Palladium-catalyzed enantioselective allylic substitution in the presence of monodentate furanoside phosphoramidites

Article abstract of DOI:10.1002/cctc.201402933

A library of monodentate furanoside phosphoramidites, easily synthesized from inexpensive D-xylose and optically pure 1,1-bi-2-naphthol (BINOL), was used as ligands for the palladium-catalyzed allylic alkylation and amination. The matched pair was formed from D-xylose-derivatives and (S)-BINOL. The asymmetric induction depends strongly on the substituent at the C5 of the carbohydrate backbone; both bulky 5-O-pivaloyl and 5-deoxy derivatives gave excellent results, whereas ligands with trityl protection at position C5 induced low ee values with reversal of configuration. The solvent used for the addition is also of great importance with highest enantioselectivities observed in diethyl ether. The best results for both alkylation and amination, up to 98-99 ee, were obtained for sterically demanding allylic acetates. Single is better: New carbohydrate ligands bearing a single 1,1-bi-2-naphthol (BINOL)-derived phosphoramidite moiety are developed and successfully applied to the palladium-catalyzed asymmetric allylic substitution. The enantioselectivities are equal or better than those obtained for similar systems containing two BINOL moieties and reach up to 99 ee.

Full text of DOI:10.1002/cctc.201402933

DOI: 10.1002/cctc.201402933
Full Papers
Palladium-Catalyzed Enantioselective Allylic Substitution
in the Presence of Monodentate Furanoside
Phosphoramidites
Maciej Majdecki,[a] Janusz Jurczak,[a, b] and Tomasz Bauer*[a]
A library of monodentate furanoside phosphoramidites, easily
synthesized from inexpensive d-xylose and optically pure 1,1’-
bi-2-naphthol (BINOL), was used as ligands for the palladium-
catalyzed allylic alkylation and amination. The matched pair
was formed from d-xylose-derivatives and (S)-BINOL. The asym-
metric induction depends strongly on the substituent at the
C5 of the carbohydrate backbone; both bulky 5-O-pivaloyl and
5-deoxy derivatives gave excellent results, whereas ligands
with trityl protection at position C5 induced low ee values with
reversal of configuration. The solvent used for the addition is
also of great importance with highest enantioselectivities ob-
served in diethyl ether. The best results for both alkylation and
amination, up to 98–99% ee, were obtained for sterically de-
manding allylic acetates.
Introduction
The allylic alkylation reaction, particularly in its enantioselective
version, is one of the most powerful and versatile carbon–
carbon bond forming reactions. Since the asymmetric catalytic
reaction was reported for the first time,[1] enantioselective allyl-
ic substitutions have continuously attracted organic chemists.
This reaction became a very important tool for the synthesis of
natural products.[2] Still, development and successful applica-
tion of chiral phosphorous ligands to reactions of various sub-
strates and nucleophiles[3] is a challenging goal. The majority
of reported effective ligands was based on (bis)phosphines[4]
or phosphinooxazolines.[5] During the last decades several new
ligands bearing the phosphoramidite moiety were successfully
applied for asymmetric allylic substitutions.[6] Naturally occur-
ring carbohydrates have become a popular source of chiral
lyzed 1,4-conjugated addition,[9] we decided to investigate the
library of furanoside monophosphoramidites of the general
structure presented in Figure 1 as ligands in asymmetric allylic
substitutions.
Figure 1. Furanoside monophosphoramidite ligands derived from 1.
amino alcohols or diamines and are used for the synthesis of Results and Discussion
diphosphoramidite and phosphite–phosphoramidite ligands.[7]
Synthesis of ligands
However, to the best of our knowledge, no carbohydrate-
based ligands bearing a single donor atom located in the
phosphoramidite moiety were reported in this area. If efficient,
such ligands would be cheaper and have lower molecular
mass than the respective diphosphoramidites. Having in mind
our successful application of d-glucosamine-derived diphenyl-
phosphinobenzoic amides in Pd-catalyzed asymmetric allylic al-
kylation[8] and monophosphoramidite furanosides in Cu-cata-
On the basis of the previous results chose the most promising
ligands L1–L5 and L8 (Figure 2), and the series of phosphora-
midite ligands was synthesized starting from d-xylose accord-
ing to our published procedures.[9] Additionally, on the basis of
the observation that decreased steric congestion at position
C5 can lead to high asymmetric induction, a new 5-deoxycar-
bohydrate core was designed and synthesized. The synthesis
of ligands L6 and L7 was accomplished through the formation
of primary and secondary amines 6 and 8, respectively, as pre-
sented at Scheme 1, and subsequent transformation into the
respective phosphoramidites. Thus, 1,2-O-isopropylidene d-
xylose 2 was selectively tosylated at position C5 to give 3,
which was reduced to the 5-deoxy derivative 4. Alcohol 4 was
oxidized to ketone 5 with excellent yield. Reductive amination
gave secondary amine 6 in a single step, and formation of
oxime 7 followed by LiAlH4 reduction led to primary amine 8.
The reaction of both amines with (S)-1,1’-binaphthyl-2,2’-diyl
phosphorochloridate gave ligands L6 and L7.
[a] M. Majdecki, Prof. J. Jurczak, Prof. T. Bauer
Department of Chemistry
University of Warsaw
Pasteura 1, PL-02-093 Warsaw (Poland)
E-mail: tbauer@chem.uw.edu.pl
[b] Prof. J. Jurczak
Institute of Organic Chemistry
Polish Academy of Science
Kasprzaka 44/52, 01-224 Warsaw (Poland)
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/cctc.201402933.
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Table 1. Pd-catalyzed asymmetric allylic alkylation in the presence of li-
gands L1–L6.[a]
Entry
Ligand
Solvent
t
[h]
Yield[b]
[%]
ee[c]
[%]
1
2
3
4
5
6
7
8
L1a
L1b
L2
L3
L4
L5
L6
L7
L8
L5
L5
L5
L5
L5
L5
L6
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
THF
acetonitrile
toluene
THF
Et2O
Et2O
24
20
20
4
86
90
96
97
80
87
98
37
trace
56
23
98
68
20
96
99
68 (S)
6 (S)
74 (S)
24 (R)
78 (S)
88 (S)
88 (S)
72 (S)
60 (S)
74 (S)[d]
48 (R)[e]
72 (S)
91 (S)
92 (S)
95 (S)
96 (S)
20
24
20
24
48
24
24
24
26
48
8
9
10
11
12
13
14
15
16
5
[a] Molar ratio: [Pd(allyl)Cl]2 (0.005 equiv.), ligand (0.01 equiv.), dimethyl
malonate (3.0 equiv.), BSA (3.0 equiv.), LiOAc (0.01 equiv.). [b] Isolated
yields. [c] The ee values were determined by HPLC analysis using a chiral
column Chiralcel AD-H. [d] KOAc was used. [e] NaH was used as a base.
Figure 2. Library of the monophosphoroamidite ligands L1–L8. TBDMSO=
tert-butyldimethylsilyl, TBDPSO=tert-butyldiphenylsilyl, Tr=triphenylmethyl,
Piv=pivaloyl.
