New chiral monophosphite ligands containing BINOL and/or H 8-BINOL bearing adamantyl substituents: Effect of ligand scaffold on the enantioselective 1,4-conjugate addition of diethylzinc to cyclic enones

Article abstract of DOI:10.1016/S1872-2067(10)60164-7

A series of new bulky monophosphite ligands were synthesized from axially chiral BINOL/H₈-BINOL (BINOL: 1-(2-hydroxynaphthalen-1-yl)naphthalen- 2-ol) and highly sterically hindered adamantylcarbonyl chloride. The effectiveness of these ligands

Full text of DOI:10.1016/S1872-2067(10)60164-7

CHINESE JOURNAL OF CATALYSIS
Volume 32, Issue 1, 2011
Online English edition of the Chinese language journal
RESEARCH PAPER
Cite this article as: Chin. J. Catal., 2011, 32: 80–85.
New Chiral Monophosphite Ligands Containing BINOL
and/or H8-BINOL Bearing Adamantyl Substituents:
Effect of Ligand Scaffold on the Enantioselective
1,4-Conjugate Addition of Diethylzinc to Cyclic Enones
WAN Bo1, KWONG Fuk Yee2,#, WANG Lailai1,*, XU Lijin3, ZHAO Qinglu1, XING Aiping1
1 State Key Laboratory for Oxo Synthesis & Selective Oxidation, Lanzhou Institute of Chemical Physics, Chinese Academy of
Sciences, Lanzhou 730000, Gansu, China
2 Open Laboratory of Chirotechnology of the Institute of Molecular Technology for Drug Discovery and Synthesis, Department of
Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Kowloon, Hong Kong, China
3 Department of Chemistry, Renmin University of China, Beijing 100049, China
Abstract: A series of new bulky monophosphite ligands were synthesized from axially chiral BINOL/H8-BINOL (BINOL:
1-(2-hydroxynaphthalen-1-yl)naphthalen-2-ol) and highly sterically hindered adamantylcarbonyl chloride. The effectiveness of these
ligands was evaluated by the Cu-catalyzed asymmetric 1,4-conjugate addition of diethylzinc to cyclic enones with enantioselectivities of up
to 79% ee. The results showed that a ligand structure comprising a partially hydrogenated 2,2ƍ-(1,1ƍ-binaphthyl)phosphite scaffold and an
adamantyl moiety was effective in improving the enantioselectivity.
Key words: enantioselective 1,4-conjugate addition; phosphite ligand; copper salt; cyclic enone; adamantyl; H8-binaphtyl
Asymmetric syntheses have been successful in the prepara-
tion of chiral motifs for the manipulation of optically active
compounds in pharmaceutical and medicinal science. In par-
ticular, the enantioselective conjugate addition of or-
ganometallic reagents to Į,ȕ-unsaturated carbonyl compounds
is an attractive method for the stereoselective construction of
carbon-carbon bonds in organic synthesis [1–4]. These addi-
tion products have been shown to have many applications in
the synthesis of natural and biologically active compounds
such as (R)-Muscone [5–7], Clavularin B [8,9], and Pumilio-
toxin C [10]. Cu-catalyzed enantioselective 1,4-conjugate
addition using chiral trivalent phosphorous ligands has been
investigated extensively since the pioneering report by Al-
exakis et al. in 1993 [11]. A plethora of chiral phosphorous
ligands such as phosphoramidites [1,12–14], phosphite ligands
[15–17], and chiral P, N ligands [18–21] have been synthesized
and successfully applied in reactions to afford good to excellent
enantioselectivities. Nevertheless, the dynamic behavior of the
equilibria among several species of organocuprate compounds
in solution is problematic. Therefore, if the more reactive cu-
prates give racemic products a loss of enantioselectivity is
unavoidable [22,23]. The design and synthesis of new chiral
ligands that can rapidly react with substrates and suppress the
formation of unwanted competing products is desirable.
