Synthesis and screening of new chiral ligands for the copper-catalysed enantioselective allylic substitution

Article abstract of DOI:10.1002/1522-2675(200210)85:10<3388::AID-HLCA3388>3.0.CO;2-I

The synthesis of the new chiral ligands 6ae, 8ae, 9ae, and 11ae starting from the chiral β[(Boc)amino]-sulfonamide 3ae is reported. The β-amino group of 3ae was deprotected and condensed with 3,5-dichlorosalicylaldehyde (4) to yield the known Schiff base 5ae, which was then reduced to the amino compound 6ae (Scheme 3). Alternatively, condensation of the free amino compound with 2-(diphenylphosphanyl)benz-aldehyde (7) afforded the imino ligand 8ae which upon reduction yielded the amino ligand 9ae (Scheme 4). The free amino compound derived from 3ae was also coupled with 2-(diphenylphosphanyl)benzoic acid (10) to give ligand 11ae (Scheme 5). These ligands were tested in the copper-catalysed allylic substitution reaction of cinnamyl (= 3-phenylprop-2-enyl) phosphate 12 with diethylzinc as a nucleophile. Ligands 5ae, 6ae, 8ae, and 11ae gave excellent ratios (100:0) of the S_N2′/S_N2 products (Scheme 6 and Table 1). Ligand 11ce, identified from the screening of a small library of ligands of general formula 11, promoted the allylic substitution reaction with moderate enantioselectivity (40% for the S_N2′ product 13 (Scheme 8 and Table 3)).

Full text of DOI:10.1002/1522-2675(200210)85:10<3388::AID-HLCA3388>3.0.CO;2-I

3388
Helvetica Chimica Acta Vol. 85 (2002)
Synthesis and Screening of New Chiral Ligands for the Copper-Catalysed
Enantioselective Allylic Substitution
by Sandrine Ongeria), Umberto Piarulli*a)b), Maryline Rouxa), Chiara Montia)c), and Cesare Gennari*a)
a
¡
) Dipartimento di Chimica Organica ed Industriale, Universita degli Studi di Milano, Istituto di Scienze e
Tecnologie Molecolari del CNR, Via Venezian 21, I-20133 Milano
(fax: ‡390250314072; e-mail: cesare.gennari@unimi.it)
b
¡
) Dipartimento di Scienze Chimiche, Fisiche e Matematiche, Universita degli Studi dell×Insubria, Via Valleggio 2,
I-22100 Como (e-mail: umberto.piarulli@uninsubria.it)
c) Department of Chemistry, University of Sheffield, Sheffield S37 HF, UK
This paper is dedicated to Professor Dieter Seebach, on the occasion of his 65th birthday, for his prominent
contributions to synthetic chemistry
The synthesis of the new chiral ligands 6ae, 8ae, 9ae, and 11ae starting from the chiral b-[(Boc)amino]-
sulfonamide 3ae is reported. The b-amino group of 3ae was deprotected and condensed with 3,5-
dichlorosalicylaldehyde (4) to yield the known Schiff base 5ae, which was then reduced to the amino compound
6ae (Scheme 3). Alternatively, condensation of the free amino compound with 2-(diphenylphosphanyl)benz-
aldehyde (7) afforded the imino ligand 8ae which upon reduction yielded the amino ligand 9ae (Scheme 4). The
free amino compound derived from 3ae was also coupled with 2-(diphenylphosphanyl)benzoic acid (10) to give
ligand 11ae (Scheme 5). These ligands were tested in the copper-catalysed allylic substitution reaction of
cinnamyl (ˆ 3-phenylprop-2-enyl) phosphate 12 with diethylzinc as a nucleophile. Ligands 5ae, 6ae, 8ae, and
11ae gave excellent ratios (100 :0) of the SN2'/SN2 products (Scheme 6 and Table 1). Ligand 11ce, identified from
the screening of a small library of ligands of general formula 11, promoted the allylic substitution reaction with
moderate enantioselectivity (40% for the SN2' product 13 (Scheme 8 and Table 3)).
Introduction. The efficiency (activity and selectivity) of a ligand for asymmetric
catalysis depends on a subtle balance of the electronic, geometric, and steric influences
between the ligand, the metal center, and the substrate. In such a complicated scenario,
the development of effective new ligands and metal complexes based purely on
intuition and trial-and-error is a very challenging task. The use of combinatorial
methodologies for the rapid synthesis and screening of a large number of structures
represents an important breakthrough in this area1). Two different basic approaches
have been considered: optimization of the reaction conditions (solvent, temperature,
stoichiometry, different ligands or metal ions) and the synthesis of new ligands via a
modular building-block strategy, where the stereoelectronic properties of a metal-
binding site (e.g. a phosphine, a sulfonamide, or a Schiff base) are tuned by variation of
the substituents and side chains. In the case of screening members of a library
containing ligands for enantioselective catalysis, the identification of a hit requires a
demanding selection procedure, since the screening ultimately involves catalysis of a
1
)
For reviews on the combinatorial development of new catalysts, see [1]. See also [2a k]. For the screening
of a pooled stereoselective polymerization catalyst library, see [2l].

Helvetica Chimica Acta Vol. 85 (2002)
3389
reaction and analysis of its stereochemical outcome. For this reason, a combinatorial
system that allows the synthesis of discrete isolated compounds is usually chosen.
Parallel synthesis (as opposed to the −split and pool× methodology) allows one to know
the identity of each ligand and keeps the ligands separate so that screening of individual
complexes can be performed.
We have recently developed a new family of chiral Schiff-base ligands of general
structure 5 (Scheme 1), which contains a set of different metal-binding sites (a phenol,
an imine, and a secondary sulfonamide moiety), with the expectation that such a
multidentate array would favor the formation of organometallic complexes with well-
organized spatial arrangements, and with the goal of obtaining ligands for asymmetric
catalysis capable of broad applicability. The main feature of these ligands is their
modular assembly through the subsequent coupling of the three components
(Scheme 1), namely sulfonyl chlorides 1, amines 2, and aldehydes 4, which make these
ligands well-suited for a combinatorial development. A library of ligands 5 (125 com-
pounds) was synthesized in solution (with resin scavenging of excess reagents and by-
products) and tested in the copper-catalysed, conjugate addition of Et2Zn to enones
[3a,c] and nitroolefins [3b].
Scheme 1. Synthesis of a Library of Chiral Schiff-Base Ligands 5 [3]
R1
O2
S
R1
NHR2
R2NH2
BocHN
+
SO2Cl
BocHN
1
2
3
R1
O
O
S
NHR2
1) Boc removal
N
CHO
2)
OH
R3
5
OH
R3
4
Results and Discussion. To broaden the scope of this approach, we undertook a
variation of the ligand structure by transformation or substitution of the phenolic
Schiff-base moiety. The newly synthesized ligands 6, 8, 9, and 11 (Fig.) containing the
chiral b-aminosulfonamide substructure were screened in the copper-catalysed allylic
substitution reaction of cinnamyl phosphate with diethylzinc as a nucleophile.
A small library of ligands of general formula 11 were prepared and screened for
enantioselective allylic substitution.
Synthesis of the Ligands. The synthesis of a few representatives of the different
ligand classes 6, 8, 9, and 11 was undertaken starting from sulfonyl chloride 1a (R1 ˆ
PhCH2) [4]. Sulfonyl chloride 1a was coupled to an excess of amine 2e (1.2 equiv.) in
the presence of dimethylketene methyl trimethylsilyl acetal (DMTA) (2.0 equiv.) and a
catalytic amount (0.2 equiv.) of N,N-dimethylpyridin-4-amine (DMAP) in CH2Cl2
(Scheme 2) [4a]. Once the coupling was complete, the reaction mixture was washed

