Acetyl-BINOL as mimic for chiral β-diketonates: A building block for new modular ligands

Article abstract of DOI:10.1016/j.tet.2010.11.037

α-Acetyl-(S)-BINOL was prepared by ortho-lithiation and subsequent acetylation of acetal-protected (S)-BINOL. The β-hydroxyketone moiety of this compound is herein a structural mimic for a β-diketonate and forms six-membered chelates with transition metal ions. The second hydroxy-function was submitted to esterification with several carboxylic acids bearing another donor function, thus, new tridentate chiral ligands were obtained. Out of this library the l-proline-α-acetyl-(S)-BINOL-ester was identified to be most effective for the titanium-mediated addition of Et₂Zn to PhCHO yielding the respective secondary alcohol with up to 93% ee, which is better than with using (S)-BINOL itself. Besides a solvent dependency (use of MeCN is optimal), the proper choice of the counter-ion is crucial: anion exchange of bromide by trifluoroacetate gave a significant increase of enantioselectivity. Copyright

Full text of DOI:10.1016/j.tet.2010.11.037

Tetrahedron 67 (2011) 334e338
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Acetyl-BINOL as mimic for chiral b-diketonates: a building block for new modular
ligands
Robert von R o€ nn, Jens Christoffers *
Institut f u€ r Reine und Angewandte Chemie, Carl von Ossietzky-Universit a€ t Oldenburg, D-26111 Oldenburg, Germany
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 5 October 2010
Received in revised form 5 November 2010
Accepted 8 November 2010
Available online 13 November 2010
a
-Acetyl-(S)-BINOL was prepared by ortho-lithiation and subsequent acetylation of acetal-protected (S)-
BINOL. The -hydroxyketone moiety of this compound is herein a structural mimic for a -diketonate and
forms six-membered chelates with transition metal ions. The second hydroxy-function was submitted to
esterification with several carboxylic acids bearing another donor function, thus, new tridentate chiral
b
b
ligands were obtained. Out of this library the
most effective for the titanium-mediated addition of Et
alcohol with up to 93% ee, which is better than with using (S)-BINOL itself. Besides a solvent dependency
use of MeCN is optimal), the proper choice of the counter-ion is crucial: anion exchange of bromide by
L-proline-
a-acetyl-(S)-BINOL-ester was identified to be
2
Zn to PhCHO yielding the respective secondary
Keywords:
Homogeneous catalysis
Chiral ligands
BINOL derivatives
Asymmetric catalysis
Titanium
(
trifluoroacetate gave a significant increase of enantioselectivity.
Ó 2010 Elsevier Ltd. All rights reserved.
Amino acid derivatives
1
. Introduction
Me
Me
O
O
Transition metal
b
-diketonato complexes are an important class
1
*
of compounds in homogeneous catalysis. However, chiral cogeners
were extraordinarily seldom reported, although they might be of
great interest for asymmetric catalysis. The reason for rare reports
on such chiral ligands might be, that stereogenic elements can only
be implemented at the periphery of the planar six-membered
chelates, making effective stereoinduction close to the catalytically
MLn
OH
D
O
2
D
*
*
1
2
Me
Me
active metal center difficult. We envisioned the
a-carbonyl phe-
nolate motif to be a reasonable structural mimic for
b
-diketonate
O
O
ligands. With an additional donor function D another chelate ring
could form and such a ligand 1 would become tridentate and ca-
pable of coordination to one face in an octahedral or tetrahedral
metal complex 2 (Scheme 1). While the initial stereogenic element
is the chiral axis, this second chelate ring would transfer the ster-
eoinformation from the periphery of the acylphenol 1 to the metal
OH
O
OH
OH
RD
+
HO2C-RD
O
4
1
3
fragment ML
center. With additional coordination sites L
n
, thus, the metal center itself is becoming a stereo-
, the stereogenic metal
Scheme 1. A library of modular
functions D as mimetics of chiral b-diketonato complexes 2 and their synthesis from
a
-acetyl-BINOL derivatives 1 with additional donor
n
center might be able to catalyze suitable CeC bond forming re-
(S)-a-acetyl-BINOL (3) and carboxylic acids 4.
actions in an asymmetric fashion.
the 3-acetyl group are a perfect mimic of a
b
-diketone, as already
0
0
We considered 3-acetyl-2,2 -dihydroxy-1,1 -binaphthyl (3) to be
a suitable scaffold for such tripodal ligands 1, since it combines all
three key features of our new ligand concept: first, the 2-OH and
0
indicated by intramolecular H-bonding. Secondly, the other 2 -OH
group is suitable for esterification with various carboxylic acids 4,
which carry the additional donor function D. Third, the chiral axis
directs the chelating group D above the planar b-hydroxycarbonyl
moiety of this scaffold, thus, providing the prerequisite for facial
coordination to an octahedral or tetrahedral metal center. Since the
*
Corresponding author. Tel.: þ49 441 798 4744; fax: þ49 441 798 3873; e-mail
address: jens.christoffers@uni-oldenburg.de (J. Christoffers).
0
040-4020/$ e see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2010.11.037

R. von R o€ nn, J. Christoffers / Tetrahedron 67 (2011) 334e338
335
3
0
BINOL moiety is a leading structure in asymmetric catalysis, it is
not surprising that tridentate BINOL derivatives have been suc-
H-bonding to the 3-acetyl group. The phenolic 2 -OH appears at
5 ppm. The signal of the acidic proton of compound 1a (and later on
in all other examples 1be1w) shows up at 12 ppm, again clearly
indicating H-bonding to the adjacent carbonyl group. Table 1 lists
carboxylic acids 4 as well as yields of corresponding esters 1. Sev-
eral benzoic acid derivatives (4be4h, entries 2e8) as well as
picolinic (4i, entry 9) and nicotinic acids (4j, entry 10) were applied.
