Enantioselective cyclopropanation with TADDOL-derived phosphate ligands

Article abstract of DOI:10.1002/adsc.200600351

The synthesis of new chiral TADDOL-derived phosphate ligands is described. The ligands were efficiently synthesized on a multi-gram scale in three steps starting from the readily available corresponding TADDOL and were fully characterized. An X-ray structure was obtained and compared to known BINOL-phosphates. Their use in the asymmetric Simmons-Smith cyclopropanation of both functionalized and unfunctionalized olefins gave the desired cyclopropanes in good yields and good to moderate enantioselectivities.

Full text of DOI:10.1002/adsc.200600351

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DOI: 10.1002/adsc.200600351
Enantioselective Cyclopropanation with TADDOL-Derived
Phosphate Ligands
Arnaud Voiturieza and AndrØ B. Charettea,*
a
DØpartement de Chimie, UniversitØ de MontrØal, P.O. Box 6128, Station Downtown, MontrØal, QC H3C 3 J7, Canada
Phone: (+1)-514–343–2432; Fax: (+1)-514–343–5900; e-mail: andre.charette@umontreal.ca
Received: July 13, 2006; Accepted: September 14, 2006
Supporting information for this article is available on the WWW under http://asc.wiley-vch.de/home/.
Abstract: The synthesis of new chiral TADDOL-de-
rived phosphate ligands is described. The ligands
were efficiently synthesized on a multi-gram scale
in three steps starting from the readily available
corresponding TADDOL and were fully character-
ized. An X-ray structure was obtained and com-
pared to known BINOL-phosphates. Their use in
the asymmetric Simmons–Smith cyclopropanation
of both functionalized and unfunctionalized olefins
gave the desired cyclopropanes in good yields and
good to moderate enantioselectivities.
agents in a number of enantioselective transforma-
tions. For example, chiral phosphoric acids derived
from BINOL,[2] VAPOL[3] and BINAM[4] have been
recently shown to catalyze reactions with excellent
enantioselectivities. Recently, we reported an alterna-
tive use of BINOL-iodomethylzinc phosphates as a
new powerful family for zinc carbenoid-mediated cy-
clopropanation of alkenes[5] (Figure 1).
In order to develop better chiral discriminating re-
agents and to increase the scope of the cyclopropana-
tion reaction, we engaged in a research program
aimed at the development of a new family of chiral
phosphates derived from TADDOL.[6] This privileged
class of ligands[7] has shown their efficiency in numer-
ous enantioselective reactions such as the titanium-
TADDOLate-catalyzed cyclopropanation reaction de-
veloped in our group.[8] In this paper, we report the
synthesis of new TADDOL-phosphate derivatives
and their effectiveness in inducing enantioselectivities
Keywords: asymmetric synthesis; Brønsted acid; cy-
clopropanes; Simmons–Smith reaction; TADDOL-
phosphate
Stereoselective organocatalysis has, over the past few in the Simmons–Smith reaction.
years, become an area of intense investigation world-
Synthesis of TADDOL derivatives and their corre-
wide.[1] Among the growing family of organocatalysts, sponding chiral phosphates: Most of the TADDOLs
chiral Brønsted acids have emerged as powerful used in the present study are known and were synthe-
Figure 1.
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sized according to literature procedures,[9] except for (Scheme 2). To introduce the phosphorus atom, the
structure 1f. The latter was prepared by Grignard ad- TADDOL ligand was treated with phosphorus tri-
dition of the biphenyl (prepared by Suzuki coupling chloride in the presence of triethylamine, followed by
in 92% yield) on the (+)-diethyl tartrate (Scheme 1). the addition of 3-hydroxypropionitrile to obtain the
The standard method found in the literature for the crude compounds 2a–f. At this step, purification by
synthesis of the BINOL-phosphates, i.e., POCl3, Et3N flash chromatography could be carried out, (69% iso-
and then H2O failed to produce any of the desired lated yield of 2c, see Table 1), but no satisfactory re-
phosphoric acids 4. In fact, we were able to introduce sults in terms of isolated yields were obtained due to
the phosphorus atom on the diol, but the correspond- the relative instability of the phosphite. Instead, the
ing phosphochloridate resisted hydrolysis. Inspired by phosphorus could be oxidized with a 30% hydrogen
works in the field of oligonucleotide synthesis,[10] we peroxide in water, and the more stable ligands 3a and
decided to use a protecting group on phosphorus. Ac- 3d–f could be easily purified by flash chromatography.
cordingly, the new phosphates 4a–f were synthesized To produce the desired acids 4a–f, the deprotection of
in three steps from the corresponding TADDOL the phosphorus was performed with 1,8-diazabicyclo-
Scheme 1. Synthesis of the new chiral TADDOL 1f.