3390
Helvetica Chimica Acta Vol. 85 (2002)
R1
R1
O2
S
O2
S
NHR2
N
H
NHR2
N
PPh2
OH
R3
8
6
R1
O
R1
O2
S
O2
S
NHR2
N
H
NHR2
N
H
PPh2
PPh2
9
11
Figure. Chiral ligands 6, 8, 9 and 11
Scheme 2. Synthesis of Sulfonamide 3ae
DMTA (2 equiv.),
DMAP (0.2 equiv.)
Ph
Ph
O2
S
H2N
+
SO2Cl
BocHN
BocHN
N
H
CH2Cl2, r.t., 2h
1a
2e
3ae
with a saturated citric acid solution, and sulfonamide 3ae was obtained in 88% yield
without the need for any further purification.
Removal of the Boc protecting group of 3ae (25% CF3COOH in CH2Cl2) afforded
the trifluoroacetate ammonium salt, which was then liberated (NaHCO3). The
resulting amino compound was then transformed into the different ligands 5ae, 6ae,
8ae, 9ae, and 11ae. Thus, condensation with 3,5-dichlorosalicylaldehyde (4) in MeOH
yielded the Schiff-base ligand 5ae in practically quantitative yield without the need for
any further purification. Schiff-base ligand 5ae was then reduced to the amino
compound 6ae by reaction with NaBH3CNin MeOH in the presence of HCl [5].
Formation of the Schiff-base ligand 8ae required a different synthetic protocol:
condensation of the amino compound obtained by deprotection of b-[(Boc)amino]-
sulfonamide 3ae with 2-(diphenylphosphanyl)benzaldehyde was performed in dry
toluene at room temperature with MgSO4 as dehydrating agent [6]. Removal of the salt
by filtration and evaporation of toluene afforded 8ae, which was not further purified.
Reduction of the imino moiety of ligand 8ae under the same conditions as described
above yielded the amino ligand 9ae in 63% yield.
For the synthesis of 11ae, the chiral b-aminosulfonamide derived from 3ae was
coupled with 2-(diphenylphosphanyl)benzoic acid (10) in the presence of BOP ((1H-
benzotriazol-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate) and
Et3N[7] (70% yield). Use of EDC ( N-[3-(dimethylamino)propyl]-N'-ethylcarbodi-
imide]) and DMAP in THF [8] proved less satisfactory (yield ꢀ 29%).
With these ligands in our hands, we considered their application in the copper-
catalysed asymmetric allylic substitution.
Allylic-Substitution Reaction. The substitution of allylic alcohol derivatives by hard
C-nucleophiles, such as organometallics, has recently attracted much attention, and

Helvetica Chimica Acta Vol. 85 (2002)
3391
Scheme 3. Synthesis of Schiff-Base Ligand 5ae and Reduction to the Amino Ligand 6ae
Ph
O2
S
1) 25%
2) NaHCO3
in CH Cl
2 2
CF COOH
3
Cl
N
N
H
3ae
OH
3)
Cl
CHO
5ae
Cl
, CH3OH
OH
Cl
NaBH3CN,
HCl, CH3OH
4
Ph
O2
Cl
S
N
H
N
H
OH
6ae
Cl
Scheme 4. Synthesis of Imino Ligand 8ae and Reduction to the Amino Ligand 9ae
Ph
O2
S
1) 25%
2) NaHCO3
in CH Cl
2 2
CF COOH
3
N
N
H
3ae
PPh2
3)
CHO
8ae
, MgSO4, toluene
PPh2
NaBH3CN,
7
HCl, CH3OH
Ph
O2
S
N
H
N
H
PPh2
9ae
several methods have been developed for the control of the regio- and stereochemistry
in this type of reaction. The leaving group can be displaced either in an a (SN2) or g
(SN2') fashion by the organometallic reagent depending on the substrate, leaving group,
organometallic, and metal source. Some enantioselective protocols that use catalytic
amounts of a chiral copper complex, and organozinc [9] or Grignard [10] reagents have
recently appeared: high ee were obtained in special cases with hindered organozinc
reagents [9a] or 3-substituted cinnamyl (ˆ 3-phenylprop-2-enyl) derivatives leading to

3392
Helvetica Chimica Acta Vol. 85 (2002)
Scheme 5. Synthesis of Amide Ligand 11ae
Ph
O
1) 25%
in CH Cl
2 2
CF COOH
3
O2
S
2) NaHCO3
N
H
N
H
3ae
COOH
3)
PPh2
BOP, Et3N, THF
11ae
PPh2
10
quaternary C-atoms [9b]. We decided to test the chiral Schiff-base ligand 5ae and the
modified ligands 6ae, 8ae, 9ae, and 11ae in the copper-catalysed allylic substitution of
cinnamyl derivatives with diethylzinc. At the beginning, we screened several cinnamyl
derivatives to find a suitable substrate; it was soon clear that halogenated derivatives
(chloride and bromide) did not give a regioselective substitution reaction (low SN2'/SN2
ratio) either in the presence or absence of ligands. In the case of cinnamyl chloride (ˆ 3-
chloro-1-phenylprop-1-ene), a smooth reaction took place in toluene at À208, even in
the absence of any copper source, yielding an equimolar mixture of SN2' and SN2
products 13 and 142). Following the discovery by Hoveyda et al. of cinnamyl phosphate
12 as a suitable substrate for the enantioselective copper-catalysed allylic substitution
with alkylzinc reagents [9b], we screened ligands 5ae, 6ae, 8ae, 9ae, and 11ae using
CuCNas the metal salt (see Scheme 6 and Table 1). All ligands (except 9ae, Entry 7)
gave fair-to-good yields in THF (the reaction did not proceed in toluene) with
practically complete SN2' regioselectivity (13/14 100 :0). As for the enantioselectivity,
all the ligands tested gave racemic mixtures, except for 11ae which gave 13 with a very
modest 9% ee (Entry 8).
Scheme 6. Copper-Catalysed Allylic Substitution of Cinnamyl Phosphate 12 with Et2Zn
O
Et2Zn, CuY, L*
+
Ph
Ph
OP(OEt)2
Ph
solvent, T (°)
12
13
14
Table 1. Copper-Catalysed Allylic Substitution of Cinnamyl Phosphate 12 with Diethylzinc (see Scheme 6)
Entry
L*
CuY
Solvent
THF
T [8]
Conversiona)
SN2'/SN2 (13/14)a)
ee (13)a)
1
2
3
4
5
6
7
8
À 30
À 30
0
0
CuCNTHF
CuCNTHF
CuCNTHF
CuCNTHF
CuCNTHF
CuCNTHF
CuCNTHF
0
39
100 : 0
5ae
6ae
8ae
9ae
11ae
À 30
À 30
À 30
À 30
À 30
100
55
53
0
100 : 0
100 : 0
100 : 0
0
0
0
91
100 : 0
9
a) Determined by chiral GC analysis (Megadex DACTBSb) with decane as internal standard.
2
)
Feringa et al. showed that cinnamyl halides can be used as substrates for the enantioselective copper-
catalysed allylic substitution only in strongly coordinating solvent (e.g., diglyme) [9c].