4
cessfully prepared and applied before. However, respective com-
pounds with a
b-diketone mimicking motif have never been
reported. For this reason, we wish to report herein on the synthesis
of ligands 1 with a different range of donor groups D. We moreover
report on the application of these ligands in a well investigated
5
model reaction: the titanium catalyzed nucleophilic addition of
Moreover, derivatives of
and -valine (4m, entry 13) were submitted to esterification. In
these and some other cases the donor function D of residues R
L- and D-proline (4ke4l, entries 11 and 12)
Et
2
Zn to benzaldehyde. This process can be realized with BINOL
L
6
D
itself with high yields and selectivities.
needed protection in order to perform the esterification step. Other
PG
carboxylic acids with protected residues R were compounds 4c,
2
. Results and discussion
4d, 4f, and 4g, which were debenzylated subsequently to the es-
terification step. Table 2 lists deprotection conditions and yields.
For anthranilic acid 4e and valine 4m the N-Boc protective group
was used, whose cleavage was unproblematic when performed
For the synthesis of ligand library 1 we envisioned introduction
of the acetyl group after ortho-metalation. For this purpose, the
ethoxyethyl (EE) protective group seemed to be a suitable acetal
function for directing the metalation.7 Twofold EE-protection of
with TFA (entries 3 and 10). Actually, we used N-Boc-L-proline in-
stead of 4k in initial experiments. It however turned out that Boc-
deprotection with TFA did not give the corresponding ester 1t. For
unknown reasons, decomposition under formation of compound 7
occurred. Therefore, Cbz was chosen as the protective group for
(
9
S)-BINOL (5) proceeded as reported earlier by others (Scheme 2,
8% yield).8 ortho-Deprotonation of bisacetal
6 underwent
smoothly with a small excess of n-BuLi, however, conversion with
different acetylating reagents turned out to be very tedious. For
example, methyl acetate gave only traces of product 7, although we
10
proline. The Cbz-group was then cleaved with HBr and the
hydrobromides 1s and 1u (entries 6 and 8) were formed. In sub-
sequent studies a significant anion dependence of enantiose-
lectivities was observed (vide infra). For this reason, the bromide
was exchanged by trifluoroacetate (ligands 1t and 1v, entries 7 and
9
had good experience with it in another project. The application of
AcCl, AcNMe
ther gave significant amounts of compound 7. Finally, the applica-
tion of excess Ac O followed by acidic workup in order to cleave the
acetal protective groups furnished -acetyl-BINOL 7 as a yellow
2
, AcCN or MeCHO (with subsequent oxidation) nei-
2
9
). This anion change was achieved by evaporating the pyrrolidi-
nium bromide with TFA. Conversion was monitored by ESI-MS
negative mode); it was complete when no more bromide was
a
solid. The esterification as diversifying synthetic step was per-
formed with carboxylic acids 4 and DCC as coupling reagent in the
presence of catalytic amounts of DMAP. This esterification was first
(
detectable.
2
of all explored with the conversion of PhCO H (4a). To our delight, it
Table 1
proceeded completely regioselective, as it is indicated by the
chemical shifts of OH groups in the NMR spectra: compound 7 has
the signal of the 2-OH-proton at 12 ppm, because it is involved in
Esterification of acetyl-BINOL 7 with carboxylic acids 4. Compounds 1ce1g and
1ke1m were subsequently deprotected (see Table 2)
Entry
RCO
PhCO
2-MeOC
2
H
Product
Yield (%)
1
2
3
4
5
6
7
8
9
2
H 4a
1a
1b
1c
1d
1e
1f
1g
1h
1i
74
53
61
51
41
49
68
64
65
64
83
49
64
6 4 2
H CO H 4b
2-BnOC
3-BnOC
6
H
H
4
CO
CO
2
H 4c
H 4d
OH
OH
(a)
OEE
OEE
6
4
2
2-BocHNC H CO H 4e
6
4
2
2-BnO
3-BnO
2
CC
CC
6
H
H
4
CO
CO
2
H 4f
H 4g
2
6
4
2
2 6 4 2
2-Ph PC H CO H 4h
2-Pyridyl-CO
3-Pyridyl-CO
(S)-N-Cbz-proline 4k
(R)-N-Cbz-proline 4l
(S)-N-Boc-valine 4m
5
6 (98%)
2
H 4i
H 4j
10
11
12
2
1j
1k
1l
(b)
13
1m
In order to establish the feasibility of our new ligand library, we
Me
Me
O
adopted a procedure for a titanium-mediated asymmetric addition
6
of Et
2
Zn to benzaldehyde as reported by Mori and Nakai, who
O
converted PhCHO with Et
2
Zn in the presence of 1.2 equiv Ti(Oi-Pr)
4
OH
O
(c)
OH
OH
and 0.1 equiv (S)-BINOL and achieved 85% ee of (S)-1-phenyl-1-
propanol (Scheme 3). First of all, we used (S)-BINOL (5) itself in
order to check our procedure and to compare it with Mori’s results.