Ligands L7 and L8, based on secondary amines, were ineffi-
cient and catalyzed the addition with low to extremely low
yield (Table 1, entries 8 and 9). Phosphoramidites obtained
from primary amines performed much better, except ligands
L1b and L3. Similarly to the 1,4-addition,[9] also (R)-1,1’-bi-2-
naphthol (BINOL) makes an unmatched pair with d-xylose (L1,
entries 1 and 2), and triphenylmethyl-protected ligand L3 gives
addition products with reversed absolute configuration
(entry 4). However, enantioselectivities were only moderate for
ligands L1a, L2, L4 (entries 1, 3, 5, respectively) and good for
ligands L5 and L6 (entries 6 and 7). Next, we tried to improve
the asymmetric induction by modification of the reaction con-
ditions. The influence of the counterion was investigated by
using KOAc instead of LiOAc under standard conditions or
using NaH in THF as a base in the presence of ligand L5. The
presence of potassium slightly diminished the enantioselectivi-
ty (entry 10), and the use of NaH led to a reversal of the direc-
tion of the asymmetric induction, albeit with only moderate
enantioselectivity and a very low yield (entry 11). The effect of
the solvent was then investigated. The reaction performed in
acetonitrile proceeded with almost quantitative yield, but with
lower enantioselectivity (entry 12), in toluene the yield was
only moderate, but the enantioselectivity improved to 91% ee
(entry 13). Further improvement to 92% was observed in THF,
but the yield dropped to unacceptable 20% (entry 14). Finally,
we decided to try diethyl ether as another ethereal solvent.
Surprisingly, not only the enantioselectivity was highest in the
series (95%), but also the chemical yield was very high (96%,
entry 15). Under these conditions, also the second most prom-
ising ligand L6 catalyzed the reaction with very high ee (96%)
and nearly quantitative yield (entry 16).
Scheme 1. Reagents and conditions: a) p-toluenesulfonyl chloride (TsCl),
Et3N, THF, RT, 81% yield; b) LiAlH4, THF, reflux, 82% yield; c) pyridinium di-
chromate, Ac2O, CH2Cl2, reflux, 99%; d) benzylamine, NaBH4, 2,2,2-trifluoroe-
thanol, 358C, 89% yield; e) NH2OH·HCl, EtOH/H2O, 92%; f) LiAlH4, THF, reflux,
55% yield.
Pd-catalyzed asymmetric allylic alkylation
Having in hand the series of ligands L1–L8, we tested their
ability to catalyze the asymmetric allylic alkylations of (E)-1,3-
diphenylallyl acetate (Scheme 2). Initially we chose [Pd(allyl)Cl]2
(0.005 equiv.), ligand (0.01 equiv.), dimethyl malonate
(3.0 equiv.), N,O -bis(trimethylsilyl)acetamide (BSA, 3.0 equiv.),
LiOAc (0.01 equiv.), and dichloromethane as a solvent for stan-
dard conditions.
Next, we investigated the influence of the ratio of [Pd(al-
lyl)Cl]2/L* (abbreviated as [Pd]/L*) and the amount of the chiral
Scheme 2. Allylic alkylation of (E)-1,3-diphenylallyl acetate. M=Li, K.
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Most of the ligands used for the palladium-catalyzed allylic
substitution give excellent results for bulky substrates such as
9 but do not perform well with less demanding cycloalkenyl
acetates or aliphatic allylic acetates such as 11 or 13, respec-
tively (Scheme 3). Although some ligands like the Trost ligands
Table 2. The influence of the amount of the palladium complex on the
asymmetric allylic alkylation using L5 in CH2Cl2 and Et2O.
Entry
[Pd]/L* ratio
[mol/mol]
Reaction time
[h]
Yield[a]
[%]
ee[b]
[%]
1
2
3
4
5
6
7
8
0.5:1
1:1
1:2
1.5:1.5
2:2
2.5:2.5
3:3
0.5:1
0.5:2
0.5:0.5
1:1
24
9
24
9
8
7
7
8
24
24
6
87
98
60
99
99
99
99
96
60
87
97
93
88 (S)[c]
86 (S)[c]
80 (S)[c]
81 (S)[c]
80 (S)[c]
81 (S)[c]
82 (S)[c]
95 (S)[d]
74 (S)[d]
93 (S)[d]
93 (S)[d]
95 (S)[d]
9
10
11
12
2:2
5
Scheme 3. Allylic alkylation of sterically nondemanding allylic acetates.
[a] Isolated yields. [b] The ee values were determined by HPLC analysis
using a chiral column Chiralcel AD-H. [c] CH2Cl2 was used as a solvent.
[d] Et2O was used as a solvent.
behave differently, our ligands follow this trend. The reaction
of cyclohexenyl acetate with dimethyl malonate was very slug-
gish, especially in Et2O, yields were low and enantioselectivities
at best moderate (Table 4, entries 1–3). We tried to improve ee
by introducing bulkier counterions to the nucleophile, but this
complex on the asymmetric induction. The results are present-
ed in Table 2. For all reactions conducted in dichloromethane,
the best enantioselectivity was observed for the ratio 0.5:1
[Pd]/L* (Table 2, entry 1), other combinations led to decreased
selectivity, however, accompanied by almost quantitative yields
(entries 2–7). For reactions performed in diethyl ether, again
the 0.5:1 [Pd]/L* ratio was the best (entry 8), but 1:1 ratio and
all its multiplications gave very similar results (entries 10–12). A
high excess of the chiral ligand over the palladium complex
was proved to be disadvantageous; the product was obtained
with moderate ee and chemical yield (entry 9).
Table 4. Pd-catalyzed asymmetric allylic alkylation of cyclohexenyl ace-
tate in the presence of ligands L5 and L6.
Entry
Ligand
Substrate
Solvent
t
[h]
Yield[c]
[%]
ee
[%]
1[a]
2[a]
3[b]
4[b]
5[b]
6[b]
7[b]
8[b]
L5
L5
L6
L6
L6
L3
L5
L6
11
11
11
11
11
13
13
13
CH2Cl2
Et2O
Et2O
Et2O
THF
CH2Cl2
Et2O
Et2O
24
23
26
43
35
38
97
94
93
20 (S)[d]
49 (S)[d]
52 (S)[d]
10 (R)[d,e]
12 (R)[d,f]
7 (S)[g]
72
120
24
24
24
Then, we attempted to improve the enantioselectivity by
lowering the reaction temperature. The reaction performed at
58C gave the addition product with slightly higher ee than
that run at room temperature (Table 3, entry 2 vs. 1), however
with concomitant decrease of chemical yield and in much
longer time. To keep the yield and the reaction time on a rea-
sonable level, we made use of the results presented in Table 2
and performed the reaction at 08C using a 2:2 [Pd]/L* ratio.
After the short time of 6 h the reaction was finished, and not
only the yield was very high, but also the enantioselectivity
was increased to 98% (entry 3).
