Chiral bis(N-sulfonylamino)phosphine- and TADDOL-phosphite-oxazoline ligands: Synthesis and application in asymmetric catalysis

Article abstract of DOI:10.1002/adsc.200404168

A series of N,P-ligands has been prepared, containing a chiral oxazoline ring and as a second chiral unit a bis(N-sulfonylamino)phosphine group embedded in a diazaphospholidine ring or a cyclic phosphite group derived from TADDOL. These modular ligands are readily synthesized from chiral amino alcohols and chiral 1,2-diamines or TADDOLs. Palladium and iridium complexes derived from these ligands were found to be efficient catalysts for enantioselective allylic alkylation and olefin hydrogenation, respectively.

Full text of DOI:10.1002/adsc.200404168

FULL PAPERS
Chiral Bis(N-sulfonylamino)phosphine- and
TADDOL-Phosphite-Oxazoline Ligands: Synthesis and
Application in Asymmetric Catalysis
Robert Hilgraf, Andreas Pfaltz*
Department of Chemistry, University of Basel, St. Johanns-Ring 19, 4056 Basel, Switzerland
Fax: (þ41)-61-267-1103; e-mail: Andreas.Pfaltz@unibas.ch
Received: June 6, 2004; Accepted: November 27, 2004
Supporting Information for this article is available on the WWW under http://asc.wiley-vch.de/home/.
Abstract: A series of N,P-ligands has been prepared, were found to be efficient catalysts for enantioselec-
containing a chiral oxazoline ring and as a second chi- tive allylic alkylation and olefin hydrogenation, re-
ral unit a bis(N-sulfonylamino)phosphine group em- spectively.
bedded in a diazaphospholidine ring or a cyclic phos-
phite group derived from TADDOL. These modular
ligands are readily synthesized from chiral amino al- Keywords: asymmetric allylic substitution; asymmet-
cohols and chiral 1,2-diamines or TADDOLs. Palladi- ric catalysis; asymmetric hydrogenation; N,P ligands;
um and iridium complexes derived from these ligands oxazolines
Introduction
tions[3] and Cu-catalyzed conjugate additions of organo-
zinc reagents to enones.[4] Recently we reported the
For a long time, C2-symmetrical bidentate ligands such bis(N-sulfonylamino)phosphine- and TADDOL-phos-
as the bisoxazolines 1 or BINAP 2 have been dominating phite-oxazolines 5 and 6 as a further extension of this
in asymmetric catalysis.[1] However, for a number of ap- structural motif (Scheme 1).[5]
plications, sterically and electronically unsymmetrical li-
These ligands are constructed in a modular fashion, al-
gands proved to be superior. In particular, the phosphi- lowing independent structural variation at different po-
nooxazolines 3 (PHOX ligands) were found to be excel- sitions of the molecule. Ligands 5 can be modified at the
lent ligands for a wide range of metal-catalyzed reac- substituents of the diazaphospholidine ring (A), the sul-
tions.[2] Variation of the PHOX structure led us to phos- fonamide groups (B) and at the oxazoline ring (C)
phite-oxazolines such as 4, which contain a binaphthyl (Scheme 2). The TADDOL-derived ligand 6 can be
system as a second chiral unit. These ligands were suc- structurally varied at the cyclic phosphite unit by replac-
cessfully employed in Pd-catalyzed allylic substitu- ing the phenyl groups with other substituents (A; R1 ¼
Scheme 1.
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DOI: 10.1002/adsc.200404168
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Robert Hilgraf, Andreas Pfaltz
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to be highly enantioselective catalysts for the hydroge-
nation of unfunctionalized olefins.
Based on these encouraging results we decided to op-
timize the ligand syntheses in order to prepare a selec-
tion of different derivatives for further studies. Here,
we report the synthesis of various representatives of
these two ligand classes, the preparation of palladium
and iridium complexes and their use in palladium-cata-
lyzed allylic alkylations and iridium-catalyzed hydroge-
nations.
Results and Discussion
Synthesis of Bis(N-sulfonylamino)phosphine-
Oxazolines 5
Although the substituents at the two stereogenic centers
in the diazaphospholidine ring are too remote from the
coordination sphere of the metal center to have a direct
influence on a catalytic reaction, they determine the
conformation of the ring and the geometry of the N-sul-
fonylamino groups. In this way, they can change the chi-
ral environment of the coordination sphere and, there-
fore, affect the activity and selectivity of a metal catalyst.
Initial studies with ligands derived from commercially
available, enantiomerically pure 1,2-diphenylethylene-
1,2-diamine and 1,2-diaminocyclohexane showed that
the sterically more demanding 1,2-diphenylethylene
backbone often resulted in higher enantioselectivity
and reactivity in Ir-catalyzed hydrogenations. There-
fore, we prepared aseries ofotherchiral ethylene-1,2-di-
amines.
Scheme 2.
(R,R)-8 and (S,S)-1,2-dicyclohexylethylenediamine
(8a) were synthesized by hydrogenation of 1,2-diphenyl-
ethylenediamine hydrochloride (7) over platinum(IV)
oxide (Scheme 4).
The synthesis of (R,R)-1,2-bis(3,5-dimethylphenyl)-
ethylenediamine (14) starts with a Wittig reaction of al-
Scheme 3.
alkyl, aryl) or introducing heteroatoms other than oxy-
gen (B; X¼N or S), and at the oxazoline ring (C). In
this way the steric and electronic properties of the li-
gands can be optimized for a specific application.
Both ligand classes revealed a considerable potential
for asymmetric catalysis. Palladium complexes of li-
gands 29 and 35 (structures: see Schemes 9 and 13) cat-
alyzed the allylic alkylation of (1’-naphthyl)prop-2-enyl
acetate with very high regio- and enantioselectivity. Iri-
Scheme 4. Synthesis of (R,R)- and (S,S)-1,2-dicyclohexylethy-
dium complexes derived from ligands 29a and 47 proved lenediamine.
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Bis(N-sulfonylamino)phosphine- and TADDOL-Phosphite-Oxazoline Ligands
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Scheme 5. Synthesis of (R,R)-1,2-bis(3,5-dimethylphenyl)ethylenediamine.
Scheme 6. Synthesis of (R,R)-1,2-diamino-1,2-di-tert-butylethane.
dehyde 9 and Wittig salt 10, which were both prepared amino-1,2-di-tert-butylethane (17). It was synthesized
from 3,5-dimethylbenzyl alcohol (Scheme 5). The E/Z- according to the procedure of Alexakis starting from
mixture of 11 was converted to the (E)-isomer by treat- glyoxal and (S)-1-phenylethylamine (Scheme 6).[7] Sim-
ment with tellurium/tellurium tetrachloride. Asymmet- ilar attempts to synthesize 14 or its 2,4,6-trimethylbenzyl
ric Sharpless dihydroxylation gave 12 with an enantio- derivate by reaction of diimine 15 with the analogous
meric excess of>99%. Diol 12 was mesylated and, be- Grignard reagents gave, independent of the reaction
cause of its low stability, directly converted to the di- conditions, only mixtures of diastereomers as minor
azide 13. The desired diamine 14 was then obtained by products.
reduction of 13 with LiAlH4. In contrast to other re-
ports,[6] it was possible to isolate and characterize the di- mild conditions. In the presence of N,N-diisopropyl-
amine 14 without any difficulties. ethylamine as base the chiral diamines were coupled
Sulfonation of the chiral diamines was achieved under
Attempts to synthesize the 2,4,6-trimethylbenzyl de- at room temperature in good yields with a series of sul-
rivative by the same route failed because the two or- fonyl chlorides, such as tosyl chloride, naphthalene-1-
tho-methyl groups shield the double bond so strongly and -2-sulfonyl chloride, trifluoromethane- and mesity-
that in the dihydroxylation reaction, hydrolysis ofthe os- lenesulfonyl chloride. The only exception was the tosy-
mium glycolate is not possible.
lation of 17 which required harsher conditions with re-
Diimine 15 is an important intermediate in the syn- fluxing in pyridine for 24 h. The enantiomers of 18, 23,
thesis of various 1,2-dialkyldiamines like (R,R)-1,2-di- 26 and 28 were also prepared from the corresponding
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Robert Hilgraf, Andreas Pfaltz
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Scheme 7.
Scheme 9. Bis(N-sulfonylamino)phosphine-oxazoline ligands.
(ent)-28 to the corresponding ligands failed, despite ex-
tensive screeningof various solvents at different temper-
atures. Steric hindrance could be a possible explanation,
consistent with the low reactivity observed in the prepa-
Scheme 8. Synthesis of bis(N-sulfonylamino)phosphine-oxa-
zoline ligands.
(S,S)-diamines to explore possible match-mismatch ef- ration of 28 and (ent)-28 from the corresponding di-
fects of the two chiral units in the N,P-ligands.
The chiral sulfonyldiamines 18–28 were treated with
amines.
As solids the ligands were found to be quite stable un-
phosphorus trichloride in toluene at ꢀ788C to give der air. Even in solution under air they showed only
the corresponding P-chlorodiazaphospholidines as traces of oxidation products in the 31P NMR spectra af-
¼
pale yellow solids in good yields. The products are mois- ter 24 hours (P ~ 120 ppm, P O ~ 20 ppm). The only ex-
ture- and air-sensitive compounds, but they could be ception was ligand 31 with two trifluoromethylsulfonyl
clearly identified by mass spectroscopy. They were di- groups, which was oxidized in solution within minutes.
rectly converted to the desired ligands 29–39 by reac- In general, the ligands could be stored under argon for
tion with the oxazoline alcohol, triethylamine and months at 08C without decomposition.
DMAP without isolation (Scheme 8). The use of
We were also interested in analogous ligands derived
DMAP proved to be advantageous, as it decreased the from unsymmetrical diamines, because they contain a
reaction time from 5 days to 12 hours and also reduced stereogenic phosphorus atom. For this purpose commer-
the number of by-products.
cially available (S)-anilinomethylpyrrolidine was chos-
Because all attempts to purify the products by column en, which has been previously used in the synthesis of li-
chromatography failed, the crude products were usually gands with stereogenic phosphorus atoms.[8] Thus (S)- 2-
purified by crystallization from chloroform/hexanes at (N-phenylaminomethyl)pyrrolidine was reacted with
08C to give white to pale yellow solids. However, in hexamethylphosphorous triamide and the resulting in-
some cases the by-products dropped out of solution as termediate subsequently refluxed with the oxazoline al-
a yellow oilwhile the main product remained in solution. cohol for 7 days to afford ligand 40 in 39% overall yield
In these cases the solution was separated from the oil us- (Scheme 10). In the beginning of the reaction both pos-
ing a syringe and evaporated to give the pure ligands. sible diastereomers could be observed by 31P NMR.
