Copper-catalyzed asymmetric addition of Et2Zn to 2-cyclohexen-1-one and 2-carbamoyloxy-2-cyclohexen-1-one with phosphoramidite, phosphite, and bidentate phosphite-oxazoline ligands

Article abstract of DOI:10.1016/j.tetasy.2009.03.017

New biphenol-backboned phosphite-oxazoline bidentate ligands were synthesized and applied in the copper-catalyzed asymmetric conjugate additions on 2-cyclohexen-1-one with Et₂Zn. In these reactions, the non-chiral oxazoline unit has demonstrated significant impact on the enantioselectivity. 2-Carbamoyloxy-2-cyclohexen-1-one is a new α-oxygenated cyclic enone substrate and was synthesized and applied to the aforementioned addition with certain phosphoramidite, phosphite, and the new bidentate ligands. Good ee has been obtained on this substrate.

Full text of DOI:10.1016/j.tetasy.2009.03.017

Tetrahedron: Asymmetry 20 (2009) 1144–1149
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Tetrahedron: Asymmetry
journal homepage: www.elsevier.com/locate/tetasy
Copper-catalyzed asymmetric addition of Et2Zn to 2-cyclohexen-1-one
and 2-carbamoyloxy-2-cyclohexen-1-one with phosphoramidite,
phosphite, and bidentate phosphite–oxazoline ligands
b
b,
Yue-Lei Chen a, , Roland Fröhlich , Dieter Hoppe
*
*
a Center for Drug Design, Academic Health Center, University of Minnesota, 8-125 Weaver Densford Hall, 308 Harvard St. SE, Minneapolis, MN 55455, USA
b Organisch-Chemisches Institut, Westfälische Wilhelms-Universität Münster, Corrensstraße 40, 48149 Münster, Germany
a r t i c l e i n f o
a b s t r a c t
Article history:
New biphenol-backboned phosphite–oxazoline bidentate ligands were synthesized and applied in the
copper-catalyzed asymmetric conjugate additions on 2-cyclohexen-1-one with Et2Zn. In these reactions,
the non-chiral oxazoline unit has demonstrated significant impact on the enantioselectivity. 2-Carba-
Received 16 February 2009
Accepted 10 March 2009
Available online 4 May 2009
moyloxy-2-cyclohexen-1-one is a new
a-oxygenated cyclic enone substrate and was synthesized and
applied to the aforementioned addition with certain phosphoramidite, phosphite, and the new bidentate
ligands. Good ee has been obtained on this substrate.
Ó 2009 Elsevier Ltd. All rights reserved.
1. Introduction
Also, we have developed 2-oxygenated 2-cyclohexen-1-one as a
new
a-oxygenated cyclic enone substrate for the aforementioned
With the contribution from many research groups,1 copper-cat-
alyzed asymmetric conjugate addition (ACA) of organozinc reagent
to cyclic enone has become a well-established model reaction
(Scheme 1). With phosphoramidite ligand (S,R,R)-2 discovered by
Feringa et al.,1h,1i excellent ee (>98%) has been achieved. However,
diversity of both ligands and substrates for this reaction is rela-
tively low. We tried to develop this reaction from both aspects. Re-
cently, we have reported that biphenol-backboned tropos-
phosphite ligands (e.g., compound 3) induce good ee for this model
reaction.2 Based on these phosphite ligands, we have synthesized
some bidentate ligands by adding a non-chiral oxazoline module.
The new phosphite–oxazoline bidentate ligands were applied to
the model ACA shown in Scheme 1. The non-chiral oxazoline mod-
ule has displayed significant impact on the asymmetric induction.
reaction shown in Scheme 1, copper-catalyzed ACA of Et2Zn was
realized for this new substrate and a good ee was obtained. Herein
we disclose those preliminary results.
2. Results and discussion
Bidentate ligands are highly useful in metal-catalyzed asymmet-
ric synthesis.3 In particular, phosphite–oxazoline ligands have been
proven to be useful in copper-catalyzed asymmetric conjugate
additions with Et2Zn, and they sometimes offer better ee than their
mono-phosphite counterparts.1a,b,4 Two reasons might account for
this: (a) the bidentate ligand may offer a better chiral environment
by adding more chelating points; or (b) phosphite–oxazoline ligand
may fall into the category of hemilabile hybrid ligand,5 which
O
P
Ph
N
Et
Ts
Et
Ts
O
O
O
O
O
N
O
O
N
P
a
O
Ph
Et
1
t-Bu
t-Bu
2
(S,R,R)-
3
Scheme 1. Reagents and conditions: (a) Et2Zn, toluene, cat. Cu(OTf)2, ligand, ꢀ40 °C, 16 h.
* Corresponding authors. Fax: +49 251 8339772.
E-mail addresses: chenx506@umn.edu (Y.-L. Chen), dhoppe@uni-muenster.de
(D. Hoppe).
0957-4166/$ - see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2009.03.017

Y.-L. Chen et al. / Tetrahedron: Asymmetry 20 (2009) 1144–1149
1145
behaves differently compared to common bidentate ligands. Hence,
it is reasonable to develop some new phosphite–oxazoline biden-
tate ligands based on our biphenol-derived phosphite ligands.
Following this idea, we chose the non-chiral alcohol 4 to con-
struct the oxazoline module. Biphenols 5a–d were condensed with
PCl3 and were then coupled with the oxazoline module 46 to yield
the target ligands 6a–d (Scheme 2). Compounds 6a–d are quite po-
lar and basic. The mobile phase for their separation by silica gel
chromatography requires Me2NEt as an additive for a complete
washing-off.
lowest ee among all examples. A more interesting fact is the fol-
lowing: the biphenol module on ligands 6a–d originated from
homologous amino alcohols; however, after being connected with
a non-chiral oxazoline module, ligands 6b and 6c yielded reversed
enantioselectivity compared to ligands 3, 6a, and 6d. All the results
clearly indicated the great impact of the non-chiral oxazoline mod-
ule on the asymmetric induction.
To extend the scope for the model reaction shown in Scheme 1,
we have synthesized 2-carbamoyloxy-2-cyclohexen-1-one 7 as a
new substrate (Scheme 3). To the best of our knowledge, this is
D
N
O
R1
S
R1
S
N
O
R2
R2
R2
O
O
R1
S
HO
R1
R2
O
P
OH
R2
R2
N
N
HO
O
O
B
R3
R3
4
N
O
O
N
O2
O2
R2
R3
R3
C
S
O2
O2
R2
A
a
R
R
R
R
5a,
6a, R=H, R1=Et, R2=R3=Me, 71%;
5b,
5c,
6b, R=R3=t-Bu, R1=s-Bu, R2=H, 75%;
6c, R=H, R1=2-methylpropan-1-yl, R2=R3=Me, 60%;
1
2
3
5d
6d
, R=t-Bu, R =Et, R =H, R =Et, 40%.