Scheme 2. Synthesis of TADDOL-phosphate derivatives.
Table 1. Yields for the synthesis of TADDOL-phosphate derivatives.
A
G
Ar
2a–f Yield [%]
3a–f Yield [%]
4a–f Yield [%]
1a
1b
1c
1d
1e
1f
U
Ph
Ph
-
-
69
-
-
75
-
-
88
49
59
99
75
83
95
99
91
A
2-Naphthyl
4-Ph-C6H4
3-Ph-C6H4
-
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Enantioselective Cyclopropanation
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[5.4.0]undec-7-ene (DBU) and this was followed by et al.[11] (Scheme 4), the P O bond lengths were
À
an acidic work-up. The ligands were obtained with found to be similar to the TADDOL-phosphate. The
À
À
overall yields of 48–84% for the three steps (see Ex- difference between the O3 P and O4 P distances in
perimental Section for details). Because of the mix- the Bnppa (1,1’-binaphthalene-2,2’-diyl hydrogen
ture of two diastereoisomers for 2b and 3b (arising phosphate) uncomplexed crystal is significantly higher
from the non-symmetrical acetal), their purification than the corresponding difference in the bnppa salt (a
was more difficult. Consequently, the synthesis of difference 0.072 Š in the acid and 0.005 Š in the salt).
ligand 4b was performed without chromatography, In our case, with a difference of 0.023 Š between the
À
À
and the light yellow solid was recrystallized (CH2Cl2/ P O21 and P O22 bonds, ligand 4a is a THF and H2O-
hexane) to provide>95% pure ligand. This practical complexed phosphate.
synthesis of new chiral Brønsted acids has been ex-
tented to a multi-gram scale.
Tests of the new chiral auxiliaries in the asymmet-
ric Simmons–Smith cyclopropanation: The Sim-
Study of the X-ray structure of 4a: An X-ray struc- mons–Smith reaction is a powerful method for the
ture of the ligand 4a was obtained (Scheme 3). All synthesis of cyclopropanes from alkenes.[12] Our
bond lengths and angles given in Scheme 3 are the group[13] and others[14] have been involved in the past
average of the data of the two molecules of few years in preparing, characterizing and studying
TADDOL-phosphate in the asymmetric unit.
new cyclopropanating reagents.
When this crystal was compared to the BINOL-
In order to evaluate the potential of our new
phosphate X-ray structure obtained by Hirayama TADDOL-derived phosphate ligands for asymmetric
Scheme 3. X-ray structure of the ligand 4a.
Scheme 4. X-ray structures obtained by Hirayama et al.[11]
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Arnaud Voituriez and AndrØ B. Charette
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cyclopropanation, we chose benzyl-protected cinnam- 75–96% were obtained. The substitution on the acetal
yl alcohol as a substrate (Table 2). moiety of the TADDOL backbone has no interesting
We first analyzed the solvent effect on the cyclo- influence (entries 1and 2).
[15]
The 3,5-dimethylben-
propanation (Table 2, entries 1–4). In chlorobenzene zene substituent gave the lowest enantioselectivity
or toluene, the reactions were not complete, and the (entry 3) while the TADDOL-phosphate with the 2-
enantioselectivities were modest, up to 54% ee (en- naphthyl groups (entry 4) was the best ligand in this
tries 1and 2). The best result in terms of enantiose-
reaction (69% ee). We believed that 4d was the best
lectivity was in dichloroethane (DCE) (entry 4, 67% ligand tested because of the propensity of the naph-
ee). Dichloromethane also gave good results, but the thyl groups to project chirality towards the zinc carbe-
enantioselectivity was slightly lower (entry 3, 65% noid, therefore providing the highest enantiodiscrimi-
ee). With DCE as solvent (entries 4–8), the conver- nation. The use of the biphenyl groups did not in-
sions were always complete and the isolated yields su- crease the selectivity (entries 5 and 6).
