish-black solid.
hyde and the bridgehead methyl and the bridge di-
methyl group of the camphor moiety. The addition of
the phosphite group on the Re-face of the benzalde-
À
hyde, concurrent formation of the Fe O bond, and
the chloride shift from one Fe to another produces in-
termediate 49. The chloride shift would possibly
happen by both intramolecular or by intermolecular
chloride exchange between 48 and triethylammonium
chloride generated from step 1. Consequently, the
General Procedure for Synthesis of Dialkyl
Phosphites
(R)-dibutyl hydroxyACTHNUGRTENUNG(phenyl)methanephosphonate 28a
is easily obtained from 48 by two routes: the one by
abstracting the proton from triethylammonium chlo-
ride, regeneration of 4a and the other by reaction
with phosphite anion 46 and regeneration of inter-
mediate 47.
To an ice-cooled solution of trialkyl phosphite (10 g,
1 equiv.) in THF (30 mL) was added a mixture of water
(1 equiv.) in THF (5 mL) under an argon atmosphere. The
resulting solution was stirred for overnight, at either room
temperature or reflux. Subsequently, the evaporation of the
THF by using a rotary evaporator and high-vacuum distilla-
tion afforded the dialkyl phosphite as a colorless liquid.
Conclusions
General Procedure for Catalytic Enantioselective
Hydrophosphonylation using 4a
In conclusion, we have synthesized new camphor-
based FeACHTUNGTRENNUNG(III)-Schiff base complexes derived from
Dibutyl phosphite (25, 1.1 equiv.) was added to a stirred THF
aminoisoborneol and implemented an catalytic asym- (60 volumes) solution of [FeClACHTNURGTNEUNG(SBAIB-d)]2 4a (0.05 equiv.,
5 mol%) and TEA (1 equiv.) in an 8-mL screw-capped vial
and stirred for 1 h. The reaction mixture was cooled to
À258C for 15 min, aldehyde (1 equiv., 100 mg) was added,
and the mixture was continually stirred at the same tempera-
ture for the mentioned time (Table 3). Subsequently, the
THF was evaporated to obtain a residue that was purified
using column chromatography. The reported yields are for
products purified by column chromatography and the ee of
the obtained products were verified before and after recrys-
tallization from ether/hexane through the chiral HPLC by
metric hydrophosphonylation reaction. In the opti-
mized reaction conditions, 5 mol% of 4a was deter-
mined to be the optimal catalyst for producing hydro-
phosphonylation products in good to excellent levels
of enantioselectivity (up to 99%) and in excellent
yields (up to 99%) for various aldehydes. The catalyt-
ic systems used in this study provide several advantag-
es. The Schiff base ligands are easily synthesizable in
a few steps by using an inexpensive starting materials
(1R)-camphor. Iron sources were FeCl3, which is also using Chiralcel OD-H, and Chiralpak AD columns.
inexpensive. The synthesized Fe(III)-SBAIB com-
AHCTUNGTRENNUNG
plexes, which are air- and moisture-stable, can be
used under aerobic reaction conditions. The optimal
reaction conditions are extremely practical. The start-
ing materials can be stirred in a vial and preventing
exposure to air and moisture is not required. The cat-
alytic system produced a high ee level for various aro-
matic, polycyclic aromatic, heteroaromatic, a,b-unsa-
turated, and aliphatic aldehydes. Furthermore, [FeCl-
Acknowledgements
The authors thank Ms. L. M. Hsu, at the Instruments Center,
National Chung Hsing University, for her help in obtaining
mass spectral data, and the National Science Council of the
Republic of China, for financially supporting this research
under the contract NSC 100-2113M-259-006-MY3.
ACHTUNGTRENNUNG(SBAIB-d)]2 is the first iron-Schiff base complex that
affords a high level of ee for the hydrophosphonyla-
tion reaction. A detailed literature survey comparison
provided additional useful information for assigning
the configuration of the a-hydroxy phosphonates. The
possible bimetallic catalytic cycle mechanism is pro-
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Adv. Synth. Catal. 0000, 000, 0 – 0
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Ramalingam Boobalan and Chinpiao Chen
FULL PAPERS
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[8] Our air-stable and moisture-insensitive Cu2ACTHNUTRGNEG(NU SBAIB-d)2
catalyst (1 mol%) has proved to be one of the best cat-
alysts for enantioselective direct Henry reaction of var-
ious aldehydes (up to 98% ee), ref.[5b] We expected that
the FeACTHNURGTNE(UNG III) complex of the same SBAIB-d could show
similar high enantioselectivity in the hydrophosphony-
lation of aldehydes.
[9] Recently, in Taiwan, many of the phosphorus com-
pounds have been banned by UN due to considerations
of safety and environment pollution, therefore, chemi-
cals that are needed for research, must be prepared in
laboratory from the available resources. Diisopropyl
phosphite was available, and we synthesized dibutyl, di-
ethyl and dimethyl phosphites from available trialkyl
phosphites. We have also synthesized bis(2,2,2-tri-
ACHUTNGERNfNUG luoroACHTUNGTNEReNUGN thyl) phosphite 27 from 2,2,2-trifluoroethanol
under the reported reaction conditions: S. D. Broady,
J. E. Rexhausen, E. J. Thomas, J. Chem. Soc. Perkin
Trans. 1 1999, 1083–1094.
[10] C. A. Hunter, J. K. M. Sanders, J. Am. Chem. Soc.
1990, 112, 5525–5534.
[11] Refer to the Supporting Information for the detailed
literature survey to assign the configurations of the ob-
tained phosphonates.
8
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ÝÝ
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FULL PAPERS
Catalytic Enantioselective Hydrophosphonylation of
Aldehydes Using the Iron Complex of a Camphor-Based
9
Tridentate Schiff Base [FeClACTHNUTRGNEN(UG SBAIB-d)]2
Adv. Synth. Catal. 2013, 355, 1 – 9
Ramalingam Boobalan, Chinpiao Chen*
Adv. Synth. Catal. 0000, 000, 0 – 0
ꢁ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
9
ÞÞ
These are not the final page numbers!