Copper-ClickFerrophos-complex-catalyzed enantioselective reductive aldol reaction

Article abstract of DOI:10.1055/s-0029-1216724

We have prepared several ClickFerrophos families and tested for the Cu(I)-catalyzed asymmetric reductive aldol reaction of ketones and aldehydes with an acrylic ester in the presence of phenylsilane. The Cu(I)-ClickFerrophos complex is efficient for the r

Full text of DOI:10.1055/s-0029-1216724

LETTER
1299
Copper–ClickFerrophos-Complex-Catalyzed Enantioselective Reductive
Aldol Reaction
E
nantioselective Redu
i
A
n
ldol
R
eactionoru Kato, Hiroshi Oki, Kenichi Ogata, Shin-ichi Fukuzawa*
Department of Applied Chemistry, Institute of Science and Engineering, Chuo University, 1-13-27 Kasuga, Bunkyo-ku, Tokyo 112-8551,
Japan
Fax +81(3)38171895; E-mail: orgsynth@kc.chuo-u.ac.jp
Received 27 January 2009
metric hydrogenation and 1,3-dipolar addition of the
Abstract: We have prepared several ClickFerrophos families and
azomethine ylide in excellent enantioselectivities (up to
tested for the Cu(I)-catalyzed asymmetric reductive aldol reaction
of ketones and aldehydes with an acrylic ester in the presence of
phenylsilane. The Cu(I)–ClickFerrophos complex is efficient for
99.7% ee).6 The ClickFerrophos ligand was found to be a
useful ligand for asymmetric synthesis and some times
the reaction of ketones with methyl acrylate to afford the erythro ad- works more effectively than Taniaphos (Figure 1), which
ducts both highly diastereo- and enantioselectively; the diastereo-
meric ratio of erythro/threo is improved when compared to the
analogous Taniaphos.
has analogous 1,5-diphos structures. We are interested in
the successful use of the Cu–Taniaphos complex in the re-
ductive aldol reaction, where it catalyzes the reaction with
a high enantioselectivity compared to other phosphine
Key words: aldol reactions, asymmetric catalysis, metallocenes,
phosphorus, copper
ligands. The efficiency of the Taniaphos ligand may due
to the 1,5-diphos unit which is a capable eight-membered-
ring chelate to the metal. ClickFerrophos also contains a
The reductive aldol reaction, which is a sequence of con-
jugate reductions of an a,b-unsaturated ester with a metal-
hydride species and trapping by an acceptor such as
ketone and aldehyde, is of current interest because it is an
efficient synthetic tactic in organic synthesis.1 The initial
reduction step generates intermediate enolate species,
which attack carbonyl groups to give the corresponding
aldol products. It should be a powerful tool for alternative
aldol reactions, offering the advantage of the in situ gen-
eration of enolates as nucleophilic condensation counter-
parts without stoichiometric amounts of strong bases. In
these processes, transition metals are typically utilized as
catalysts with silane or borane reductants. Shibasaki’s2
and Riant’s3 groups independently developed the asym-
metric version of the reaction using copper–chiral diphos-
phine complexes in the presence of hydrosilane or borane.
Nishiyama’s group reported the rhodium–phebox-
catalyzed asymmetric reductive aldol reactions.4 Each
reaction is successful in giving products with high
enantioselection. Lam’s group reported the intramolecu-
lar version of the reaction of w-carbonyl-a,b-unsaturated
esters giving b-hydroxylactones with good enantiomeric
excess using a chiral copper–diphosphine catalyst.5a They
also reported the cobalt-catalyzed diastereoselective intra-
and intermolecular reactions with a,b-unsaturated
amides.5b The reductive aldol reactions are nevertheless
still developing and have room for improvement regard-
ing substrate scope, yields, and enantioselectivity.