perior to 81%. The order of addition of diethylzinc
Finally, the scope of the reaction was explored
and the ligand had no effects (entries 4 and 5). For using ligand 4d in the cyclopropanation of functional-
practical purposes, all cyclopropanation reactions ized (substrates A–E) and unfunctionalized (substrate
were tested as follows: to the ligand and solvent in a F) alkenes (Table 4).
flame-dried flask was added sequentially diethylzinc,
The benzyl-protecting group was not necessary for
diiodomethane and finally the substrate. When the re- high enantioselectivities in the cyclopropanation reac-
action was run at 08C, 69% ee was observed tion with the ligand 4d. In fact, with a methyl-protect-
(entry 6). At À158C, the enantiomeric ratio was not ed cinnamyl alcohol,
a 73% ee was obtained
improved (entry 7). Increasing the quantity of ligand (entry 2). A similar enantiomeric excess (69% ee,
with respect to the Et2Zn and CH2I2 did not signifi- entry 3) was found with an electron-donating group
cantly change the enantioselectivity (entry 8). It is on the aromatic ring (substrate C). The best result
noteworthy that the chiral ligand could be readily re- was obtained with substrate D (75% ee, entry 4).
covered after the reaction.
Even for the cyclopropanation of a non-styrenic sub-
With these optimized conditions (DCE, 08C) in strate (substrate E), often recognized as difficult, a
hand, we turned our attention to the influence of the 69% ee was achieved with ligand 4d (entry 5). How-
ligand structure on the activity and the selectivity ever, it remains a great challenge to cyclopropanate
(Table 3).
unfunctionalized alkenes, i.e., alkenes which do not
In each case, complete conversion in the cyclopro- contain a directing functional group.[13a,16] To the best
panation reaction was observed, and isolated yields of of our knowledge, there are no universal ligands for
Table 2. Optimization of the benzyl-protected cinnamyl alcohol cyclopropanation with 4d.
Entry
Solvent
T [8C]
Time [h]
Yield [%][a]
ee [%][c]
[b]
1PhCl
2
3
rt
48
rt
rt
rt
rt
36
49
48
49
49
72
68
68
46
54
65
67
66
69
68
70
Toluene
CH2Cl2
DCE
DCE
DCE
59[b]
90
4
82
92
96
91
5[d]
6
0
7
DCE
DCE
À15
8[e]
À15
81
[a]
Isolated yield after flash chromatography.
Determined by H NMR using an internal standard.
Determined by SFC on chiral stationary phase.
Addition of the ligand to ZnEt2.
1.40 equivs. of ligand/1.25 equivs. of Et2Zn and CH2I2.
[b]
[c]
[d]
[e]
1
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Enantioselective Cyclopropanation
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Table 3. Ligand screening in the cyclopropanation reaction.
Entry
1
Ligand
C
Ar
Yield [%][a]
85
ee [%][b]
4a
42
2
3
4b
4c
C
77
75
39
24
4
5
4d
4e
4f
G
96
89
86
69
56
65
6
[a]
Isolated yield after flash chromatography.
Determined by SFC on chiral stationary phase.
[b]
the Simmons–Smith reaction, in other words ligands good selectivities. For the first time, a single class of
that can cyclopropanate functionalized and unfunc- ligands has shown enantioselectivities for the cyclo-
tionalized substrates. With the previously synthesized propanation of both functionalized and unfunctional-
chiral ligands and auxiliaries,[5,14] an allylic hydroxy ized alkenes. Further improvement in the design of
group was essential as a directing group to provide new chiral phosphate ligands and their application to
good conversion and stereocontrol for the cyclopropa- other asymmetric reactions are currently ongoing in
nation. There is only one efficient ligand for the cy- our laboratory.
clopropanation of unfunctionalized substrates;[16c]
however, the scope was limited to the styrenes and
silyl enol ethers.[17] In our case, with the ligand 4a,
even though the conversion was modest (15%) with
Experimental Section
1.25 equivalents of the chiral carbenoid, an enantio-
meric excess of 40% was achieved (entry 6). The con-
version was increased to 38% with the use of 2 equiv-
alents of carbenoid, without any change in enantiose-
lectivity (entry 7). For this substrate, the ligand 4d did
not provide better results (entry 8).