,
Scheme 2. Reagents and conditions: (a) PCl3, TEA, toluene, 90 °C, 16 h, then compound 4, 90 °C, overnight. The designations of R–R3 for the substituents and A–D for the rings
are used in the Experimental for assigning the NMR data.
The single crystal of compound 6c was obtained from diethyl
ether and n-pentane, analyzed with X-ray and is illustrated in Fig-
ure 1.7
the first a-oxygenated cyclic enone that undergoes copper-cata-
lyzed ACA with organozinc reagents. Compound 7 was readily pre-
pared by condensing 1,2-cyclohexandione and CbCl. Moderate yield
was obtained probably due to the decomposition of the unstable
starting material at room temperature or with the strong base. With
Et2Zn, compound 7 undergoes copper-catalyzed conjugate addition
to yield compound 8. Although this reaction is significantly acceler-
ated by phosphoramidite (S,R,R)-2,1a it is still slower than the model
ACA shown in Scheme 1, and hence has to be performed at ꢀ25 °C
for a good yield. With phosphoramidite ligand (S,R,R)-2, 81% yield
was observed after an overnight reaction. Unfortunately, we were
not able to resolve compound 8 completely by chiral GC or chiral
HPLC, probably due to its high polarity. However, we found that
the ACA intermediate of compound 7 and Et2Zn, which should be
a pair of enantiomers, can be quenched by TBDMSOTf in situ to
yield compound 9.8 Compound 9 was readily resolved by chiral
HPLC, and it brought us the chiral information of the ACA step.
It is worth mentioning that employing a stable OCb protection
is advantageous compared to simple ester protection or even other
carbamates for the 2-oxygen. A less stable 2-O-protection may par-
tially migrate when the metalated enol is formed as the intermedi-
ate of the ACA. In fact this undesired reaction was observed with 2-
O-CONPh2 protection.9 However, with 2-OCb protection, no migra-
tion was detected.
Figure 1. Crystal structure of compound 6c. Hydrogens are omitted in the image.
New ligands 6a–d were subjected to the model ACA shown in
Scheme 1 and the resulting ees are listed out in Table 1. Compared
to the optimized phosphite ligand 3,2 the new bidentate ligands
Table 1
Ligands applied to the model reaction shown in Scheme 1
As demonstrated in Scheme 3 and Table 2, ligand (S,R,R)-2 pro-
duced an ee of 81% (>98% ee was achieved for the model reaction
shown in Scheme 1 with this ligand) and a moderate yield for
the conversion from compound 7 to 9, while the ligand (S,S,S)-2
produced practically the same ee of 82% (75% ee was achieved
for the model reaction shown in Scheme 1 with (S,S,S)-210) and a
similar yield. This indicated a significant influence of the binaph-
thalene module on the asymmetric induction,11 since the matched
or mismatched bis(1-phenylethyl)amine module on ligands 2 had
little effect on the asymmetric induction. Our phosphite ligand 3
has induced moderate ee (50%) and yield. The newly synthesized
bidentate ligands 6a–d gave no noticeable ee for the conversion
of substrate 7 to compound 9. The fact that ligand 3 failed to in-
Entry
Ligand
Yielda
eeb (%)
1c
2
3
4
5
3
Quant.
Quant.
87%
Quant.
95%
+83
+16
ꢀ37
ꢀ23
+11
6a
6b
6c
6d
a
GC yield.
b
Measured by chiral GC on a Supelco
a-Dex 225, 30 m ꢁ 0.32 mm column;
symbol ‘+’ denotes (R:S), ‘ꢀ’ denotes (S:R).
c
Data in this entry were published before.2
6a–d produced a lower ee. In particular, compound 6d, which
has biphenol modules that are identical to those of ligand 3, gave

1146
Y.-L. Chen et al. / Tetrahedron: Asymmetry 20 (2009) 1144–1149
O
OCb
b
O
Et
O
O
8,
OCb
dr = 1.86
O
a
81%
c
Cb =
N(i-Pr)2
OTBDMS
54%
OCb
7
69%
Et
9, ee = 81%
Scheme 3. Reagents and conditions: (a) NaH, THF, CbCl, rt; (b) ꢀ25 °C overnight, Cu(OTf)2, Et2Zn, ligand (S,R,R)-2, toluene; (c) ꢀ25 °C overnight, Cu(OTf)2, Et2Zn, ligand
(S,R,R)-2, toluene, then TBDMSOTf, rt, 4 h. Compound 9 was resolved by chiral HPLC on a Nucleosil 100-5 Chiral-2 (Macherey-Nagel) column.
duce a good ee as it does for the model reaction shown in Scheme
1, is probably because of its high steric hindrance on the ortho-po-
sition of the biphenol backbone, which exhibits, synergistically
with the bulky 2-OCb substitution on the substrate, negative ef-
fects on the coordination with copper and the asymmetric induc-
tion. This presumption is supported by the early investigations
on ACA with biphenol-backboned ligands from the group of Alexa-
kis.12 For the same reason, the more sterically hindered ligands 6a–
d, gave no noticeable ee for this substrate 7.
distilled from sodium, and THF was distilled from potassium. For
low temperatures reactions, a Julabo FT902 kryostat and an acetone
bath were used. All moisture-sensitive reactions were performed
under Ar (ca. +1.3 bar) in heating-gun (500–600 °C)/vacuum-dried
glassware sealed with a rubber septum. Medium pressure liquid
chromatography (MPLC) was performed on Merck 60 Silica Gel
(40–60 lm, 230–400 mesh ASTM), and monitored by thin layer
chromatography (TLC) on Merck 60 F254 TLC-plates. NMR data
were collected on a Bruker AV 300, an AV 400, an ARX 400, a Varian
Inova 500 or a Unity Plus 600. Spectra from solutions in CDCl3
(dC = 77.0 ppm) are calibrated relative to SiMe4 (dH = 0.00 ppm).
IR data were collected on a Varian 3100 Excalibur Series with Spe-
cac Golden Gate Single Reflection ATR. Mass data were collected on
a Bruker MicroTof (ESI). Optical rotation data were collected on a
Perkin Elmer 341 or 241. Melting point (not corrected) was mea-
sured on a Stuart Scientific SMP3. Elemental analyses were per-
formed on an Elementar-Analysensysteme Vario EL III. GC data
were collected on an Agilent 6890. Non-chiral GC was performed
on a 30 m ꢁ 0.32 mm HP-5 column (GC condition: 1.5 mL ꢁ minꢀ1
H2; starting at 50 °C, 10 °C ꢁ minꢀ1 to 300 °C, 15 min at 300 °C).