Traces of DMAP, which remained as contaminants after Over the course of several days the equilibrium was
crystallization, were removed by sublimation at 908C shifted towards the thermodynamically more stable dia-
under high vacuum to give the ligands in yields between stereomer 40, which was isolated in pure form by column
50 to 80%. All attempts to convert 28 or its enantiomer chromatography.
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Bis(N-sulfonylamino)phosphine- and TADDOL-Phosphite-Oxazoline Ligands
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Scheme 10. Synthesis of ligand 40 with a stereogenic phos-
phorus atom.
Synthesis of TADDOL-Phosphite-Oxazolines 6
Scheme 11. Synthesis of TADDAMIN.
a,a,a’,a’-Tetraaryl-1,2-dioxolane-4,5-dimethanol
(TADDOL) derivatives have found numerous applica-
tions in stoichiometric and catalytic enantioselective re-
actions.[9] Because they are readily prepared and their
structure can be easily varied, they are an attractive al-
ternative to BINOL. In view of the various successful
applications of BINOL-derived phosphite-oxazolines
of type 4, it seemed obvious that analogous TADDOL
derivatives 6 could be a useful extension of this ligand
family. Independent from our studies, Heldmann and
Seebach recently prepared such ligands and reported
that corresponding rhodium complexes are efficient cat-
alysts for the enantioselective hydrosilylation of keto-
nes.[9b]
Scheme 12. Synthesis of methylated TADDAMIN.
TADDOL 41 and the tetra(2-naphthyl) derivative 42
were prepared by the known procedure via the dioxo-
lane-dicarboxylates and subsequent Grignard reac-
tion.[10] By replacing the hydroxy groups with amino
groups, which could bear further electron-withdrawing
or -donating groups, the steric and electronic properties
of the ligand could be additionally changed. (4R,5R)-
2,2-Dimethyl-a,a,a’,a’-tetraphenyl-1,3-dioxolane-4,5-
dimethylamine (TADDAMIN) 44 was prepared from
(R,R)-TADDOL 41 according to the procedure of See-
bach et al. (Scheme 11).[11]
All approaches to tosylate TADDAMIN 44 failed.
Only monotosylated TADDAMIN was detected as mi-
nor product in about 20% yield. Introduction of other
electron-withdrawing groups by reacting TADDAMIN
with trifluoroacetic anhydride was successful but the re-
sulting product could not be converted to the corre-
sponding N,P-ligand. TADDAMIN 44 reacted with
methyl iodide in DMPU to afford the dimethylated
TADDAMIN 45 in 38% yield after separation of the tri-
Scheme 13. TADDOL-phosphite-oxazoline ligands.
The TADDOL-phosphite-oxazoline ligands were
methylated side product 46 by column chromatography prepared in the same manner as the bis(N-sulfonylami-
(Scheme 12).[11]
no)phosphine-oxazoline ligands. Reaction of the TAD-
All attempts to prepare sulfur analogues of TADDOL DOL derivatives 41, 42 and 45 with phosphorus trichlor-
gave unsatisfactory results. Reaction of dichloride 43 ide at ꢀ788C in toluene and subsequent reaction with
with thiourea afforded the desired dithiol but also oxazoline alcohol, triethylamine and DMAP gave li-
50% of the disulfide. Separation of the two compounds gands 47–50 in 50–80% yield (Scheme 13). The TAD-
was not possible whereas the reduction of the disulfide DOL-phosphite ligands were purified by column chro-
led to a mixture of products. Direct conversion of the matography or recrystallization. Ligand 47a derived
diol 41 to the dithiol with Lawessonꢁs reagent gave from (S,S)-TADDOL was prepared in order to study
only the monothiol in very low yield.
match/mismatch effects of the two chiral units.
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Figure 1. X-ray structures of Ir- and Rh-complexes of ligand 30a.
X-Ray Structures
Applications in Asymmetric Catalysis
Structural information about the bis(N-sulfonylamino)- With this diverse set of bis(N-sulfonylamino)phosphine-
phosphine-oxazoline ligands geometry could be ob- oxazoline and TADDOL-derived ligands in hand, we
tained from crystal structures of an Ir and an Rh com- evaluated their scope in the Pd-catalyzed allylic alkyla-
plex derived from ligand 30a.[12] Addition of the ligand tion and Ir-catalyzed hydrogenation of olefins.
to a solution of [M(COD)Cl]2 (X¼Ir, Rh) followed by
ꢀ
anion exchange from Clꢀ to PF6 afforded the com-
plexes 51 and 52 in good yields. Slow recrystallization Pd-Catalyzed Allylic Alkylation
from ethyl acetate/cyclohexane at ꢀ188C yielded or-
ange needles suitable for X-ray analyses.
Allylic alkylation is one of the most efficient methods
ꢀ
The two complexes adopt a similar geometry with the for C C bond formation. Mild reaction conditions and
diazaphospholidine ring in a nearly planar conforma- high tolerance of functional groups are advantages
tion. The tosyl and phenyl groups of the diazaphospho- which makethis reaction apowerfultoolfor organicsyn-
lidine ring shield the coordination sphere next to the thesis. PHOX ligands 3 were found to be excellent li-
phosphorus atom, similar to the P-phenyl groups of gands for this reaction.[2,13] The best results were ob-
the PHOX ligand 3 or the BINOL moiety of ligand 4. tained with symmetrically substituted allyl systems
One of the sulfonyl oxygen atoms and one tolyl group whereas for 1- and 3-monosubstituted substrates only
are located relatively close to the coordination sphere moderate enantioselectivities and low branched/linear
and, therefore, are expected to interact more strongly ratios could be achieved. This led to the design of chiral
with a metal-bound reactant than the BINOL group in phosphite-oxazoline ligands of type 4, which gave im-
ligands 4. This could explain the higher selectivity often proved regio- and enantioselectivities for 1- and 3-mono-
observed for ligands 5 compared to 4.
arylallyl acetates.[3] Because the new ligands of type 5
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Table 1. Enantioselective Pd-catalyzed allylic alkylation of (E)-3-phenyl-2-propen-1-yl acetate.[a]
Entry
Ligand
Conversion [%][b]
ee [%][c]
br/l
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
29
29a
30
32
33
34
35
35a
36
37
38
39
47
47a
50
100
100
100
100
100
100
100
100
100
100
100
100
100
100
100
94 (S)
93 (S)
89 (S)
94 (S)
94 (S)
94 (S)
95 (S)
88 (S)
90 (S)
96 (S)
91 (S)
96 (S)
87 (S)
70 (S)
97 (S)
84: 16
53: 47
38: 62
33: 67
67: 33
84: 16
60: 40
30: 70
65: 35
62: 38
82: 18
77: 23
26: 74
18: 82
21: 79
[a]
All reactions were carried out with 1 mol % of [Pd(C3H5)Cl]2 and 2.5 mol % of ligand in CH2Cl2 at room temperature for
20 h.
[b]
[c]
Determined by GC. The yields of the pure products were 85–95% (100% conversion).
Determined by GC or HPLC using chiral columns.
and 6 have similar steric and electronic properties as BI- tio- and regioselectivity than PHOX ligands 3 or BI-
NOL-derived ligands 4, we decided to examine their po- NOL-derived ligands 4 (Table 2, Entry 1). Replacement
tential for enantio- and regiocontrol in allylic alkylation. of the tosyl groups with (2’-naphthyl)sulfonyl groups in
Using (E)-3-phenyl-2-propen-1-yl acetate as sub- ligand 34 resulted in an exceptionally high regioselectiv-
strate (Table 1), the new bis(N-sulfonylamino)phos- ity (>99.5:0.5) with similar enantiocontrol (Entry 4).
phine-oxazoline ligands 29–39 gave similar or better re- Ligand 35 with a chiral cyclohexanediamine backbone
sults in terms of enantio- and regioselectivity in compar- afforded a very high ee of 99.4% which is the best value
ison to PHOX ligands 3 and phosphite-oxazolines 4. In reported so far for a Pd catalyst but with a slightly lower
general, ligands derived from (R,R)-diamines and (S)- regioselectivity (Entry 5). TADDOL-derived ligands
oxazolines were superior to the corresponding diaster- such as 47 gave moderate to good enantiomeric excesses
eomers derivedfrom (S,S)-diamines for all substrates re- but low regioselectivities (Entry 9).
ported (Entries 1, 2, 7, 8). Ligand 29 proved to be the
As expected, the enantio- and regioselectivites with 2-
most effective for regio- and enantiocontrol. Variations alkenyl acetates, (E)-2-buten-1-yl acetate and (E)-2-
of the substituent in the oxazoline ring or of the tosyl hexen-1-yl acetate, were lower. However, both new li-
group resulted in lower regio- and enantioselectivities gand classes gave better results than PHOX ligands 3
(Entries 3–6). Ligands 35 and 37, containing cyclohex- and BINOL-derived ligands 4 (Tables 3 and 4). Ligand
anediamine as the chiral backbone afforded even better 29 again proved to be most effective for enantio- and re-
enantioselectivities than ligand 29 but lower regioselec- giocontrol (Entry 1, Tables 3 and 4). TADDOL-derived
tivities (Entries 7 and 10). Additional methyl substitu- ligand 50 afforded a high ee of 62% for (E)-2-hexen-1-yl
ents at the chiral diphenyldiamine backbone had the acetate but with low regioselectivity (Entry 6, Table 4).