24
24
9 (S)[g]
16 (S)[g]
[a] Molar ratio: [Pd(allyl)Cl]2 (0.005 equiv.), ligand (0.01 equiv.), dimethyl
malonate (3.0 equiv.), BSA (3.0 equiv.), LiOAc (0.01 equiv.). [b] Molar ratio:
[Pd(allyl)Cl]2 (0.02 equiv.), ligand (0.02 equiv.), dimethyl malonate
(3.0 equiv.), BSA (3.0 equiv.), LiOAc (0.01 equiv.). [c] Isolated yields. [d] The
ee values were determined by HPLC analysis using a chiral column Chiral-
cel AS-H. [e] Tetraheptylammonium chloride was added. [f] NaH was used
as a base. [g] The ee values were determined by GC analysis using
a chiral column Intercap Chiramix.
method, developed and successfully used by Trost, did not
work properly in our case. Although the enantioselectivity
changed by approximately 60 percentage points, this was ac-
companied by the reversal of the direction of the asymmetric
induction, so the net results were 10 and 12% ee with R con-
figuration (entries 4 and 5). Similarly, addition to pent-3-en-2-yl
carbonate proceeded with excellent yield and very low asym-
metric induction (entries 6–8).
Table 3. The influence of reaction temperature on the asymmetric allylic
alkylation using L5 in Et2O.[a]
Entry
T
[8C]
t
[h]
Yield[b]
[%]
ee[c]
[%]
1
2
3
20
5
0
8
20
6
96
84
94
95 (S)
96 (S)
98 (S)[d]
[a] Molar ratio: [Pd(allyl)Cl]2 (0.005 equiv.), L5 (0.01 equiv.), dimethyl malo-
nate (3.0 equiv.), BSA (3.0 equiv.), LiOAc (0.01 equiv.). [b] Isolated yields.
[c] The ee values were determined by HPLC analysis using a chiral column
Chiralcel AD-H. [d] Molar ratio: [Pd(allyl)Cl]2 (0.02 equiv.), ligand
(0.02 equiv.), dimethyl malonate (3.0 equiv.), BSA (3.0 equiv.), LiOAc
(0.01 equiv.).
Finally, we investigated the regioselectivity of the addition
to unsymmetrical substrates (Scheme 4). For (E)-4-phenylbut-3-
en-2-yl acetate 15 the attack of the nucleophile was directed
to the less hindered allylic terminus. However, the 3.5:1 ratio
was not impressive and the enantioselectivity moderate in the
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Table 5. Pd-catalyzed asymmetric allylic alkylation using (E)-4-phenylbut-
3-en-2-yl acetate as the substrate.[a]
Entry Ligand Substrate t
Regioselectivity Yield[b] ee[c] ee[c] ee[c]
[h]
[%]
(16) (17) (21)
[%] [%] [%]
1[d]
2
3
4
L5
L6
L5
L6
15
15
18
19
24 16/17 3.5:1
24 16/17 3:1
24 20/21 94:6
2.5 20/21 93:7
36
34
73
95
45
8
–
32
90
–
–
–
68 (S)
79 (S)
–
–
[a] Molar ratio: [Pd(allyl)Cl]2 (0.005 equiv.), ligand (0.01 equiv.), amine
(3.0 equiv.), BSA (3.0 equiv.), LiOAc (0.01 equiv.), Et2O as a solvent. [b] Iso-
lated yields. [c] The ee values were determined by HPLC analysis using
a chiral column Chiralcel OD-H. [d] CH2Cl2 as a solvent.
Scheme 4. Allylic alkylation of unsymmetrical substrates.
presence of ligand L5 for both products. In the presence of
ligand L6 the ratio was slightly worse, but ee was high, un-
fortunately for the minor product, whereas it was very low for
the major one.
The addition to cinnamyl alcohol acetate 18 and 1-phenylall-
yl acetate 19 was, as expected for palladium-catalyzed allylic
substitution, highly regioselective toward the linear product
(Table 5).
Scheme 5. Allylic amination of (E)-1,3-diphenylallyl acetate. HNR1R2 =primary
or secondary amine.
Then, we turned our attention to the second best ligand in
asymmetric alkylations, L6. The results were comparable to
those obtained with L5. However, some improvements were
observed. Addition of benzylamine proceeded in dichlorome-
thane with almost acceptable conversion (41–45%) and good
Pd-catalyzed asymmetric allylic amination
Next, we turned our attention to the asymmetric allylic amina-
tion of allylic acetate 9 (Scheme 5). The first results were rather
disappointing. The addition of benzylamine in the
presence of L5 proceeded with very low yield, low
conversion, and moderate enantioselectivity even in
the presence of increased amounts of the catalyst
(Table 6, entries 1–3). The addition in the absence of
BSA did not proceed at all (entry 4). However, re-
placement of the primary amine with the secondary
one completely changed the picture. The addition of
morpholine in the presence of 0.05 mol% of palladi-
um complex was completed after only 3 h in 95%
isolated yield and 96% ee (entry 5). The reaction in
the presence of the increased amount of the catalyst
was even more selective (entry 6), and the reaction
performed at 08C proceeded with almost complete
selectivity, albeit with slightly diminished chemical
yield (entry 7). However, the chemical yield was im-
proved if the solvent was changed to CH2Cl2, but
with a simultaneous drop of the enantioselectivity
(entry 8). The attempt to increase both values by per-
forming the reaction in a mixture of solvents (Et2O/
CH2Cl2 1:2) failed and both yield and ee were lower
than in pure Et2O (entry 9). The addition of piperidine
proceeded with >99% ee, but with only 21% con-
version (97% isolated yield, entry 10), and the addi-
tion of pyrrolidine resulted in moderate ee and yield
(entry 11). However, modification of the reaction con-
ditions and conducting the reaction with a smaller
excess of pyrrolidine and BSA led to a significant
improvement of the enantioselectivity to 98% ee
(entry 12).
Table 6. Pd-catalyzed asymmetric allylic amination in the presence of ligands L1–L7.[a]
Entry Ligand Solvent
HNR1R2
[Pd]/L*
[mol%] [h] [%]
t
Yield[b] ee[c]
[%]
1
2
3
4
5
6
7
8
L5
L5
L5
L5
L5
L5
L5
L5
L5
L5
L5
L5
L6
L6
L6
L6
L6
L6
L6
L6
L6
L6
L5
L6
L7
L7
Et2O
benzylamine
benzylamine
benzylamine
benzylamine
morpholine
morpholine
morpholine
morpholine
0.5:1
2:4
3:3
3:3
0.5:1
3:3
3:3
3:3
3:3
3:3
24
24
24
48 NR
3
3
7
6
8
24
24
5
24
24
5
6
24
8
6
24
20
3.5 89
24
15
21
37
86 (R)
CH2Cl2
CH2Cl2
Et2O
Et2O
Et2O
83 (R)
85 (R)
–
96 (R)
98 (R)
99 (R)[e]
83 (R)
[d]
95
96
83
91
78
21
66
80
45
41
97
91
72
95
95
32
63
Et2O
CH2Cl2
9
Et2O/CH2Cl2 (1:2) morpholine
Et2O
Et2O
Et2O
CH2Cl2
Et2O/CH2Cl2
Et2O
Et2O
Et2O
87 (R)
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
piperidine
>99 (R)
74 (R)
pyrrolidine
pyrrolidine
benzylamine
benzylamine
morpholine
pyrrolidine
pyrrolidine
pyrrolidine
3:3
3:3
98 (R)[f]
89 (R)
0.5:1
0.5:1
0.5:1
0.5:1
0.5:1
0.5:1
0.5:1
0.5:1
0.5:1
93 (R)g
97 (R)
98 (R)[g]
95 (R)
CH2Cl2
92 (R)[g]
95 (R)[g]
98 (R)[f]
99 (R)[g]
99 (R)[d]
90 (R)[f]
88 (R)[g]
64 (R)
Et2O/CH2Cl2 (5:1) pyrrolidine
Et2O
Et2O/CH2Cl2
Et2O
Et2O
Et2O
CH2Cl2
CH2Cl2
piperidine
piperidine
N-benzylpiperazine 0.5:1
p-MeOBnNH2
p-MeOBnNH2
BnNH2
3:3
0.5:1
0.5:1
1:2
28
23
18
45
24
24
24
BnNH2
65 (R)
[a] Molar ratio: amine (3.0 equiv.), BSA (3.0 equiv.), LiOAc (0.01 equiv.). [b] Isolated
yields. [c] The ee values were determined by HPLC. [d] Without BSA. [e] Reaction car-
ried out at 08C. [f] Molar ratio: amine (1.5 equiv.), BSA (1.05 equiv.), LiOAc (0.01 equiv.).