HPLC data were collected with a Knauer Smartline PDA detector
2600, a Pump 1000, an Autosampler 3900, and a Manager 5000.
Table 2
Asymmetric induction for the conversion from compound 7 to compound 9
Entry
Ligand
Yielda (%)
eeb (%)
1
2
3
4
5
6
7
(S,R,R)-2
(S,S,S)-2
67
69
63
61
59
60
55
81
82
50
<5
<5
<5
<5
3
6a
6b
6c
6d
a
Isolated yield.
b
Measured by chiral HPLC on a Nucleosil 100-5 Chiral-2 (Macherey-Nagel) col-
umn. Absolute stereochemistry of product 9 was not assigned.
The enantioenriched products 8 and 9, with three contiguous
substituents on the six-membered ring, can serve as potential
building blocks for complex structures.
4.2. 3-Ethylcyclohexanone 1
A mixture of Cu(OTf)2 (2 mg, 0.0055 mmol, 2.5% equiv) and the
ligand (0.0055 mmol, 2.5% equiv) in 1 mL of toluene was stirred at
rt for 1 h. Then 2-cyclohexen-1-one (21 mg in 1 mL toluene,
0.22 mmol) was added dropwise. The mixture was cooled to
ꢀ40 °C, followed by addition of 1 M Et2Zn in hexane (0.27 mL,
0.27 mmol, 1.2 equiv) and was stirred at this temperature for
16 h. 1 M HCOOH solution in MeOH (0.3 mL) was added to quench
the reaction. Internal standard MeOPh (9 mg) was then added. The
mixture was passed through a short pad of silica gel, which was
then washed several times by Et2O. Combined organic phases were
evaporated (not less than 150 mbar/45 °C) and the residue was
purified by MPLC (n-pentane/diethyl ether = 20:1 to 10:1 to 5:1
to 1:1) to yield the product or was directly analyzed by chiral
3. Conclusions
In summary, based on our biphenol-backboned tropos-phos-
phite ligands, by incorporating a non-chiral oxazoline module,
we have prepared four new phosphite–oxazoline bidentate li-
gands. These ligands were applied to the copper-catalyzed ACA
onto 2-cyclohexen-1-one with Et2Zn. Although lower ees were ob-
tained compared to those obtained with their parent phosphite
monodentate ligands and the phosphoramidite ligands discovered
by Feringa et al., the non-chiral oxazoline module has demon-
strated its significant impact on the asymmetric induction. In addi-
tion, we have invented 2-carbamoyloxy-2-cyclohexen-1-one as a
GC. Analyses match the reported data.13 Chiral GC: Supelco
a-
Dex 225, 30 m ꢁ 0.32 mm, 50 °C; t(MeOPh) = 22.0 min, t(2-cyclohexen-
new a-oxygenated substrate for the above-mentioned ACA. Phos-
1-one) = 57.6 min, t(R)-1 = 78.9 min, t(S)-1 = 83.7 min.
phoramidite, phosphite, and the new phosphite–oxazoline biden-
tate ligands were applied with this new substrate. Good ee has
been achieved with phosphoramidite ligands 2 discovered by
Feringa et al. The enantioenriched products 8 and 9 can serve as
potential building blocks for complex structures.
4.3. 2-(4,4-Dimethyl-4,5-dihydrooxazol-2-yl)propan-2-ol 4
2-Hydroxy-2-methylpropanoic acid (3.12 g, 3.0 mmol) and 2-
amino-2-methyl-1-propanol (2.67 g, 3.0 mmol) were suspended
in 400 mL of xylene (mixture of regioisomers) and were refluxed
for 20 h with continuous separation of water. The resulting mix-
ture was directly purified by MPLC (n-pentane/diethyl ether = 5:1
to 2:1 to 1:1 to 1:2) to yield the product as a white solid
(990 mg, 0.63 mmol, 21%). The product can be further purified by
sublimation at 45 °C and 10 mbar to give colorless crystals. mp
4. Experimental
4.1. General
All solvents were dried and purified prior to use: Et2O was dis-
tilled from sodium with benzophenone as indicator, toluene was

Y.-L. Chen et al. / Tetrahedron: Asymmetry 20 (2009) 1144–1149
1147
60–62 °C (crystals from sublimation). Rf = 0.07 (ethyl acetate/
O–CH–NB), 6.13 (s, 1H, O–CH–NB), 3.99–3.86 (m, 2H, O–CH2–CH-
s-BuB), 3.90–3.70 (m, 4H, O–CH2–CH-s-BuB and O–CH2–C(Me)2D),
3.44–3.40 (m, 2H, O–CH2–CH-s-Bu B), 1.96–1.79 (m, 6H, CHR1 and
CH2R1 ), 1.50 (s, 3H, O–C(CH3)2D), 1.49 (s, 3H, HO–C(CH3)2D), 1.26–
1.19 (m, 36H, t-Bu), 1.19–1.17 (m, 6H, CH3D), 1.00–0.92 (m, 12H,
MeR1 ). 13C NMR (100 MHz, CDCl3): d/ppm = 165.94 (O–C@ND),
155.81 (CC), 155.53 (CC), 146.20 (CA), 145.66 (CA), 145.21 (CA),
145.13 (CA), 144.10 (CA), 144.07 (CA), 133.38 (CC), 133.33 (CC),
128.16 (CA), 128.00 (CA), 127.22 (2C, CC), 127.14 (2C, CC), 127.07
(CA), 126.31 (CA), 124.97 (2C, CC), 124.71 (2C, CC), 124.27 (CA),
124.00 (CA), 88.02 (O–CH–NB), 87.05 (O–CH–NB), 78.41 (O–CH2–
C(Me)2D), 74.47 (O–C(CH3)2D), 67.70 (O–CH2–CH-s-BuB), 67.51
(O–CH2–CH-s-BuB), 66.61 (O–CH2–C(Me)2D), 63.80 (O–CH2–CH-s-
BuB), 63.09 (O–CH2–CH-s-BuB), 37.17 (CHR1 ), 36.45 (CHR1 ), 34.10
(t-Bu), 34.06 (t-Bu), 33.64 (t-Bu), 33.45 (t-Bu), 30.41 (4C, t-Bu),
30.38 (4C, t-Bu), 30.03 (4C, t-Bu), 27.01 (CH3D), 26.97 (CH3D),
26.91 (HO–C(CH3)2D), 26.72 (HO–C(CH3)2D), 25.45 (CH2R1 ), 25.21
(CH2R1 ), 14.36 (MeR1 ), 14.27 (MeR1 ), 10.86 (MeR1 ), 10.68 (MeR1 ).