same effect (Entry 12). The TADDOL-derived ligand Recently, a further variant of N,P-ligands, containing a
50 showed the highest ee value of 97%, but as observed ferrocene backbone, was reported that resulted in high
for all other TADDOL-derived ligands, the regioselec- regio- and enantioselectivity for the 1,3-dimethylallyl
tivity was significantly lower (Entry 15). In all cases, acetate (97:3, 94% ee).[14]
(R,R)-TADDOL-derived ligands with (S)-oxazoline
units showed better results than the corresponding alyzed allylic alkylation of three symmetrically substi-
(S,S) diastereoisomers (Entries 13 and 14). tuted allyl substrates. With (E)-1,3-diphenyl-2-propenyl
All synthesized ligands were also tested in the Pd-cat-
With (E)-3-(1’-naphthyl)-2-propen-1-yl acetate as acetate as substrate, only moderate enantioselectivities
substrate, ligand 29 again gave significantly higher enan- could be achieved (Table 5). Interestingly, substitution
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Robert Hilgraf, Andreas Pfaltz
Table 2. Enantioselective Pd-catalyzed allylic alkylation of (E)-3-(1’-naphthyl)-2-propen-1-yl acetate.[a]
FULL PAPERS
Entry
Ligand
Conversion [%][b]
ee [%][c]
br/l
1
2
3
4
5
6
7
8
9
29
30
33
34
35
37
38
39
47
100
100
100
100
100
100
100
100
100
98 (S)
85 (S)
93 (S)
97 (S)
99.4 (S)
98 (S)
89 (S)
97 (S)
94 (S)
98: 2
93: 7
93: 7
>99.5: 0.5
93: 7
93: 7
99.5: 0.5
93: 7
66: 34
[a]
All reactions were carried out with 1 mol % of [Pd(C3H5)Cl]2 and 2.5 mol % of ligand in CH2Cl2 at room temperature for
20 h.
[b]
[c]
Determined by GC. The yields of the pure products were 85–95% (100% conversion).
Determined by GC or HPLC using chiral columns.
Table 3. Enantioselective Pd-catalyzed allylic alkylation of (E)-2-buten-1-yl acetate.[a]
Entry
Ligand
Conversion [%][b]
ee [%][c]
br/l
1
2
3
4
5
6
7
8
9
29
30
34
35
36
38
39
40
50
100
100
100
100
100
100
100
100
100
60 (S)
4 (S)
55: 45
64: 36
45: 55
26: 74
23: 77
56: 44
44: 56
33: 67
33: 67
41 (S)
50 (S)
40 (S)
48 (S)
48 (S)
41 (R)
39 (S)
[a]
All reactions were carried out with 1 mol % of [Pd(C3H5)Cl]2 and 2.5 mol % of ligand in CH2Cl2 at room temperature for
20 h.
[b]
[c]
Determined by GC. The yields of the pure products were 85–95% (100% conversion).
Determined by GC or HPLC using chiral columns.
ofthe tert-butylgroup ofthe oxazoline ring with aphenyl BINOL-derived ligands (47: 61%; 3: 79%; 4: 50%) (En-
group in ligand 30 improved the ee from 60% to 88% try 3)
(Entries 1 and 2) whereas the same exchange resulted
With 2-cyclohexen-1-yl acetate, ligand 38 with cyclo-
in lower enantioselectivity for the unsymmetrical sub- hexanediamine as chiral backbone afforded a respecta-
strate (E)-3-phenyl-2-propen-1-yl acetate (Entries 1 ble enantiomeric excess of 85% (Entry 5, Table 7). Li-
and 2, Table 1). Ligand 40 containing a stereogenic gand 40 containing a stereogenic phosphorus atom
phosphorus atom afforded an ee of 84% (Entry 6).
gave a somewhat lower ee of 75% (Entry 6). In general,
Using (E)-4-hepten-3-yl acetate as substrate, bis(N- most new ligands proved to be superior to analogous
sulfonylamino)phosphine-oxazoline ligands 29 and 35 phosphite or PHOX ligands for this substrate.
gave unsatisfactory enantioselectivities (Entries 1–2,
In summary, both new ligand classes, bis(N-sulfonyl-
Table 6). However, the ee induced by the TADDOL-de- amino)phosphine-oxazoline and TADDOL-derived li-
rived ligand 47 was in the same range as with PHOX and gands, induced high enantioselectivities and regiocon-
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Table 4. Enantioselective Pd-catalyzed allylic alkylation of (E)-2-hexen-1-yl acetate.[a]
Entry
Ligand
Conversion [%][b]
ee [%][c]
br/l
1
2
3
4
5
6
29
34
35
38
39
50
100
100
100
100
100
79
51
54
26
44
52
62
21: 79
17: 83
9: 91
33: 67
16: 84
8: 92
[a]
All reactions were carried out with 1 mol % of [Pd(C3H5)Cl]2 and 2.5 mol % of ligand in CH2Cl2 at room temperature for
20 h.
[b]
[c]
Determined by GC. The yields of the pure products were 85–95% (100% conversion).
Determined by GC or HPLC using chiral columns.
Table 5. Enantioselective Pd-catalyzed allylic alkylation of
(E)-1,3-diphenyl-2-propen-1-yl acetate.[a]
Table 6. Enantioselective Pd-catalyzed allylic alkylation of
(E)-4-hepten-3-yl acetate.[a]
Entry
Ligand
Conversion [%][b]
ee [%][c]
Entry
Ligand
Conversion [%]
ee [%][c]
1
2
3
29
35
47
53
100
100
20
9
61
1
2
3
4
5
6
7
29
30
35
37
38
40
48
100
100
100
100
100
100
100
60 (S)
88 (S)
52 (S)
60 (S)
65 (S)
84 (S)
56 (S)
[a]
All reactions were carried out with 1 mol % of [Pd-
(C3H5)Cl]2 and 2.5 mol % of ligand in CH2Cl2 at room
temperature for 20 h.
Determined by GC. The yields of the pure products were
85–95% (100% conversion).
[b]
[c]
[a]
All reactions were carried out with 1 mol % of [Pd-
(C3H5)Cl]2 and 2.5 mol % of ligand in CH2Cl2 at room
temperature for 20 h.
Determined by GC. The yields of the pure products were
85–95% (100% conversion).
Determined by GC or HPLC using chiral columns.
[b]
[c]
lective hydrogenation of imines and olefins. Remarka-
bly high enantioselectivities were obtained in the hydro-
genation of trisubstituted 1-alkyl-1,2-diarylalkenes, a
substrate class of unfunctionalized alkenes for which
very few catalytic systems have been reported before.
Determined by GC or HPLC using chiral columns.
trol in the Pd-catalyzed allylic alkylation, in most cases In order to extend the application range of these cata-
surpassing the selectivities obtained with phosphine- lysts to other substrate classes, we started a systematic
or phosphite-oxazolines. In particular, bis(N-sulfonyl- investigation of Ir complexes containing other N,P-li-
amino)phosphine-oxazoline ligands proved to be very gands, including the new ligand classes 5 and 6.
efficient in the allylic alkylation of 3-arylallyl acetates.
Iridium(COD) complexes with bis(N-sulfonylami-
Recent studies showed that these ligands are also suita- no)phosphine-oxazoline and TADDOL-derived li-
ble for kinetic resolution of racemic 1,3-disubstituted gands were readily prepared according to our standard
allyl esters.[15]
protocol by refluxing a solution of [Ir(COD)Cl]2 and
the corresponding N,P-ligand in dichloromethane.[16]
For the exchange of the chloride ion with BArF {tetra-
kis[3,5-bis(trifluoromethyl)phenyl]borate}, the com-
plexes were treated with NaBArF in a two-phase di-
Ir-Catalyzed Hydrogenation of Olefins
Iridium phosphinooxazoline complexes have emerged chloromethane-water system. The resulting orange/red
as a promising new class of catalysts for the enantiose- BArF salts were purified by column chromatography
Adv. Synth. Catal. 2005, 347, 61–77
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69

Robert Hilgraf, Andreas Pfaltz
FULL PAPERS
Table 7. Enantioselective Pd-catalyzed allylic alkylation of 2-
Table 9. Enantioselective Ir-catalyzed hydrogenation of (E)-
cyclohexen-1-yl acetate.[a]
2-(4-methoxyphenyl)-phenylpropene.[a]
Entry
Ligand
Conversion [%][b]
ee [%][c]
Entry
Ligand
Conversion [%][b]
ee [%][c]
1
2
3
4
5
6
29a
36
38a
48
49
57
26
60
100
100
78
92 (R)
74 (R)
92 (R)
85 (R)
85 (R)
84 (R)
1
2
3
4
5
6
7
29
33
34
35
38
40
47
100
74
71 (R)
65 (R)
71 (R)
1 (R)
85 (R)
75 (R)
46 (S)
100
100
100
100
100
50
[a]
All reactions were carried out with 4 mol % of catalyst in
CH2Cl2 at 100 bar at room temperature for 2 h.
Determined by GC.
[b]
[c]
[a]
All reactions were carried out with 1 mol % of [Pd-
(C3H5)Cl]2 and 2.5 mol % of ligand in CH2Cl2 at room
temperature for 20 h.
Determined by GC. The yields of the pure products were
85–95% (100% conversion).
Determined by GC or HPLC using chiral columns.
[b]
[c]
general, this particular trisubstituted alkene is an unpro-
blematic substrate, reacting with high enantioselectivity
with many different Ir catalysts.[17] Interestingly, ligands
29a and 38a containing 1,2-diphenyl- and 1,2-dicyclo-
hexyldiamine backbones were more efficient for this
substrate than the corresponding diastereomers 29 and
38, in contrast to allylic alkylation where ligands 29
and 38 gave better results (Table 8, Entries 1 and 2, 6
and7). However, replacement of ligand 35 containing a
cyclohexanediamine backbone and TADDOL-derived
ligand 47 by the corresponding diastereomers 35a and
47a resulted in lower ees and conversions (Entries 3
and 4, 8 and 9). Substitution of the p-tolyl substituents
of ligand 35 with sterically more demanding 2-naphthyl
groups (ligand 37) resulted in higher conversion with
similar enantioselectivity (Entries 3 and 5). The TAD-
DAMIN-derived ligand 50 afforded a higher ee than
the TADDOL-derived ligand 47 (Entries 8 and 10).
As shown in Table 9, the p-methoxy derivative gave
very similar results as the unsubstituted methylstilbene.
Both ligands systems show comparable or lower enan-
tioselectivities than PHOX ligands although with lower
conversions.