Recently, Reetz et al. [24] reported a helical C3-symmetric
monophosphite ligand with a sterically encumbered adamantyl
group (Scheme 1), which gave respectable enantioselectivities
(79%–98% ee) in Rh-catalyzed asymmetric hydrogenation.
Inspired by this excellent work, we undertook phosphite ligand
development and focused on the bulky adamantyl moiety
(Scheme 2, R group).
In addition to the chiral element from the binaphthyl skele-
ton, the partially hydrogenated H8-binapthyl (5,5ƍ,6,6ƍ,7,7ƍ,
8,8ƍ-octahydro-1,1ƍ-binaphthyl) scaffold is also of interest.
Received 11 July 2010. Accepted 20 October 2010.
*Corresponding author. Tel: +86-931-4968161; Fax: +86-931-4968129; E-mail: wll@licp.cas.cn
#Corresponding author. Tel: +852-3400-8682; Fax: +852-2364-9932; E-mail: bcfyk@inet.polyu.edu.hk
Foundation item: Supported by the National Natural Science Foundation of China (20343005, 20473107, 20673130, 20773147).
Copyright © 2011, Dalian Institute of Chemical Physics, Chinese Academy of Sciences. Published by Elsevier BV. All rights reserved.
DOI: 10.1016/S1872-2067(10)60164-7

WAN Bo et al. / Chinese Journal of Catalysis, 2011, 32: 80–85
coupling constants (J) are given in ppm and in Hz, respectively.
R
Spin multiplicities are reported as s (singlet), d (doublet), t
(triplet), and m (multiplet) as well as b (broad). All the melting
points were determined on an X-4 melting point apparatus and
were uncorrected.
O
O
O
R
O
O
O
P
O
1.2 Synthesis of chiral monophosphite ligands
1.2.1 General protocol for the preparation of carboxylic
acid esters of BINOL
O
O
R
R = 1-adamantyl
Scheme 1. Reetz’s helical C3-symmetric monophosphite ligand.
A flame-dried flask was charged with BINOL (2.5 mmol),
4-dimethylaminopyridine (DMAP, 25 mg), 10 ml of THF, and
Et3N (3.25 mmol), and cooled to –10 °C. Acyl chloride or
acetic anhydride (2.5 mmol) was added to the
above-mentioned solution dropwise. Once the addition was
complete the reaction mixture was left at room temperature
until the near complete disappearance of the starting material.
After 24 h, the reaction was quenched with distilled water (2.5
ml) and the mixture was extracted with ethyl acetate (5 ml × 3).
The combined organic phases were washed successively with a
saturated aqueous solution of NaHCO3, brine, and then dried
over anhydrous sodium sulfate, filtered, and concentrated in
vacuo. The crude product was purified by flash chromatogra-
phy (EtOAc/ hexanes) to provide the title compound (S)-2a,
(S)-2b, or (S)-2c as a solid with > 95% yield (Scheme 3).
provides additional fine-
tuning to chiral pocket
O
R
O
O
O
P
O
provides secondary
stereo-induction
provides primary
stereo-induction
Scheme 2. Design of a modulated ligand bearing a bulky R group.
Chiral phosphorus donor ligands based on the H8-binaphtyl
moiety have received considerable attention recently [25–29].
The improved stereo-communication in H8-BINOL compared
to BINOL in asymmetric reactions has been explicitly high-
lighted [30–33]. Herein, we report the synthesis of a new se-
ries of bulky monophosphite ligands L1–L9 based on the
(S)-BINOL and the (S)-H8-BINOL skeleton. The effectiveness
of these ligands was examined in the copper-catalyzed enan-
tioselective 1,4-conjugate addition of diethylzinc to cyclic
enones.