[g] Molar ratio: amine (1.5 equiv.), BSA (1.5 equiv.), LiOAc (0.01 equiv.).
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Quatro LC Micromass, and LCT Micromass TOF HiRes apparatus. In-
frared spectra were recorded on an FTIR Jasco 6200 spectrometer
in CH2Cl2 solution or KBr pellet. Reactions were performed under
atmosphere of argon using Schlenk techniques if necessary. Flash
column chromatography was performed on silica gel (Kieselgel-60,
Merck, 230–400 mesh). HPLC was conducted on Diacel Chiracel
OD-H, AD-H, AS-H columns. Analytical gas chromatography was
conducted on chiral column Intercap Chiramix. Compounds L1–L5
and L8 are known and were prepared by our own or modified lit-
erature method.[9]
enantioselectivity (Table 6, entry 13), and conducting this reac-
tion in the mixture of solvents led to a better enantioselectivity
(entry 14). Moreover, the addition of pyrrolidine performed in
the mixture of solvents proceeded with very good chemical
yield and enantioselectivity (entry 19), whereas the reactions
performed in diethyl ether (entry 17) or dichloromethane
(entry 18) alone furnished the product with diminished yield
(Et2O) or ee (CH2Cl2). Addition of piperidine and N-benzylpiper-
azine proceeded with excellent enantioselectivity and good to
very good yields (entries 21 and 22, respectively). Reaction
with p-methoxybenzylamine gave similar results to those ob-
tained for benzylamine (entries 23 and 24) and no reaction oc-
curred with dibenzylamine, cyclohexylamine, phthalimide,
nBuNH2 and iPrNH2.
1,2-O-Isopropylidene-a-d-xylofuranoside (2)
To the round-bottom flask containing acetone (260 mL) and con-
centrated sulfuric acid (10 mL), d-xylose (10 g, 67 mmol) was
added. The mixture was stirred for 30 min and a solution of
Na2CO3 (13 g, 66 mmol) in water (120 mL) was slowly added. The
mixture was further stirred for 3 h, and the pH was brought to >7
by the addition of solid Na2CO3. Inorganic salts were filtered off,
and the remaining solution was evaporated under vacuum. The
crude product was purified by flash chromatography (EtOAc/hex-
anes 6:4, v/v) to give 1,2-O-isopropylidene-a-d-xylofuranoside 2 as
The addition of benzylamine conducted in the presence of
tertiary phosphoramidite L7 led to worse results than those
obtained for ligands L5 and L6, so further research using
ligand L7 and other amines was not continued.
Conclusions
a colorless oil (8.46 g, 44.6 mmol, 68% yield) solidifying upon
20
standing in the freezer. ½aꢀ2D0 =ꢁ19.6 (c=1.0, CHCl3), lit.[10] ½aꢀD
=
We developed new carbohydrate ligands bearing a single
phosphoramidite moiety and applied them successfully to the
asymmetric allylic substitution. The high enantioselectivities
(up to 99%) achieved for (E)-1,3-diphenylallyl acetate are com-
parable or better than those reported for phosphite–phosphor-
amidite or diphosphoramidite ligands. The results are highly
dependent on the solvent used for the reaction, the steric con-
gestion introduced by the substituent at C5 of the carbohy-
drate core, and/or the bulkiness of the counterion of the nucle-
ophile. The explanation of these results requires further thor-
ough studies of the transition states of the addition. So far, we
were unable to obtain X-ray-quality crystals of the palladium
complexes, however, efforts are underway. The envisioned
studies will help to understand, why the change from the
bulky tert-butyldimethylsilyl and pivaloyl protection to the
even bulkier trityl one resulted in the reversal of the direction
of the asymmetric induction. Another problem that has to be
explained is the similar selectivity observed for pivaloyl-pro-
tected ligand L5 and the least sterically demanding ligand L6.
In the light of results obtained for ligands L2–L4 and L3, this
behavior is quite obscure. Hopefully, the obtained knowledge
will help to modify the structure of ligands and reaction condi-
tions to make them more selective for less sterically demand-
ing substrates.
ꢁ13.9 (c=0.34, CHCl3), lit.[11] ½aꢀD20 =ꢁ22.4 (c=1.1, CHCl3). H NMR:
d=6.00 (d, J=3.6 Hz, 1H), 4.53 (d, J=3.6 Hz, 1H), 4.20–3.85 (m,
4H), 3.10–2.80 (m, 1H), 1.49 (s, 3H), 1.33 ppm (s, 3H). 13C NMR: d=
112.1, 150.1, 85.9, 78.8, 61.4, 27.0, 26.4 ppm.
1
1,2-O-Isopropylidene-5-O-tosyl-a-d-xylofuranoside (3)
To a magnetically stirred solution of 2 (8.46 g, 44.6 mmol) and Et3N
(12.44 mL, 89.2 mmol) in THF (40 mL) at 08C, a solution of TsCl
(8.5 g, 49.06 mmol) in THF (20 mL) was added dropwise. The mix-
ture was stirred overnight at ambient temperature. As soon as
thin-layer chromatography evidenced the disappearance of the
substrate, the reaction was quenched with MeOH and solvents
were evaporated. The residue was dissolved in EtOAc (50 mL) and
washed with H2O (15 mL), saturated with NaHCO3 (15 mL) and
brine (15 mL). The organic phase was dried over anhydrous MgSO4,
filtered, and evaporated under vacuum. The residue was recrystal-
lized from hexane/ethyl acetate to give 3 (12.44 g, 36.12 mmol,
81% yield) as white crystals. ½aꢀ2D0 =ꢁ18.5 (c=1.0, CHCl3), lit.[12]
½aꢀD26 =ꢁ13.6 (c=1.5, CHCl3). M.p. 133–1348C, lit.[13] m.p. 134–
1
1358C. H NMR: d=7.80 (d, J=8.4 Hz, 2H), 7.35 (d, J=8.2 Hz, 2H),
4.53 (d, J=3.5 Hz, 1H), 4.35–4.25 (m, 2H), 4.20–4.10 (m, 1H), 3.20–
3.05 (m, 2H), 2.45 (s, 3H), 1.45 (s, 3H), 1.29 ppm (s, 3H). 13C NMR:
d=145.2, 132.4, 130.0, 128.9, 128.0, 112.0, 105.0, 85.1, 76.6, 74.2,
66.9, 26.8, 26.2, 21.6 ppm.