Determined by GC or HPLC using chiral columns.
Table 8. Enantioselective Ir-catalyzed hydrogenation of (E)-
1,2-diphenylpropene.[a]
Entry
Ligand
Conversion [%][b]
ee [%][c]
1
2
3
4
5
6
7
8
9
29
29a
35
35a
37
38
38a
47
47a
50
16
49
15
11
73
71
59
100
100
69
86 (R)
87 (R)
94 (R)
72 (R)
91 (R)
68 (R)
92 (R)
75 (R)
48 (R)
84 (R)
10
[a]
All reactions were carried out with 4 mol % of catalyst in
CH2Cl2 at 100 bar at room temperature for 2 h.
Determined by GC.
Ethyl b-methylcinnamate could be reduced to the cor-
responding saturated ester with up to 92% ee, while Ir-
PHOX complexes gave lower enantioselectivities of
up to 82% ee (Table 10). The TADDOL-derived li-
[b]
[c]
Determined by GC or HPLC using chiral columns.
on silica gel. All complexes were stable against oxygen gands, in general, gave higher conversions than bis(N-
and moisture. Hydrogenations were carried out in di- sulfonylamino)phosphine-oxazoline ligands (Entries
chloromethane at room temperature for 2 h at 100 bar 6–8). The highest ee was achieved using ligand 40 con-
hydrogen pressure using 4 mol % catalyst. Lower cata- taining a stereogenic phosphorus atom (Entry 5). Substi-
lyst loading or hydrogen pressure resulted in reduced tution of the tolyl substituents of ligand 35 with 1-naph-
conversions and enantioselectivities.
thyl substituents resulted again in higher conversions,
Using (E)-1,2-diphenylpropene as substrate, both but this time with a significant decrease in enantiocon-
new ligand classes induce moderate to high enantiose- trol (Entries 2 and 3).
lectivities but mostly with low conversions. Longer reac-
(E)- and (Z)-2-aryl-2-butenes are more difficult to hy-
tion times did not result in higher conversions suggesting drogenate with high enantioselectivity than (E)-1-alkyl-
that the catalyst is deactivated during the reaction. In 1,2-diarylalkenes. With (E)-2-aryl-2-butene as substrate,
70
ꢀ 2005 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
Adv. Synth. Catal. 2005, 347, 61–77

Bis(N-sulfonylamino)phosphine- and TADDOL-Phosphite-Oxazoline Ligands
FULL PAPERS
Table 10. Enantioselective Ir-catalyzed hydrogenation of
ethyl b-methylcinnamate.[a]
Table 12. Enantioselective Ir-catalyzed hydrogenation of
(Z)-2-(4-methoxyphenyl)-2-butene.[a]
Conversion [%][b]
ee [%][c]
Entry
Ligand
Conversion [%][b]
ee [%][c]
Entry
Ligand
1
2
3
4
5
6
29a
35
36
38a
47
49
100
55
100
100
100
100
35 (R)
42 (R)
44 (S)
44 (R)
90 (S)
95 (S)
1
2
3
4
5
6
7
8
29a
35
36
37
40
47
48
49
43
32
100
46
86 (R)
91 (R)
65 (R)
81 (R)
92 (R)
75 (R)
76 (R)
87 (R)
80
100
100
100
[a]
All reactions were carried out with 4 mol % of catalyst in
CH2Cl2 at 100 bar at room temperature for 2 h.
Determined by GC.
[b]
[c]
[a]
All reactions were carried out with 4 mol % of catalyst in
CH2Cl2 at 100 bar at room temperature for 2 h.
Determined by GC.
Determined by GC or HPLC using chiral columns.
[b]
[c]
Determined by GC or HPLC using chiral columns.
Table 11. Enantioselective Ir-catalyzed hydrogenation of
(E)-2-(4-methoxyphenyl)-2-butene.[a]
Table 13. Enantioselective Ir-catalyzed hydrogenation of 6-
methoxy-1-methyl-3,4-dihydronaphthalene.[a]
Entry
Ligand
Conversion [%][b]
ee [%][c]
Entry
Ligand
Conversion [%][b]
ee [%][c]
1
2
3
4
5
29a
37
38a
47
100
100
100
100
70
55 (S)
25 (S)
86 (S)
35 (S)
61 (S)
1
2
3
4
5
6
7
29a
35
37
38a
40
48
100
65
85 (R)
84 (R)
71 (R)
90 (R)
91 (R)
84 (R)
81 (R)
100
100
100
100
100
48
[a]
All reactions were carried out with 4 mol % of catalyst in
CH2Cl2 at 100 bar at room temperature for 2 h.
Determined by GC.
49
[b]
[c]
[a]
All reactions were carried out with 4 mol % of catalyst in
CH2Cl2 at 100 bar at room temperature for 2 h.
Determined by GC.
Determined by GC or HPLC using chiral columns.
[b]
[c]
Determined by GC or HPLC using chiral columns.
and 38a afforded products of the same configuration (R)
with both isomers, whereas the other ligands behaved in
the best results were achieved with bis(N-sulfonyl- the same way as PHOX ligands. The reason for this dif-
amino)phosphine-oxazoline ligands 38a and 40 with up ference remains unclear at this point. A possible explan-
to 91% ee (Table 11, Entries 4 and 5). TADDOL-de- ation could be that partial cis-trans isomerization takes
rived ligands 48 and 49 gave similar enantioselectivities place during hydrogenation. Thus, in those reactions
as PHOX ligands (Entries 6 and 7).
(Table 12, Entries 1, 2 and 4) which afford the unexpect-
For the corresponding (Z)-alkene remarkably high ed (R)-enantiomer, the major pathway proceeds via hy-
enantioselectivities of up to 95% ee could be obtained drogenation of the more stable (E)-isomer.
using TADDOL-derived ligands 47 and 49 (Table 12,
Hydrogenation of 6-methoxy-1-methyl-3,4-dihydro-
Entries 5 and 6). Replacement of the phenyl groups in naphthalene with an endocyclic double bond gave only
the TADDOL backbone with sterically more demand- moderate enantioselectivities using PHOX ligands. Li-
ing 2-naphthylgroups increased the enantiomeric excess gand 38a afforded a clearly improved enantiocontrol
from 90% to 95%. Ir complexes of bis(N-sulfonylami- of 86% ee, whereas all other tested ligands gave lower
no)phosphine-oxazoline ligands gave only moderate to enantioselectivities (Table 13).
low enantioselectivities (Entries 1–4). Using PHOX li-
With 3-methyl-2-cyclohexenone as substrate, PHOX
gands, the (E)- and (Z)-isomers afford products of oppo- ligands gave very low conversions and enantioselectivi-
site absolute configuration. Interestingly, ligands 29a, 35 ties (15% conversion, 3% ee). Ligands 36 and 47 afford-
Adv. Synth. Catal. 2005, 347, 61–77
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71

Robert Hilgraf, Andreas Pfaltz
FULL PAPERS
Table 14. Enantioselective Ir-catalyzed hydrogenation of 3-
Experimental Section
methyl-2-cyclohexenone.[a]
General Remarks
NMR spectra were recorded on a Bruker Advance DRX 500
(1H: 500 MHz, 13C: 125.8 MHz), Bruker AMX 400 (1H:
400 MHz, 13C: 100.6 MHz), Varian Gemini 300 (1H:
300 MHz, 13C: 85 MHz, 31P: 122 MHz) or on a Bruker AC 200
(1H: 200 MHz, 13C: 50 MHz, 31P: 81 MHz). All signals were ex-
pressed as ppm down field from tetramethylsilane used as an
internal standard (d value in CDCl3). MS was measured on Fin-
negan MAT 312 (FAB), VG 70-SE (70 eV) (EI) in m/z (% of
basic peak). IR spectra were obtained with a Perkin Elmer
1600 FTIR-spectrometer. Optical rotation was measured
with a Perkin Elmer 341 polarimeter. Melting points were ob-
tained on a Bꢂchi 535 apparatus, values are uncorrected.
HPLC was measured on a Shimadzu SCL-10A. Elemental
analyses were performed by the Microanalytical Laboratory
of the Institut fꢂr Organische Chemie, Universitꢃt Basel. Col-
umn chromatography was conducted on silica gel 60, 0.040–
0.063 nm, 230–400 mesh, available from Uetikon Chemie.
TLC was performed with Macherey-Nagel Polygram SIL G/
UV254 plates, detection by UVor common detecting agents [al-
kaline KMnO4 solution, Ce(SO4)2/phosphomolybdic acid solu-
tion] followed by heating. Solvents were dried and distilled
shortly before use. All reagents were purchased from Fluka,
Aldrich and Strem and used without further purification. All
reactions were carried out under an atmosphere of argon.
For analytical data of compounds 19–27, ligands 30–39, 47–
50 and iridium complexes 29a–40, 47–50 see Supporting Infor-
mation.
Entry
Ligand
Conversion [%]b)
ee [%]c)
1
2
3
4
5
29a
36
38a
47
6
3 (S)
41 (R)
4 (S)
58 (R)
54 (R)
100
12
97
8
49
[a]
All reactions were carried out with 4 mol % of catalyst in
CH2Cl2 at 100 bar at room temperature for 2 h.
Determined by GC.
[b]
[c]
Determined by GC or HPLC using chiral columns.
ed respectable ee values for this demanding substrate
with essentially full conversion (Entries 2 and 4). Com-
parison of the results for ligands 47 and 49 in which phe-
nyl groups were replaced by 2-naphthyl groups clearly
shows the sensitivity of this substrate to small changes
in the ligand structure: the conversion decreased from
97% to 8% with similar enantioselectivity (Entries 4
and 5).
In conclusion, iridium complexes derived from Bis(N-
sulfonylamino)phosphine- and TADDOL-phosphite-
oxazolines proved to be efficient catalysts for enantiose-
lective hydrogenation. Several types of olefins, for which
Ir-PHOX complexes gave unsatisfactory ee values,
could be hydrogenated with good enantioselectivity.