Helvetica Chimica Acta Vol. 85 (2002)
3393
A screening of the copper sources was then performed with 11ae as ligand
(Table 2), and a more-interesting 30% ee was obtained by lowering the temperature to
À558 and running the reaction in the presence of copper(I) triflate dimer (benzene
complex) (Entry 1). The use of copper(II) triflate gave almost complete SN2'
regioselectivity and the same ee, albeit in much lower yield (Entry 2).
Table 2. Copper-Catalysed Allylic Substitution of Cinnamyl Phosphate 12 with Diethylzinc, Chiral Ligand 11ae,
and Different Copper Sources
Entry
L*
CuY
Solvent
T [8]
Conversiona)
SN2'/SN2 (13/14)a)
ee (13)a)
1
2
3
4
5
11ae
11ae
11ae
11ae
11ae
[(CuOTf)2 ¥ C6H6]
Cu(OTf)2
CuCNTHF
CuBr¥ SMe2
CuI
THF
THF
À 55
À 55
À 55
À 55
À 55
95
15
0
10
0
89 : 11
100 : 0
30
30
THF
THF
85 : 15
0
a) Determined by chiral GC analysis (Megadex DACTBSb) with decane as internal standard.
Based on these results, we undertook the synthesis of a small library of ligands of
general formula 11, changing the residues at the b-position of the b-aminosulfonamide
(R1) and at the N-atom of the amide moiety (R2). Thus 14 different ligands were
prepared starting from the 4-different b-aminosulfonyl chlorides [4] 1a d (R1 ˆ Me,
i
i
PhCH2, Pr, Bu) and 7 different amines 2e k according to the general procedure
described above3)4) (Scheme 7).)
The screening of the ligands required complexation in situ with [(CuOTf)2 ¥ C6H6] in
THF at room temperature for 45 min. After addition of phosphate 12, the reaction
mixture was cooled to À788, and Et2Zn was added. The mixtures were warmed to À558
and stirred for 20 h before quenching with NH4Cl (Scheme 8). The ee and conversions
were measured by GC with a chiral column and with decane as an internal standard.
The absolute configuration of the stereogenic center of 13 was assigned as (S), based
on the sign of the optical rotation [11]. The results are summarized in Table 3.
From these results, one can draw the following conclusions: a) The stereogenic
center bearing R1 dictates the absolute configuration of compound 13, and not the
stereogenic center present in R2 (cf. Entries 4 and 5, Table 3). b) The ee of 13 depends
on a subtle balance of the mutual influences of R1 and R2; no linear relationship
between the steric hindrance of these residues and ee can be clearly identified. c) The
best combination of R1 and R2 (R1 ˆ iPr and R2 ˆ (S)-ChxCH(Me)), i.e. ligand 11ce,
gave 13 with an ee of 40% and a ratio 13/14 of 90 :10.
Conclusions. We reported the synthesis of the new chiral ligands 6, 8, 9, and 11
(Fig.), encompassing the chiral b-aminosulfonamide substructure. These ligands were
3
)
We did not synthesize the full matrix of all possible different ligands (i.e. 7 ¥ 4 ˆ 28), but only half of them
(14). We followed a sort of −positional scanning× approach, e.g., synthesized ligands 11ce ck with all seven
possible R2 (e k) in the case of the best R1 (c).
In some cases, after removal of the Boc protecting group from the amino group, the amino derivative was
obtained from the intermediate trifluoroacetate salt by treatment with Et3N(2 equiv.) in THF. The resulting
solution was used directly in the following coupling step with 2-(diphenylphosphanyl)benzoic acid.
4
)

3394
Helvetica Chimica Acta Vol. 85 (2002)
Scheme 7. Synthesis of the Library of Ligands 11
DMTA (2 equiv.),
DMAP (0.2 equiv.)
R1
R1
O2
S
+
R2NH2
SO2Cl
BocHN
BocHN
NHR2
CH2Cl2, r.t., 2h
3ae, 3af,...3dk
1a-1d
2e-2k
O
R1
1) 25%
in CH Cl
2 2
CF COOH
O2
S
2) NaHCO3, or Et3N in THF
3
N
H
NHR2
COOH
3)
PPh2
BOP, Et3N, THF
PPh2
11ae, 11af,...11dk
10
2e R2 = (S)-ChxCH(Me)
R2 = (R)-ChxCH(Me)
1a R1 = PhCH2
b R1 = Me
f
g R2 =
c R1 =
PhCH2
i
i
Pr
2
d R1 = iBu
h R = Pr
i
R2 = Ph2CH
R2 = (S)-CH2 (OH)CH(Ph)
j
k R2 = (S)PhCH(Me)
Scheme 8. Screening of the Library of Ligands 11 in the Copper-Catalysed Allylic Substitution of Cinnamyl
Phosphate 12 with Et2Zn
Et2Zn,
[(CuOTf)2 · C6H6], L*
Et
O
+
Ph
Et
Ph
OP(OEt)2
Ph
THF, -78
-55 °
13
14
12
O
R1
O2
S
R2
N
H
N
H
L* =
PPh2
11
tested in the copper-catalysed allylic substitution reaction of cinnamyl phosphate with
diethylzinc as a nucleophile. Ligands 5, 6, 8, and 11 gave excellent ratios (100 :0) of the
SN2'/SN2 products 13 and 14. The screening of a small library of ligands of general
formula 11 (14 compounds) allowed the identification of 11ce as the best ligand for
enantioselective allylic substitution (ee 40% for the SN2' product 13). Work is now in
progress to test the applicability of these ligand structures to other catalytic asymmetric
reactions of interest.