1,2-O-Isopropylidene-5-deoxy-a-d-xylofuranoside (4)
Experimental Section
Magnetically stirred solution of 3 (12.44 g, 36.12 mmol) in THF
(80 mL) was cooled to 08C, LiAlH4 (1.64 g, 43.34 mmol) was added
in portions, and the mixture was heated to reflux for 2 h. The mix-
ture was cooled to 08C, EtOAc (50 mL) was added slowly, followed
by a dropwise addition of H2O (3.4 mL), 15% NaOH (3.4 mL) and
H2O (10.3 mL). The suspension was stirred for 30 min, inorganic
salts were filtered off by using Celite pad, and the suspension was
washed thoroughly with EtOAc (3ꢁ30 mL). The combined extracts
were washed with brine and dried over anhydrous MgSO4, filtered,
and evaporated under vacuum. Residue was purified by flash chro-
General
Melting points were determined using a Kofler hot stage appara-
tus. Specific rotations were recorded using a PerkinElmer PE-241
polarimeter with a thermally jacketed 10 cm cell. H, 13C NMR, and
31P spectra were recorded in CDCl3 using Varian200 Unity Plus,
Bruker300, and Varian500 Unity Plus spectrometers. All chemical
shifts are quoted in parts per million relative to Me4Si (d, 0.00 ppm)
as an internal standard or H3PO4 (31P) as an external standard. Mass
1
spectra were recorded on
a Mariner instrument (Biosystem),
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&
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Full Papers
matography (EtOAc/hexane 4:6, v/v) to give 4 (5.16 g, 29.63 mmol,
82% yield) as a white solid. ½aꢀ2D0 =ꢁ21.2 (c=1.0, CHCl3), lit.[14]
½aꢀ2D0 =ꢁ15.6 (c=2.0, CHCl3), lit.[15] ½aꢀD29 =ꢁ20.7 (c=1.9, CHCl3).
3.9 Hz, 1H), 4.47 (t, J=4.2 Hz, 1H), 3.80–3.66 (m, 1H), 2.74–2.64 (m,
1H), 1.53 (s, 3H), 1.41 (s, 2H), 1.34 (s, 3H), 1.31 ppm (d, J=6.3 Hz,
3H). 13C NMR: d=111.5, 103.8, 80.6, 76.6, 61.0, 26.4, 26.3, 16.9 ppm.
(CH2Cl2): n˜max =3386, 3316, 2979,1376, 1214, 1017, 874 cmꢁ1. High-
resolution electrospray ionization mass spectrometry (HRESIMS)
[M++Na] calcd for [C8H15NO3+Na]: 196.0950; found: 196.0948.
1
M.p.=82–838C, lit.[13] m.p. 82–838C. H NMR: d=5.89 (d, J=3.9 Hz,
1H), 4.53 (d, J=3.6 Hz, 1H), 4.31 (dq, J=6.4 Hz, 2.7 Hz, 1H), 3.90–
4.10 (m, 1H), 1.94 (d, J=4.2 Hz, 1H), 1.50 (s, 3H), 1.35–1.25 ppm
(m, 6H). 13C NMR: d=111.4, 104.3, 85.5, 76.3, 76.0, 26.5, 26.1,
12.7 ppm.
1,2-O-Isopropylidene-3-benzylamino-3,5-dideoxy-a-d-ribo-
furanoside (6)
1,2-O-Isopropylidene-3-oxo-5-deoxy-a-d-xylofuranoside (5)
The magnetically stirred solution of 5 (0.172 g, 1.0 mmol) in 2,2,2-
trifluoroethanol (2 mL) was warmed to 378C and, after 5 min, ben-
zylamine (0.11 mL, 1.01 mmol) was added dropwise. The mixture
was stirred at this temperature for 15 min. After this time the
NaBH4 (0.076 g, 2.0 mmol) was added portionwise. The suspension
was stirred for another 15 min, filtered through silica gel pad, and
solids were washed twice with EtOAc (10 mL). The volatiles were
evaporated and the residue was purified by flash chromatography
(EtOAc/hexane 1:9, v/v) to give 6 (0.234 g, 0.89 mmol, 89% yield)
To the magnetically stirred solution of 4 (5.16 g, 29.63 mmol) in
CH2Cl2 (60 mL), pyridinium dichromate (7.8 g, 20.74 mmol) and
freshly distilled Ac2O (9.23 mL, 97.78 mmol) were added and the
mixture was heated to reflux for 1.5 h. As soon as thin-layer chro-
matography evidenced the disappearance of the substrate, the re-
action was cooled to RT and EtOAc (100 mL) was added. The reac-
tion mixture was filtered through a pad of silica gel. The solids
were thoroughly washed with EtOAc and the filtrate was co-evapo-
1
as a colorless oil. ½aꢀ2D0 = +160.0 (c=1.0, CHCl3). H NMR: d=7.42–
rated twice with toluene (10 mL) by using a rotary evaporator to
20
7.20 (m, 5H), 5.75 (d, J=3.9 Hz, 1H), 4.54 (t, J=4.2 Hz, 1H), 3.94 (d,
J=13.5 Hz, 1H), 3.83–3.69 (m, 2H), 2.60–2.51 (m, 1H), 1.90 (s, 1H),
1.51 (s, 3H), 1.34 (s, 3H), 1.30 ppm (d, J=6.3 Hz, 3H). 13C NMR: d=
140.2, 128.3, 128.0, 127.0, 111.4, 104.2, 77.3, 75.8, 66.5, 52.0, 26.5,
26.4, 17.5 ppm. (CH2Cl2): n˜max =3341, 3028, 2979, 1455, 1214, 1099,
give 5 (5.05 g, 29.33 mmol, 99% yield) as a colorless solid. ½aꢀD
=
+129.0 (c=1.0, CHCl3), lit.[16] ½aꢀD23 = +181.4 (c=1.6, CHCl3), lit.[17]
½aꢀ2D1 = +175.0 (c=0.5, CHCl3). M.p. 40–418C, lit.[16] m.p. 39–418C.
1H NMR: d=6.05 (d, J=4.5 Hz, 1H), 4.44 (q, J=6.9 Hz, 1H), 4.35 (d,
J=4.5 Hz, 1H), 1.51 (s, 3H), 1.40 (s, 3H), 1.32 ppm (d, J=6.9 Hz,
3H). 13C NMR: d=209.7, 114.3, 102.2, 75.6, 73.7, 27.5, 27.0,
15.4 ppm.
.
1015, 875 cmꢁ1 HRESIMS [M++H] calcd for [C15H21NO3+H]:
264.1594; found: 264.1603.