1,5-diphos unit and it could effectively work in the reac-
tion. We have prepared several ClickFerrophos families9
and tested them for Cu(I)-catalyzed asymmetric reductive
aldol reaction of ketones and aldehydes with acrylic
esters.
Me2N
Me
PR1
Fe
PR2
PR1
Fe
2
2
N
N
N
PR2
2
2
R3
Taniaphos
T1: R1 = R2 = Ph
T2: R1 = R2 = Cy
ClickFerrophos
CF1: R1 = R2 = R3 = Ph
CF2: R1 = R2 = Ph, R3 = H
CF3: R1 = R2 = Cy, R3 = Ph
CF4: R1 = R2 = Cy, R3 = H
CF5: R1 = R2 = c-C5H9, R3 = Ph
CF6: R1 = R3 = Ph, R2 = Cy
Figure 1 ClickFerrophos and Taniaphos Families
In our initial experiment, we screened the (S,Rp)-Click-
Ferrophos ligand family (CF1–CF6) for the reaction of
acetophenone 1a (Ar = Ph) with methyl acrylate 2a (1.2
equiv) using a catalytic amount of [CuF(PPh3)3]·2MeOH
and a stoichiometric quantity of phenylsilane at –50 °C in
toluene.7 The results are summarized in Table 1. In the
presence of the Cu(I) complex of (S,Rp)-CF1 (1.0 mol%),
the reaction proceeded smoothly and was complete in one
hour affording the aldol adduct as a mixture of diastereo-
mers; the erythro-3a (Ar = Ph) and threo-4a (Ar = Ph)
were obtained in the ratio of erythro/threo = 71:29. The
erythro-3a was the major diastereomer and its enantio-
meric excess and absolute configuration were determined
using a chiral GC column and compared to the reported
result;3a (2S,3R)-3a was produced in –73% ee (entry 1).
In a previous study, we developed a new chiral ferrocenyl
ligand, the ClickFerrophos, using click chemistry meth-
odology, and reported its metal-complex-catalyzed asym-
SYNLETT 2009, No. 8, pp 1299–1302
x
x.
x
x.
2
0
0
9
Advanced online publication: 17.04.2009
DOI: 10.1055/s-0029-1216724; Art ID: U00809ST
© Georg Thieme Verlag Stuttgart · New York

1300
M. Kato et al.
LETTER
The disubstituted triazole derivative of the ClickFerro-
phos CF2 similarly gave the (2S,3R)-3a as the major dia-
stereomer in the ratio of erythro/threo = 69:31 with a
higher enantioselectivity (–84% ee, entry 2). The use of
dicyclohexyl derivative CF3 successfully improved dia-
stereoselectivity up to erythro/threo = 96:4, and (2R,3S)-
3a was obtained in up to 83% ee as the enantiomer of
those which were obtained using CF1 (entries 3 and 4).
The disubstituted triazole CF4 and the dicyclopentyl de-
rivative CF5 also gave (2R,3S)-3a in a good diastereo-
selectivity with a moderate enantioselectivity (69% ee and
76% ee, respectively; entries 5 and 6). The use of the
monocyclohexyl derivatives CF6 was not successful for
the reaction producing (2S,3R)-3a with low diastereo-
selectivity and enantioselectivity (entry 7). The results of
the reaction using the Taniaphos ligands (T1 and T2) are
also shown for comparison (entries 8–10). The results
may suggest that CF1 and CF3 tend to give slightly high-
er diastereoselectivities than the Taniaphos in each case,
although the enantioselectivity was not as high as that
with the Taniaphos.