Helvetica Chimica Acta Vol. 85 (2002)
3395
Table 3. Copper-Catalysed Allylic Substitution of Cinnamyl Phosphate 12 with Diethylzinc, [(CuOTf)2 ¥ C6H6],
and a Library of Ligands 11 (see Scheme 8)
Entry
L*
R1
R2
Conversiona)
SN2'/SN2 (13/14)a)
ee (13)a)b)
1
2
3
4
5
6
7
8
9
10
11
12
13
14
11ae
11be
11de
11ce
11cf
PhCH2
Me
(S)-ChxCH(Me)
(S)-ChxCH(Me)
(S)-ChxCH(Me)
(S)-ChxCH(Me)
(R)-ChxCH(Me)
Ph2CH
95
50
76
93
55
41
75
7
80
3
50
17
65
100
89 : 11
89 : 11
89 : 11
90 : 10
87: 13
83 : 17
57: 43
75 : 25
80 : 20
30
30
38
40
21
13
0
iBu
iPr
iPr
11ci
iPr
11cg
11ch
11cj
11ck
11ak
11dk
11ah
11bg
iPr
PhCH2
iPr
iPr
0
13
iPr
(S)-CH2(OH)CH(Ph)
(S)-PhCH(Me)
(S)-PhCH(Me)
(S)-PhCH(Me)
iPr
iPr
PhCH2
iBu
PhCH2
Me
90 : 10
90 : 10
90 : 10
70 : 30
27
0
22
13
PhCH2
a) Determined by chiral GC analysis (Megadex DACTBSb) with decane as internal standard. b) The absolute
configuration of the stereogenic center of 13 was assigned as (S), based on the sign of the optical rotation [11].
We thank the European Commission (IHP Network grant −CombiCat× HPRN-CT-2000-00014) for financial
support, postdoctoral fellowships to M. Roux and S. Ongeri (at Milan University), and a postgraduate fellowship
to C. Monti (at Sheffield University). We also like to thank the −Merck Research Laboratories× (Merck×s
Academic Development Program Award to C. Gennari, 2001) for financial support. U. Piarulli thanks the
Department of Organic and Industrial Chemistry (Milan University) for the hospitality.
Experimental Part
General. Manipulations involving air-sensitive compounds were carried out under Ar by Schlenk and
syringe techniques. Anh. solvents were obtained from Na (toluene), sodium benzophenone ketyl (oxidodiphen-
ylmethyl sodium salt; THFand Et2O), or by refluxing over CaH2 for at least 4 h prior to use. Reagents were used
as received without any further purification and were generally purchased from Aldrich and Fluka AG.
Compounds 3ae [3c], 5ae [3c], and 12 [9a] were obtained as previously described. Anal. TLC: Merck silica-gel
60 F254 glass plates; visualization with UV light and by staining with a cerium reagent followed by heating. Flash
chromatography [12] (FC): silica gel 60 (230 400 mesh) from Macherey Nagel. GC: Dani GC-3800 instrument
equipped with a FID and a chiral capillary column (Megadex DACTBSb, decane as internal standard); tR in min.
Optical rotations: Perkin-Elmer 241 polarimeter. IR Spectra: Perkin-Elmer 681; in cmÀ1. NMR Spectra: Bruker
instruments (AC-200 and 400 Avance); d in ppm rel. to SiMe4; J in Hz.
1. (2S)-N-[(1S)-1-Cyclohexylethyl]-2-[(3,5-dichloro-2-hydroxybenzyl)amino]-3-phenylpropane-1-sulfon-
amide (6ae). To a soln. of 5ae (240 mg, 0.48 mmol) in MeOH (27 ml), NaBH3CNwas added (155 mg,
2.46 mmol). The soln. was stirred for 5 min and 37% (w/w) conc. HCl soln. (263 ml) was added dropwise. The
yellow soln. discolored, and stirring was maintained for 2 h at r.t. A 3m KOH soln. was added until the pH of the
soln. became basic, the mixture was diluted with H2O (50 ml) and extracted several times with CH2Cl2. The
combined org. extract was washed with brine, dried (Na2SO4), and evaporated; and the residue was purified by
FC (hexane/AcOEt 80 :20): 171 mg (71%) of pure 6ae. 1H-NMR (CDCl3, 400 MHz, 208): 1.75 0.83 (m, 14 H,
Chx, Me); 3.12 2.83 (m, CH2SO2, ChxCH(Me), PhCH2); 3.49 3.45 (m, ChxCH(Me)); 3.99 (s, CH2NH); 4.68
(br. s, NHSO2); 7.36 6.87 (m, arom. 7 H). 13C-NMR (CDCl3, 100.13 MHz): 19.4; 26.0; 26.2; 28.6; 28.8; 39.4;
43.5; 49.5; 54.9; 55.2; 55.8; 121.7; 123.6; 124.9; 126.7; 127.2; 128.6; 129.0; 129.3; 136.5; 152.3. IR (CHCl3): 1099
(CN), 1333 (SO2), 1435, 2857, 2932, 3387 (NH). [a]2D5 ˆ ‡15.2 (c ˆ 0.25, CHCl3). HR-EI-MS: 498.1276
‡
(C24H32Cl2N2O3S ; calc. 498.15).
2. (2S)-N-[(1S)-1-Cyclohexylethyl]-2-{[2-(diphenylphosphanyl)benzylidene]amino}-3-phenylpropane-1-
sulfonamide (8ae). b-[(Boc)amino]sulfonamide 3ae (50 mg, 0.12 mmol) was dissolved in 25% CF3COOH in
CH2Cl2 (5.2 ml). The resulting soln. was stirred for 1 h, and sat. aq. NaHCO3 soln. was added until pH 7. The aq.