In summary, we have reported a practical synthesis
of six new chiral TADDOL-phosphates, which were
fully characterized, including an X-ray structure of 4a.
These ligands were used in the Simmons–Smith cyclo-
Crystallographic data (excluding structure factors) for the
structure reported in this paper have been deposited with
the Cambridge Crystallographic Data Centre as supplemen-
tary publication no. CCDC-610459. Copies of the data can
be obtained free of charge on application to CCDC,
12 Union Road, Cambridge CB2 1EZ, UK [Fax: int. code
+ 44(1223)336–033; E-mail: deposit@ccdc.cam.ac.uk].
A
Below is a representative synthesis of ligand 4a. Syntheses
of all other ligands mentioned in this manuscript are avail-
propanation reaction and gave excellent yields and able in the Supporting Information.
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Arnaud Voituriez and AndrØ B. Charette
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Table 4. Scope of the reaction.
Entry
Ligand
Substrate
T [8C]
Yield [%][a]
ee [%][b]
1
2
3
4
4d
4d
4d
4d
4d
4a
4a
4d
A
B
C
D
E
F
0
0
0
0
rt
rt
rt
rt
96
69
87
97
88
69
73[c]
69
75
69
5 40
40
31
5
[d]
6
1
7[e]
8
F
F
38[d]
6[d]
[a]
Isolated yield after flash chromatography.
Determined by SFC on chiral stationary phase.
Determined by HPLC on chiral stationary phase.
Determined by GC analysis.
[b]
[c]
[d]
[e]
2.00 equivs. of L*ZnCH2I.
Substrates:
white solid; yield: 5.62 g (75% for two steps); Rf =0.41
(Et2O pure); mp 114–1168C; H NMR (300 MHz, CDCl3):
3-{[(3aR,8aR)-2,2-Dimethyl-6-oxido-4,4,8,8-tetra-
1
phenyltetrahydro
[1,3]dioxolo
G
N
d=7.61–7.55 (m, 4H, H-Ph), 7.46–7.22 (m, 16H, H-Ph), 5.43
(d, J=8.1Hz, 1H, -C H-CPh2-), 5.15 (d, J=8.1Hz, 1H, -C H-
CPh2-), 3.92–3.85 (m, 1H, -OCH2CHHCN), 3.43–3.35 (m,
1H, -OCHHCH2CN), 2.22–2.14 (m, 1H, -OCH2CHHCN),
2.01–1.91 (m, 1H, -OCHHCH2CN), 0.83 (s, 3H, CH3), 0.50
(s, 3H, CH3); 13C NMR (75 MHz, CDCl3): d=143.8, 143.7,
143.2, 143.2, 139.5 (d, JP,C =6.7 Hz), 139.0 (d, JP, C =10.0 Hz),
129.0, 128.6, 128.4, 128.3, 128.0, 128.0, 127.7, 127.3, 126.9,
116.2, 113.9, 88.8 (d, JP, C =7.5 Hz), 88.4 (d, JP, C =8.3 Hz),
phosphepin-6-yl]oxy}propanenitrile (3a)
To a stirred solution of (R,R)-(Me,Me)-TADDOL-(Ph) 1a
(6.02 g, 12.9 mmol) and triethylamine (6.09 mL, 43.9 mmol,
3.4 equivs.) in dry THF (50 mL) at 08C was added dropwise
PCl3 (1.18 mL, 13.6 mmol, 1.05 equivs.). The resulting mix-
ture was stirred at 08C for 1h. A solution of 3-hydroxypro-
pionitrile (969 mL, 14.2 mmol, 1.1 equivs.) in dry THF
(50 mL) was then added dropwise via cannula. The reaction
mixture was allowed to warm to room temperature and stir-
red for 2 h. The reaction mixture was diluted with THF and
the triethylammonium chloride salts were filtered through a
celite pad. The solvent was removed under vacuum. The ob-
tained light yellow solid 2a was directly used without purifi-
cation in the oxidation step. To the crude phosphite in
CH2Cl2 (80 mL) was added 30% aqueous H2O2 (8.77 mL,
77.4 mmol, 6.0 equivs.). The biphasic mixture was stirred
vigorously for 20 min and then quenched by the addition of
100 mL of saturated aqueous NaHCO3. The mixture was ex-
tracted with CH2Cl2 and the combined organic extracts were
washed with saturated aqueous NaCl, dried (MgSO4), fil-
tered and concentrated. Purification by flash chromatogra-
phy (hexane/Et2O: 80/20 to pure Et2O) afforded 3a as a
80.0, 78.2, 62.0 (d, JP, C =4.9 Hz), 26.9, 26.2, 19.0 (d, JP, C
=
=
8.5 Hz); 31P NMR (162 MHz, CDCl3): d=À11.95; IR: nmax
3060, 2989, 2935, 2254 (CN), 1601, 1495, 1447, 1383, 1287,
1215, 1165, 1006, 941, 741, 696 cmÀ1; HR-MS (ESI): m/z=
604.1843, calcd. for C34H32NO6NaP [M+Na]+: 604.1859;
[a]2D0: À196.5 (c 1.79, CHCl3).