1
(S)-2a: White solid; H NMR (400 MHz, CDCl3) į 5.30 (s,
1H), 7.14í7.15 (m, 1H),7.16í7.45 (m, 8H), 7.54í7.56 (m, 2H),
7.65í7.67 (m, 2H), 7.78í7.80 (m, 2H), 8.00 (d, J = 8.4, 1H),
8.12 (d, J = 8.8, 1H); 13C NMR (100 MHz, CDCl3) į 113.9,
118.2, 121.9, 123.2, 123.4, 124.6, 125.8, 126.3, 126.7, 127.5,
128.0, 128.3, 128.4, 128.7, 129.0, 130.0, 130.4, 130.8, 132.3,
133.5, 133.6, 133.7, 148.3, 151.8, 165.9.
(S) 2b: White solid; 1H NMR (400 MHz, CDCl3) į 1.86 (s,
3H), 5.20 (s, 1H), 7.03 (d, 1H, J = 8.4 Hz), 7.23í7.49 (m, 7H),
7.85 (d, 1H, J = 8.0 Hz), 7.90 (d, 1H, J = 9.2 Hz), 7.96 (m, 1H),
8.06 (d, 1H, J = 8.8 Hz); 13C NMR (100 MHz, CDCl3) į 20.4,
114.0, 118.2, 121.8, 123.1, 123.5, 124.5, 125.7, 126.3, 126.7,
127.5, 128.0, 128.3, 129.0, 130.4, 130.8, 132.2, 133.4, 133.5,
148.0, 151.7, 170.4.
1 Experimental
1.1 General
(S)-2c: White solid; 1H NMR (400 MHz, CDCl3) į
1.39í1.45 (m, 9H), 1.54í1.57 (d, J = 12.4, 3H), 1.77 (s, 3H),
5.14 (s, 1H), 7.05 (d, J = 8.4, 1H), 7.25í7.38 (m, 6H), 7.50 (m,
1H), 7.82 (d, J = 8.0, 1H), 7.88 (d, J = 9.2, 1H), 8.00 (d, J = 8.4,
1H), 8.06 (d, J = 8.8, 1H); 13C NMR (100 MHz, CDCl3) į 27.6,
36.2, 38.0, 40.7, 114.3, 118.3, 121.9, 123.0, 123.5, 124.6, 125.6,
126.1, 126.6, 127.4, 127.9, 128.3, 129.0, 130.2, 130.7, 132.2,
133.5, 133.6, 148.4, 151.8, 177.0.
All experiments were carried out under nitrogen using
standard Schlenk techniques. Reactions were monitored by
thin layer chromatography (TLC). Column chromatography
was carried out using silica gel. Toluene, ether, and tetrahy-
drofuran (THF) were distilled from sodium. Dichloromethane
was distilled over calcium hydride. The other commercially
available reagents were used as received without further puri-
fication. NMR (nuclear magnetic resonance) spectroscopy
1
was recorded on a Bruker 400 MHz spectrometer. H NMR
and 13C NMR spectra are reported in parts per million and
TMS (į = 0.00) was used as an internal standard. 31P NMR
spectra are reported in parts per million and 85% H3PO4 was
used as an external reference. Proton chemical shifts (į) and
1.2.2 Synthesis of chiral monophosphite ligands
In a typical procedure for ligand synthesis, to a stirred solu-
tion of compound 2 (1.0 mmol) in THF (10 ml) was added Et3N

WAN Bo et al. / Chinese Journal of Catalysis, 2011, 32: 80–85
O
O
O
Cl
Ph
Cl
O
P
O
O
or
O
R
OH
O
*
R
O
O
DMAP
*
*
O
Et3N, 0 oC to RT
Et3N, RT
Me
P
Me
O
*
OH
OH
or
O
1
2
ꢀ
O
(S)-2a: R = Ph
(S)-2b: R = Me
(S)-2c: R = 1-adamantyl
L1 L9
Cl
Effect of R group size
O
Effect on configurations of binaphthyl
O
O
R
O
O
O
O
O
P
P
O
O
(S,S)-L1: R = 1-adamantyl
(S,S)-L2: R = Ph
(S,S)-L3: R = Me
(NOTE: the first configuration denotes left hand side
binaphthyl skeleton while the second one denotes the
right hand side scaffold)
(R,R)-L4
(R,S)-L5
(S,R)-L6
Effects between binaphthyl and H8-binaphthyl skeleton
O
O
O
O
O
O
O
O
O
O
O
O
P
P
P
O
O
O
(S,S)-L7
(S,S)-L8
Scheme 3. Synthesis of the bulky monophosphite ligands.