3396
Helvetica Chimica Acta Vol. 85 (2002)
phase was extracted with AcOEt (6 Â 10 ml) and the combined org. extract dried (Na2SO4) and evaporated. The
residue was suspended in dry toluene (5 ml), and 2-(diphenylphosphanyl)benzaldehyde (33 mg, 0.12 mmol) and
anh. MgSO4 (14 mg, 0.12 mmol) were added. The resulting suspension was stirred at r.t. for 15 h under Ar. The
solid salts were filtered and washed with AcOEt, and the combined filtrates were evaporated to yield 70 mg
(quant.) of 8ae. 1H-NMR (CDCl3, 400 MHz, 208): 1.81 0.74 (m, 14 H, Chx, Me); 2.87 2.57 (m, CH2SO2);
3.29 3.19 (m, ChxCH(Me), PhCH2); 3.95 3.92 (m, CHNˆCH); 4.13 (d, J ˆ 8.78, NHSO2); 7.38 6.93
(m, 19 arom. H); 8.64 (s, CHˆN). 13C-NMR (CDCl3, 100.13 MHz): 18.8; 26.1; 26.3; 28.5; 29.0; 42.3; 43.7;
54.5; 57.8; 67.9; 126.6; 128.3; 128.6; 128.8; 128.9; 129.4; 129.6; 130.5; 133.5; 133.9 (d, J ˆ 19.6); 135.0 (d, J ˆ 18.8);
136.9 (d, J ˆ 19.5); 137 (d, J ˆ 19.7); 141.8 (d, J ˆ 27.8); 161.2; 161.4. IR (CHCl3): 960, 1340 (SO2), 1456 (CH2,
‡
Me), 1640 (CˆN), 3412 (NH). [a]D25 ˆ À155.71 (c ˆ 0.21, CHCl3). HR-EI-MS: 596.2664 (C36H41N2O2PS ; calc.
596.2626).
3. (2S)-N-[(1S)-1-Cyclohexylethyl]-2-{[2-diphenylphosphanyl)benzyl]amino}-3-phenylpropane-1-sulfon-
amide (9ae). As described for 6ae, with 8ae (290 mg, 0.48 mmol), MeOH (27 ml), NaBH3CN(149 mg,
2.37 mmol), and 37% (w/w) conc. HCl soln. (200 ml): 114 mg (39%) of pure 9ae. 1H-NMR (CDCl3, 400 MHz,
208): 1.84 0.82 (m, 15 H, Chx, Me, NH); 2.92 2.61 (m, CH2SO2); 3.07 2.99 (m, PhCH2); 3.27 3.25 (m, Chx,
CHMe); 3.51 3.47 (m, PhCH2CH); 4.26 3.93 (dd, J ˆ 114.69, 12.89, CH2NH); 4.97 (d, J ˆ 8.38, NHSO2);
7.49 6.91 (m, 19 arom. H). 13C-NMR (CDCl3, 100.13 MHz): 18.7; 26.1; 26.3; 28.5; 28.7; 40.0; 43.7; 49.7; 49.9;
54.3; 55.8; 56.6; 71.8; 126.6; 127.6; 128.6; 128.8; 128.9; 129.2; 129.4; 129.5; 133.7 (d, J ˆ 18.5); 134.0; 135.7 (d, J ˆ
18.8); 136.4 (d, J ˆ 19.5); 137.3 (d, J ˆ 19.7); 143.7 (d, J ˆ 23.6). IR (nujol): 710 (CÀP), 746 (SÀN), 1099 (CN),
‡
1310 (SO2), 3283 (NH). [a]2D5 ˆ ‡5.9 (c ˆ 0.51, CHCl3). HR-EI-MS: 598.2754 (C36H43N2O2PS ; calc. 598.2783).
4. Ligands 11. General Procedure a. b-(Boc)aminosulfonamide 3 (1 equiv.) was dissolved in 25%
CF3COOH in CH2Cl2 (0.1m based on the sulfonamide). The resulting soln. was stirred for 1 h, and sat. aq.
NaHCO3 soln. was added until pH 7. The aq. phase was extracted with AcOEt (6 Â 10 ml). The combined org.
extracts were dried (Na2SO4) and evaporated. In a separate flask, (1H-benzotriazol-1-yloxy)tris(dimethylami-
no)phosphonium hexafluorophosphate (BOP, 1 equiv.) was added to a soln. of 2-(diphenylphosphanyl)benzoic
acid in dry THF (1 equiv., 0.07m) and Et3N(1 equiv.). After 10 min, a soln. of the deprotected amino compound
in THF (0.35m) was added, and the mixture was stirred overnight. The mixture was evaporated and AcOEt
(10 ml) was added. The soln. was washed with 5% HCl, sat. NaHCO3 soln., and brine, and was dried (Na2SO4).
Purification by FC (hexane/AcOEt:) afforded pure 11.
General Procedure b. b-[(Boc)amino]sulfonamide 3 (1 equiv.) was dissolved in 25% CF3COOH in CH2Cl2
(0.1m based on the sulfonamide). The resulting soln. was stirred for 1 h and then evaporated. The residue was
dissolved in THF (0.35m based on the sulfonamide), and Et3N(2 equiv.) was added. The resulting soln. was
stirred for 30 min and directly used in the subsequent coupling step. In a separate flask, BOP (1 equiv.) was
added to a soln. of 2-(diphenylphosphanyl)benzoic acid in dry THF (1 equiv., 0.07m) and Et3N(1 equiv.). After
10 min, the soln. of the deprotected amino compound in THF/CF3COOH was added, and the mixture was
stirred overnight. After evaporation, AcOEt (10 ml) was added. The soln. was washed with 5% HCl soln. sat.
NaHCO3 soln., and brine, and was dried (Na2SO4). Purification by FC (hexane/AcOEt 8 :2) afforded pure 11.
N-{(1S)-1-Benzyl-2-{[(1S)-1-cyclohexylethyl]sulfamoyl}ethyl}-2-(diphenylphosphanyl)benzamide (11ae):
1H-NMR (CDCl3, 400 MHz, 208): 1.75 0.89 (m, 14 H, Chx, Me); 3.03 2.84 (m, CH2SO2); 3.14 3.13
(m, PhCH2); 3.31 3.26 (m, ChxCH(Me)); 4.73 4.68 (m, PhCH2CH); 4.79 (d, J ˆ 8.68, NHSO2); 6.5 (br.,
NHCO); 7.38 7.02 (m, 19 arom. H). 13C-NMR (CDCl3, 100.13 MHz): 19.4; 26.1; 26.3; 28.5; 29.0; 39.6; 43.6;
48.0; 54.8; 55.3; 57.0; 126.9; 127.6; 128.7; 129.1; 129.4; 130.4; 133.7 (d, J ˆ 19.1); 134.3; 136.7. IR (nujol): 734
(CÀP), 750 (SÀN), 1322 (SO2), 1646 (CˆN), 3440 (NH). [a]2D5 ˆ ‡9.0 (c ˆ 0.40, CHCl3). HR-EI-MS:
‡
612.2587 (C36H41N2O3PS ; calc. 612.2576).
N-{(1S)-2-{[(1S)-1-Cyclohexylethyl]sulfamoyl}-1-methylethyl}-2-(diphenylphosphanyl)benzamide (11be):
1H-NMR (CDCl3, 400 MHz, 208): 1.79 0.96 (m, 17 H, Chx, 2 Me); 3.23 3.08 (m, CH2SO2); 3.38 3.32
(m, ChxCH(Me)); 4.57 4.51 (m, N HCH(Me)); 4.69 (d, J ˆ 8.74, NHSO2); 7.67 6.96 (m, 14 arom. H).
13C-NMR (CDCl3, 100.13 MHz): 19.2; 19.7; 26.1; 26.3; 28.5; 29.0; 42.5; 43.7; 54.7; 58.1; 127.8; 128.6; 129.0;
130.3; 133.8 (d, J ˆ 16.5); 134.1; 134.8 (d, J ˆ 18.0); 136.3 (d, J ˆ 19.5); 136.8 (d, J ˆ 19.5); 142.8 (d, J ˆ 26.8);
168.7. IR (nujol): 698 (CÀP), 743 (SÀN), 1130, 1306 (SO2), 1520, 1640 (CˆN), 3221 (NH). [a]2D5 ˆ ‡14.0 (c ˆ
‡
0.30, CHCl3). HR-EI-MS: 536.2216 (C30H37N2O3PS ; calc. 536.2262).
N-{(1S)-1-{{[(1S)-1-Cyclohexylethyl]sulfamoyl}methyl}-3-methylbutyl}-2-(diphenylphosphanyl)benz-
amide (11de): 1H-NMR (CDCl3, 400 MHz, 208): 0.87 2.06 (m, 23 H, 3 Me, Chx, Me2CH, Me2CHCH2); 3.16
i
3.14 (m, CH2SO2); 3.38 (m, ChxCH(Me)); 4.44 (br. m, BuCH); 4.80 4.78 (m, NHSO2); 6.38 (br. s, CONH);
7.40 7.26 (m, 14 arom. H). 13C-NMR (CDCl3, 100.13 MHz): 19.4; 21.8; 22.8; 24.7; 26.2; 26.3; 28.6; 29.0;
42.9; 43.7; 44.8; 54.8; 57.4; 128.6; 130.3; 133.7 (d, J ˆ 19.2); 134.3; 135.0 (d, J ˆ 18.8); 136.9 (d, J ˆ 19.5); 137.0