Table 1 Asymmetric Reductive Aldol Reaction of Acetophenone
1a with Methyl Acrylate 2a Catalyzed by Cu(I)–ClickFerrophos
Complexesa
Entry
L
Yield (%) 3a/4a
ee (%) of 3a [ee (%) of 4a]b
–73 (–53)
–84 (–56)
83 (55)
1
2
CF1
CF2
CF3
CF3
CF4
CF5
CF6
T1
91
83
90
65
93
51
54
92
99
99
71:29
69:31
96:4
3
4c
5
91:9
81 (29)
95:5
69 (31)
6
95:5
76 (53)
7
89:11
64:36
76:24
92:8
–37 (–1)
8
–83 (–94)
–85 (–94)
95 (72)
9d
10d
T1
T2
a Compound 1a (1.0 mmol), 2 (1.2 mmol), [CuF(PPh3)3]·2MeOH
(0.01 mmol), ligand (0.01 mmol), PhSiH3 (1.4 mmol), toluene (5.0
mL), –50 °C, 1 h.
O
O
Cu–L
b Determined by chiral GC column (CP CHIRASIL DEX CB, 25 m).
c The reaction was carried out in THF.
+
OMe
Ar
Me
Ph3SiH
toluene
–50 °C, 1 h
d The reported result, see ref. 3a.
1
2
O
O
Me
Ar
OH
Me
diastereoselectivity affording higher diastereomeric ratios
than the Taniaphos ligand although it bears improving the
ee values.
Me
Ar
OH
Me
+
OMe
OMe
threo-4
erythro-3
Table 2 Cu(I)–CF3-Complex-Catalyzed Asymmetric Reductive
Aldol Reaction of 1 with 2aa
Scheme 1 The Cu–ClickFerrophos-catalyzed reductive aldol reac-
tion of ketones 1 with methyl acrylate 2a
Entry
1
Ar
Yield (%)b
3/4
ee (%) of 3b
Thus, the dicyclohexyl derivative CF3 was revealed to be
the most effective for the reaction, and we next examined
the scope of the reaction with respect to the ketone sub-
strate using CF3 under similar conditions.10 The results
for the representative substituted acetophenones and thie-
nyl methyl ketones are shown in Table 2. The reaction of
these ketones with 2 successfully proceeded to give the
corresponding aldol adducts in high diastereoselectivities
and enantioselectivities. The reaction with the p- and m-
haloacetophenones gave the corresponding erythro aldol
adducts 3 in as high diastereo- (ratio of erythro/threo) and
enantioselectivities as the acetophenone (entries 2–4).
The introduction of the CF3 substituent at the para posi-
tion may affect the stereoselectivity, thus decreasing the
enantioselectivity and diastereoselectivity (entries 5 and
6). The rate of the reaction decreased and extending the
reaction time to three hours was necessary for a satisfac-
tory yield. The 4-methoxy substituent increased both the
Ph
90
93
83
68
49
83
36
65
82
96:4
95:5
95:5
96:4
91:9
90:10
99:1
98:2
97:3
83
84
85
80
73
74
87
84
84
2
4-FC6H4
4-ClC6H4
3-ClC6H4
4-F3CC6H4
4-F3CC6H4
4-MeOC6H4
2-thienyl
3-thienyl
3
4
5
6c
7c
8d
9d
a Compound 1 (1.0 mmol), 2 (1.2 mmol), [CuF(PPh3)3]·2MeOH (0.01
mmol), CF3 (0.01 mmol), PhSiH3 (1.4 mmol), toluene (5.0 mL),
–50 °C, 1 h.
b Determined by GC (CP CHIRASIL DEX CB).
c Reaction time 3 h.
diastereomeric ratio and enantiomeric excess of the eryth- d Reaction time 24 h.