31P NMR (121.5 MHz, CDCl3): d/ppm = 151.2. HRMS (ESI+) calcd
/cmꢀ1, ATR): 3396
~
cyclohexane = 1:2). tR = 5.2 min (HP-5). IR (
m
(br), 2975 (s), 2934 (m), 2895 (m), 1662 (s), 1464 (s), 1119 (s).
1H NMR (400 MHz, CDCl3): d/ppm = 3.95 (s, 2H, O–CH2–C(Me)2–
N), 3.19 (s, 1H, OH), 1.37 (s, 6H, (Me)2C–OH), 1.21 (s, 6H, O–CH2–
C(Me)2–N). 1H NMR matches the reported data.6 13C NMR
(100 MHz, CDCl3): d/ppm = 170.73 (O–C@N), 80.41 (O–CH2–
C(Me)2–N), 68.62 ((Me)2–C–OH), 66.94 (O–CH2–C(Me)2–N), 28.18
(2C, O–CH2–C(Me)2–N), 27.72 (2C, (Me)2C–OH). HRMS (ESI+) calcd
for C8H15NO2H+ = 158.1181, C8H15NO2Na+ = 180.1000, found
[M+H]+ = 158.1180, [M+Na]+ = 180.0999.
4.4. General procedure for the syntheses of ligands 6a–d
One of the diols 5a–d (0.1 mmol, 1.0 equiv) and triethylamine
(0.33 mmol, 3.3 equiv) were mixed in 3 mL of toluene, and this
was followed by addition of PCl3 (1.0 mmol, 1.0 equiv) at rt. The
reaction mixture was then stirred at 90 °C for 16 h, before the
oxazoline module 4 (1.2 mmol, 1.2 equiv) was added. The resulting
mixture was further stirred overnight at 90 °C, and was directly
subjected to MPLC separation (n-pentane/diethyl ether = 10:1 to
5:1 to 2:1 to 1:1 to 1:2 to 1:5, all the eluents contain 5% v/v Me2-
NEt) to yield the product 6a–d.
for
C62H88N3O10PS2H+ = 1130.5727,
C62H88N3O10PS2Na+ =
1152.5546, found [M+H]+ = 1130.5719, [M+Na]+ = 1152.5532.
4.4.3. (2S,20S,4S,40S)-2,20-[6-(2-(4,4-Dimethyl-4,5-dihydrooxazol-
2-yl) propan-2-yloxy)dibenzo-[d,f][1,3,2]dioxaphosphepine-4,8-
diyl]bis[4-isobutyl-3-(mesitylsulfonyl)oxazolidine] 6c
Compound was obtained as a white foam (60%) which can be
recrystallized from diethyl ether and n-petane. Mp 177–180 °C
(diethyl ether and n-pentane). Rf = 0.27 (ethyl acetate/cyclohex-
/cmꢀ1, ATR): 2959
~
m
4.4.1. (2S,20S,4S,40S)-2,20-[6-(2-(4,4-Dimethyl-4,5-dihydrooxazol-
2-yl)propan-2-yloxy)dibenzo-[d,f][1,3,2]dioxaphosphepine-4,8-
diyl]bis[4-ethyl-3-(mesitylsulfonyl)oxazolidine] 6a
Compound was obtained as a white foam, yield: 71%. Rf = 0.15
(ethyl acetate/cyclohexane = 1:2). ½a D20
ꢂ
¼ ꢀ38:2 (c 0.50, CHCl3). IR
ane = 1:2). ½a 2D0
ꢂ
¼ þ30:2 (c 0.50, CHCl3). IR (
~
(
m
/cmꢀ1, ATR): 2971 (s), 2938 (m), 2877 (m), 1666 (m), 1604 (m),
(s), 2936 (m), 2871 (m), 1663 (m), 1604 (m), 1453 (s), 1313 (s),
1154 (s), 971 (s), 888 (s), 729 (s). For the subscripts and super-
scripts used in the following NMR data, see Scheme 2. 1H NMR
(400 MHz, CDCl3): d/ppm = 7.35–7.31 (m, 2H, HA), 7.05–6.93 (m,
4H, HA), 6.49 (s, 2H, HC), 6.38 (s, 2H, HC), 6.27 (s, 1H, O–CH–NB),
6.16 (s, 1H, O–CH–NB), 4.31–4.19 (m, 2H, O–CH2–CH–NB), 4.13–
3.85 (m, 6H, O–CH2–CH–NB and O–CH2–C(Me)2D), 2.46 (s, 6H,
CH3C), 2.41 (s, 6H, CH3C), 1.98 (s, 3H, CH3C), 1.90 (s, 3H, CH3C),
1.78–1.71 (m, 2H, CHR1 ), 1.70–1.60 (m, 4H, CHR1 ), 1.62 (s, 3H, O–
C(CH3)2D), 1.60 (s, 3H, O–C(CH3)2D), 1.28 (s, 6H, CH3D), 0.94–0.88
(m, 12H, MeR1 ). 13C NMR (100 MHz, CDCl3): d/ppm = 166.01 (O–
C@ND), 146.97 (CA), 146.08 (CA), 141.81 (CC), 141.62 (CC), 139.75
(2C, CC), 139.61 (2C, CC), 130.56 (2C, CC), 130.25 (2C, CC), 129.61
(CC), 129.29 (CC), 129.11 (CA), 129.05 (2C, CA), 128.68 (2C, CA),
128.64 (CA), 127.09 (CA), 126.74 (CA), 122.97 (CA), 122.62 (CA),
85.95 (O–CH–NB), 85.86 (O–CH–NB), 79.55 (O–CH2–C(Me)2D),
78.81 (HO–C(CH3)2D), 70.41 (O–CH2–CHNB), 70.14 (O–CH2–CHNB),
66.86 (O–CH2–C(Me)2D), 55.76 (O–CH2–CHNB), 55.20 (O–CH2–
CHNB), 42.93 (CH2R1 ), 42.56 (CH2R1 ), 27.20–26.99 (4C, HO–
C(CH3)2D and O–CH2–C(CH3)2D), 26.67 (CHR1 ), 24.76 (CHR1 ), 22.11
(2C, MeR1 ), 22.01 (4C, CH3C), 20.76 (2C, MeR1 ), 19.86 (CH3C),
19.82(CH3C). 31P NMR (121.5 MHz, CDCl3): d/ppm = 151.8. HRMS
(ESI+) calcd for C52H68N3O10PS2H+ = 990.4162, C52H68N3O10PS2-
Na+ = 1012.3981, found [M+H]+ = 990.4133, [M+Na]+ = 1012.3942.