Helvetica Chimica Acta Vol. 85 (2002)
3397
(d, J ˆ 19.7); 141.8 (d, J ˆ 27.8); 169.6. IR (nujol): 720 (CÀP), 753 (SÀN); 1168, 1315 (SO2), 1512, 1651 (CˆN),
‡
3378 (NH). [a]2D5 ˆ ‡16.5 (c ˆ 0.51, CHCl3). HR-EI-MS: 578.2705 (C33H43N2O3PS ; calc. 578.2732).
N-{(1S)-1-{{[(1S)-1-Cyclohexylethyl]sulfamoyl}methyl}-2-methylpropyl}-2-(diphenylphosphanyl)benza-
mide (11ce): 1H-NMR (CDCl3, 400 MHz, 208): 0.87 (d, J ˆ 6.8, Me); 0.91 (d, J ˆ 6.7, Me); 1.82 0.95 (m, 14 H,
Chx, Me); 2.04 1.96 (m, Me2CH); 3.21 3.10 (m, CH2SO2); 3.46 3.37 (m, ChxCH(Me)); 4.52 4.46
(m, iPrCH); 5.01 (d, J ˆ 8.6, NHSO2); 6.26 (d, J ˆ 9.1, NHCO); 7.71 6.98 (m, 14 arom. H). 13C-NMR (CDCl3,
100.13 MHz): 18.2; 18.8; 19.3; 26.1; 26.2; 26.3; 28.5; 29.0; 31.3; 43.7; 51.3; 54.7; 54.9; 127.6; 127.7; 128.5; 128.6;
128.7; 128.8; 129.0; 130.2; 133.6 (d, J ˆ 19.9); 134.4; 135.0 (d, J ˆ 18.8); 136.9 (d, J ˆ 19.5); 137.0 (d, J ˆ 19.7);
141.8 (d, J ˆ 27.8); 169.6. IR (nujol): 723 (CÀP), 746 (SÀN), 1161, 1310 (SO2), 1512, 1651 (CˆN), 3430 (NH).
‡
[a]2D5 ˆ ‡40.6 (c ˆ 0.50, CHCl3). HR-EI-MS: 564.2601 (C32H41N2O3PS ; calc. 564.2575).
N-{(1S)-1-{{[1(R)-1-Cyclohexylethyl]sulfamoyl}methyl}-2-methylpropyl}-2-(diphenylphosphanyl)benz-
amide (11cf): 1H-NMR (CDCl3, 400 MHz, 208): 0.90 0.88 (m, 2 Me); 1.94 0.95 (m, 15 H, Chx, 1 Me, Me2CH);
3.18 3.16 (m, CH2SO2); 3.42 3.37 (m, ChxCH(Me)); 4.52 4.48 (m, iPrCH); 5.37 (m, NHSO2); 6.28 (br.,
NHCO); 7.72 7.03 (m, 14 arom. H). 13C-NMR (CDCl3, 100.13 MHz): 18.4; 18.6; 19.0; 26.1; 26.2; 28.7; 31.7;
43.8; 51.1; 54.2; 54.6; 127.6; 128.4; 128.5; 128.6; 128.7; 130.2; 133.5 (d, J ˆ 19.5); 133.7; 134.5 (d, J ˆ 18.8); 136.9
(d, J ˆ 19.5); 137.0 (d, J ˆ 19.7); 142.0 (d, J ˆ 27.8); 169.6. IR (nujol): 710 (CÀP), 750 (SÀN), 1130, 1310 (SO2),
‡
1521, 1645 (CˆN), 3280 (NH). [a]D25 ˆ ‡55.4 (c ˆ 0.52, CHCl3). HR-EI-MS: 564.2591 (C32H41N2O3PS ; calc.
564.2576).
N-{(1S)-1-[(Benzhydrylsulfamoyl)methyl]-2-methylpropyl}-2-(diphenylphosphanyl)benzamide (11ci).
1H-NMR (CDCl3, 400 MHz, 208): 0.62 0.57 (m, 2 Me); 1.45 1.40 (m, Me2CH); 3.00 2.69 (m, PhCH2);
4.12 4.05 (m, Me2CHCH); 5.8 (d, J ˆ 8.96, NHSO2); 6.07 (br. s, NHCO); 7.50 6.90 (m, 24 arom. H).
13C-NMR (CDCl3, 100.13 MHz): 17.6; 18.4; 31.8; 50.3; 54.5; 61.4; 127.2; 127.7; 128.0; 128.2; 128.4; 128.9;
130.2; 133.5 (d, J ˆ 19.6); 134.6; 135.0 (d, J ˆ 18.8); 136.9 (d, J ˆ 19.5); 137 (d, J ˆ 19.7); 141.2 (d, J ˆ 27.8);
169.6. IR (nujol): 723 (CÀP), 750 (SÀN), 1315 (SO2), 1536, 1645 (CˆN), 3452 (NH). [a]2D5 ˆ 66.83 (c ˆ 0.41,
‡
CHCl3). HR-EI-MS: 620.2273 (C37H37N2O3PS ; calc. 620.2263).
N-{(1S)-1-[(Benzylsulfamoyl)methyl]-2-methylpropyl}-2-(diphenylphosphanyl)benzamide
(11cg):
1H-NMR (CDCl3 , 400 MHz, 208): 0.74 0.72 (d, J ˆ 6.84, Me); 0.78 0.76 (d, J ˆ 7.53, Me); 1.68 1.80
(m, Me2CH); 3.13 2.85 (m, CH2SO2); 4.43 4.25 (m, iPrCH, PhCH2); 6.30 6.08 (br., NHSO2, NHCO);
7.85 7.07 (m, 19 arom. H). 13C-NMR (CDCl3, 100.13 MHz): 17.7; 18.0; 18.7; 31.1; 31.7; 47.2; 50.8; 51.4; 52.3;
54.0; 127.8; 128.3; 128.6; 128.7; 128.8; 129.2; 130.3; 131.8; 132.3; 133.5; 133.6 (d, J ˆ 12.6); 133.8; 134.4; 137.1;
137.2; 170.0. IR (nujol): 696 (CÀP), 723 (SÀN), 1150, 1308 (SO2), 1541, 1641 (CˆN), 3190, 3356 (NH). [a]D25
ˆ
‡
‡48.04 (c ˆ 0.51, CHCl3). HR-EI-MS: 544.1984 (C31H33N2O3PS ; calc. 544.1949).
2-(Diphenylphosphanyl)-N-{(1S)-1-[(isopropylsulfamoyl)methyl]-2-methylpropyl}benzamide (11ch):
1H-NMR (CDCl3, 400 MHz, 208): 0.86 0.89 (m, 2 Me); 1.26 1.24 (m, 2 Me); 1.57 (m, Me2CH); 3.17 3.16
(m, CH2SO2); 3.68 3.63 (m, SO2CH(Me)); 4.57 4.51 (m, iPrCH); 5.06 5.04 (m, NHSO2); 6.20 (br., NHCO);
7.70 6.98 (m, 14 arom. H). 13C-NMR (CDCl3, 100.13 MHz): 21.9; 22.7; 24.0; 24.4; 24.6; 43.0; 44.8; 46.3; 57.0;
127.9; 128.6; 128.9; 130.3; 133.6 (d, J ˆ 19.9); 134.2; 135.0 (d, J ˆ 18.8); 136.9 (d, J ˆ 19.5); 137.0 (d, J ˆ 19.7);
141.8 (d, J ˆ 27.8); 169.6. IR (nujol): 698 (CÀP), 735 (SÀN), 900, 1009, 1159, 1300 (SO2), 1539, 1649 (CˆN),
2251, 3215, 3369 (NH). [a]2D5 ˆ ‡14.0 (c ˆ 0.50, CHCl3). EI-MS: 495, 433, 388, 348, 332, 304 (100), 289, 277, 261,
241, 226, 212, 199, 183, 165, 149, 139, 123, 108, 91, 83, 77, 69, 57, 43, 29.
2-(Diphenylphosphanyl)-N-{(1S)-1-{{[(1S)-2-hydroxy-1-phenylethyl]sulfamoyl}methyl}-2-methylpropyl}-
1
benzamide (11cj): H-NMR (CDCl3, 400 MHz, 208): 0.69 0.98 (m, 2 Me); 1.98 1.63 (m, Me2CH); 3.83 2.65
(m, PhCH2, CH2OH, CH2SO2, CHCH2OH); 4.82 4.58 (m, iPrCH); 6.45 6.12 (m, NHSO2); 7.70 6.83
(m, 19 arom. H). IR (nujol): 730 (CÀP), 748 (SÀN), 1312 (SO2), 1518, 1655 (CˆN), 3398 (NH). [a]D25
ˆ
‡124.7 (c ˆ 0.51, CHCl3). EI-MS: 573, 557, 513, 497, 423, 374, 363, 330, 305 (100), 289, 277, 254, 241, 226, 211, 199,
183, 165, 152, 120, 105, 91, 77, 69, 41.
2-(Diphenylphosphanyl)-N-{(1S)-2-methyl-1-{{[(1S)-1-phenylethyl]sulfamoyl}methyl}propyl}benzamide
(11ck): 1H-NMR (CDCl3, 400 MHz, 208): 0.53 (d, J ˆ 6.91, Me); 0.67 (d, J ˆ 6.85, Me); 0.94 0.88 (m, Me2CH);
1.58 (d, J ˆ 6.99, Me); 2.87 2.59 (m, CH2SO2); 3.90 3.80 (m, Me2CHCH); 4.63 4.53 (m, PhCH); 7.64 7.06
(m, 21 H, arom. H, NHSO2, NHCO). 13C-NMR (CDCl3, 100.13 MHz): 17.3; 17.9; 24.0; 30.8; 50.9; 52.0; 54.0;
126.8; 127.6; 128.5; 128.6; 128.7; 129.0; 129.1; 129.6; 129.7; 131.7; 131.8; 132.1; 133.6 (d, J ˆ 11.9); 135.0 (d, J ˆ
18.8); 136.9 (d, J ˆ 19.5); 137 (d, J ˆ 19.7); 141.8 (d, J ˆ 27.8); 143.6; 169.2. IR (nujol): 723 (CÀP), 754 (SÀN),
1315 (SO2), 1556, 1670 (CˆN), 3267; 3384 (NH). [a]2D5 ˆ ‡132.0 (c ˆ 0.50, CHCl3). EI-MS: 531, 497, 481, 454,
391, 376, 348, 322, 305 (100), 292, 277, 258, 244, 227, 199, 183, 166, 152, 120, 105, 91, 77, 69.
N-{(1S)-1-Benzyl-2-{[(1S)-1-phenylethyl]sulfamoyl}ethyl}-2-(diphenylphosphanyl)benzamide (11ak):
1H-NMR (CDCl3, 400 MHz, 208): 1.53 (d, J ˆ 7.03, Me); 2.48 2.80 (m, CH2SO2, ‡ PhCH2); 4.68 4.30