With this experiment, we furthermore established a reference for
the absolute configuration of the product. Conversion as well as
enantiopurity of the product was determined by GLC on a chiral
phase after quenching a sample of the reaction mixture with
R
O
1
7 (39%)
PG
D
R = R
R = R
(
d)
aqueous NH
4
Cl. In order to compare reaction rates with different
ꢀ
ligands, we stopped every batch after 1 h stirring at 0 C and listed
the respective conversion in the Tables 3e5. Quantitative conver-
sions could of course be achieved in all cases when running the
reactions over night. The control experiment with (S)-BINOL (5)
resulted in 78% conversion and 81% ee (Table 3, entry 1). Next we
checked the effect of acetyl-BINOL 7, which gave lower ee than
BINOL (entry 2). Furthermore, benzoic ester 1a without a third
Scheme 2. Synthesis of library of modular
tional donor functions D. Reagents and conditions: (a) 4 equiv EVE, 0.1 equiv PPTS,
a-acetyl-BINOL derivatives 1 with addi-
ꢀ
ꢀ
ꢀ
ꢀ
CH
ꢀ
2 2
5 min, 23 C, 15 min; 3. HCleH O, 23 C, 30 min; (c) 1 equiv RCO
2
Cl
2
, 23 C, 16 h; (b) 1. 1.2 equiv n-BuLi, THF, 0 C, 15 min; 2. 10 equiv Ac
2
O, 0 C,
H 4, 1.2 equiv DCC,
, 60 C, 16 h; for residues R (R or R ) and yields see Table 1;
d) for deprotection details and conditions see Table 2; EVE¼ethylvinylether,
PPTS¼pyridinium para-toluenesulfonate, DCC¼dicyclohexylcarbodiimide, DMAP¼4-
dimethylamino)pyridine, EE¼1-ethoxyethyl.
1
0
(
ꢀ
D
PG
2 2
.1 equiv DMAP, CH Cl
(

336
R. von R o€ nn, J. Christoffers / Tetrahedron 67 (2011) 334e338
Table 2
Deprotection and anion exchange
Entry
Educt
RD
Deprotection conditions
Product
Yield (%)
ꢀ
ꢀ
1
2
3
4
5
6
7
8
9
1c
1d
1e
1f
1g
1k
1s
1l
1u
1m
2-C
3-C
2-C
2-C
3-C
6
6
6
6
6
H
H
H
H
H
4
4
4
4
4
OH
OH
NH
1 bar H
1 bar H
TFA, CH
1 bar H
1 bar H
HBr/AcOH, 23 C, 45 min
TFA, 23 C, 12 h
HBr/AcOH, 23 C, 45 min
TFA, 23 C, 12 h
TFA, CH
2
, cat. Pd/C, EA, 23 C, 4 h
1n
1o
1p
1q
1r
1s
1t
1u
1v
1w
58
81
63
86
73
88
89
79
85
85
2
, cat. Pd/C, EA, 23 C, 28 h
ꢀ
2
2
Cl
2
, 23 C, 20 h
ꢀ
ꢀ
CO
CO
2
H
H
2
, cat. Pd/C, EA, 23 C, 3 h
2
2
, cat. Pd/C, EA, 23 C, 6 h
ꢀ
(S)-2-Pyrrolidinium bromide
(S)-2-Pyrrolidinium trifluoroacetate
(R)-2-Pyrrolidinium bromide
(R)-2-Pyrrolidinium trifluoroacetate
(S)-i-PrCHNH
ꢀ
ꢀ
ꢀ
ꢀ
10
2
Cl
2 2
, 23 C, 20 h
donor function RD gave racemic product (entry 3). Application of
D
1
.2 eq. Ti(OiPr)4
OH
ligand with an ortho-donor function R ¼OMe (1b, entry 4), PPh
2
PhCHO
+
xs. Et2Zn
(1h, entry 5), CO
2
H (1q, entry 11) as well as 2-pyridyl (1i) gave
Me
cat. ligands
Ph
D
moderate enantioselectivities of 43e65% ee. With ortho-R ¼OH
D
(
1n, entry 8), and NH
2
(1p, entry 10) and meta-R ¼CO
2
H (1r, entry
Scheme 3. Screening reaction; for conditions see Tables 3e5.
1
2), OH (1o, entry 9) and 3-pyridyl (1j, entry 7) low (10e23% ee) or
even zero enantioselectivities were achieved. In contrast and to our
delight, proline and valine esters 1s (entry 13) and 1w (entry 15)
gave 75% ee and 69% ee, respectively. We had used the proline-
derivative 1s as the hydrobromide-salt, which was in contrast to
our initial plans to use and deprotect an N-Boc group. Since we
were assuming a significant counter-ion effect, we have prepared
the trifluoroacetate 1t by anion exchange from 1s. And indeed, the
selectivity achieved with this salt 1t (85% ee) is higher than we
observed with (S)-BINOL. It is noteworthy to mention that the
mode of coordination must now be significantly different from that
of BINOL. We suggest tridentate coordination as already indicated
in structure 2 (Scheme 1), but this has been not proven so far.
As reported already by others, the solvents can have a significant
impact on the selectivity achieved in the reaction shown in Scheme
Table 3
First screening. Conditions: 1 equiv PhCHO, 3 equiv Et
2
Zn, 1.2 equiv Ti(Oi-Pr)
C
4
,
ꢀ
ꢀ
0.1 equiv ligand 1, toluene, 30 min at ꢁ78 C, then 1 h at 0
Entry
Ligand
RD
Conv. (%)
eea (%)
1
2
3
4
5
6
7
8
9
5
7
1a
1b
1h
1i
d
78
75
65
68
79
90
56
48
96
35
70
80
41
66
90
81
60
0
58
44
65
0
23
0
0
43
10
75
84
69
d
Ph
2-C
2-C
2-Pyridyl
3-Pyridyl
2-C
3-C
2-C
2-C
3-C
6
H
H
4
OMe
PPh
6
4
2
1j
1n
1o
1p
1q
1r
1s
1t
1w
H
6 4
H
6 4
H
6 4
H
6 4
H
6 4
OH
OH
NH
10
11
12
13
14
15
2
CO
CO
2
H
H
2 2
3. In particular CH Cl has been reported to have a beneficial in-
11
2
fluence. With THF, a racemate was formed, which can be
(S)-2-Pyrrolidinium bromide
(S)-2-Pyrrolidinium trifluoroacetate
(S)-i-PrCHNH
explained by the good coordinating properties of the solvent in
competition with the ligand. In cyclohexane and CH
2 2
Cl the ligand
2
1t gave lower selectivities compared to results achieved with tol-
a
In all cases with ee>0% the major isomer is (S)-1-phenyl-1-propanol.6
uene (Table 4, entries 5 and 6). However, use of MeCN, which was to
the best of our knowledge never been reported for the Ti-mediated
2
addition of Et Zn to PhCHO, gave again increased optical purity of
Table 4
the product (93% ee, entry 2). Since ligand 1t has two stereogenic
elements, we prepared the diastereoisomer 1v starting from (S)-
BINOL (5) and N-Cbz-(R)-proline (4l, Table 1, entry 12 and Table 2,
entries 8 and 9). This (S,R)-configuration of ligand 1v seems to
represent the mismatch situation, since the selectivity in MeCN is
lower (78% ee) than for the (S,S)-ligand 1t. For comparison, results
achieved with the hydrobromides 1s and 1u in MeCN are also listed
in Table 4.