However, catalyst activity was lower than with Ir-
PHOX complexes, requiring higher catalyst loadings
(4 mol %) to achieve full conversion. More recently,
we found that replacement of the N-sulfonyl groups in
ligands 5 by N-aryl or N-alkyl substituents resulted in
higher catalyst activity and often higher enantioselectiv-
ity.[17]
(R,R)-1,2-Dicyclohexylethane-1,2-diamine (8)
(R,R)-1,2-Diphenylethylenediamine (1.0 g, 4.71 mmol) was
dissolved in a mixture of CH2Cl2 and Et2O (60 mL, 1:1). A sol-
ution of HCl in ether (4.71 mL, 9.42 mmol, 2 N in Et2O) was
added and the reaction mixture was stirred overnight at
room temperature. The precipitate was filtered off and dis-
solved in 25% sulfuric acid (60 mL) and hydrogenated at 1
atm hydrogen pressure after addition of PtO2 (0.9 g) for 24 h.
The reaction mixture was filtered through a silica gel pad and
washed with MeOH and the filtrate was evaporated under re-
duced pressure. The residue was carefully added to 25% aque-
ous NH4OH (300 mL) and MTBE (300 mL) was added. The
two phase system was stirred overnight at room temperature
and the phases were separated. The organic phase was dried
over MgSO4 and concentrated. The product was obtained as
a white solid; yield: 896 mg (85%); mp 788C; [a]2D0: 29.4 (c
0.52, CHCl3); 1H NMR (300 MHz, CDCl3): d¼0.89–1.41 (m,
16H, 6ꢁCH2 þ2ꢁNH2), 1.61–1.88 (m, 8H, 4ꢁCH2), 2.43
(d, J¼6.4 Hz, 2H, 2ꢁCH); 13C NMR (75.5 MHz, CDCl3):
d¼26.6, 28.7, 30.4 (CH2), 40.6 (CH2CH), 55.6 (NH2CH); MS
(FAB): m/z¼225; MS (EI): m/z¼141 (11), 113 (13), 112
(100), 95 (26), 56 (16), 55 (13), 41. IR (NaCl): n¼3381 w,
3050 m, 2925 s, 2852 s, 2360 s, 1578 m, 1449 m, 1388 w, 1362 w,
1303 w, 1265 m, 1196 w, 1166 w, 1082 w, 958 w, 892 w, 819 w,
Conclusion
With the bis(N-sulfonylamino)phosphine- and TAD-
DOL-phosphite-oxazolines we have added two useful li-
gand classes to the family of chiral oxazoline-based N,P-
ligands. The two chiral units in these ligands are derived
from readily available chiral precursors. Our results
show that ligands of this type can induce high enantiose-
lectivities both in Pd- and Ir-catalyzed reactions. The
modular construction and facile synthesis of these li-
gands should make it possible to optimize their structure
for many other metal-catalyzed processes.
738 s, 704 w, 668 w cmꢀ1
.
72
ꢀ 2005 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
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Adv. Synth. Catal. 2005, 347, 61–77

Bis(N-sulfonylamino)phosphine- and TADDOL-Phosphite-Oxazoline Ligands
FULL PAPERS
12H, 4ꢁCH3), 6.47 (s, 2H, 2ꢁCH), 6.92 (s, 2H, HAr), 7.03 (s,
4H, HAr); 13C NMR (75.5 MHz, CDCl3): d¼21.3 (CH3), 124.3
(CH), 128.5, 129.2 (HCAr), 137.4, 138.1 (CAr); MS (EI): m/z¼
237 ([MþH]þ, 27), 236 (100), 221 (12), 206 (33); IR (KBr):
3,5-Dimethylbenzaldehyde (9)
3,5-Dimethylbenzyl alcohol (22.72 g, 166.8 mmol) was dis-
solved in CH2Cl2 (1200 mL) and freshly grinded molecular
sieves 4 ꢄ (30 g) were added. The suspension was stirred at
room temperature for 15 min then cooled to 08C and pyridini-
um dichromate (115.97 g, 308.3 mmol) was added. The reac-
tion mixture was stirred at 08C for 1 h and followed by 2 h at
room temperature. After filtration through a silica pad and
washing with MTBE (2000 mL) the combined organic phases
were dried over MgSO4 and evaporated to give the product
as a pale yellow liquid; yield: 18.80 g (84%); bp 1998C;
1H NMR (300 MHz, CDCl3): d¼2.37 (s, 6H, 2ꢁCH3), 7.42
(s, 1H, HAr), 7.47 (s, 2H, HAr), 9.93 (s, 2H, CHO); 13C NMR
(75.5 MHz, CDCl3): d¼20.9 (CH3), 127.4, 136.4 (HCAr),
137.7, 138.6 (CAr), 192.6 (CHO); MS (EI): m/z¼134 (Mþ,
90), 133 (100), 105 (71), 103 (12), 91 (23), 79 (15), 77 (24), 63
(10), 51 (13), 43 (29), 39 (15).
n¼3050 m, 1600 s, 1580 m, 1450 s, 960 m cmꢀ1
.
(S,S)-1,2-Bis(3,5-dimethylphenyl)ethane-1,2-diol (12)
A mixture of potassium osmate (78 mg, 0.21 mmol), O-(4-
chlorobenzoyl)hydroquinine (1.31 g, 2.82), K3Fe(CN)6
(20.87 g, 63.40 mmol) and K2CO3 (8.74 g, 63.40 mmol) were
dissolved in a mixture of tert-butyl alcohol/water (280 mL,
1:1) and stirred for 5 min. Compound 11 (5.0 g, 21.2 mmol)
was added and the heterogeneous reaction mixture was stirred
for two days at room temperature. Na2SO3 (105 g, 833.1 mmol)
was added and the reaction mixture was stirred for further
30 min. After separation of the phases the water phase was ex-
tracted with CH2Cl2 (2ꢁ100 mL). The combined organic phas-
es were evaporated and the residue was dissolved in EtOAc
(150 mL) and washed with 1 N H2SO4 (2ꢁ100 mL), saturated
NaHCO3 (2ꢁ100 mL) and brine (2ꢁ100 mL). The organic
phases were dried over Na2SO4 and evaporated. The residue
was purified by chromatography (hexanes/EtOAc, 4:1) to
give the product as a white solid; yield: 3.34 g (59%); mp
1068C [<99% ee based on chiral HPLC (Chiralcel OD)];
3,5-Dimethylbenzylphosphonium Bromide (10)
3,5-Dimethylbenzyl bromide (56.42 g, 283.4 mmol) and PPh3
(74.30 g, 283.2 mmol) were dissolved in toluene (640 mL)
and heated at 808C for 3 h. After cooling to room temperature
the solid was filtered off and washed with a small amount of
MTBE to give the product as a white solid; yield: 98.25 g
1
[a]2D0: ꢀ66.3 (c 0.89, CHCl3); H NMR (300 MHz, CDCl3):
1
(75%); mp 2238C; H NMR (300 MHz, CDCl3): d¼2.07 (s,
d¼2.27 (s, 12H, 4ꢁCH3), 2.65 (br s, 2H, 2ꢁOH), 4.68 (s, 2H,
2ꢁCH), 6.84 (s, 4H, HAr), 6.89 (s, 2H, HAr); 13C NMR
(75.5 MHz, CDCl3): d¼21.3 (CH3), 78.4 (C-OH), 124.4, 129.4
(HCAr), 137.7, 140.1 (CAr); MS (EI): m/z¼137 (12), 136
(100), 135 (36), 121 (27), 107 (41), 105 (11), 91 (26); IR
(KBr): n¼3885 m, 2909 m, 2880 w, 1647 m, 1636 m, 1609 m,
6H, 2ꢁCH3), 5.24 (s, 1H, CH2a), 5.29 (s, 1H, CH2b), 6.58 (s,
2H, HAr), 6.84 (s, 1H, HAr), 7.23–7.80 (m, 15H, HAr);
13C NMR (75.5 MHz, CDCl3): d¼21.0 (CH3), 126.3, 126.4,
129.1, 129.9, 130.1 (HCAr), 138.2, 138.3 (CAr); 31P NMR
(121.5 MHz, CDCl3): d¼22.7; MS (FAB): m/z¼461; MS
(EI): m/z¼380 (24), 379 (22), 263 (15), 262 (72), 261 (10),
195 (10), 185 (10), 184 (19), 183 (100), 165 (13), 152 (16), 119
(59), 115 (13), 108 (23), 107 (22), 91 (16), 77 (17), 51 (25), 39
(12); IR (NaCl): n¼3045 w, 2989 w, 2878 w, 2849 m, 2729 m,
2483 w, 2360 w, 2257 w, 2006 w, 1811 w, 1597 w, 1588 w, 1482
w, 1438 w, 1407 m, 1378 w, 1333 w, 1266 w, 1249 m, 1190 w,
1176 w, 1157 m, 1109 s, 1028 w, 995 m, 952 w, 860 m, 763 m,
1464 s, 1159 s, 1072 m, 849 w, 727 m, 704 w, 687 m cmꢀ1
.
(R,R)-1,2-Diazido-1,2-bis(3,5-dimethylphenyl)ethane
(13)
743 m, 726 w, 704 w, 690 m, 626 w, 552 w, 523 w, 500 w cmꢀ1
.
A mixture of triethylamine (2.47 mL, 17.70 mmol) and metha-
nesulfonyl chloride (1.37 mmol, 17.70 mmol) was added drop-
wise to a solution of 12 (2.2 g, 8.14 mmol) in CH2Cl2 (31 mL)
and stirred for 3 h at room temperature. The reaction mixture
was quenched with water and the phases were separated. The
aqueous phase was extracted with CH2Cl2 (2ꢁ100 mL). The
combined organic phases were dried over Na2SO4 and the sol-
vent was evaporated. The residue was purified by chromatog-
raphy (Et2O) to give the bismesylate as a white solid; yield:
3.44 g (99%).