AHCTREUNG
A
N
ACHTREUNG
To a stirred solution of 3a (5.06 g, 8.70 mmol) in dry CH2Cl2
(100 mL) was added, dropwise at room temperature, 1,8-
diazabicyclo[5.4.0]undec-7-ene (DBU) (1.39 mL, 9.13 mmol,
G
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Enantioselective Cyclopropanation
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1.05 equivs.). The solution was stirred 30 min at room tem-
perature and when the reaction was complete by TLC,
AcOH (0.5 mL) was added, followed by H2O (50 mL). The
organic layer was then washed two times with a 0.3M HCl
solution, saturated aqueous NaCl solution, and dried
(MgSO4), filtered and concentrated. The resulting white
solid 4a was dried under vacuum, and can be used directly
in asymmetric cyclopropanation; yield: 4.56 g (99%); mp
154–1568C;. This compound was kept several months at
À208C without degradations. 1H NMR (400 MHz, CDCl3):
d=7.65–7.60 (m, 4H, H-Ph), 7.50–7.40 (m, 4H, H-Ph), 7.37–
7.22 (m, 12H, H-Ph), 5.32 (s, 2H, -CH-CPh2-), 0.74 (s, 6H,
2”CH3); 13C NMR (100 MHz, CDCl3): d=143.5, 139.6 (d,
Moisan, Angew. Chem. 2004, 116, 5248–5286; Angew.
Chem. Int. Ed. 2004, 43, 5138–5175.
[2] a) T. Akiyama, J. Itoh, K. Yokota, K. Fuchibe, Angew.
Chem. 2004, 116, 1592–1594; Angew. Chem. Int. Ed.
2004, 43, 1566–1568; b) T. Akiyama, H. Morita, J. Itoh,
K. Fuchibe, Org. Lett. 2005, 7, 2583–2585; c) T. Akiya-
ma, Y. Tamura, J. Itoh, H. Morita, K. Fuchibe, Synlett
2006, 141–143; d) D. Uraguchi, M. Terada, J. Am.
Chem. Soc. 2004, 126, 5356–5357; e) D. Uraguchi, K.
Sorimachi, M. Terada, J. Am. Chem. Soc. 2004, 126,
11804–11805; f) D. Uraguchi, K. Sorimachi, M. Terada,
J. Am. Chem. Soc. 2005, 127, 9360–9361; g) M. Terada,
K. Machioka, K. Sorimachi, Angew. Chem. 2006, 118,
2312–2315; Angew. Chem. Int. Ed. 2006, 45, 2254–
2257; h) M. Rueping, E. Sugiono, C. Azap, T. Theiss-
mann, M. Bolte, Org. Lett. 2005, 7, 3781–3783; i) M.
Rueping, E. Sugiono, C. Azap, Angew. Chem. 2006,
118, 2679–2681; Angew. Chem. Int. Ed. 2006, 45, 2617–
2619; j) M. Rueping, A. P. Antonchick, T. Theissmann,
Angew. Chem. 2006, 118, 3765–3768; Angew. Chem.
Int. Ed. 2006, 45, 3683–3686; k) S. Hoffmann, A. M.
Seayad, B. List, Angew. Chem. 2005, 117, 7590–7593;
Angew. Chem. Int. Ed. 2005, 44, 7424–7427; l) J.