ro-3, but in low yield (entry 7). The reaction with the 2-
and 3-thienyl methyl ketones gave the erythro aldol ad-
We further examined the copper-catalyzed reductive aldol
reaction of aldehydes using the ClickFerrophos families
CF1–CF4 under the same conditions as the reaction with
duct in high diastereomeric ratio and enantiomeric excess
(entries 8 and 9). Based on the results in Table 2, the CF3
ligand was revealed to be superior with respect to the
Synlett 2009, No. 8, 1299–1302 © Thieme Stuttgart · New York

LETTER
Enantioselective Reductive Aldol Reaction
1301
the acetophenone. The results are shown in Table 3. For In conclusion, the copper–ClickFerrophos (CF3) com-
the reaction of the cyclohexanecarbaldehyde with methyl plex very effectively worked in the reductive aldol reac-
acrylate 2a, the use of CF1 afforded a mixture of the syn- tion of ketones with methyl acrylate to give the
(2S,3R)-6a (R = Me) and anti-(2S,3S)-7a (R = Me) ad- corresponding erythro adduct in both high diastereo- and
ducts in the ratio of syn/anti = 67:33 with 52% ee (syn) enantioselectivities. The CF1 was effective for the reac-
and 58% ee (anti), respectively (entry 1); the enantiomeric tion of aldehydes with tert-butyl and cyclohexyl acrylate
excess and absolute configuration were determined using to give the syn adduct with a high enantioselectivity, but
a chiral GC column comparing to the reported result without any diastereoselectivity.
(Scheme 2).3b,4 The reaction at a lower temperature (–78 °C)
hardly affected the enantioselectivity for both 6 and 7 (en-
References and Notes
try 2).8 The reaction with the tert-butyl 2b and cyclohexyl
(1) For a review, see: Matsuda, I. In Modern Rhodium-
Catalyzed Organic Reactions; Evans, P. A., Ed.; Wiley-
VCH: Weinheim, 2005, Chap. 6, 111–128.
(2) (a) Zhao, D.; Oisaki, K.; Kanai, M.; Shibasaki, M.
Tetrahedron Lett. 2006, 47, 1403. (b) Zhao, D.; Oisaki, K.;
Kanai, M.; Shibasaki, M. J. Am. Chem. Soc. 2006, 128,
14440.
(3) (a) Deschamp, J.; Chuzel, O.; Hannedouche, J.; Riant, O.
Angew. Chem. Int. Ed. 2006, 45, 1292. (b) Chuzel, O.;
Deschamp, J.; Chausteur, C.; Riant, O. Org. Lett. 2006, 8,
5943.
esters 2c increased the enantioselectivity for 6 up to 89%
ee in the ratio of 6/7 being almost 50:50 (entries 3–5). The
reaction with the CF2–CF4 ligands was unsuccessful,
giving low diastereo- and enantioselectivities although
the smooth reaction proceeded to give the aldol adduct in
a moderate to good yield (entries 6–8). The reaction of
benzaldehyde with tert-butyl acrylate using CF1 under
the same conditions gave the anti adduct with 72% ee in
the ratio of syn/anti = 22:78.
(4) (a) Nishiyama, H.; Shiomi, T.; Tsuchiya, Y.; Matsuda, I.
J. Am. Chem. Soc. 2005, 127, 6972. (b) Ito, J.-i.; Shiomi, T.;
Nishiyama, H. Adv. Synth. Catal. 2006, 348, 1235.
(c) Shiomi, T.; Ito, J.-i.; Yamamoto, Y.; Nishiyama, H. Eur.
J. Org. Chem. 2006, 5594. (d) Shiomi, T.; Nishiyama, H.
Org. Lett. 2007, 9, 1651. (e) Nishiyama, H.; Ito, J.-i. Chem.
Rec. 2007, 7, 159.
O
O
Cu–L
+
OR
Cy
H
Ph3SiH
toluene
–50 °C, 1 h
5
2
OH
O
O
OH
(5) (a) Lumby, R. J. R.; Joensuu, P. M.; Lam, H. W. Org. Lett.
2007, 9, 4367. (b) Lam, H. W.; Joensuu, P. M. Org. Lett.
2005, 7, 4225.
(6) (a) Fukuzawa, S.-i.; Oki, H.; Hosaka, M.; Sugasawa, J.;
Kikuchi, S. Org. Lett. 2007, 9, 5557. (b) Fukuzawa, S.-i.;
Oki, H. Org. Lett. 2008, 10, 1747.