General procedure for the synthesis of ligands L1–L6
1,2-O-Isopropylidene-3-oxo-5-deoxy-a-d-xylofuranoside
oxime (7)
The amine 8 (0.5 mmol) was placed in a Schlenk tube and dis-
solved in THF (1 mL). Subsequently, Et3N (140 mL, 1 mmol) was
added, the mixture was cooled to 08C, and a 0.35m solution of (S)-
1,1’-binaphthyl-2,2’-diyl phosphorochloridate (1.57 mL, 0.55 mmol)
in toluene was added dropwise. The mixture was stirred at RT for
4 h, diluted with Et2O (10 mL), filtered through silica gel pad, and
the solids were washed twice with Et2O (20 mL). The volatiles were
evaporated and the residue was purified by flash chromatography
(EtOAc/hexanes 1:9 v/v) to give ligands L1–L6 as white foams.
To the magnetically stirred solution of 5 (5.05 g, 29.33 mmol) in
75% EtOH (80 mL), NH2OH·HCl (6.52 g, 93.86 mmol) and NaHCO3
(8.13 g, 96.79 mmol) were added and the mixture was heated to
reflux for 3.5 h. After cooling, the mixture was extracted with Et2O
(3ꢁ40 mL), the combined extracts were washed with brine and
dried over anhydrous MgSO4, filtered, and evaporated under
vacuum. The residue was purified by flash chromatography
(EtOAc/hexanes 3:7, v/v) to give 7 (5.05 g, 26.98 mmol, 92% yield)
as a white solid. ½aꢀD20 = +252.9 (c=1.0, CHCl3), lit.[16] ½aꢀ2D2 = +245.5
(c=1.0, CHCl3). M.p. 89–908C (petroleum ether), lit.[16] m.p. 90.5–
1,2-O-Isopropylidene-3-((11bS)-dinaphtho[2,1-d:1’,2’-f]
[1,3,2]dioxaphosphepin-4-ylamino)-3,5-dideoxy-a-d-ribofura-
noside (L6)
918C, lit.[18] mp.=898C. H NMR: d=5. 93 (d, J=4.5 Hz, 1H), 5.31
(dd, J=4.5 Hz, 1.2 Hz, 1H), 4.83 (qd, J=5.4 Hz, 0.9 Hz, 1H), 1.53 (s,
3H), 1.46–1.37 ppm (m, 6H). 13C NMR: d=103.7, 78.2, 76.6, 73.8,
72.7, 27.0, 26.9, 17.2 ppm.
1
Yield 88% (214 mg). ½aꢀ2D0 = +444.0 (c=1.0, CHCl3). M.p. 149–
1508C. 31P NMR: d=151.15 ppm. 1H NMR: d=8.01–7.49 (m, 1H),
7.94–7.89 (m, 3H), 7.55–7.51 (m, 1H), 7.46–7.39 (m, 4H), 7.30–7.22
(m, 3H), 5.76 (d, J=4.0 Hz, 1H), 4.58 (t, J=4 Hz, 1H), 3.78–3.68 (m,
1H), 3.59–3.49 (m, 1H), 3.25–3.13 (m, 1H), 1.44 (s, 3H) 1.39 (s, 3H),
1.35 ppm (d, J=6 Hz, 3H). 13C NMR: d=151.8, 149.1, 147.3, 147.2,
132.7, 132.6, 131.5, 131.1, 130.4, 129.4, 128.4, 128.3, 127.0, 126.9,
126.2, 126.1, 125.0, 124.8, 122.8, 121.7, 111.8, 103.7, 80.0, 59.9, 69.7,
26.5, 26.4, 16.7 ppm. (KBr): n˜max =3325, 3067, 2981, 1230, 1019, 950,
822 cmꢁ1. HRESIMS [M++Na] calcd for [C28H26NO5+Na]: 510.1446;
found: 510.1440.
1,2-O-Isopropylidene-3-amino-3,5-dideoxy-a-d-ribofurano-
side (8)
The magnetically stirred solution of 7 (5.05 g, 26.98 mmol) in THF
(100 mL) was cooled to 08C, LiAlH4 (2.05 g, 53.96 mmol) was added
in portions, and the mixture was heated to reflux for 1.5 h. The
mixture was cooled to 08C, diluted with Et2O (100 mL) and H2O
(2.5 mL), and 15% NaOH (2.5 mL) and H2O (7.7 mL) were added
dropwise. The suspension was stirred for 30 min, inorganic salts
were filtered off by using Celite pad, and the suspension was
washed thoroughly with CH2Cl2 (3ꢁ30 mL). The combined extracts
were washed with brine and dried over anhydrous MgSO4, filtered,
and evaporated under vacuum. The residue was purified by flash
General procedure for the synthesis of ligands L7
The amine 6 (0.5 mmol) was placed in the Schlenk tube and dis-
solved in THF (1 mL). The mixture was cooled to ꢁ788C and nBuLi
(2.2m in toluene, 227 mL, 0.5 mmol) was added dropwise. After
10 min, the reaction mixture was allowed to warm up to 08C and
chromatography (CH2Cl2/MeOH 95:5, v/v) to give
8 (2.57 g,
14.84 mmol, 55% yield) as a colorless oil. ½aꢀ2D0 = +55.1 (c=1.0,
CHCl3), lit.[16] ½aꢀD23 = +164.8 (c=1.0, CHCl3). H NMR: d=5.78 (d, J=
1
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13
a 0.35m solution of (S)-1,1’-binaphthyl-2,2’-diyl phosphorochlori-
date (1.57 mL, 0.55 mmol) in toluene was added dropwise. The
mixture was stirred at RT for 5 h, diluted with Et2O (10 mL), filtered
through silica gel pad, and the solids were washed twice with Et2O
(20 mL). The volatiles were evaporated and the residue was puri-
fied by flash chromatography (EtOAc/hexanes 1:9, v/v) to give li-
gands L7 as a white foam.
C NMR: d=168.2, 167.7, 140.3, 136.8, 131.8, 129.1, 128.4, 128.5,
127.9, 127.5, 127.2, 126.3, 57.7, 52.6, 52.4, 49.2 ppm. Daicel Chiralcel
AD-H, hexane/iPrOH=9:1, flow rate 0.8 mLminꢁ1, detected at
254 nm. tR =15.8 min for enantiomer (R), and tR =21.2 min for
enantiomer (S).
(ꢁ)-(S, E)-Dimethyl 2-(cyclohex-2-enyl)malonate
52% ee ½aꢀ2D0 =ꢁ29.3 (c=1.0, CHCl3), [lit.[20] ½aꢀ2D0 = +32.1 (c=0.91,
1,2-O-Isopropylidene-3-((11bS)-dinaphtho[2,1-d:1’,2’-f]
[1,3,2]dioxaphosphepin-4-yl(benzylamino)-3,5-dideoxy-a-d-
ribofuranoside (L7)
1
CHCl3), 74% ee (R)]. H NMR: d=5.78 (m, 1H), 5.52 (m, 1H), 3.75 (s,
3H), 3.74 (s, 3H), 3.29 (d, J=9.4 Hz, 1H), 2.91 (m, 1H), 2.00 (m, 2H),
1.80–1.27 ppm (m, 4H). 13C NMR: d=169.1, 129.9, 127.5, 57.0, 52.6,
35.6, 26.8, 25.1, 21.0 ppm. Daicel Chiralcel AS-H, hexane/iPrOH=
96:4, flow rate 1.0 mLminꢁ1, detected at 230 nm. tR =6.0 min for
enantiomer (S), and tR =6.9 min for enantiomer (R).