3398
Helvetica Chimica Acta Vol. 85 (2002)
(m, PhCH2CH, PhCH); 5.76 (br. d, NHSO2); 6.2 (br., NHCO); 7.71 6.80 (m, 24 arom. H). IR (nujol): 723
(CÀP), 750 (SÀN), 1161, 1312 (SO2), 1510, 1648 (CˆN), 3415 (NH). [a]2D5 ˆ ‡60.2 (c ˆ 0.50, CHCl3). EI-MS:
591, 529, 515, 501, 421, 409, 393, 357, 330, 305 (100), 289, 277, 254, 241, 226, 212, 199, 183, 165, 144, 117, 105, 91, 77,
65, 51.
2-(Diphenylphosphanyl)-N-{(1S)-3-methyl-1-{{[(1S)-1-phenylethyl]sulfamoyl}methyl}butyl}benzamide
(11dk). 1H-NMR (CDCl3, 400 MHz, 208): 0.62 (d, J ˆ 6.5, 1 Me); 0.65 (d, J ˆ 6.6, 1 Me); 1.07 1.48 (m, Me2CH,
Me2CHCH2); 1.57 (d, J ˆ 5.1, 1 Me); 2.82 2.73 (m, CH2SO2); 4.10 4.01 (m, PhCH(Me)); 4.69 4.63
(m, iBuCH); 7.63 7.06 (m, 19 arom. H). 13C-NMR (CDCl3, 100.13 MHz): 21.5; 22.5; 23.8; 23.9; 24.2; 43.1;
44.9; 53.9; 54.4; 126.5; 126.7; 127.5; 128.6; 128.7; 128.8; 128.9; 130.2; 132.1 (d, J ˆ 17.3); 134.4; 135.0 (d, J ˆ 18.8);
136.9 (d, J ˆ 19.5); 137.0 (d, J ˆ 19.7); 141.8 (d, J ˆ 27.8). IR (nujol): 700 (CÀP), 752 (SÀN), 1159, 1308 (SO2),
‡
1528, 1645 (CˆN), 3390 (NH). [a]D25 ˆ ‡58.0 (c ˆ 0.40, CHCl3). HR-EI-MS: 573.2266 (C33H38N2O3PS , [M ‡
‡
1] ; calc. 573.2341).
N-[(1S)-1-Benzyl-2-(isopropylsulfamoyl)ethyl]-2-(diphenylphosphanyl)benzamide (11ah): 1H-NMR
(CDCl3, 400 MHz, 208): 1.21 1.11 (m, 2 Me); 2.98 2.81 (m, CH2SO2); 3.12 (d, J ˆ 6.27, PhCH2); 3.59 3.51
(m, Me2CH); 4.70 4.65 (m, PhCH2CH); 4.97 4.95 (m, NHSO2); 6.40 (br. s, NHCO); 7.41 6.98 (m, 19 ar-
om. H). 13C-NMR (CDCl3, 100.13 MHz): 23.8; 24.3; 39.7; 46.3; 47.8; 55.0; 127.0; 127.5; 128.6; 128.7; 128.8; 129.4;
130.3; 133.7 (d, J ˆ 19.9); 134.2; 135.2 (d, J ˆ 19.0); 136.5 (d, J ˆ 19.5); 137.2 (d, J ˆ 19.7); 141.8 (d, J ˆ 27.8);
169.6. IR (nujol): 733 (CÀP), 748 (SÀN), 1161, 1314 (SO2), 1645 (CˆN), 3227, 3356 (NH). [a]2D5 ˆ ‡18.8 (c ˆ
‡
0.50, CHCl3). HR-EI-MS 544.1954 (C31H33N2O3PS ; calc. 544.1949).
N-[(1S)-2-(Benzylsulfamoyl)-1-methylethyl]-2-(diphenylphosphanyl)benzamide (11bg): 1H-NMR (CDCl3,
400 MHz, 208): 1.11 (d, J ˆ 6.83, 1 Me); 1.90 (m, MeCH); 3.14 2.91 (dm, CH2SO2); 4.40 4.29 (m, PhCH2,
MeCH); 5.67 (t, J ˆ 6.1, NHSO2); 6.19 (d, J ˆ 7.92, NHCO); 7.39 6.95 (m, 19 arom. H). 13C-NMR (CDCl3,
100.13 MHz): 19.9; 42.3; 47.2; 57.1; 127.9; 128.2; 128.7; 129.0; 130.3; 133.8 (d, J ˆ 19.9); 134.0; 135.4 (d, J ˆ 18.8);
137.1 (d, J ˆ 19.5); 137.2 (d, J ˆ 19.7); 142.0 (d, J ˆ 27.8). IR (nujol): 698 (CÀP), 741 (SÀN), 1150, 1317 (SO2),
‡
1537, 1638 (CˆN), 3354 (NH). [a]D25 ˆ ‡29.2 (c ˆ 0.51, CHCl3). HR-EI-MS: 516.1750 (C29H29N2O3PS ; calc.
516.1636).
5. Representative Procedure for the Allylic Alkylation Reaction. A Schlenk tube was charged with
(CuOTf)2 ¥ C6H6 (4.3 mg, 0.0085 mmol) and the ligand 11ce (10 mg, 0.018 mmol) under Ar. After addition of
THF (0.5 ml), the mixture was stirred at r.t. for 45 min. A soln. of diethyl 3-phenylprop-2-enyl phosphate (12;
47 mg, 0.174 mmol) in THF (0.5 ml) was then added. After 15 min, the mixture was cooled to À788, and 1m
Et2Zn in toluene (0.522 mmol) was added dropwise. The mixture was allowed to warm to À558, stirred for 20 h,
and quenched by addition of a sat. NH4Cl soln. A sample of the org. layer was analyzed by GC for the
determination of conversion and ee. The org. layer was evaporated and the residue purified by FC (hexane): 13/
14, inseparable mixture. GC (Megadex DACTBSb, 25 m, film 0.25 mm; H2 (70 kPa); injector 2008, detector 2008,
oven temp. 508; 18/min to 708, then 48/min to 2008): tR (13) 13.9 ((3R) enantiomer) and 14.1 ((3S) enantiomer),
tR (14) 27.7, tR (12) 53.5.
REFERENCES
[1] C. Gennari, H. P. Nestler, U. Piarulli, B. Salom, Liebigs Ann./Recl. 1997, 637; K. D. Shimizu, M. L. Snapper,
A. H. Hoveyda, Chem. Eur. J. 1998, 4, 1885; B. Jandeleit, D. J. Schaefer, T. S. Powers, H. W. Turner, W. H.
Weinberg, Angew. Chem., Int. Ed. 1999, 38, 2494; M. T. Reetz, Angew. Chem., Int. Ed. 2001, 40, 284; S.
Dahmen, S. Br‰se, Synthesis 2001, 1431; M. T. Reetz, Angew. Chem., Int. Ed. 2002, 41, 1335 and ref. cit.
therein.
[2] a) G. Liu, J. A. Ellman, J. Org. Chem. 1995, 60, 7712; b) K. D. Shimizu, B. M. Cole, C. A. Krueger, K. W.
Kuntz, M. L. Snapper, A. H. Hoveyda, Angew. Chem., Int. Ed. 1997, 36, 1704; c) C. Gennari, S. Ceccarelli,
U. Piarulli, C. A. G. N. Montalbetti, R. F. W. Jackson, J. Org. Chem. 1998, 63, 5312; d) A. M. Porte,
J.Reibenspies, K. Burgess, J. Am. Chem. Soc. 1998, 120, 9180; e) S. R. Gilbertson, X. Wang, Tetrahedron
1999, 55, 11609; f) B. M. Francis, E. N. Jacobsen, Angew. Chem., Int. Ed. 1999, 38, 937; g) M. T. Reetz,
M. H. Becker, H. W. Klein, D. Stˆckigt, Angew. Chem., Int. Ed. 1999, 38, 1758; h) K. Ding, A. Ishii, K.
Mikami, Angew. Chem., Int. Ed. 1999, 38, 497; i) M. S. Sigman, P. Vachal, E. N. Jacobsen, Angew. Chem.,
Int. Ed. 2000, 39, 1279; j) M. T. Reetz, K. M. K¸hling, A. Deege, H. Hinrichs, D. Belder, Angew. Chem., Int.
Ed. 2000, 39, 3891; k) M. T. Reetz, K. E. Jaeger, Chem. Eur. J. 2000, 6, 407; l) J. Tian, G. W. Coates, Angew.
Chem., Int. Ed. 2000, 39, 3626.