(S,S)-L9
(1.0 mmol) under nitrogen. The mixture was then cooled to 0
°C and BINOL or H8-BINOL-derived chlorophosphite (1.1
mmol) was slowly added. The reaction mixture was allowed to
warm to room temperature and stirred overnight. The Et3N·HCl
salt precipitate was then removed by filtration. The solvent was
removed in vacuo and the residue was purified by flash chro-
matography using toluene as the eluent to yield a white foamy
solid in 50%–60% yield.
132.7, 145.9, 146.0, 146.5, 146.6, 174.3; 31P NMR (161 MHz,
CDCl3) į 145.2.
(S,S)-L2: White solid; mp 128–130 °C; [Į]D20 = +110.5 (c
0.2, CHCl3); 1H NMR (400 MHz, CDCl3) į 6.58 (d, J = 8.8,
1H), 7.04–7.27 (m, 15H), 7.40 (m, 2H), 7.49 (d, J = 7.2, 2H),
7.62 (d, J = 8.8, 2H), 7.75–7.80 (m, 5H) 7.91 (d, J = 8.0, 1H),
8.01 (d, J = 9.2, 1H); 13C NMR (100 MHz, CDCl3) į 119.8,
120.7, 120.8, 122.9, 123.8, 124.1, 124.3, 124.8, 124.9, 125.1,
125.2, 125.3, 126.0, 127.1, 127.3, 128.0, 128.6, 128.8, 129.1,
129.2, 129.8, 130.2, 130.5, 130.7, 132.0, 146.0, 146.5, 163.4;
31P NMR (161 MHz, CDCl3) į 145.0.
(S,S)-L1: White solid; mp 232–233 °C; [Į]D20 = +92 (c 0.2,
1
CHCl3); H NMR (400 MHz, CDCl3) į 1.24–1.36 (m, 9H),
1.46–1.49 (m, 3H), 1.66 (s, 3H), 6.59 (d, J = 8.8, 1H),
7.18–7.53 (m, 15H), 7.70 (d, J = 8.8, 1H), 7.87–7.96 (m, 6H),
8.03 (d, J = 8.8, 1H); 13C NMR (100 MHz, CDCl3) į 26.5, 35.1,
36.8, 39.4, 119.6, 119.7, 120.7, 120.8, 121.1, 121.4, 121.4,
121.5, 121.5, 122.8, 123.2, 123.3, 123.7, 124.0, 124.1, 124.6,
124.9, 125.2, 125.3, 125.7, 125.8, 125.8, 125.9, 127.1, 128.5,
128.8, 129.1, 129.8, 130.1, 130.4, 130.5, 131.3, 131.7, 132.7,
(S,S)-L3: White solid; mp 78–80 °C; [Į]D20 = +59 (c 0.16,
CHCl3); 1H NMR (400 MHz, CDCl3) į 1.64 (s, 3H), 6.41 (d, J
= 8.8, 1H), 7.19–7.37 (m, 13H), 7.44 (m, 2H), 7.61 (d, J = 8.8,
1H), 7.78–7.88 (m, 6H); 7.99 (d, J = 8.8, 1H); 13C NMR (100
MHz, CDCl3) į 28.7, 120.7, 120.9, 123.8, 124.1, 124.2, 124.8,
124.9, 125.1, 125.2, 125.9, 125.9, 126.0 126.9, 127.0, 127.1,

WAN Bo et al. / Chinese Journal of Catalysis, 2011, 32: 80–85
127.2, 127.3, 128.0, 128.5, 128.6, 129.0, 129.2, 129.8, 130.1,
BINOL or H8-BINOL by their reaction with phosphorochlo-
ridite in the presence of triethylamine (Scheme 3). The desired
ligands were found to be stable on silica gel during the purifi-
cation procedure and fairly air-stable at room temperature.