(E)-1,2-Bis(3,5-dimethylphenyl)ethene (11)
n-BuLi (45 mL, 72.0 mmol, 1.6 M in hexanes) was added drop-
wise at ꢀ788C to a suspension of 10 (27.85 g, 60.4 mmol) in
THF (555 mL) and stirred for 2 h at room temperature. After
adding 9 (8.11 g, 60.4 mmol) dissolved in THF (18 mL) the sol-
ution was stirred for 3 h at room temperature. The solvent was
evaporated. The residue was dissolved in MTBE (250 mL), fil-
tered through silica and washed with MTBE. The solvent was
removed and the residue was purified by chromatography
(hexanes/EtOAc, 4:1) to give the product as an (E)/(Z)-mix-
ture. The mixture was dissolved in CHCl3 (300 mL) and
TeCl4 (2.15 g) and a small amount of tellurium were added
and the reaction mixture was stirred for 5 h at room tempera-
ture. After filtration over Celite the organic phase was washed
with 5% aqueous Na2CO3-solution (100 mL) and dried over
Na2SO4. After evaporation of the solvent the solid was recrys-
tallized from hexanes and purified by chromatography (hex-
anes/EtOAc, 4:1) to give the product as a white solid; 6.97 g
The bismesylate (3.44 g, 8.06 mmol) was dissolved in DMF
(44 mL) and NaN3 (1.16 g, 17.84 mmol) was added. The reac-
tion mixture was heated at 808C overnight. After cooling to
room temperature H2O (40 mL) was added and the water
phase was extracted with EtOAc (3ꢁ150 mL). The combined
organic phases were dried over Na2SO4 and the solvent evapo-
rated. The residue was purified by chromatography (hexanes/
EtOAc, 8:1) to give the product as a pale yellow oil which crys-
tallized upon cooling (48C); yield: 1.39 g (54%); mp 388C;
1
[a]2D0: ꢀ141.5 (c 0.99, CHCl3); H NMR (300 MHz, CDCl3):
d¼2.25 (s, 12H, 4ꢁCH3), 4.57 (s, 2H, 2ꢁCH), 6.74 (s, 4H,
HAr), 6.90 (s, 2H, HAr); 13C NMR (75.5 MHz, CDCl3): d¼21.2
(CH3), 70.4 (CH), 125.4, 130.1 (HCAr), 135.8, 138.0 (CAr); MS
1
(49%); mp 2078C; H NMR (300 MHz, CDCl3): d¼2.34 (s,
Adv. Synth. Catal. 2005, 347, 61–77
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Robert Hilgraf, Andreas Pfaltz
FULL PAPERS
(EI): m/z¼236 (24), 133 (34), 132 (100), 131 (18), 116 (25), 106
(11), 105 (79), 103 (14), 91 (12), 79 (17), 77 (21); IR (KBr): n¼
3320 m, 3018 m, 2920 w, 2855 w, 2479 m, 2120 m, 2074 m,
1609 m, 1470 s, 1380 m, 1305 s, 1291 m, 1252 w, 934 m, 849 m
vent the product was obtained as a pale yellow oil; yield:
1
8.29 g (77%); [a]2D0: 29.5 (c0.30, CHCl3); H NMR (300 MHz,
CDCl3): d¼0.79 (s, 18H, 2ꢁt-butyl), 1.23 (d, J¼6.5 Hz, 6H,
2ꢁCH3), 2.36 (s, 2H, 2ꢁHC-t-butyl), 3.71 (q, J¼6.5 Hz, 2H,
2ꢁCH), 7.15–7.45 (m, 10H, HAr); 13C NMR (75.5 MHz,
CDCl3): d¼23.6, 35.8 (CH3), 57.0 (HC), 62.2 (HC-t-butyl),
126.4, 126.8, 128.1 (HCAr), 147.8 (CAr).
cmꢀ1
.
(R,R)-1,2-Bis(3,5-dimethylphenyl)ethane-1,2-diamine
(14)
(R,R)-1,2-Di-tert-butylethane-1,2-diamine (17)
A solution of 13 (2.19 g, 6.84 mmol) in THF (44 mL) was added
dropwise at 08C to a suspension of LiAlH4 (524 mg,
13.81 mmol) in THF (44 mL) and stirred for 3 h at room tem-
perature. The reaction was quenched by adding a saturated
aqueous KF solution (26.0 mL, 468.1 mmol). The reaction mix-
ture was filtered over Celite and washed with EtOAc. The com-
bined organic phases were dried over Na2SO4 and the solvent
was evaporated. The residue was purified by chromatography
(EtOAc/MeOH, 4:1) to give the product as a white solid; yield:
730 mg (40%); mp 568C; [a]2D0: 61.0 (c 0.24, CHCl3); 1H NMR
(300 MHz, CDCl3): d¼1.46 (br s, 4H, 2ꢁNH2), 2.30 (s, 12H,
4ꢁCH3), 4.15 (s, 2H, 2ꢁCH), 6.90 (s, 2H, HAr), 6.97 (s, 4H,
HAr); 13C NMR (75.5 MHz, CDCl3): d¼21.3 (CH3), 69.0
(CH), 124.6, 128.6 (HCAr), 137.9, 143.3 (CAr); MS (EI): m/z¼
135 (13), 134 (100), 107 (11), 91 (11). IR (NaCl): n¼3639 w,
3378 m, 3300 m, 3011 m, 2911 m, 2867 m, 2733 w, 1606 s,
1461 m, 1378 m, 1300 w, 1261 w, 1156 w, 1089 w, 1037 w, 959
To a solution of 16 (4.60 g, 12.09 mmol) in MeOH (150 mL)
were added Pd(OH)2 (1.23 g) and ammonium formate
(4.60 g, 72.68 mmol). The reaction mixture was heated at
608C under vigorous stirring for 2 h. After cooling to room
temperature the mixture was filtered over Celite and the sol-
vent evaporated. The residue was dissolved in MTBE
(60 mL) and stirred with K2CO3 (10 g) for 30 min. After filtra-
tion and evaporation of the solvent the product was obtained
after distillation of the residue as a colorless liquid; yield:
1.21 g (58%); bp 2428C; [a]2D0: ꢀ15.6 (c 0.67, CHCl3);
1H NMR (300 MHz, CDCl3): d¼0.91 (s, 18H, 6ꢁCH3), 2.55
(s, 2H, 2ꢁCH); 13C NMR (75.5 MHz, CDCl3): d¼26.6
(C(CH3)3), 35.4 (C(CH3)3), 57.2 (CH); MS (EI): m/z¼174
([Mþ2H]þ, 10), 173 ([MþH)þ, 100), 86 (15).
w, 848 s, 708 m cmꢀ1
.
General Procedure for the Bis-Sulfonylation of Chiral
Diamines
The diamine (1 equiv.) was dissolved in CH2Cl2 (3.5 mL/
mmol), cooled to 08C and stirred for 15 min. After adding
N,N-diisopropylethylamine (4.5 equivs.) the reaction mixture
was stirred for further 10 min at 08C. After cooling the reaction
mixture to ꢀ408C the sulfonyl chloride (2 equivs.) was added.
The reaction mixture was warmed to room temperature and
stirred for 2 h. The reaction was quenched by addition of 1 M
HCl. The phases were separated and the aqueous phase was ex-
tracted with CH2Cl2. The combined organic phases were wash-
ed with brine and dried over Na2SO4. The solvent was evapo-
rated and the residue was purified by recrystallization or chro-
matography to give the product.
N,N’-Bis((S)-1-phenylethyl)ethanediimine (15)
A mixture of glyoxal (4.67 mL, 32.24 mmol, 40% aqueous sol-
ution), a-(S)-methylbenzylamine (8.0 g, 66.02 mmol), formic
acid (0.21 mL, 5.57 mmol) and MgSO4 (16.5 g) was stirred in
CH2Cl2 (65 mL) for 30 min at 208C. (It is important to keep
the temperature below 208C, as even slightly higher tempera-
tures give by-products and decreased yields.) The reaction mix-
ture was filtered over Celite and evaporated. The residue was
dissolved in cyclohexane (70 mL), dried over Na2SO4 and the
solvent was evaporated to give the product as a pale yellow
1
oil; yield: 7.75 g (90%); H NMR (300 MHz, CDCl3): d¼1.58
(d, J¼7.0 Hz, 6H, 2ꢁCH3), 4.51 (q, J¼7.0 Hz, 2H, 2ꢁCH),
(1R,2R)-1,2-N,N’-Bis(p-toluenesulfonylamino)-1,2-diphe-
nylethane (18): White solid (recrystallized from CH2Cl2/hex-
anes); yield: 79%; mp 898C; [a]2D0: 43.9 (c 1.74, CHCl3);
1H NMR (400 MHz, CDCl3): d¼2.32 (s, 6H, 2ꢁCH3), 4.48
(d, J¼6.9 Hz, 2H, 2ꢁCH), 5.64 (br s, 2H, 2ꢁNH), 6.67 (d,
J¼8.4 Hz, 4H, HAr), 6.94–7.07 (m, 10H, HAr), 7.47 (d, J¼
8.4 Hz, 4H, HAr); 13C NMR (101.6 MHz, CDCl3): d¼21.4
(CH3), 62.2 (CH), 127.2, 127.6, 127.8, 128.1, 129.3 (HCAr),
136.4, 136.9, 143.2 (CAr); MS (EI): m/z¼261 (16), 260 (100),
155 (31), 106 (35), 91 (49); IR (KBr): n¼3338 m, 3312 m,
3066 w, 3032 w, 2947 w, 2926 w, 1598 w, 1496 w, 1457 m, 1402
w, 1329 s, 1306 m, 1158 s, 1120 w, 1090 m, 1064 m, 927 m,
7.10–7.38 (m, 10H, HAr), 8.05 (s, 2H, N CH); 13C NMR
¼
(75.5 MHz, CDCl3): d¼24.0 (CH3), 69.7 (CH), 126.7, 127.2,
¼
128.6 (HCAr), 143.7 (CAr), 160.7 (C N).
N,N’-Bis((S)-1-phenylethyl)-(R,R) -1,2-di-tert-
butylethane-1,2-diamine (16)
A
solution of tert-butylmagnesium chloride (40.5 mL,
81.0 mmol, 2M in Et2O) in hexanes (400 mL) was heated at
508C for 20 min. Then a solution of 15 (7.5 g, 28.37 mmol) in
hexanes (120 mL) was added dropwise and the reaction mix-
ture was stirred at 508C for 45 min. After cooling to room tem-
perature the reaction was quenched by adding sat. NH4Cl sol.