(7) The use of other silanes such as dimethylphenylsilane,
diethylmethylsilane, and triethoxysilane resulted in poor
yields and selectivities under the same conditions.
(8) Additives such as the triethylamine and tricyclohexyl
phosphine did not affect the stereoselectivity.
+
Cy
OR
Cy
OR
Me
anti-7
Me
syn-6
Scheme 2 The Cu–ClickFerrophos-catalyzed reductive aldol reac-
tion of cyclohexanecarbaldehyde 5 with acrylates 2
Table 3 Asymmetric Reductive Aldol Reaction of Cyclohexane-
carbaldehyde 5 with Acrylate 2a–c Catalyzed by Cu(I)–ClickFerro-
phos Complexesa
(9) Preparation of (S,Rp)-5-(Diphenylphosphino)-1-{1-[2-
(diphenylphosphino)ferrocenyl]ethyl}-1H-1,2,3-triazole
(CF2)
Entry
L
R
Conversion 6/7b
(%)
ee (%) of 6b
[ee (%) of 7]
A 100 mL round-bottom flask containing a magnetic stirring
bar was charged with 1-(1-azidoethyl)-2-bromoferrocene
(400 mg, 1.20 mmol), trimethylsilylacetylene (180 mL, 1.32
mmol), t-BuOH (3.0 mL), and H2O (3.0 mL). Sodium
ascorbate (257 mg, 1.32 mmol) was added to the flask
followed by CuSO4·7H2O (162 mg, 0.65 mmol), and the
resulting mixture was magnetically stirred for 24 h. The
mixture was then extracted with CH2Cl2 (10 × 3 mL). The
combined extracts were washed(brine), dried (MgSO4), and
the solvent was removed on a rotary evaporator to leave a
yellow residue. The residue was treated overnight with a
THF (5.0 mL) solution of TBAF (1.5 mmol) in THF at
50 °C. THF was removed by using a rotary evaporator and
diluted with CH2Cl2 (20 mL) The solution was washed with
H2O, dried (MgSO4), and the solvent was removed using a
rotary evaporator. The residue was subjected to column
chromatography on SiO2 (hexane–EtOAc = 2:1 as eluent) to
give the pure (S,Rp)-1-[1-(2-bromoferrocenyl)ethyl]-1H-
1,2,3-triazole. Yellow solid; yield 140 mg, 0.40 mmol, 33%;
mp 120–121 °C; [a]D25 +81 (c 0.36, CHCl3). 1H NMR (300
MHz, CDCl3): d = 2.04 (d, 3 H, J = 6.4 Hz), 4.26 (s, 5 H),
4.42 (s, 1 H), 4.53 (s, 1 H), 5.88 (q, 1 H, J = 6.9 Hz), 7.30 (s,
1 H), 7.56 (s, 1 H). 13C NMR (75 MHz, CDCl3): d = 21.0,
54.9, 64.9, 66.9, 71.1, 71.5, 79.1, 84.6, 121.7, 132.9.
1
CF1 Me 99
CF1 Me 99
CF1 t-Bu 99
CF1 t-Bu 99
CF1 Cy 99
CF2 Me 99
CF3 Me 99
CF4 Me 89
67:33
50:50
46:54
52:48
41:59
60:40
26:74
22:78
51:49
52 (58)
55 (54)
89 (54)
80 (38)
74 (73)
19 (25)
–30 (–25)
7 (7)
2c
3
4c
5
6
7
8
9
T1
Me 99
78 (59)
a Compound 1 (1.0 mmol), 2 (1.2 mmol), [CuF(PPh3)3]·2MeOH (0.01
mmol), CF3 (0.01 mmol), PhSiH3 (1.4 mmol), toluene (5 mL),
–50 °C, 1 h.
b Determined by chiral GC column (CP CHIRASIL DEX CB, 25 m).
c The reaction was carried out at –78 °C.