C52H68N3O10PS2 (990.21): C 63.07, H 6.92, N 4.24. Found: C
63.15, H 7.03, N 4.06.
1454 (s), 1316 (s), 1157 (s), 969 (s), 889 (s), 677 (s). For the sub-
scripts and superscripts used in the following NMR data, see
Scheme 2. 1H NMR (400 MHz, CDCl3): d/ppm = 7.33–7.29 (m, 2H,
HA), 6.99–6.88 (m, 4H, HA), 6.44 (s, 2H, HC), 6.33 (s, 2H, HC), 6.22
(s, 1H, O–CH–NB), 6.13 (s, 1H, O–CH–NB), 4.20–3.91 (m, 8H, HB
D), 2.44 (s, 6H, CH3C), 2.40 (s, 6H, CH3C), 2.02–1.95 (m, 2H,
and
CH2R1 ), 1.95 (s, 3H, CH3C), 1.86 (s, 3H, CH3C), 1.84–1.69 (m, 2H,
CH2R1 ), 1.61 (s, 3H, O–C(CH3)2D), 1.60 (s, 3H, O–C(CH3)2D), 1.28 (s,
6H, CH3D), 0.99–0.92 (m, 6H, CH3R1 ). 13C NMR (100 MHz, CDCl3):
d/ppm = 166.98 (O–C@ND), 147.92 (CA), 146.99 (CA), 142.76 (CC),
142.59 (CC), 140.75 (2C, CC), 140.57 (2C, CC), 131.52 (2C, CC),
131.21(2C, CC), 130.49 (CC), 130.14 (CC), 130.02 (CA), 129.98 (2C,
CA), 129.88 (2C, CA), 129.55 (CA), 128.08 (CA), 128.74 (CA), 124.00
(CA), 123.62 (CA), 87.18 (O–CH–NB), 87.12 (O–CH–NB), 79.83 (O–
CH2–C(Me)2D), 75.83 (O–CH2–C(Me)2D), 70.92 (O–CH2–CHEtB),
70.53 (O–CH2–CHEtB), 67.87 (O–CH2–C(Me)2D), 59.61 (O–CH2–
CHEtB), 59.16 (O–CH2–CHEtB), 27.73 (2C, CH2R1 ), 28.15–28.01 (4C,
O–C(CH3)2D and O–CH2–C(CH3)2D), 23.09 (2C, CH3C), 23.01 (2C,
CH3C), 20.87 (CH3C), 20.82 (CH3C), 11.01 (CH3R1 ), 10.96 (CH3R1 ). 31P
NMR (121.5 MHz, CDCl3): d/ppm = 151.6. HRMS (ESI+) calcd for
C48H60N3O10PS2H+ = 934.3536,
C48H60N3O10PS2Na+ = 956.3355,
found [M+H]+ = 934.3519, [M+Na]+ = 956.3344.
4.4.2. (2S,20S,4S,40S)-2,20-[2,10-Di-tert-butyl-6-(2-(4,4-dimethyl-
4,5-dihydrooxazol-2-yl)propan-2-yloxy)dibenzo[d,f][1,3,2]diox
aphosphepine-4,8-diyl]bis[4-sec-butyl-3-(4-tert-butylphenyl-
sulfonyl)oxazolidine] 6b
4.4.4. (2S,20S,4S,40S)-2,20-[2,10-Di-tert-butyl-6-(2-(4,4-dimethyl-
4,5-dihydrooxazol-2-yl)propan-2-yloxy)dibenzo[d,f][1,3,2]
dioxaphosphepine-4,8-diyl]bis[4-ethyl-3-tosyloxazolidine] 6d
Compound was obtained as a white foam, yield: 40%. Rf = 0.12
Compound was obtained as a white foam, yield: 75%. Rf = 0.41
(ethyl acetate/cyclohexane = 1:2). ½a D20
ꢂ
¼ ꢀ3:4 (c 0.50, CHCl3). IR
~
(
m
/cmꢀ1, ATR): 2964 (s), 2873 (m), 1662 (m), 1595 (m), 1477 (s),
1354 (s), 1169 (s), 1088 (s), 909 (s), 730 (s), 643 (s). For the sub-
scripts and superscripts used in the following NMR data, see
Scheme 2. 1H NMR (400 MHz, CDCl3): d/ppm = 7.68 (d, J = 8.6 Hz,
2H, HC), 7.65 (d, J = 8.6 Hz, 2H, HC), 7.58 (d, J = 2.4 Hz, 1H, HA),
7.41 (d, J = 2.4 Hz, 1H, HA), 7.37 (d, J = 8.6 Hz, 2H, HC), 7.29 (d,
J = 8.6 Hz, 2H, HC), 7.27 (m, 1H, HA), 7.18 (m, 1H, HA), 6.26 (s, 1H,
(ethyl acetate/cyclohexane = 1:2). ½a D20
ꢂ
¼ þ3:3 (c 0.50, CHCl3). IR
~
(
m
/cmꢀ1, ATR): 2965 (s), 2935 (m), 2905 (m), 2872 (m), 1662 (m),
1598 (m), 1463 (s), 1353 (s), 1165 (s), 1124 (s), 1094 (s), 971 (s),
911 (s), 881 (s), 867 (s), 729 (s), 666 (s), 596 (s). For the subscripts
and superscripts used in the following NMR data, see Scheme 2. 1H
NMR (400 MHz, CDCl3): d/ppm = 7.77 (d, J = 8.4 Hz, 2H, HC), 7.70 (d,

1148
Y.-L. Chen et al. / Tetrahedron: Asymmetry 20 (2009) 1144–1149
J = 8.1 Hz, 2H, HC), 7.63 (d, J = 2.5 Hz, 1H, HA), 7.50 (d, J = 2.5 Hz, 1H,
HA), 7.38 (d, J = 2.5 Hz, 1H, HA), 7.31 (d, J = 2.5 Hz, 1H, HA), 7.28 (d,
J = 8.4 Hz, 2H, HC), 7.19 (d, J = 8.1 Hz, 2H, HC), 6.47 (s, 1H, O–CH–
NB), 6.25 (s, 1H, O–CH–NB), 3.99–3.95 (m, 1H, O–CH2–CHEtB),
3.94–3.89 (m, 2H, O–CH2–CHEtB and O–CH2–CHEtB), 3.88–3.86
(m, 2H, O–CH2–C(Me)2D), 3.76–3.60 (m, 3H, O–CH2–CHEtB), 2.42
(s, 3H, CH3C), 2.38 (s, 3H, CH3C), 2.17–2.08 (m, 1H, CH2R1 ), 2.08–
2.01 (m, 1H, CH2R1 ), 1.91–1.83 (m, 1H, CH2R1 ), 1.79–1.69 (m, 1H,
CH2R1 ), 1.62 (s, 3H, HO–C(CH3)2D), 1.61 (s, 3H, HO–C(CH3)2D), 1.37
(s, 9H, t-Bu), 1.34 (s, 9H, t-Bu), 1.27 (s, 3H, CH3D), 1.26 (s, 3H,
CH3D), 1.11 (t, J = 7.4 Hz, 3H, CH3R1 ), 1.07 (t, J = 7.5 Hz, 3H, CH3R1 ).