Second screening. Conditions: 1 equiv PhCHO, 2 equiv Et
2
ꢀ
4
Zn, 1.2 equiv Ti(Oi-Pr) ,
C
ꢀ
0.15 equiv ligand 1, MeCN, 30 min at ꢁ40 C, then 1 h at 0
Entry
Ligand
RD
Conv. (%)
eea (%)
1
2
3
4
5
6
1s
1t
1u
1v
1t
1t
(S)-2-Pyrrolidinium bromide
(S)-2-Pyrrolidinium trifluoroacetate
(R)-2-Pyrrolidinium bromide
(R)-2-Pyrrolidinium trifluoroacetate
(S)-2-Pyrrolidinium trifluoroacetate
(S)-2-Pyrrolidinium trifluoroacetate
36
75
35
64
51
85
93
81
78
b
73
a
c
80
40
Finally, we adopted our optimized conditions from Table 4 with
ligand 1t to other aldehydes. Electron rich para-methoxy-
benzaldehyde (Table 5, entry 1) gave the same enantioselectivity
a
Major isomer is (S)-1-phenyl-1-propanol.
b
c
CH
2 2
Cl as solvent.
Cyclohexane as solvent.
(
93% ee), but reacted significantly slower (only 39% conversion
ꢀ
within 1 h at 0 C). An ortho-methyl group did not significantly
slow down the reaction (70% conversion), but the enantiose-
lectivity decended below 90% (entry 2). A para-nitro-function
seemed not to be compatible with our reaction conditions (entry 3).
Table 5
Other substrates with ligand 1t. Conditions: 1 equiv aldehyde, 2 equiv Et
2
Zn,
C
, 0.15 equiv ligand 1, MeCN, 30 min at ꢁ40 ꢀC, then 1 h at 0 ꢀ
1.2 equiv Ti(Oi-Pr)
4
3
The CF -group lowered both, the reaction rate (56% conversion,
Entry
Aldehyde
4-MeOC
2-MeC
2-O NC
4-F CC
CyCHO
Conv. (%)
eea (%)
entry 4) as well as the enantioselectivity (63% ee). Finally, aliphatic
cyclohexane carbaldehyde gave low conversion and the product
was formed as the racemate (entry 5).
1
2
1
2
3
4
5
6
H
4
CHO
39
70
24
56
40
93
86
0
63
0
1
3
6 4
H CHO
H CHO
6 4
1
4
2
1
5
In summary, we reported on a new concept for chiral tridentate
3
6
1
H
4
CHO
2b
ligands 1 based on
a
-acetyl-BINOL (7). The
b-hydroxyketone moi-
a
ety is herein a structural mimic for a
hydroxy group allows for modular attachment of another co-
ordinating donor group, which transfers the stereogenic axis to the
b
-diketonate. The second
We assume (S)-configuration for all three optically active alcohols, since the
order of enantiomers in GLC on the chiral phase is the same as for (S)-enriched 1-
phenyl-1-propanol.

R. von R o€ nn, J. Christoffers / Tetrahedron 67 (2011) 334e338
337
metal center. Several examples for this ligand type have been
prepared and tested in a model reaction: the titanium-mediated
solution of compound 6 (1.7 g, 3.9 mmol, 1 equiv) in abs THF (ca.
8 ml). The resulting mixture was stirred for 15 min at 0 C and then
ꢀ
formation of 1-phenyl-1-propanol from PhCHO and Et
able to identify two members of our ligand library, the
2
Zn. We were
-proline-
transferred via a cannula into ice-cold Ac
2
O (4.0 g, 39 mmol,
ꢀ
ꢀ
L
a
-
10 equiv). After stirring at 0 C for 15 min and then at 23 C for
further 15 min, the reaction mixture was poured into 5 ml hydro-
acetyl-BINOL-esters (as hydrobromide 1s and TFA-salt 1t, re-
spectively), which gave the same or even better enantioselectivities
as achieved with (S)-BINOL (5) itself. While the proper choice of the
solvent is crucial (MeCN), the most significant feature of our in-
vestigation is a remarkable anion dependency of enantioselectivity:
the hydrobromide 1s gave 85% ee, whereas the trifluoroacetate 1t
reached 93% ee.