Synlett 2009, No. 8, 1299–1302 © Thieme Stuttgart · New York

1302
M. Kato et al.
LETTER
Compound CF3 was prepared by a similar preparative
In a 20 mL Schlenk tube containing a magnetic stirring bar
were charged the triazole bromoferrocene prepared above
(100 mg, 0.28 mmol) and dry THF (3.0 mL) under a slight
pressure of nitrogen. The flask was cooled at –78 °C, and a
hexane solution of n-BuLi (0.44 mL, 0.70 mmol, 1.6 M) was
then added using a syringe through the septum with mag-
netic stirring. After 10 min, Ph2PCl (130 mL, 0.70 mmol) was
injected into the mixture at –78 °C and stirred for 1 h. When
the addition was completed, the mixture was allowed to
warm to r.t. and then stirred for an additional 2 h. The
reaction was quenched with sat. NH4Cl, and the solution was
then extracted with Et2O (3 × 20 mL). The combined extracts
were washed(brine), dried (Na2SO4), filtered, and the
solvent was removed on a rotary evaporator to leave a
yellow solid. The crude CF2 was purified by recrystal-
lization from hexane–CH2Cl2. Yellow solid; yield, 130 mg,
0.20 mmol, 73%; mp 167–168 °C; [a]D25 +95 (c 0.34,
CHCl3). 1H NMR (300 MHz, CDCl3): d = 1.61 (d, 3 H,
J = 6.8 Hz), 3.81 (s, 1 H), 4.10 (s, 5 H), 4.45 (t, 1 H, J = 2.6
method for CF1 by replacing Ph2PCl with Cy2PCl according
to a previous study.6a Yellow solid; mp 100–101 °C; [a]D
25
+97 (c 0.31, CHCl3). 1H NMR (300 MHz, CDCl3): d = 0.90–
2.30 (m, 47 H) including 2.04 (d, J = 6.9 Hz), 4.19 (s, 1 H),
4.29 (s, 5 H), 4.33 (s, 1 H), 6.17 (m, 1 H), 7.30–7.40 (m, 5
H). 13C NMR (75 MHz, CDCl3): d = 23.6 (dd, J = 3.2, 7.7
Hz), 26.0–36.0 (several cyclohexyl signals), 54.2, 68.5,
69.7, 71.2, 71.3, 78.4 (d, J = 25.3 Hz), 95.3 (d, J = 24.8),
127.9, 128.1, 128.4 (d, J = 30. 0 Hz), 129.3, 133.2, 151.6. 31
P
NMR (121 MHz, CDCl3): d = –28.7 (s), –18.0 (s). HRMS:
m/z calcd for C44H61FeN3P2 [M + H+]: 750.3768; found:
750.3767.
(10) General Procedure for Cu/CF3-Mediated Reductive
Aldol Reaction of Ketones 1 with Methyl Acrylate (2)
Under nitrogen, a 20 mL well-dried Schlenk tube equipped
with a magnetic stirrer was charged with
CuF(PPh3)3·2MeOH (9.0 mg, 0.01 mmol), CF3 (7.5 mg,
0.01 mmol), and toluene (4.8 mL). The catalyst solution was
stirred for 30 min at r.t., and phenylsilane (180 mL, 1.40
mmol) was then added at the same temperature. After
cooling the solution at –50 °C, methyl acrylate (2, 110 mL,
1.20 mmol) and acetophenone (120 mg, 1.00 mmol) were
simultaneously added to the solution. The mixture was
stirred for 1 h at –50 °C, and then quenched by adding an aq
NH4F soln (5 mL). The aqueous layer was extracted by three
portions of Et2O (5 mL). The combined organic layers were
then washed with brine (20 mL), dried over MgSO4, filtered
and concentrated by an evaporator. The residue was
subjected to short SiO2 column chromatography (hexane–
EtOAc as the eluent) to give a diastereomeric mixture of the
aldol adduct. The dr (erythro/threo) and ee values were
determined by GC (CP CHIRASIL DEX CB 25 m) with
reference to the literature.