Helvetica Chimica Acta Vol. 85 (2002)
3399
[3] a) I. Chataigner, C. Gennari, U. Piarulli, S. Ceccarelli, Angew. Chem., Int. Ed. 2000, 39, 916; b) S. Ongeri,
U. Piarulli, R. F. W. Jackson, C. Gennari, Eur. J. Org. Chem. 2001, 803; c) I. Chataigner, C. Gennari, S.
Ongeri, U. Piarulli, S. Ceccarelli, Chem. Eur. J. 2001, 7, 2628.
[4] a) M. Gude, U. Piarulli, D. Potenza, B. Salom, C. Gennari, Tetrahedron Lett. 1996, 37, 8589; b) C. Gennari,
M. Gude, D. Potenza, U. Piarulli, Chem. Eur. J. 1998, 4, 1924.
[5] J. R. Porter, J. F. Traverse, A. H. Hoveyda, M. L. Snapper, J. Am. Chem. Soc. 2001, 123, 984.
[6] S. J. Degrado, H. Mizutani, A. H. Hoveyda, J. Am. Chem. Soc. 2001, 123, 755.
[7] D. Wernic, J. DiMaio, J. Adams, J. Org. Chem. 1989, 54, 4224.
[8] G. C. Lloyd-Jones, S. C. Stephen, Chem. Eur. J. 1998, 4, 2539.
[9] a) F. D¸bner, P. Knochel, Angew. Chem., Int. Ed. 1999, 38, 379; b) C. A. Luchaco-Cullis, H. Mizutani, K. E.
Murphy, A. H. Hoveyda, Angew. Chem., Int. Ed. 2001, 40, 1456; c) H. Malda, A. W. van Zijl, L. A. Arnold,
B. L. Feringa, Org. Lett. 2001, 3, 1169.
[10] G. J. Meuzelaar, A. S. E. Karlstrˆm, M. van Klaveren, E. S. M. Persson, A. del Villar, G. van Koten, J. E.
B‰ckvall, Tetrahedron 2000, 56, 2895; A. S. E. Karlstrˆm, F. F. Huerta, G. J. Meuzelaar, J. E. B‰ckvall,
Synlett 2001, 923; A. Alexakis, C. Malan, L. Lea, C. Benhaim, X. Fournoux, Synlett 2001, 927.
[11] T. Hayashi, T. Hagihara, Y. Katsuro, M. Kumada, Bull. Chem. Soc. Jpn. 1983, 56, 363.
[12] W. C. Still, M. Kahn, A. Mitra, J. Org. Chem. 1978, 43, 2923.
Received June 1, 2002