ꢁ
1
ꢀ
chloric acid (6 mol l ). After stirring at 23 C for another 30 min,
the mixture was diluted with CH Cl (15 ml). The aqueous layer was
extracted with CH Cl
(2ꢂ5 ml). The combined organic layers were
washed with H
O (2ꢂ10 ml), satd aqueous solution of NaHCO
(2ꢂ10 ml), and dried over MgSO . After filtration, the solvent was
evaporated and the crude mixture purified by chromatography
2
2
2
2
2
3
4
(
SiO
2
, hexane/EA 3:1, R
f
¼0.15). The title compound 7 (499 mg,
ꢀ
3
3
. Experimental section
1.52 mmol, 39%) was isolated as intense yellow solid, mp 227 C.
Alternatively, the product can be purified by recrystallization from
1
.1. General methods
THF/MTBE/hexane (1:3:6). H NMR (CDCl
3
, 500 MHz):
d
¼2.89 (s,
3
H), 4.97 (s, 1H, OH), 7.06 (d, J¼8.4 Hz, 1H, H-8), 7.16e7.19 (m, 1H),
Preparative column chromatography was carried out using
7.23 (ddd, J¼1.3, 7.0, 8.3 Hz, 1H), 7.31 (ddd, J¼1.0, 7.0, 8.0 Hz, 1H),
7.36 (d, J¼9.0 Hz, 1H), 7.38e7.41 (m, 2H), 7.86 (d, J¼8.1 Hz, 1H), 7.92
(d, J¼8.9 Hz, 1H), 7.94e7.97 (m, 1H), 8.60 (s, 1H), 11.97 (s, 1H, OH)
Merck SiO
2
(0.035e0.070 mm, type 60 A) with hexane, ethyl ac-
etate (EA), and tert-butylmethylether (MTBE) as eluents. TLC was
performed on Merck SiO
1
13
13
1
2
F
254 plates on aluminum sheets. H, C,
ppm. C{ H} NMR (CDCl
3
, 125 MHz):
d¼27.02 (CH
3
), 113.87 (C),
19
and F NMR spectra were recorded on a Bruker Avance DRX 500.
Multiplicities of carbon signals were determined with DEPT ex-
periments. MS and HRMS spectra were obtained with a Finnigan
MAT 95 (EI, CI) and a Waters Q-TOF Premier (ESI) spectrometer. IR
spectra were recorded on a Bruker Tensor 27 spectrometer
115.11 (C), 117.72 (CH), 121.23 (C), 123.41 (CH), 124.52 (CH), 124.60
(CH), 124.80 (CH), 126.60 (CH), 127.14 (C), 128.30 (CH), 129.30 (C),
129.97 (CH), 130.26 (CH), 130.63 (CH), 133.43 (C), 134.90 (CH),
137.73 (C), 151.40 (C), 155.65 (C), 204.76 (C) ppm. IR (ATR):
~
n
¼ 3343ðwÞ; 3054 (w), 2365 (w),1736 (w),1619 (s), 1595 (m), 1503
equipped with
a
‘GoldenGate’ diamond-ATR unit. Elemental
(m), 1430 (m), 1380 (m), 1336 (m), 1312 (s), 1201 (s), 1147 (m), 1079
(m), 957 (m), 935 (m), 897 (m), 814 (m), 745 (s), 703 (m) cm
ꢁ
1
analyses were measured with a Euro EA-CHNS from HEKAtech and
optical rotations with a Perkin Elmer polarimeter 343. GLC on
a chiral phase was performed with a Focus/Triplus (Thermo
Electron) with FID on a column Lipodex E (25 mꢂ0.25 mm) with
hydrogen carrier gas (0.4 bar). All starting materials were com-
mercially available.
.
þ
HRMS (CI, iso-butane): found 329.1178 [MþH ], calcd 329.1178 (for
2
0
C
22
17
H O
3
). [
a]
D
ꢁ33.0 (c 1.0, CHCl
3
16 3
). C22H O (328.11).
0
0
0
3.4. (S,S)-2-(3 -Acetyl-2 -hydroxy-1,1 -binaphthyl-2-yl) 1-
benzyl pyrrolidine-1,2-dicarboxylate (1k)
0
0
ꢀ
3
.2. (S)-2,2 -Bis(1-ethoxyethoxy)-1,1 -binaphthyl (6)
DCC (173 mg, 800
ture of N-Cbz- -proline (4k) (181 mg, 700
(8.6 mg, 70 mol, 0.1 equiv) in 2 ml CH Cl
about 5 min, until a white solid precipitated. A solution of com-
pound 7 (230 mg, 700 mol, 1 equiv) in 5 ml CH Cl was added and
m
mol, 1.2 equiv) was added at 0 C to a mix-
L
m
mol, 1 equiv) and DMAP
. The solution was stirred
PPTS (219 mg, 0.871 mmol, 0.1 equiv) and EVE (1.88 g, 26.2 mmol,
equiv) were added to a suspension of (S)-BINOL (2.50 g, 8.70 mmol,
equiv) in 15 ml CH
for 16 h at 23 C. After evaporation of all volatile materials, the crude
m
2
2
3
1
Cl
2 2
. The resulting light brown mixture was stirred
m
2
ꢀ
2
ꢀ
the resulting mixture was stirred for 16 h at 60 C. After filtration,
2
product was purified by flash chromatography (SiO , hexane/EA 5:1,
the organic layer was washed successively with a satd aqueous
R
f
¼0.44) to furnish compound 6 (3.54 g, 8.22 mmol, 94%) as pale yel-