Indeed, the precursors 2 (carboxylic acid esters of BINOL or
H8-BINOL) were easily accessible from axially chiral
H8-BINOL/BINOL and acyl chloride/acetic anhydride ac-
cording to a previous reported procedure [24].
130.5, 130.7, 131.3, 131.7, 131.8, 132.6, 132.7, 145.9, 146.0,
146.3, 168.0; 31P NMR (161 MHz, CDCl3) į 144.5.
(S,S)-L7: White solid; mp 132–134 °C; [Į]D20 =+36.5 (c 0.2,
1
CHCl3); H NMR (400 MHz, CDCl3) į 1.54–1.84 (m, 31H),
2.10–2.35 (m, 6H), 2.61–2.80 (m, 10H) , 6.25 (d, J = 8.0, 1H),
6.90 (m, 3H), 7.02 (m, 3H), 7.15 (m, 1H); 13C NMR (100 MHz,
CDCl3) į 21.4, 21.5, 21.6, 21.7, 21.8, 21.9, 22.0, 26.2, 26.7,
26.8, 26.9, 28.1, 28.2, 28.5, 28.6, 28.7, 35.4, 37.2, 39.7, 118.4,
128.0, 132.4, 132.6, 133.6, 136.0, 136.3, 136.7, 137.3, 137.3,
145.5, 174.6; 31P NMR (161 MHz, CDCl3) į 137.89.
Since the modulated ligands consist of two chiral elements
(i.e. from two binaphthyl moieties), we were interested in a
match/mis-match study with different configurations of the
binaphthyl scaffolds. Our previous study [34] was concerned
with the application of ligands L1 and L4–L6 to the
Cu-catalyzed enantioselective 1,4-conjugate additions of di-
ethylzinc to 2-cyclohexenone. We found that two BI-
NOL-derived moieties with the (S)-configuration in ligand L1
were matched to give moderate to good enantioselectivities.
The absolute configuration of the 2,2ƍ-o,o-(1,1ƍ-binaphthyl)-
dioxophosphite moiety (non-ester containing binaphthyl group)
of the ligand was found to be of primary importance in deter-
mining the sense of asymmetric induction. Diethyl ether
proved to be more effective than other solvents (such as toluene,
dichloromethane, and THF).
(S,S)-L8: White solid; mp 126–128 °C; [Į]D20 = +130.8 (c
0.2, CHCl3); 1H NMR (400 MHz, CDCl3) į 1.51–1.80(m, 23H),
2.14–2.42 (m, 4H), 2.80 (m, 4H), 6.85 (d, J = 8.8, 1H), 7.04 (m,
3H), 7.24 (m, 3H), 7.31–7.44 (m, 5H), 7.77 (d, J = 8.8, 1H),
7.90 (m, 3H); 13C NMR (100 MHz, CDCl3) į 22.8, 22.9, 23.0,
27.2, 27.8, 29.6, 36.4, 38.2, 40.7, 119.6, 121.9, 122.3, 124.7,
125.0, 125.3, 125.9, 126.2, 126.9, 127.1, 128.3, 129.1, 129.5,
130.2, 131.2, 131.5, 132.4, 132.8, 133.8, 134.8, 137.4, 137.9,
146.5, 175.6; 31P NMR (161 MHz, CDCl3) į 146.0.