(120 mL) and MTBE (120 mL). After subsequent stirring at
room temperature for further 30 min the phases were separat-
ed. The aqueous phase was extracted with MTBE (2ꢁ
100 mL). The combined organic phases were dried over
Na2CO3 and filtered over silica. After evaporation of the sol-
813 m, 768 w, 700 m, 670 m, 572 m, 549 m, 524 w cmꢀ1
.
General Procedure for the Bis-Sulfonylation to Afford
28 and ent-28
Thediamine (1 equiv.) was dissolved inpyridine(28 mL/mmol)
and heated to 1308C. A solution of the sulfonyl chloride (2.2
74
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Adv. Synth. Catal. 2005, 347, 61–77

Bis(N-sulfonylamino)phosphine- and TADDOL-Phosphite-Oxazoline Ligands
FULL PAPERS
equivs.) in pyridine was added dropwise and the reaction mix-
ture was stirred at 1308C for 18 h. After cooling to room tem-
perature water and 1 N HCl were added and the reaction mix-
ture was stirred for 30 min. CH2Cl2 was added, the phases were
separated and the aqueous phase was extracted with CH2Cl2.
The combined organic phases were washed with 1 N HCl and
water and dried over Na2SO4. The solvent was evaporated
and the residue was purified by chromatography to give the de-
sired product.
105 (88), 77 (11), 73 (64), 43 (13); IR (KBr): n¼3590 m,
3090 m, 3060 m, 3010 w, 2940 m, 1950 w, 1900 m, 1810 m,
1600 w, 1490 s, 1450 s, 1380 m, 1370 s, 1320 m, 1300 m,
1180 m, 1080 m, 1066 m, 1040 s, 1020 s, 1000 w, 930 m, 900 w,
870 w, 860 m, 840 m, 650 w, 630 w cmꢀ1
.
(4R,5R)-Bis(aminodiphenylmethyl)-2,2-dimethyl-1,3-
dioxolane (44)
(1R,2R)-1,2-N,N’-Bis(p-toluenesulfonylamino)-1,2-di-tert-
butylethane (28): White solid (chromatography, hexanes/
EtOAc, 8:1); yield: 48%; mp 718C; [a]2D0: 39.2 (c 0.358,
To a solution of 43 (5.30 g, 10.49 mmol) in DMF (55 mL) was
added dropwise
a solution of sodium azide (2.73 g,
1
41.99 mmol) in water (10 mL) and the reaction mixture was
heated at 808C for 5 h. After cooling to room temperature
Et2O (160 mL) and water (100 mL) were added and the phases
were separated. The aqueous phase was extracted with Et2O.
The combined organic phases were washed with water (2ꢁ
100 mL), concentrated (to 100 mL) and dried over MgSO4.
The solution was added dropwise to a suspension of LiAlH4
(3.20 g, 84.32 mmol) in Et2O (100 mL) and stirred for 2 h at
room temperature. The reaction was quenched by adding a sa-
turated aqueous Na2SO4 solution (30 mL). The suspension was
filtered and washed with Et2O (300 mL). The solvent was
evaporated, the residue was heated under reflux in hexanes
(23 mL) for 60 min and the solid was filtered off. The crude
product was purified by chromatography (Et2O) to give the
product as a pale yellow solid; yield: 1.33 g (27%); mp 1958C;
CHCl3); H NMR (300 MHz, CDCl3): d¼0.86 [s, 18H, 2ꢁ
C(CH3)3], 2.43 (s, 6H, 2ꢁCH3), 3.62 (d, J¼9.6 Hz, 2H, 2ꢁ
CH), 4.44 (d, J¼6.1 Hz, 2H, 2ꢁNH), 7.29 (d, J¼8.3 Hz, 4H,
HAr), 7.70 (d, J¼8.3 Hz, 4H, HAr); 13C NMR (75.5 MHz,
CDCl3): d¼21.5, 27.2 (CH3), 36.0 (C(CH3)3), 60.2 (CH),
126.4, 129.6 (HCAr), 139.2, 143.4 (CAr); MS (FAB): m/z¼481;
MS (EI): m/z¼481 ([M]þ, 1), 241 (16), 240 (100), 211 (13),
155 (51), 139 (12), 92 (13), 91 (92), 86 (17), 65 (15), 57 (37),
41 (19); IR (NaCl): n¼3568 w, 3309 w, 3064 w, 2961 m, 2875
w, 2360 w, 1918 w, 1598 m, 1496 w, 1480 w, 1419 m, 1370 w,
1322 s, 1235 w, 1200 w, 1156 s, 1120 w, 1081 m, 1018 m, 930 m,
886 w, 814 m, 737 w, 708 w, 687 w, 670 m, 554 w cmꢀ1
.
(1S,2S)-1,2-N,N’-Bis(p-toluenesulfonylamino)-1,2-di-tert-
butylethane (ent-28): White solid (chromatography, hexanes/
EtOAc, 8:1); yield: 51%; mp 728C; [a]2D0: ꢀ37.1 (c 0.262,
1
[a]2D0: 41.5 (c 0.51, CHCl3); H NMR (300 MHz, CDCl3): d¼
1
CHCl3); H NMR (300 MHz, CDCl3): d¼0.86 [s, 18H, 2ꢁ
1.10 (s, 6H, 2ꢁCH3), 2.32 (br s, 4H, 2ꢁNH2), 4.26 (s, 2H, 2ꢁ
CH), 7.13–7.56 (m, 20H, HAr); 13C NMR (75.5 MHz, CDCl3):
d¼27.5 (CH3), 62.3 (C-NH2), 82.1 (CH), 107.3 [C(CH3)2],
126.9, 127.5, 127.8, 127.8, 128.1, 128.4, 129.9 (HCAr), 144.9,
150.5 (CAr); MS (EI): m/z¼466 ([M]þ, 20), 465 (54), 431 (18),
237 (40), 195 (13), 183 (22), 182 (100), 180 (18), 179 (50), 178
(19), 167 (34), 105 (21), 104 (13), 56 (12), 43 (11); IR (NaCl):
n¼3360 m, 3150 w, 3090 m, 3060 m, 3010 m, 2990 m, 2940 m,
1950 w, 1890 m, 1820 w, 1600 w, 1500 s, 1450 s, 1380 m, 1370 s,
1350 m, 1170 m, 1070 m, 1030 s, 1000 w, 950 m, 920 w, 890 w,
C(CH3)3], 2.43 (s, 6H, 2ꢁCH3), 3.62 (d, J¼9.6 Hz, 2H, 2ꢁ
CH), 4.42 (d, J¼6.1 Hz, 2H, 2ꢁNH), 7.29 (d, J¼8.6 Hz, 4H,
HAr), 7.71 (d, J¼8.6 Hz, 4H, HAr); 13C NMR (75.5 MHz,
CDCl3): d¼21.5, 27.1 (CH3), 36.1 [C(CH3)3], 60.2 (CH),
126.4, 129.7 (HCAr), 139.3, 143.4 (CAr); MS (FAB): m/z¼481;
MS (EI): m/z¼241 (16), 240 (100), 211 (13), 155 (32), 91
(50), 86 (17), 57 (24); IR (NaCl): n¼3568 w, 3319 w, 3065 w,
2960 m, 2875 w, 2360 w, 1918 w, 1598 m, 1480 w, 1418 m, 1369
w, 1322 s, 1236 w, 1200 w, 1155 s, 1120 w, 1078 m, 1017 m, 972
w, 930 m, 890 w, 814 m, 736 w, 708 w, 688 w, 666 m, 542 w cmꢀ1
.
860 m, 660 m cmꢀ1
.
(4R,5R)-4,5-Bis(chlorodiphenylmethyl)-2,2-dimethyl-
1,3-dioxolane (43)
(4R,5R)-Bis[(N-methylamino)diphenylmethyl]-2,2-
dimethyl-1,3-dioxolane (45)
Toa refluxing solution of (4R,5R)-2,2-dimethyl-a,a,a’,a’-tetra-
phenyl-1,3-dioxolan-4,5-dimethanol (6.0 g, 12.86 mmol) and
thionyl chloride (2.9 mL, 39.76 mmol) in CH2Cl2 (80 mL) was
To a suspension of 44 (5.0 g, 10.72 mmol) and NaHCO3
(10.75 g, 128.1 mmol) in DMPU (55 mL) was added iodome-
thane (1.40 mL, 22.49 mmol). After stirring for 24 h the reac-
tion mixture was poured into Et2O (200 mL), washed with wa-
ter (5ꢁ100 mL), dried over K2CO3 and the solvent was evapo-
rated. The residue was purified by chromatography (hexanes/
EtOAc, 4:1–1:1) to obtain the product as a white solid; yield:
2.02 g (38%); mp 1998C; [a]2D0: 50.3 (c 0.62, CHCl3); 1H NMR
(300 MHz, CDCl3): d¼0.99 (s, 6H, 2ꢁCH3), 2.01 (s, 6H, 2ꢁN-
CH3), 3.38 (br s, 2H, 2ꢁNH), 4.14 (s, 2H, 2ꢁCH), 7.05–7.41
(m, 16H, HAr), 7.55–7.65 (m, 4 H, HAr); 13C NMR (75.5 MHz,
CDCl3): d¼27.5, 30.9 (CH3), 67.9 (C-NH), 80.4 (CH), 107.2
[C(CH3)2], 126.6, 127.2, 127.4, 127.9, 129.9, 130.8 (HCAr), 141.9,
144.5 (CAr); MS (EI): m/z¼494 ([M]þ, 28), 493 (72), 431 (24),
237 (28), 208 (10), 197 (17), 196 (100), 182 (11), 179 (49), 178
(15), 167 (22), 118 (10), 105 (12); IR (NaCl): n¼3230 w, 3090 m,
3060 w, 3010 w, 2990 m, 2940 s, 2800 m, 1600 m, 1490 s, 1450 w,
1380 m, 1370 m, 1340 w, 1170 m, 1100 w, 1080 w, 1020 m, 1000 s,
added dropwise
a solution of triethylamine (9.03 mL,
64.79 mmol) in CH2Cl2 (80 mL). The reaction mixture was
heated under reflux for additional 30 min. After cooling to
108C the reaction mixture was poured into a cold solution of
saturated NaHCO3 (220 mL) and stirred vigorously for 4 h.