13C NMR (100 MHz, CDCl3): d/ppm = 167.05 (O–C@ND), 147.08
(CA), 146.83 (CA), 145.99 (CA), 145.26 (CA), 143.74 (CC), 143.45
(CC), 134.98 (CC), 134.85 (CC), 131.76 (CA), 130.42 (CA), 129.71
(2C, CC), 129.42 (2C, CC), 129.13 (2C, CA), 128.19 (2C, CC) 128.05
(2C, CC), 128.02 (CA), 127.50 (CA), 125.09 (CA), 125.03 (CA), 88.92
(O–CH–NB), 87.80 (O–CH–NB), 79.39 O–CH2–C(Me)2D), 75.54 (O–
C(CH3)2D), 70.32 (O–CH2–CHEtD), 70.24 (O–CH2–CHEtB), 67.57 (O–
CH2–C(Me)2D), 61.54 (O–CH2–CHEtB), 60.80 (O–CH2–CHEtB), 34.66
(t-Bu), 34.51 (t-Bu), 31.44 (3 C, t-Bu), 31.36 (3 C, t-Bu), 28.19
(CH2R1 ), 27.96 (CH3D), 27.91 (CH3D), 27.75 (O–C(CH3)2D), 27.69
(O–C(CH3)2D), 27.49 (CH2R1 ), 21.54 (2C, CH3C), 10.85 (CH3R1 ),
10.67 (CH3R1 ). 31P NMR (121.5 MHz, CDCl3): d/ppm = 151.5. HRMS
(ESI+) calcd for C52H68N3O10PS2H+ = 990.4162, C52H68N3O10PS2-
Na+ = 1012.3981, found [M+H]+ = 990.4147, [M+Na]+ = 1012.3956.
Anal. Calcd for C52H68N3O10PS2 (990.21): C, 63.07; H, 6.92; N,
4.24. Found: C, 62.84; H, 6.79; N, 4.04.
added to quench the reaction. The quenched mixture was passed
through a short pad of silica gel, which was then washed several
times by Et2O. Combined organic phases were evaporated and
the residue was purified by MPLC (n-pentane/diethyl ether = 20:1
to 10:1 to 5:1 to 1:1) to yield the product 8 (48 mg, 0.18 mmol,
81%) as a colorless oil. Rf = 0.33 (ethyl acetate/cyclohexane = 1:2).
tR = 15.1 min (major), 15.5 (minor) (HP-5) (dr = 1.86:1).
½
a 2D0
ꢂ
¼ ꢀ18:9 (produced with (S,R,R)-2, as the 1.86:1 diastereo-
~
meric mixture, c 1.0, CHCl3). IR (
m
/cmꢀ1, ATR): 2966 (s), 2935 (s),
2874 (m), 1733 (s), 1687 (s), 1434 (s), 1368 (s), 1293 (s), 1215
(s), 1134 (s), 1089 (s), 1048 (s), 632 (s), 609 (s). NMR data were re-
corded from the diastereomeric mixture and were resolved sepa-
rately as following. NMR of major diastereoisomer: 1H NMR
(400 MHz, CDCl3): d/ppm 4.95 (d, J = 11.8 Hz, 1H, CH–OCb), 4.10–
3.95 (m, 1H, Cb), 3.94–3.77 (m, 1H, Cb), 2.47–2.32 (m, 2H, CH2ring),
2.08–2.00 (m, 2H, CH2ring), 1.80–1.77 (m, 1H, CH–Et), 1.75–1.68 (m,
1H, CH2Et), 1.64–1.44 (m, 2H, CH2ring), 1.37–1.32 (m, 1H, CH2Et),
1.31–1.15 (m, 12H, Cb), 0.93 (t, J = 7.5 Hz, 3H, MeEt). 13C–NMR
(100 MHz, CDCl3): d/ppm 205.90 (C@O), 154.90 (C@O), 80.36
(CH–OCb), 46.38 (Cb), 45.67 (Cb), 45.67 (CH–Et), 40.43 (CH2ring),
28.94 (CH2ring), 25.66 (CH2ring), 25.33 (CH2Et), 21.73 (CH3Cb), 21.26
(CH3Cb), 20.51 (CH3Cb), 20.33 (CH3Cb), 10.53 (MeEt). NMR of minor
diastereoisomer: 1H NMR (400 MHz, CDCl3): d/ppm 5.15 (d,
J = 4.8 Hz, 1H, CH–OCb), 4.10–3.95 (m, 1H, Cb), 3.94–3.77 (m, 1H,
Cb), 2.47–2.32 (m, 2H, CH2ring), 2.20–2.15 (m, 1H, CH–Et), 1.92–
1.77 (m, 2H, CH2ring), 1.64–1.54 (m, 1H, CH2Et), 1.51–1.44 (m, 2H,
CH2ring), 1.31–1.15 (m, 12H, Cb), 1.19–1.15 (m, 1H, CH2Et), 0.90 (t,
J = 7.5 Hz, 3H, MeEt). 13C NMR (100 MHz, CDCl3): d/ppm 206.80
(C@O), 154.60 (C@O), 79.98 (CH–OCb), 46.38 (Cb), 45.67 (Cb),
43.91 (CH–Et), 39.80 (CH2ring), 26.01 (CH2ring), 22.83 (CH2ring),
21.73 (CH3Cb), 21.26 (CH3Cb), 20.51 (CH3Cb), 20.33 (CH3Cb), 20.33
(CH2Et), 11.37 (MeEt). HRMS (ESI+) calcd for C15H27NO3-
Na+ = 292.1889, found [M+Na]+ = 292.1883. Anal. Calcd for
C15H27NO3 (269.38): C, 66.88; H, 10.10; N, 5.20. Found: C, 66.92;
H, 10.00; N, 5.38.