(S,S)-L9: White solid; mp 146–148 °C; [Į]D20 = +10 (c 0.2,
1
CHCl3); H NMR (400 MHz, CDCl3) į 1.28–1.52(m, 15H),
1.72 (m, 8H), 2.14–2.19 (m, 2H), 2.57 (m, 2H), 2.74 (m, 4H),
6.06 (d, J = 8.0 Hz, 1H), 6.83 (d, J = 8.4 Hz, 2H), 6.99 (d, J =
8.4 Hz, 1H), 7.23–7.30 (m, 4H), 7.38–7.49 (m, 4H), 7.86 (d, J
= 8.0 Hz, 1H), 7.93 (m, 2H), 8.05 (d, J = 8.8 Hz, 1H); 13C NMR
(100 MHz, CDCl3) į 22.4, 22.5, 22.6, 22.7, 27.6, 27.7, 29.1,
29.2, 36.2, 37.8, 40.5, 118.8, 122.1, 123.9, 124.9, 125.3, 125.5,
126.7,127.6, 128.0, 128.2, 128.9, 129.3, 129.6, 130.8, 131.6,
133.7, 134.7, 137.1, 138.4 , 145.6, 145.9, 147.5, 147.8, 147.9,
175.4; 31P NMR (162 MHz, CDCl3) į 137.1.
The influence of R group bulkiness on the carboxylic esters
was initially studied. The copper-catalyzed conjugated addi-
tion of 2-cyclohexenone to diethylzinc was used as a model
reaction for our prototypical investigation (Table 1). L2 and
L3 bearing R = Ph and R = Me, respectively, gave poor enan-
tioselectivity of the addition product (Table 1, entries 2 and 3).
To our delight, the bulkier adamantyl ester L1 afforded a sig-
nificant increase in enantioselectivity (entry 1). These results
suggest that the highly sterically encumbered adamantly moi-
ety is beneficial for stereo-communication between the
binaphthyl moieties and the substrate.
1.3 Typical procedure for asymmetric conjugate addition
In a typical procedure for asymmetric conjugate addition, to
a solution of the copper salt (0.01 mmol) and the ligand (0.02
mmol) in anhydrous diethyl ether (4.0 ml) that was stirred at
room temperature for 1 h under N2, 2-cyclohexenone (0.5
mmol) and diethylzinc (1.2 mmol) were added sequentially
after the complex was cooled to 0 °C. The solution was stirred
for 4 h at this temperature and then quenched with water (~2
ml) and hydrochloric acid solution (2.0 mol/L, ~2 ml). The
mixture was extracted with ethyl acetate (5 ml × 3). The com-
bined organic layers were washed with a saturated NaHCO3
solution, brine, and then dried with anhydrous Na2SO4. The
crude organic phase was concentrated under reduced pressure.
The residue was purified by flash column chromatography on
silica gel to yield the desired products L1–L9.
We then examined the asymmetric induction ability of the
chiral binaphthyl and H8-binaphthyl scaffolds of the phosphite
ligands in the Cu-catalyzed asymmetric conjugate addition of
diethylzinc to cyclic enones. Results for the application of
ligands (S,S)-L7, (S,S)-L8, and (S,S)-L9 are shown in Table 1
(entries 4–6). A comparison of ligands L8 and L9 reveals that
the H8-binaphthyl scaffold (as the non-ester containing ring)
was better at driving the asymmetric induction (entries 5–6).
L9 gave a slightly better result than L1 (entry 6 vs. entry 1).
Ligand L7, with both the (S)-H8-BINOL moieties, gave similar
results to its parent ligand L1 (entry 4 vs. entry 1). It is known
that the copper precursor plays a crucial role in the high cata-
lytic activity and enantioselectivity of these reactions [35,36].
In our study, the copper precursors Cu(OTf)2 and
(CuOTf)2·C6H6 gave similar results (entries 6 and 7). When the
temperature was decreased from 0 to –40 °C the ee of the
addition product improved significantly from 66% to 79%. The
best ee was achieved when the reaction temperature was –40
°C (entries 7–10).