solution of NH
(3ꢂ10 ml), and H
and evaporation of volatile materials the crude mixture was puri-
fied by chromatography (SiO , hexane/MTBE 1:2, R
¼0.21) to yield
the title compound 1k (325 mg, 581 mol, 83%) as an intense yel-
4
Cl (3ꢂ10 ml), satd aqueous solution of NaHCO
3
1
13
1
low oil. The H and the C{ H} NMR spectra showed double signal sets
2
O (3ꢂ10 ml). After drying over MgSO , filtration
4
1
due to three diastereoisomers. H NMR (CDCl
J¼7.0 Hz, 6H), 1.05e1.09 (m,12H),1.19e1.23 (m, 6H), 3.13e3.21 (m, 2H),
.24e3.32 (m, 2H), 3.39e3.52 (m, 4H), 5.11 (q, J¼5.2 Hz, 2H), 5.21 (q,
J¼5.2 Hz, 2H), 7.10e7.25 (m, 2ꢂ4H), 7.32e7.37 (m, 4H), 7.57e7.60 (m,
3
, 500 MHz):
d¼0.96 (t,
2
f
3
m
ꢀ
1
13
1
low solid, mp 78 C. The H and the C{ H} NMR spectra showed
partly doubled signal sets due to E/Z isomers of the amide and
13
1
2
ꢂ2H), 7.87 (d, J¼8.1 Hz, 2ꢂ2H), 7.92 (d, J¼9.0 Hz, 2ꢂ2H) ppm. C{ H}
NMR (CDCl , 125 MHz): ), 15.16 (2ꢂCH ), 20.12 (CH ),
¼15.02 (2ꢂCH
0.18 (CH ), 20.21 (CH ), 20.24 (CH ), 60.97 (CH ), 61.00 (CH ), 61.02
CH ), 61.28 (CH ), 100.38 (CH), 100.53 (CH), 100.77 (CH), 100.85 (CH),
19.26 (CH),119.45 (CH),119.77 (CH) 119.85 (CH),122.16 (C),122.34 (C),
22.43 (C), 122.54 (C), 123.99 (2ꢂCH), 124.05 (2ꢂCH), 125.67 (CH),
25.70 (CH), 125.74 (CH), 125.77 (CH), 126.11 (CH), 126.12 (CH), 126.15
CH),126.18 (CH),127.79 (4ꢂCH),129.10 (2ꢂCH),129.13 (2ꢂCH),129.83
CH),129.93 (CH),129.96 (CH),130.01 (CH),134.07 (C),134.10 (C),134.17
C), 134.23 (C), 152.56 (CeO), 152.61 (CeO), 152.69 (2ꢂCeO) ppm. IR
1
3
d
3
3
3
carbamate moieties. H NMR (CDCl
3
, 500 MHz):
), 3.15e3.23 (m, 2H), 4.09e4.18 (m, 1H),
4.93e5.08 (m, 2H), 6.93e6.96 (m, 1H), 7.18e7.45 (m, 11H),
d
¼1.30e1.71 (m,
2
(
1
1
1
(
(
(
3
3
3
2
2
4H), 2.79 (s, 3H, CH
3
2
2
13
7.81e7.90 (m, 3H), 8.44e8.46 (m, 1H), 11.63e11.65 (m, 1H) ppm. C
1
{ H} NMR (CDCl
(2CH ), 26.90 (2CH
(CH ), 58.63 (CH), 59.16 (CH), 66.82 (CH
3
, 125 MHz):
d
¼22.80 (CH
), 29.89 (CH
), 66.88 (CH
2
2
), 23.63 (CH
), 46.10 (CH
), 116.86 (C),
2
), 25.54
2
2
), 28.90 (CH
3
2
2
), 46.58
2
2
117.08 (C), 120.78 (C), 120.87 (C), 121.39 (CH), 121.89 (CH), 123.39
(C), 123.52 (C), 124.15 (CH), 124.19 (CH), 124.91 (2CH), 125.11 (2CH),
125.54 (2CH), 125.62 (2CH), 126.54 (CH), 126.58 (C), 126.63 (CH),
127.63 (2CH), 127.81 (CH), 127.84 (CH), 127.88 (2CH), 128.20 (CH),
128.27 (CH), 128.36 (2CH), 128.43 (2CH), 129.41 (CH), 129.45 (2CH),
129.50 (CH), 129.97 (2CH), 130.06 (CH), 131.83 (C), 131.88 (C), 133.18
(C),133.81 (2CH),136.56 (C),136.64 (C),137.27 (C),137.42 (C),146.57
~
(ATR):
n
¼ 3059ðwÞ; 2978 (m), 2934 (m),1623 (m),1594 (m),1507 (m),
1
8
381 (m), 1329 (m), 1226 (s), 1120 (s), 1074 (s), 977 (s), 946 (s), 865 (s),
09 (s), 751 (s) cm . MS (ESI, positive mode), m/z (%): 437 (100)
ꢁ
1
þ
þ
20
[
MþLi ], 453 (15) [MþNa ]. [
a]
D
3 30 4
ꢁ11.1 (c 1.0, CHCl ). C28H O
(430.54): calcd C 78.11%, H 7.02%; found C 78.12%, H 7.13%.
(
CeO), 146.85 (CeO), 153.89 (CeO), 154.67 (C]O), 154.74 (C]O),
0
0
~
n
3
.3. (S)-3-Acetyl-2,2 -dihydroxy-1,1 -binaphthyl (7)
170.33 (C]O), 204.57 (C]O) ppm. IR (ATR):
¼ 3508ðwÞ; 2931
(w), 2814 (w), 1763 (m), 1702 (s), 1643 (s), 1607 (w), 1502 (w), 1411
ꢁ
1
n-BuLi (4.7 mmol, 3.0 ml of a 1.6 mol l solution in hexanes,
.2 equiv) was added under an inert atmosphere at 0 C to a stirred
(s),1342 (s),1306 (s),1254 (w),1206 (m),1143 (s),1130 (s),1081 (m),
1038 (w), 1022 (w), 959 (w), 909 (w), 856 (w), 808 (w), 790 (w), 748
ꢀ
1

338
R. von R o€ nn, J. Christoffers / Tetrahedron 67 (2011) 334e338
ꢁ
1
þ
(
m), 697 (m), 647 (w) cm . HRMS (EI, 70 eV): found 559.1995 [M ],
128.38 (CH),130.17 (CH),130.22 (CH),130.46 (CH),131.96 (C),132.79
(C), 135.09 (CH), 136.76 (C), 145.53 (CeO), 154.37 (CeO), 167.23 (C]
2
0
calcd 559.2001 (for C35
(
N 2.48%.