Yield 58% (167 mg). ½aꢀ2D0 = +265.6 (c=1.0, CHCl3). M.p. 117–
119 8C. 31P NMR: d=144.63 ppm. 1H NMR: d=8.00 (d, J=8.5 Hz,
1H), 7.94–7.90 (m, 1H), 7.85–7.78 (m, 2H), 7.61–7.57 (m, 1H), 7.45–
7.15 (m, 12H), 5.60 (d, J=4.5 Hz, 1H), 4.61–4.51 (m, 1H), 4.16–4.06
(m, 2H), 3.99–3.86 (m, 1H), 2.94–2.83 (m, 1H), 1.71 (s, 3H), 1.36 (s,
3H), 1.29 ppm (d, J=6 Hz, 3H). 13C NMR: d=150.1, 150.0, 146.1,
138.8, 132.8, 132.6, 131.4, 130.6, 130.4, 130.3, 130.0, 129.9, 129.5,
128.4, 128.3, 128.2, 127.3, 127.1, 127.0, 126.1, 126.0, 124.9, 124.6,
122.0, 121.9, 121.8, 112.0, 103.6, 72.2, 71.9, 60.4, 50.7, 26.6, 26.5,
16.8 ppm. (KBr): n˜max =3057, 2975, 1589, 1258, 1230, 1021, 948,
822 cmꢁ1. HRESIMS [M++Na] calcd for [C35H32NO5P+Na]: 600.1910;
found: 600.1881.
(ꢁ)-(S,E)-Dimethyl 2-(pent-3-en-2-yl)malonate
16% ee ½aꢀ2D0 =ꢁ10.2 (c=1.0, CHCl3), [ lit.[20] ½aꢀ2D0 =ꢁ25.1 (c=1.1,
1
CHCl3), 74% ee (S)]. H NMR: d=5.53 (dq, J=15.2 Hz, 6.4 Hz, 1H),
5.48 (ddq, J=15.2 Hz, 6.2 Hz, 1.6 Hz, 3H), 5.30 (dk, J=9.0 Hz,
6.4 Hz, 1H), 3.73 (s, 3H), 3.69 (s, 3H), 3.27 (d, J=9.0 Hz, 1H), 1.63
(dd, J=6.4 Hz, 1.6 Hz, 3H), 1.28 ppm (d, J=6.6 Hz, 3H). 13C NMR:
d=169.0, 132.5, 126.5, 58.2, 52.5, 52.4, 37.6, 18.6, 18.1 ppm. GC
analysis was performed by using a chiral column Intercap Chiramix
at 1088C constant. tR =15.2 min for the minor, and tR =15.7 min for
the major product.
General procedures for the palladium-catalyzed allylic alky-
lation of allylic acetates in the presence of L1–L8
Procedure A: The ligand Ln (0.01 mmol) and [Pd(h3-C3H5)Cl]2
(1.8 mg, 0.005 mmol) were placed in a Schlenk tube and dissolved
in an appropriate solvent (2 mL). After 30 min stirring under argon,
a solution of allylic acetate (1 mmol) in the same solvent (2 mL)
was added. A resulting yellow solution was stirred for another
30 min, then dimethyl malonate (350 mL, 3.0 mmol), N,O-bis(trime-
thylsilyl)acetamide (740 mL, 3.0 mmol), and a pinch of the acetate
salt were added. The reaction mixture was stirred for the required
time and quenched with the addition of saturated NH4Claq (5 mL).
The mixture was extracted with Et2O (2ꢁ20 mL). Combined organic
layers were washed with brine and dried over anhydrous MgSO4,
filtered, and evaporated under vacuum. The residue was purified
by flash chromatography (hexane/EtOAc 95:5, v/v) to give the de-
sired product.
(E)-Dimethyl 2-(4-phenylbut-3-en-2-yl)malonate
1H NMR (300 MHz): d=7.37–7.15 (m, 5H), 6.45 (d, J=15.9 Hz, 1H),
6.12 (dd, J=15.9 Hz, 8.7 Hz, 1H), 3.75 (s, 3H), 3.67 (s, 3H), 3.40 (d,
J=9 Hz, 1H), 3.20–3.05 (m, m, 1H), 1.19 ppm (d, J=6.9 Hz, 3H).
Daicel Chiralcel OD-H, hexane/iPrOH=99:1, flow rate 0.3 mLminꢁ1
,
detected at 254 nm. tR =36.7 min for the minor and tR =44.7 min
for the major product.
(E)-Dimethyl 2-(1-phenylbut-2-enyl)malonate
1H NMR: d=7.37–7.15 (m, 5H), 5.64–5.53 (m, 2H), 4.04 (dd, J=
11.0 Hz, 7.2 Hz, 1H), 3.82 (d, J=10.9 Hz, 1H), 3.73 (s, 3H), 3.48 (s,
3H), 1.63 ppm (d, J=4.8 Hz, 3H). Daicel Chiralcel OD-H, hexane/
iPrOH=99:1, flow rate 0.3 mLminꢁ1, detected at 215 nm. tR =
25.3 min for the minor, and tR =27.9 min for the major product.
Procedure B: The ligand Ln (0.01 mmol) and [Pd(h3-C3H5)Cl]2
(1.8 mg, 0.005 mmol) were placed in a Schlenk tube and dissolved
in dry THF (2 mL). After 30 min stirring under argon, a solution of
allylic acetate (1 mmol) in THF (2 mL) was added. The resulting
yellow solution was stirred for another 30 min, and then a freshly
prepared solution of sodium dimethyl malonate (350 mL, 3.0 mmol)
in THF (2 mL) was added. The reaction mixture was stirred for the
require time and quenched with the addition of saturated NH4Claq
(5 mL). The mixture was extracted with Et2O (2ꢁ20 mL). Combined
organic layers were washed with brine and dried over anhydrous
MgSO4, filtered, and evaporated under vacuum. Residue was puri-
fied by flash chromatography (hexanes/EtOAc 95:5, v/v) to give
the desired product.
(S)-Dimethyl 2-(1-phenylallyl)malonate
1H NMR: d=7.25–7.17 (m, 5H), 6.05–5.93 (m, 1H), 5.17–5.05 (m,
2H), 4.16–4.05 (m, 1H), 3.75 (s, 3H), 3.51 ppm (s, 3H). Daicel Chiral-
cel OJ-H, hexane/iPrOH=93:7, flow rate 0.5 mLminꢁ1, detected at
220 nm. tR =32.4 min for enantiomer (S), and tR =35.6 min for
enantiomer (R).