2 Results and discussion
A new series of modulated monophosphite ligands L1–L9
were prepared in high yield from the carboxylic acid esters of

WAN Bo et al. / Chinese Journal of Catalysis, 2011, 32: 80–85
Table 1 Cu-catalyzed enantioselective conjugate addition of diethylzinc to cyclic enones
O
O
Et2Zn
*
Et
n
n
n = 0,1,2
Ligand
Entry
1
n
1
1
1
1
1
1
1
1
1
1
0
2
Cu salt
Temperature (°C)
Yielda (%)
eeb (%) (Config.)
61 (S)
(S,S)-L1
(S,S)-L2
(S,S)-L3
(S,S)-L7
(S,S)-L8
(S,S)-L9
(S,S)-L9
(S,S)-L9
(S,S)-L9
(S,S)-L9
(S,S)-L9
(S,S)-L9
Cu(OTf)2
Cu(OTf)2
0
0
88
20
98
57
51
88
96
93
98
81
42
46
2
33 (S)
3
Cu(OTf)2
0
40 (S)
4
Cu(OTf)2
0
62 (S)
5
Cu(OTf)2
0
33 (S)
6
Cu(OTf)2
0
66 (S)
7
(CuOTf)2·C6H6
(CuOTf)2·C6H6
(CuOTf)2·C6H6
(CuOTf)2·C6H6
(CuOTf)2·C6H6
(CuOTf)2·C6H6
0
66 (S)
8
– 20
– 40
– 60
– 40
– 40
73 (S)
9
79 (S)
10
11
12
69 (S)
23 (S)
34 (S)
Reaction conditions: Cu salts 0.01 mmol, L*/Cu salts molar ratio = 2, Et2Zn 1.2 mmol, cyclic enone 0.5 mmol, solvent ether 4.0 ml, 4 h.
aDetermined by GC using dodecane as an internal standard with a SE-30 column (50 m × 0.25 mm).
bThe ee values of 3-ethylcyclohexanone and 3-ethylcyclopentenone were determined using a GC equipped with a Chiraldex A-TA column (50 m × 0.25
mm). The ee values of 3-ethylcycloheptenone were determined using a GC equipped with a Chiralsil-DEX-CB column (25 m × 0.25 mm). The absolute
configuration of the product was determined by comparison with authentic samples.
5
6
7
8
9
Scafato P, Cunsolo G, Labano S, Rosini C. Tetrahedron, 2004,
To evaluate the effectiveness of the new catalyst system, we
carried out conjugate additions of Et2Zn to other cyclic enones
of different ring size. Low enantioselectivities in the reaction
between 2-cyclopentenone and 2-cycloheptenone were ob-
tained (entries 11 and 12).
60: 8801
Iuliano A, Scafato P, Torchia R. Tetrahedron: Asymmetry, 2004,
15: 2533
Ito K, Eno S, Saito B, Katsuki T. Tetrahedron Lett, 2005, 46:
3981
Degrado S J, Mizutani H, Hoveyda A H. J Am Chem Soc, 2001,
3 Conclusions
123: 755
Mizutani H, Degrado S J, Hoveyda A H. J Am Chem Soc, 2002,
124: 779
In summary, we prepared a series of new bulky mono-
phosphite ligands derived from axially chiral BINOL and
H8-BINOL with highly sterically encumbered adamantane-
carbonyl chloride. The results indicate that the ligand structure
comprising a partially hydrogenated 2,2ƍ-(1,1ƍ-binaphthyl)
phosphite scaffold and a bulky adamantyl moiety was effec-
tive in enhancing the stereo-induction to the substrate and thus
the enantioselectivity of the product. Further fine-tuning and
application of these ligands in other asymmetric catalytic re-
actions are currently underway.
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