H
29NO
6
). [
a]
D
ꢁ82.7 (c 1.0, THF). C35
H
29NO
6
1
9
1
559.20): calcd. C 75.12%, H 5.22%, N 2.50%; found C 74.86%, H 5.62%,
O), 205.08 (C]O) ppm.
F{ H} NMR (CDCl
¼ 2926ðwÞ; 2714 (w), 1761 (m), 1644
m), 1607 (w), 1577 (w), 1504 (w), 1452 (w), 1432 (w), 1342 (m),
1306 (m), 1202 (s), 1081 (w), 1038 (w), 1022 (w), 958 (w), 940 (w),
3
,
470 MHz):
~
d
¼ꢁ75.5 ppm. IR (ATR):
n
(
0
0
0
3
.5. (S,S)-2-[(3 -Acetyl-2 -hydroxy-1,1 -binaphthyl-2-yl)
ꢁ
1
oxycarbonyl]pyrrolidiniumbromide (1s)
919 (w), 894 (w), 811 (w), 792 (w), 748 (s), 704 (m), 628 (w) cm
.
ꢁ
MS (ESI, positive mode), m/z (%): 426 (100) [MꢁCF
3
COO ], 448 (6)
þ
þ
A solution of HBr in AcOH (590 mg, 2.40 mmol, 33% w/w,
equiv) was added to compound 1k (330 mg, 590 mol, 1 equiv)
under an inert atmosphere. The resulting dark red mixture was
[MꢁCF
3
COOHþNa ], 466 (15) [MꢁCF
3
COOHþK ]. MS (ESI, nega-
ꢁ
ꢁ
4
m
tive mode), m/z (%): 69 (35) [CF
3
], 113 (100) [CF
3
COO ]. HRMS (EI,
ꢁ
70 eV): found 426.1694 [MꢁCF
3
COO ], calcd 426.1700 (for
2
0
stirred until TLC showed complete conversion (ca. 30e45 min). Abs
C
27
H
24NO
4
). [
a
]
D
ꢁ140.7 (c 1.5, CHCl
3 24 3 6
). C29H F NO (539.16).
Et
cipitated. The supernatant was removed via syringe. After repeti-
tion with another 1 ml of abs. Et O, the resulting crude product was
washed with n-hexane (3ꢂ1 ml) and dried under reduced pressure.
The title compound 1s (253 mg, 500 mol, 85%) was isolated as
NMR (DMSO-d 500 MHz):
2
O (1 ml) was added under vigorous stirring and a solid pre-
Acknowledgements
2
We are grateful to Anike N o€ rder for initial experiments and to
Katrin Elberfeld for supporting us in the laboratory.
m
ꢀ
1
brown solid, mp 129 C.
H
6
,
d
¼0.87e0.90 (m, 1H), 1.27e1.30 (m, 1H), 1.51e1.63 (m, 2H),
References and notes
2
1
8
.30e2.80 (m, 2H), 2.93 (s, 3H), 4.24e4.15 (m, 1H), 6.80e6.90 (m,
H), 7.31 (d, J¼7.1 Hz, 1H), 7.44e7.54 (m, 3H), 7.56e7.65 (m, 2H),
.09e8.25 (m, 3H), 9.04 (s, 1H), 9.5e10.2 (br s, 2H), 11.79 (s, 1H, OH)
1. Review: (a) Mehrotra, R. C. Pure Appl. Chem. 1988, 60, 1349e1356; (b) Chris-
toffers, J.; Frey, H. Chim. Oggi/Chem. Today Suppl. 2008, 26, 26e28.
2
. (a) Bocknack, B. M.; Wang, L.-C.; Hughes, F. W.; Krische, M. J. Tetrahedron 2005,
13
1
ppm. C{ H} NMR (CDCl
1.79 (CH ), 52.08 (CH ), 62.55 (CH), 116.18 (C), 121.69 (CH), 123.72
C), 123.91 (CH), 125.20 (CH), 125.81 (CH), 126.47 (CH), 126.96 (C),
27.54 (CH), 128.96 (CH), 129.19 (CH), 129.66 (CH), 131.32 (CH),
32.94 (C), 132.97 (C), 133.34 (CH), 137.31 (C), 139.47 (C), 145.99
CeO), 154.84 (CeO), 167.64 (C]O), 205.72 (C]O) ppm. IR (ATR):
3
, 125 MHz):
d
¼25.89 (CH
2 3
), 28.44 (CH ),
61, 6266e6275; (b) Albrecht, M.; Dehn, S.; Raabe, G.; Fr o€ hlich, R. Chem. Com-
mun. 2005, 5690e5692; (c) Albrecht, M.; Dehn, S.; Schmid, S.; De Groot, M.
Synthesis 2007, 155e158; (d) Albrecht, M.; Schmid, S.; Dehn, S.; Wickleder, C.;
Zhang, S.; Bassett, A. P.; Pikramenou, Z.; Fr o€ hlich, R. New J. Chem. 2007, 31,
3
(
1
1
2
2
1755e1762.
3. Reviews: (a) Chen, Y.; Yeka, S.; Yudin, A. K. Chem. Rev. 2003, 103, 3155e3211; (b)
Au-Yeung, T. T.-L.; Chan, S.-S.; Chan, A. S. C. Adv. Synth. Catal. 2003, 345,
(
537e555; (c) Brunel, J. M. Chem. Rev. 2005, 105, 857e897.