General procedure for the palladium-catalyzed allylic amina-
tion of 9 in the presence of ligands L5–L7
(ꢁ)-(S, E)-Dimethyl 2-(1,3-diphenyl-2-propenyl)malonate
The ligand Ln (0.01 mmol) and [Pd(h3-C3H5)Cl]2 (1.8 mg,
0.005 mmol) was placed in a Schlenk tube and dissolved in an ap-
propriate solvent (4 mL). After 30 min stirring under argon, a solu-
tion of allylic acetate (1 mmol) in the same solvent (2 mL) was
added. The resulting yellow solution was stirred for another
98% ee ½aꢀ2D0 =ꢁ22.3 (c=1.0, CHCl3), [lit.[19] ½aꢀ2D0 =ꢁ19.9 (c=0.55,
CHCl3), 96% ee (S)]. 1H NMR: d=7.36–7.17 (m, 10H), 6.49 (d, J=
15.9 Hz, 1H), 6.32 (dd, J=16 Hz, 8 Hz, 1H), 4.27 (dd, J=7.9 Hz,
3 Hz, 1H), 3.96 (d, J=11 Hz, 1H), 3.70 (s, 3H), 3.25 ppm (s, 3H).
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30 min, then an amine (350 mL, 3.0 mmol), N,O-bis(trimethylsilyl)a-
cetamide (740 mL, 3.0 mmol) and a pinch of the acetate salt were
added. The reaction was stirred for the required time and
quenched with the addition of saturated NH4Claq (5 mL). The mix-
ture was extracted with Et2O (2ꢁ20 mL). The combined organic
layers were washed with brine and dried over anhydrous MgSO4,
filtered, and evaporated under vacuum. The residue was purified
by flash chromatography (hexanes/EtOAc 95:5, v/v) to give the de-
sired product.
15.9 Hz), 6.31 (dd, J=15.9 Hz, 7.5 Hz, 1H), 4.38 (d, J=7.5 Hz, 1H),
3.80 (s, 3H), 3.75–3.68 (m, 2H), 1.67 ppm (s, 1H). 13C NMR: d=
158.6, 143.0, 137.0, 132.7, 132.5, 130.3, 129.4, 128.6, 128.5, 127.5,
127.4, 127.3, 126.4, 113.8, 64.5, 55.3, 50.8 ppm. Daicel Chiralcel AD-
H, hexane/iPrOH=94:6, flow rate 0.7 mLminꢁ1
, detected at
254 nm. tR =15.6 min for enantiomer (S), and tR =17.2 min for
enantiomer (R).
(R, E)-N-Benzyl-(1,3-diphenyl-2-propenyl)amine
93% ee ½aꢀ2D0 =ꢁ18.2 (c=1.0, CHCl3), lit.[6f] ½aꢀ2D5 =ꢁ18.5 (c=1.0,
CHCl3), 94% ee (S). 1H NMR: d=7.46–7.19 (m, 15H), 6.58 (d, J=
16 Hz, 1H), 6.31 (dd, J=15.9, 7.4 Hz, 1H), 4.40 (d, J=7.4 Hz, 1H),
3.78 (s, 2H), 1.70 ppm (s, 1H). 13C NMR: d=143.1, 140.6, 137.1,
132.8, 130.5, 128.8, 128.7, 128.6, 128.4, 127.7, 127.6, 127.50, 127.1,
126.9, 126.6, 64.7, 64.8, 51.6 ppm. Daicel Chiralcel OD-H, hexane/
(ꢁ)-(R, E)-4-(1,3-Diphenyl-2-propenyl)morpholine
99% ee ½aꢀ2D0 =ꢁ7.8 (c=1.0, CHCl3), [lit.[21] ½aꢀ2D5 =ꢁ7.4 (c=0.34
CHCl3), 76% ee (R) ], [lit.[22] ½aꢀD24 =ꢁ8.4 (c=0.7, CHCl3), 95% ee (R).
1H NMR: d=7.46–7.12 (m, 10H), 6.57 (d, J=15.6 Hz, 1H), 6.27 (dd,
J=16 Hz, 8.8 Hz, 1H), 3.78 (d, J=8.6 Hz, 1H), 3.71 (t, J=4.6 Hz,
4H), 2.64–2.28 ppm (m, 4H). 13C NMR: d=141.7, 136.9, 131.8,
131.6, 128.9, 128.7, 128.2, 127.8, 127.5, 126.6, 75.0, 67.4, 52.4 ppm.
iPrOH=99:1,flow rate 0.5 mLminꢁ1
, detected at 254 nm. tR =
24.8 min for enantiomer (R), and tR =27.5 min for enantiomer (S).
Daicel Chiralcel OD-H, hexane/iPrOH=9:1, flow rate 1.0 mLminꢁ1
,
detected at 254 nm. tR =6.9 min for enantiomer (S), and tR =
12.3 min for enantiomer (R).
Acknowledgements
This research was financed by the European Union within the Eu-
ropean Regional Development Fund, Project POIG.01.01.02.-14-
102/09.
(ꢁ)-(R, E)-N-(1,3-Diphenyl-2-propenyl)pyrrolidine
98% ee ½aꢀ2D0 =ꢁ2.5 (c=1.0, CHCl3), [lit.[23] ½aꢀ2D0 = +2.9 (c=1.0,
CHCl3), 68% ee (S). 1H NMR: d=7.44–7.12 (m, 10H), 6.55 (d, J=
15.6 Hz, 1H), 6.40 (dd, J=15.6 Hz, 8.4 Hz, 1H), 2.60–2.36 (m, 4H),
1.85–1.68 ppm (m, 4H). 13C NMR: d=143.2, 137.1, 133.2, 129.8,
128.6, 128.5, 127.7, 127.4, 127.1, 126.4, 74.4, 53.2, 23.4 ppm. Daicel
Chiralcel OD-H, hexane/iPrOH=200:1, flow rate 0.3 mLminꢁ1, de-
tected at 254 nm. tR =14.2 min for enantiomer (R), and tR =
15.2 min for enantiomer (S).
Keywords: allylic compounds
·
asymmetric catalysis
·
carbohydrates · palladium · P ligands
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H, hexane/iPrOH=200:1, flow rate 0.3 mLminꢁ1
, detected at
254 nm. tR =26.2 min for enantiomer (S), and tR =28.4 min for
enantiomer (R).
(ꢁ)-(R, E)-N-(1,3-Diphenyl-2-propenyl)piperidine
99% ee ½aꢀ2D0 =ꢁ13.4 (c=1.0, CHCl3), lit.[21] ½aꢀ2D5 =ꢁ11.7 (c=0.32,
CHCl3), 56% ee (R). 1H NMR: d=7.48–7.10 (m, 10H), 6.53 (d, J=
15.8 Hz, 1H), 6.33 (dd, J=15.8 Hz, 8.6 Hz, 1H), 3.80 (d, J=8.4 Hz,
1H), 2.60–2.20 (m, 4H), 1.66–1.50 (m, 4H), 1.50–1.32 ppm (m, 2H).
13C NMR: d=142.6, 137.3, 132.5, 131.1, 128.7, 128.6, 128.2, 127.5,
127.1, 126.5, 74.9, 52.9, 26.4, 24.9 ppm. Daicel Chiralcel AD-H,
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tR =8.2 min for enantiomer (R), and tR =9.2 min for enantiomer (S).
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Received: November 24, 2014
Published online on && &&, 0000
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M. Majdecki, J. Jurczak, T. Bauer*
Single is better: New carbohydrate li-
gands bearing a single 1,1’-bi-2-naph-
thol (BINOL)-derived phosphoramidite
moiety are developed and successfully
applied to the palladium-catalyzed
asymmetric allylic substitution. The
enantioselectivities are equal or better
than those obtained for similar systems
containing two BINOL moieties and
reach up to 99% ee.
&& – &&
Palladium-Catalyzed Enantioselective
Allylic Substitution in the Presence of
Monodentate Furanoside
Phosphoramidites
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