Hz), 4.90 (s, 1 H), 6.30 (m, 1 H), 6.60–7.60 (m, 21 H). 13
C
NMR (75 MHz, CDCl3): d = 21.6, 53.9 (dd, J = 9.2, 11.7),
69.8, 70.2, 70.8 (d, J = 3.7 Hz), 71.8 (d, J = 4.9 Hz), 75.3 (d,
J = 10.2 Hz), 92.4 (d, J = 26.0 Hz), 127.0, 127.7 (d, J = 5.5
Hz), 127.9 (d, J = 8.1 Hz), 128.1 (d, J = 6.8 Hz), 128.3 (d,
J = 7.2 Hz), 128.7, 128.8, 129.2, 129.8, 130.9 (d, J = 16.9
Hz), 132.4 (d, J = 18.6 Hz), 133.1 (d, J = 7.2 Hz), 133.3,
133.4, 133.5 (d, J = 7.9 Hz), 134.0, 134.1 (d, J = 21.5 Hz),
135.4 (d, J = 21.1 Hz), 137.1 (d, J = 8.5 Hz), 138.6, 139.1 (d,
J = 9.6 Hz). 31P NMR (121 MHz, CDCl3): d = –40.4 (d,
J = 37.0 Hz), –24.5 (d, J = 37.0 Hz). HRMS: m/z calcd for
C38H33FeN3P2 [M + H+]: 650.1577; found: 650.1573. The
crystallographic data can be obtained free of charge from
The Cambridge Crystallographic Data Centre via
www.ccdc.cam.ac.uk/data_request/cif. CCDC-717051.
Compound CF4 was similarly prepared by replacing Ph2Cl
with Cy2PCl. Yellow solid; yield, 58%; mp 100–102 °C;
[a]D25 +197 (c 0.24, CHCl3). 1H NMR (300 MHz, CDCl3):
d = 0.90–2.10 (m, 47 H) including 2.04 (d, J = 7.0 Hz), 4.18
(s, 1 H), 4.26 (s, 5 H), 4.38 (s, 1 H), 6.12 (m, 1 H), 7.66 (s, 1
H). 13C NMR (75 MHz, CDCl3): d = 23.2, 53.9 (dd, J = 9.6,
12.0 Hz), 26.0–36.0 (several cyclohexyl signals), 69.0, 69.3,
69.6, 71.3 (d, J = 4.3 Hz), 79.3 (d, J = 24.6 Hz), 93.8 (d,
erythro-Methyl 3-Hydroxy-2-methyl-3-phenylbutanoate
(3a)
1H NMR (300 MHz, CDCl3): d = 1.32 (d, 3 H, J = 7.0 Hz),
1.46 (s, 3 H), 3.03 (q, 1 H, J = 7.0 Hz), 3.45 (s, 3 H), 4.02 (s,
1 H), 7.20–7.40 (m, 5 H). 13C NMR (75 MHz, CDCl3): d =
12.45, 26.6, 48.5, 51.6, 74.6, 124.6, 126.7, 128.1, 147.5,
177.1. GC Chirasil-Dex CB, 25 mm; isotherm 120 °C,
tR(major) = 18.5 min, tR(minor) = 19.4 min. Other aldol
products are fully characterized by spectroscopic analysis
and the dr and ee values of products were determined by GC.
J = 25.8 Hz), 131.7 (d, J = 24.3 Hz), 137.8 (d, J = 4.7). 31
NMR (121 MHz, CDCl3): d = –33.0 (s), –19.3 (s). HRMS:
m/z calcd for C38H57FeN3P2 [M + H+]: 674.3455; found:
674.3456.
P
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