Seayad, A. M. Seayad, B. List, J. Am. Chem. Soc. 2006,
128, 1086–1087; m) S. Mayer, B. List, Angew. Chem.
2006, 118, 4299–4301; Angew. Chem. Int. Ed. 2006, 45,
4193–4195; n) R. I. Storer, D. E. Carrera, Y. Ni,
D. W. C. MacMillan, J. Am. Chem. Soc. 2006, 128, 84–
86.
J
P, C =8.7 Hz), 128.8, 128.2, 128.2, 127.7, 127.3, 127.0, 113.7,
87.9 (d,
J
P,C =5.2 Hz), 79.6, 26.7; 31P NMR (162 MHz,
CDCl3): d=À8.13; IR: nmax =3060, 2989, 2935, 1600, 1495,
1448, 1383, 1287, 1215, 1165, 1009, 997, 733, 695 cmÀ1; HR-
MS (ESI): m/z=551.1589, calcd. for C31H29O6NaP [M+
Na]+: 551.1593; [a]D20: À210.8 (c 2.64, CHCl3).
General Procedure for the Cyclopropanation using
Chiral Phosphate Ligands Derived from TADDOL
4a–f
To a solution of the ligand (0.31mmol, 1.25 equivs.) in DCE
(1.5 mL) at À158C was added ZnEt2 (32 mL, 0.31mmol,
1.25 equivs.) dropwise. This solution was stirred for 15 min
after which CH2I2 (25 mL, 0.31mmol, 1.25 equivs.) was
added dropwise. This solution was stirred for an additional
20 min.A solution of substrate (0.25 mmol, 1.0 equiv.) in
DCE (1.0 mL) was added and the resulting solution was stir-
red for 48 h. The reaction was quenched with saturated
NH4Cl solution, washed with saturated aqueous NaCl, dried
(MgSO4), filtered and concentrated. It is noteworthy that
the chiral ligand could be readily recovered after the reac-
tion by simple precipitation with CH2Cl2/hexane and filtra-
tion. The crude product was purified by flash chromatogra-
phy to afford the pure desired cyclopropane derivative. All
the cyclopropanes synthesized have spectral and physical
data identical to the data reported in the literature.
[3] G. B. Rowland, H. Zhang, E. B. Rowland, S. Chenna-
madhavuni, Y. Wang, J. C. Antilla, J. Am. Chem. Soc.
2005, 127, 15696–15697.
[4] M. Terada, K. Sorimachi, D. Uraguchi, Synlett 2006,
133–136.
[5] M.-C. Lacasse, C. Poulard, A. B. Charette, J. Am.
Chem. Soc. 2005, 127, 12440–12441.
[6] During the preparation of this manuscript, Akiyama
et al. reported, without synthetic details, the use of sim-
ilar chiral phosphates in a Mannich-Type reaction: T.
Akiyama, Y. Saitoh, H. Morita, K. Fuchibe, Adv. Synth.
Catal. 2005, 347, 1523–1526.
[7] For a general review on TADDOL: D. Seebach, A. K.
Beck, A. Heckel, Angew. Chem. 2001, 113, 96–142;
Angew. Chem. Int. Ed. 2001, 40, 92–138.
Acknowledgements
[8] a) A. B. Charette, C. Brochu, J. Am. Chem. Soc. 1995,
117, 11367–11368; b) A. B. Charette, C. Molinaro, C.
Brochu, J. Am. Chem. Soc. 2001, 123, 12160–12167;
c) A. B. Charette, C. Molinaro, C. Brochu, J. Am.
Chem. Soc. 2001, 123, 12168–12175.
This work was supported by NSERC (Canada) and the Uni-
versitØ de MontrØal. We acknowledge Francine BØlanger-Gar-
iepy for X-ray technical support.
[9] a) A. K. Beck, B. Bastani, D. A. Plattner, W. Petter, D.
Seebach, H. Braunschweiger, P. Gysi, L. LaVeccia,
Chimia, 1991, 45, 238–244; b) D. Seebach, R. Dahin-
den, R. E. Marti, A. K. Beck, D. A. Plattner, F. N. M.
Kꢁhnle, J. Org. Chem. 1995, 60, 1788–1799.