4.5. 6-Oxocyclohex-1-enyl N,N-diisopropylcarbamate 7
At first, NaH (600 mg, 60% in oil, 15 mmol, 1.5 equiv) was sus-
pended in 40 mL of THF and cooled with an ice bath. To this sus-
pension, a solution of 1,2-cyclohexanedione (1.12 g, 10 mmol) in
40 mL of THF was added dropwise. The reaction mixture was then
warmed to rt, followed by addition of CbCl (2460 mg, 15 mmol,
1.5 equiv). The resulting suspension was stirred at rt for 4 h. 2 N
HCl (30 mL) was added to quench the reaction. Water phase was
separated and extracted several times with diethyl ether. Com-
bined organic layers were washed with 2 N HCl, satd aq NaHCO3,
and brine in turn and were evaporated to dryness. The residue
was purified by MPLC (n-pentane/diethyl ether = 10:1 to 5:1 to
1:1 to 1:2) to yield the product as a yellow oil (1.29 g, 5.4 mmol,
54%) which turns into solid upon storage at +4 °C. Rf = 0.28 (ethyl
~
4.7. 2-(tert-Butyldimethylsilyloxy)-6-ethylcyclohex-1-enyl N,N-
diisopropylcarbamate 9
A mixture of Cu(OTf)2 (2 mg, 0.0055 mmol, 2.5% equiv) and the
ligand (0.0055 mmol, 2.5% equiv) in 1 mL of toluene was stirred at
rt for 1 h. Then the starting material 7 (53 mg in 1 mL of toluene,
0.22 mmol) was added dropwise. The mixture was cooled to
ꢀ25 °C, followed by addition of 1 M Et2Zn in hexane (0.27 mL,
0.27 mmol, 1.2 equiv) and was stirred at this temperature for
16 h. Then TBDMSOTf (143 mg, 0.54 mmol, 2.4 equiv) was added
and the reaction mixture was warmed to rt. After being stirred at
rt for 4 h, the reaction mixture was quenched by satd aq NaHCO3
solution. The water phase was separated and extracted with
diethyl ether. Each batch of the organic washings was passed
through a short silica gel column (the same column for all batches).
Combined organic phases were evaporated and the residue was
purified by MPLC (n-pentane/diethyl ether = 40:1 to 30:1 to 20:1
to 10:1) to yield the product 9 (yields are described in Table 2)
acetate/cyclohexane = 1:2). tR = 14.6 min (HP-5). IR (m
/cmꢀ1, ATR):
3036 (m), 2969 (s), 2935 (s), 2875 (m), 2837 (m), 1711 (s), 1689
(s), 1652 (m), 1433 (s), 1369 (s), 1312 (s), 1292 (s), 1140 (s),
1108 (s), 1044 (s), 903 (s), 630 (s), 605 (s). 1H NMR (400 MHz,
CDCl3): d/ppm 6.50 (t, J = 4.4 Hz, 1H, CH@), 3.91–3.84 (m, 2H,
Cb), 2.49–2.46 (m, 2H, CH2), 2.44–2.40 (m, 2H, CH2), 1.99 (dt,
J = 6.1 Hz, 12.4 Hz, 2H, CH2), 1.20 (d, J = 6.7 Hz, 12H, Cb). 13C NMR
(100 MHz, CDCl3): d/ppm 192.88 (C@O), 153.03 (C@O), 145.49
(CbOC@), 134.99 (CH@), 46.54 (Cb), 46.51 (Cb), 38.27 (CH2),
24.84 (CH2), 22.71 (CH2), 21.17 (2C, Cb), 20.36 (2C, Cb). HRMS
(ESI+)
calcd
for
C13H21NO3Na+ = 262.1419,
found
[M+Na]+ = 262.1408. Anal. Calcd for C13H21NO3 (239.31): C,
65.25; H, 8.84; N, 5.65. Found: C, 64.98; H, 8.60; N, 5.56.
as a colorless oil. Rf = 0.63 (ethyl acetate/cyclohexane = 1:2).
tR = 18.1 min (HP-5). chiral-HPLC: Nucleosil 100-5 Chiral-2
(Macherey-Nagel), isopropanol/n-hexane = 1:2000, 0.6 mL/min,
4.6. 2-Ethyl-6-oxocyclohexyl N,N-diisopropylcarbamate 8
41 min, 45 min. ½a D20
ꢂ
¼ þ19:0 (produced with (S,S,S)-2, ee = 82%, c
~
1.0, CHCl3). IR (
m
/cmꢀ1, ATR): 2961 (s), 2931 (s), 2859 (s), 1708
A mixture of Cu(OTf)2 (2 mg, 0.0055 mmol, 2.5% equiv) and the
ligand (S,R,R)-2 (3 mg, 0.0055 mmol, 2.5% equiv) in toluene (1 mL)
was stirred at rt for 1 h. Then the starting material 7 (53 mg in 1 mL
of toluene, 0.22 mmol) was added dropwise. The mixture was
cooled to ꢀ25 °C, followed by addition of 1 M Et2Zn in hexane
(0.27 mL, 0.27 mmol, 1.2 equiv) and was stirred at this tempera-
ture for 16 h. Then, 1 M HCOOH solution in MeOH (0.3 mL) was
(s), 1429 (s), 1361 (s), 1314 (s), 1212 (s), 1114 (s), 1045 (s), 939
(s), 836 (s), 781 (s), 632 (s). 1H NMR (400 MHz, CDCl3): d/ppm
4.26–4.17 (m, 1H, Cb), 3.73–3.65 (m, 1H, Cb), 2.44–2.37 (m, 1H,
CH–Et), 2.17–2.14 (m, 2H, CH2-3), 1.79–1.76 (m, 1H, CH2-5),
1.72–1.62 (m, 2H, CH2-4) 1.59–1.56 (m, 1H, CH2Et), 1.47–1.41 (m,
1H, CH2-5), 1.32–1.29 (m, 6H, Cb), 1.28–1.26 (m, 1H, CH2Et),
1.23–1.21 (m, 6H, Cb), 0.93–0.92 (m, 9H, t-Bu), 0.89 (t, J = 7.5 Hz,

Y.-L. Chen et al. / Tetrahedron: Asymmetry 20 (2009) 1144–1149
1149
3H, MeEt), 0.15 (s, 3H, Si–CH3), 0.14 (s, 3H, Si–CH3). 13C NMR
(100 MHz, CDCl3): d/ppm 152.44 (C@O), 138.92 (C@C–OSi),
133.11 (C@C–OCb), 46.74 (Cb), 45.46 (Cb), 37.83 (CH–Et), 30.18
(CH2-3), 27.33 (CH2-5), 25.80 (3 C, Met-Bu), 24.86 (CH2,Et), 21.33
(Cb), 20.96 (Cb), 20.74 (Cb), 20.52 (Cb), 20.40 (CH2-4), 18.13 (Cq,t-
Bu), 11.36 (MeEt). HRMS (ESI+) calcd for C21H41NO3Si-
Na+ = 406.2753, found [M+Na]+ = 406.2753. Anal. Calcd for
C21H41NO3Si (383.64): C, 65.75; H, 10.77; N 3.65. Found: C,
65.49; H, 10.89; N, 3.63.