~
n
¼ 2926ðwÞ; 2713 (w), 1760 (m) 1643 (m), 1606 (w), 1575 (w),
4
. (a) Carreira, E. M.; Singer, R. A.; Lee, W. J. Am. Chem. Soc. 1994, 116, 8837e8838;
(b) Saha, S.; Moorthy, J. N. Tetrahedron Lett. 2010, 51, 912e916; (c) Review:
Frantz, D. E.; F €a ssler, R.; Tomooka, C. S.; Carreira, E. M. Acc. Chem. Res. 2000, 33,
1
1
503 (w), 1431 (w), 1341 (m), 1305 (m), 1205 (s), 1080 (w), 1038 (w),
021 (w), 958 (w), 940 (w), 894 (w), 811 (w), 790 (w), 747 (s), 704
373e381.
ꢁ
1
ꢁ
(
m), 627 (w) cm . HRMS (EI, 70 eV): found 426.1681 [MꢁBr ],
5. (a) Shen, X.; Guo, H.; Ding, K. Tetrahedron: Asymmetry 2000, 11, 4321e4327; (b)
Nakamura, Y.; Takeuchi, S.; Okumura, K.; Ohgo, Y.; Curran, D. P. Tetrahedron
2
0
calcd 426.1700 (for
C
27
H24NO
4
).
[
a]
D
ꢁ100.1 (c 1, CHCl
3
).
2
(
2
002, 58, 3963e3969; (c) Harada, T.; Kanda, K. Org. Lett. 2006, 8, 3817e3819;
d) Ma, L.; Jin, R.-Z.; L u€ , G.-H.; Bian, Z.; Ding, M.-X.; Gao, L.-X. Synthesis 2007,
461e2470; (e) Abreu, A. R.; Pereira, M. M.; Bayon, J. C. Tetrahedron 2010, 66,
C
27
H
24BrNO
4
(505.09).
0
0
0
3
.6. (S,S)-2-[(3 -Acetyl-2 -hydroxy-1,1 -binaphthyl-2-yl)
743e749; (f) Review: Walsh, P. J. Acc. Chem. Res. 2003, 36, 739e749.
6. Mori, M.; Nakai, T. Tetrahedron Lett. 1997, 38, 6233e6236.
oxycarbonyl]pyrrolidiniumtrifluoroacetate (1t)
7. Review: Whisler, M. C.; MacNeil, S.; Snieckus, V.; Beak, P. Angew. Chem. 2004,
1
16, 2256e2276; Angew. Chem., Int. Ed. 2004, 43, 2206e2225.
Compound 1s (90 mg, 18
TFA at 23 C for 12 h. After evaporation of all volatile materials, title
m
mol) was stirred with excess (2.5 ml)
8. Buisman, G. J. H.; van der Veen, L. A.; Klootwijk, A.; de Lange, W. G. J.; Kamer, P.
C. J.; van Leeuwen, P. W. N. M.; Vogt, D. Organometallics 1997, 16, 2929e2939.
. W u€ rdemann, M.; Christoffers, J. Org. Biomol. Chem. 2010, 8, 1894e1898.
0. Ben-Ishai, D.; Berger, A. J. Org. Chem. 1952, 17, 1564e1570.
11. (a) Zhang, F.-Y.; Yip, C.-W.; Cao, R.; Chan, A. S. C. Tetrahedron: Asymmetry 1997, 8,
585e589; (b) Balsells, J.; Davis, T. J.; Carroll, P.; Walsh, P. J. J. Am. Chem. Soc.
ꢀ
9
1
compound 1t (94 mg, 0.17 mmol, 96%) was obtained as light brown
ꢀ
1
solid, mp 97 C. H NMR (DMSO-d
H), 1.29e1.31 (m, 1H), 1.51e1.63 (m, 2H), 2.93 (s, 3H), 2.99e3.07
m, 2H), 4.34e4.38 (m, 1H), 6.89e6.93 (m, 1H), 7.20 (d, J¼7.2 Hz,
H), 7.44e7.54 (m, 3H), 7.56e7.65 (m, 2H), 8.09e8.25 (m, 3H), 9.04
6
, 500 MHz):
d
¼0.86e0.88 (m,
1
(
1
(
1
5
(
2003, 124, 10336e10348.
1
2. (a) Allred, E. A.; Sonnenberg, J.; Winstein, S. J. Org. Chem. 1960, 25, 26e29; (b)
Mao, J.; Wan, B.; Wang, R.; Wu, F.; Lu, S. J. Org. Chem. 2004, 69, 9123e9127.
13. Budhram, R. S.; Palaniswamy, V. A.; Eisenbraun, E. J. J. Org. Chem. 1986, 51,
13
1
s, 1H), 9.5e10.2 (br s, 2H), 11.77 (s, 1H) ppm. C{ H} NMR (CDCl
25 MHz): ), 28.34 (CH ), 30.87 (CH ), 47.10 (CH
¼23.88 (CH
9.83 (CH), 115.68 (C), 120.75 (C), 121.28 (CH), 123.53 (C), 124.45
CH), 124.58 (CH), 125.86 (CH), 126.16 (CH), 126.45 (C), 126.93 (CH),
3
,
1
402e1406.
4. Xu, J.; Wei, T.; Zhang, Q. J. Org. Chem. 2004, 69, 6860e6866.
5. (a) Hatano, M.; Miyamoto, T.; Ishihara, K. J. Org. Chem. 2006, 71, 6474e6484; (b)
Hatano, M.; Miyamoto, T.; Ishihara, K. Adv. Synth. Catal. 2005, 347, 1561e1568.
d
2
3
2
2
),
1
1