[10] a) Review of phosphorus protection strategies for poly-
nucleotide synthesis: H. Kossel, H. Seliger, Fortschr.
Chem. Org. Naturst. 1975, 32, 297–508; b) phosphite
protected by a 2-cyanoethyl group: N. D. Sinha, J. Bier-
nat, H. Kçster, Tetrahedron Lett. 1983, 24, 5843–5846;
c) D. A. Evans, J. R. Gage, J. L. Leighton, J. Am.
Chem. Soc. 1992, 114, 9434–9453.
References
[1] For recent reviews, see: a) B. List , Tetrahedron 2002,
58, 5573–5590; b) B. List, Acc. Chem. Res. 2004, 37,
548–557; c) A. Berkessel, H. Grçger. Asymmetric Or-
ganocatalysis - From Biomimetic Concepts to Applica-
tions in Asymmetric Synthesis Wiley-VCH, Weinheim,
2005; d) W. Notz, F. Tanaka, C. F. Barbas, III, Acc.
Chem. Res. 2004, 37, 580–591; e) P. I. Dalko, L.
Moisan, Angew. Chem. 2001, 113, 3840–3864; Angew.
Chem. Int. Ed. 2001, 40, 3726–3748; f) P. I. Dalko, L.
Adv. Synth. Catal. 2006, 348, 2363 – 2370
ꢀ 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.asc.wiley-vch.de
2369

Arnaud Voituriez and AndrØ B. Charette
COMMUNICATIONS
[11] I. Fujii, N. Hirayama, Helv. Chim. Acta 2002, 85, 2946–
2960.
Shibasaki, M. Ohno, N. Imai, S. Kobayashi, Tetrahedron
1995, 51, 12013–12026; c) S. E. Denmark, S. P. OꢂCon-
nor, J. Org. Chem. 1997, 62, 584–594.
[12] a) H. E. Simmons, T. L. Cairns, S. A. Vladuchick, C. M.
Hoiness, Org. React. 1973, 20, 1–131; b) A. B. Charette,
A. Beauchemin, Org. React. 2001, 58, 1–415; c) H.
Lebel, J. F. Marcoux, C. Molinaro, A. B. Charette,
Chem. Rev. 2003, 103, 977–1050.
[13] a) A. B. Charette, S. Francoeur, J. Martel, N. Wilb,
Angew. Chem. 2000, 112, 4713–4716; Angew. Chem.
Int. Ed. 2000, 39, 4539–4542; b) A. B. Charette, A.
Beauchemin, S. Francoeur, J. Am. Chem. Soc. 2001,
123, 8139–8140; c) A. Charette, A. Beauchemin, S.
Francoeur, F. BØlanger-GariØpy, G. D. Enright , Chem.
Commun. 2002, 466–467; d) A. B. Charette, H. Juteau,
H. Lebel, C. Molinaro, J. Am. Chem. Soc. 1998, 120,
11943–11952.
[15] With the corresponding simple diol TADDOL(Ph), we
obtained only 52% conversion with 12% ee in the cy-
clopropanation of benzyl-protected cinnamyl alcohol.
[16] a) Z. Q. Yang, J. C. Lorentz, Y. Shi, Tetrahedron Lett.
1998, 39, 8621–8624; b) J. C. Lorentz, J. Long, Z. Q.
Yang, S. Xue, Y. Xie, Y. Shi, J. Org. Chem. 2004, 69,
327–334; c) J. Long, Y. Yuan, Y. Shi, J. Am. Chem.
Soc. 2003, 125, 13632–13633; d) J. Long, H. Du, K. Li,
Y. Shi, Tetrahedron Lett. 2005, 46, 2737–2740; e) H.
Du, J. Long, Y. Shi Org. Lett. 2006, 8, 2827–2829.
[17] In the cyclopropanation of the benzylated cinnamylic
alcohol (substrate A with Shiꢂs ligand (the dipeptide N-
Boc-l-Val-l-Pro-OMe) 7% ee was obtained with 81%
yield (unpublished results).
[14] a) H. Kitajima, Y. Aoki, K. Ito, T. Katsuki, Chem. Lett.
1995, 1113–1114; b) H. Takahashi, M. Yoshioka, M.
2370
www.asc.wiley-vch.de
ꢀ 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2006, 348, 2363 – 2370