3. Several excellent reviews: (a) Breit, B. Angew. Chem., Int. Ed. 2005, 44, 6816–
6825; (b) Guiry, P. J.; Saunders, C. P. Adv. Synth. Catal. 2004, 346, 497–537; (c)
van Leeuwen, P. W. N. M.; Kamer, P. C. J.; Reek, J. N. H.; Dierkes, P. Chem. Rev.
2000, 100, 2741–2770.
4. For a review, see: McManus, H. A.; Guiry, P. J. Chem. Rev. 2004, 104, 4151–4202.
and references therein.
5. (a) Bonnaventure, I.; Charette, A. B. J. Org. Chem. 2008, 73, 6330–6340; For
review, see: (b) Bassetti, M. Eur. J. Inorg. Chem. 2006, 4473–4482.
6.
Pridgen, L. N.; Miller, G. J. Heterocycl. Chem. 1983, 20, 1223–1230.
7. X-ray crystal structure analysis for compound 6c: formula C52H68N3O10PS2,
M = 990.18,
b = 10.8509(5), c = 27.7865(14) Å, b = 94.857(2)°, V = 2642.3(2) Å3, qcalc
1.245 g cmꢀ3 = 1.673 mmꢀ1, empirical absorption correction (0.788 6 T 6
0.936), Z = 2, monoclinic, space group P21 (No. 4), k = 1.54178 Å, T = 223 K,
and u scans, 20,350 reflections collected ( h, k, l), [(sinh)/k] = 0.60 Åꢀ1, 7136
independent (Rint = 0.077) and 5863 observed reflections [I P 2 (I)], 627
colorless
crystal
0.15 ꢁ 0.10 ꢁ 0.04 mm,
a = 8.7952(4),
=
,
l
x
Acknowledgments
r
refined parameters, R = 0.058, wR2 = 0.162, Flack parameter 0.00(2), max.
residual electron density 0.22 (ꢀ0.27) e Åꢀ3, hydrogen atoms calculated and
refined as riding atoms. Data set was collected with a Nonius KappaCCD
diffractometer. Programs used: data collection COLLECT (Nonius B.V., 1998), data
reduction Denzo-SMN (Otwinowski, Z.; Minor, W. Methods Enzymol., 1997, 276,
307–326), absorption correction Denzo (Otwinowski, Z.; Borek, D.; Majewski,
W.; Minor, W. Acta Crystallogr., Sect. A. 2003, 59, 228–234), structure solution
SHELXS-97 (Sheldrick, G. M. Acta Crystallogr., Sect. A 1990, 46, 467–473), structure
refinement SHELXL-97 (Sheldrick, G. M. Universität Göttingen, 1997), graphics
Mopict (Brüggemann, M. Universität Münster, 2001). CCDC 719443 contains
the supplementary crystallographic data for this paper. These data can be
obtained free of charge at www.ccdc.cam.ac.uk/conts/retrieving.html [or from
the Cambridge Crystallographic Data Centre, 12 Union Road, Cambridge CB2
1EZ, UK; fax: (internat.) +44(1223)336-033, E-mail: deposit@ccdc.cam.ac.uk].
8. Knopff, O.; Alexakis, A. Org. Lett. 2002, 4, 3835–3837.
Generous support from the Fonds der Chemischen Industrie and
the Deutsche Forschungsgemeinschaft is gratefully acknowledged.
References
1. Examples using phosphite ligands: (a) Alexakis, A.; Vastra, J.; Burton, J.;
Benhaim, C.; Mangeney, P. Tetrahedron Lett. 1998, 7869–7872; (b) Alexakis, A.;
Benhaim, C.; Fournioux, X.; van den Heuvel, A.; Leveque, J. M.; March, S.;
Rosset, S. Synlett 1999, 1811–1813; Using phosphite–oxazoline ligands: (c)
Knöbel, A. K. H.; Escher, I. H.; Pfaltz, A. Tetrahedron 2000, 56, 2879–2888; (d)
Escher, I. H.; Pfaltz, A. Synlett 1997, 1429–1431; Using phosphonite ligands: (e)
Reetz, M.; Gosberg, A.; Goddard, R.; Kyung, S. H. Chem. Commun. 1998, 2077–
2078; Using phosphine ligands (f) Yamanoi, Y.; Imamoto, T. J. Org. Chem. 1999,
64, 2988–2989; (g) Morimoto, T.; Yamaguchi, Y.; Suzuki, M.; Saitoh, A.
Tetrahedron Lett. 2000, 10025–10029; Using phosphoramidte ligands: (h)
Feringa, B. L.; Pineschi, M.; Arnold, L. A.; Imbos, R.; de Vries, A. H. M. Angew.
Chem., Int. Ed. 1997, 36, 2620–2623; (i) Feringa, B. L. Acc. Chem. Res. 2000, 33,
346–353; Using non-phosphorous ligands: (j) Chataignier, I.; Gennari, C.;
Piarulli, U.; Ceccarelli, S. Angew. Chem., Int. Ed. 2000, 39, 916–918; For a general
review, see: (k) Alexakis, A.; Bäckvall, J. E.; Krause, N.; Pa`mies, O.; Die´guez, M.
Chem. Rev. 2008, 108, 2796–2823.
9. Unpublished results in this group.
10. Alexakis, A.; Rosset, S.; Allamand, J.; March, S.; Guillen, F.; Benhaim, C. Synlett
2001, 1375–1378.
11. Review (a) Muñiz, K.; Bolm, C. Chem. Eur. J. 2000, 6, 2309–2316; (b) Zhang, S. Y.;
Girard, C.; Kagan, B. Tetrahedron: Asymmetry 1995, 6, 2637–2640.
12. Alexakis, A.; Polet, D.; Rosset, S.; March, S. J. Org. Chem. 2004, 69, 5660–
5667.
13. Shi, M.; Wang, C.-J.; Zhang, W. Chem. Eur. J. 2004, 10, 5507–5516.
2. Wünnemann, S.; Fröhlich, R.; Hoppe, D. Org. Lett. 2006, 8, 2455–2458.