The organic phase was separated, dried over MgSO4 and
evaporated. The residue was heated under reflux in methanol
(39 mL) and the product was filtered off as a pale brown solid;
yield: 5.29 g (81%); mp 161–1648C; [a]2D0: ꢀ11.7 (c 0.50,
CHCl3); 1H NMR (300 MHz, CDCl3): d¼0.97 (s, 6H, 2ꢁ
CH3), 3.45 (s, 2H, 2ꢁCH), 7.14–7.48 (m, 20H, HAr); 13C-
NMR (75.5 MHz, CDCl3): d¼28.7 (CH3), 77.8 (C-Cl), 84.3
(CH), 113.7 [C(CH3)2], 127.7, 128.2, 128.2, 128.3, 128.4, 128.4,
129.0, 129.1, 129.1, 129.2 (HCAr), 143.4, 144.8 (CAr); MS (EI):
m/z¼318 (18), 238 (18), 237 (100), 198 (12), 197 (80), 195
(16), 183 (11), 180 (13), 179 (88), 178 (23), 167 (48), 165 (18),
880 m, 830 w, 640 m cmꢀ1
.
Adv. Synth. Catal. 2005, 347, 61–77
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75

Robert Hilgraf, Andreas Pfaltz
FULL PAPERS
145.8 (CAr), 169.4 (C N); 31P NMR (121.5 MHz, CDCl3): d¼
¼
General Procedure for the Synthesis of Ligands 29–39
and 47–50
129.6.
Triethylamine (4.2 equivs.) was dissolved in toluene (1.5 mL/
mmol) and cooled to ꢀ788C. Freshly distilled phosphorus tri-
chloride (1.4 equivs.) and a suspension of sulfonated diamine (1
equiv.) in toluene (18 mL/mmol) were added and the reaction
mixture was allowed to slowly warm to room temperature
overnight. After filtration under argon and removal of the sol-
vent under high vacuum, the residue was dissolved in toluene
(25 mL/mmol) and cooled to ꢀ788C. A solution of NEt3 (10
equivs.) and DMAP (1.02 equivs.) in toluene (1 mL/mmol
NEt3) was added very slowly dropwise followed by a solution
of the oxazoline alcohol (1 equiv.) in toluene (5 mL/mmol).
The reaction mixture was allowed to slowly warm to room tem-
perature overnight. After filtration under argon and evapora-
tion of the solvent, the crude product was recrystallized from
chloroform/hexanes at 08C. Trace amounts of remaining
DMAP were then removed at 908C/0.01 mbar to give the de-
sired product.
General Procedure for the Synthesis of Iridium
Complexes of Ligands 29–39 and 47–50
The ligand (1.0 equiv.) was dissolved in CH2Cl2 (36 mL/mmol)
and [Ir(COD)Cl]2 (0.5 equivs.) was added and heated under re-
flux for 2 h. After cooling to room temperature NaBArF (1.5
equivs.) and water (11 mL/mmol) were added and the reaction
mixture was stirred vigorously for 30 min. The phases were sep-
arated and the aqueous phase was extracted twice with CH2Cl2.
The combined organic phases were washed with water and the
solvent was evaporated. The residue was purified by chroma-
tography (CH2Cl2) to give the product.
Iridium Complex of Ligand 29: Orange solid; yield: 48%; mp
1048C; [a]2D0: 73.8 (c 0.65, CHCl3); 1H NMR (300 MHz, CDCl3):
d¼1.12 [s, 9H, C(CH3)3], 1.48–2.75 [m, 8H, 4ꢁH2C(COD)],
2.02 (s, 3H, CH3), 2.11 (s, 3H, CH3), 2.28 (s, 6H, 2ꢁC6H5-
CH3), 4.11 (t, J¼8.8 Hz, 1H, H2C4’), 4.23 [br m, 1 H,
HC(COD)], 4.36 (d, J¼9.1 Hz, 2H, H2C5’), 4.60 (d, J¼
8.1 Hz, 1H, CH), 4.69 [br m, 1H, HC(COD)], 4.76 (d, J¼
8.1 Hz, 1H, CH), 4.99 [br m, 1 H, HC(COD)], 5.78 [br m, 1
H, HC(COD)], 6.51–7.32 (m, 18H, HAr), 7.53 (br s, 4H,
BArF), 7.73 (br s, 8 H, BArF); 31P NMR (121.5 MHz, CDCl3):
d¼89.4; MS (FAB): m/z¼1034; IR (NaCl): n¼2964 m, 2307
w, 1732 w, 1610 m, 1598 m, 1458 w, 1399 w, 1354 s, 1278 s,
1162 m, 1126 s, 1025 w, 951 m, 887 w, 839 w, 802 w, 786 w, 741
w, 713 w, 700 w, 682 m, 672 m, 586 w cmꢀ1; anal. calcd.: C
49.37, H 3.61, N 2.21; found: C 49.51, H 3.72, N 2.14.
Ligand 29: White solid; yield: 71%; mp 788C; [a]2D0: 14.0 (c
1
0.26, CHCl3); H NMR (500 MHz, CDCl3): d¼0.90 [s, 9H,
C(CH3)3], 1.88 [br s, 6H, C(CH3)2], 2.24 (s, 3H, C6H5-CH3),
2.34 (s, 3H, C6H5-CH3), 3.90 (dd, J¼10.2, 6.7 Hz, 1H, HC4’),
4.21 (m, 2H, H2C5’), 4.61 (d, J¼8.3 Hz, 1H, CH), 4.84 (d, J¼
8.2 Hz, 1H, CH), 6.84–7.55 (m, 18H, HAr); 13C NMR
(125.7 MHz, CDCl3): d¼21.4, 21.5 (C6H5-CH3), 25.9
[C(CH3)3], 27.7, 27.8 [2ꢁd, JCP ¼10.7 Hz, C(CH3)2], 33.8
[C(CH3)3], 62.0 [C(CH3)2], 69.2 (H2C5’), 72.1 (d, JCP ¼6.9 Hz,
CH), 74.3 (d, JCP ¼6.1 Hz, CH), 75.7 (HC4’), 127.1, 127.4,
127.5, 127.5, 127.5, 127.6, 127.7, 127.7, 127.9, 128.0, 128.1,
128.1, 128.1, 128.6, 128.7, 128.9, 129.5, 129.7 (HCAr), 136.0,
136.4, 138.6, 138.9, 142.9, 143.6 (CAr), 167.9 (C N); 31P NMR
¼
(121.5 MHz, CDCl3): d¼121.3; MS (EI): m/z¼734 ([Mþ1]þ
, 18), 733 ([M]þ, 42), 578 (18), 260 (29), 169 (11), 168 (100),
155 (16), 152 (15), 139 (12), 111 (10), 91 (29); IR (KBr): n¼
3030 w, 2960 m, 2869 w, 1916 m, 1702 m, 1655 m, 1598 m,
1496 w, 1476 w, 1456 w, 1353 s, 1306 w, 1261 m, 1210 w,
1186 m, 1165 s, 1130 m, 1085 m, 1020 w, 975 m, 940 w, 919 m,
Iridium Complex 51
Ligand 30a (579 mg, 0.77 mmol) and [Ir(COD)Cl]2 (258 mg,
0.38 mmol) were dissolved in CH2Cl2 (2 mL) and heated at
508C for 2 h. After cooling to room temperature NH4PF6
(140 mg, 0.86 mmol) was added and the reaction mixture was
stirred for 10 min. The solvent was evaporated, the residue dis-
solved in a small amount of CH2Cl2 and washed with some wa-
ter. The solvent was evaporated. Crystals suitable for X-ray
analysis were obtained by slow recrystallization from ethyl ace-
tate/cyclohexane at ꢀ188C. [a]2D0: 33.7 (c 1.06, CHCl3);
1H NMR (400 MHz, CDCl3): d¼1.43–3.29 [m, 8H, 4ꢁH2
C(COD)], 2.21 (s, 6H, 2ꢁCH3), 2.37 (s, 6H, 2ꢁC6H5-CH3),
3.90 [br m, 1H, HC(COD)], 4.24 [br m, 1H, HC(COD)], 4.47
(m, 2H, H2C5’), 4.86 [br m, 1H, HC(COD)], 4.93 (s, 1H, CH),
4.97 (s, 1H, CH), 5.19 (m, 1H, H2C4’), 5.83 [br m, 1H,
HC(COD)], 6.62–7.74 (m, 23H, HAr); 31P NMR (121.5 MHz,
CDCl3): d¼ ꢀ161.3, ꢀ156.0, ꢀ151.6, ꢀ147.2, ꢀ142.8,
ꢀ138.4, ꢀ133.7, 82.7; MS (FAB): m/z¼1054; IR (NaCl): n¼
3034 w, 2962 w, 2362 w, 1619 m, 1540 w, 1495 w, 1456 m, 1399
w, 1350 s, 1308 w, 1261 w, 1226 w, 1187 w, 1161 s, 1087 m,
1025 m, 948 s, 916 w, 874 w, 842 s, 784 w, 754 m, 701 m, 671 m,
600 w, 588 w, 557 w cmꢀ1. For the crystal data of iridium com-
plex 51, see the Supporting Information.
875 w, 840 w, 815 m, 760 m, 700 m, 674 s, 586 w, 567 w cmꢀ1
;
anal. calcd.: C 62.19, H 6.04, N 5.73; found: C 62.08, H 6.09, N
5.66.
Ligand 40
Tris(dimethylamino)phosphine (230 mg, 1.41 mmol) and (S)-
2-anilinomethylpyrrolidine (250 mg, 1.42 mmol) were dis-
solved in degassed toluene (3 mL) and heated under reflux
for 2 h. (ꢀ)-(S)-2-[2’-(Hydroxy)prop-2’-yl]-4-tert-butyloxazo-
line (263 mg, 1.42 mmol) was added and the reaction mixture
was heated under reflux for 7 days. After cooling to room tem-
perature the solvent was evaporated and the residue was puri-
fied by chromatography (hexanes/EtOAc, 2:1) to obtain the
product as a colorless viscous oil; yield: 215 mg (39%);
1H NMR (300 MHz, CDCl3): d¼0.89 [s, 9H, C(CH3)3], 1.3–
2.04 (m, 4H, 2ꢁCH2-7þ-8], 1.47 (s, 3H, CH3), 1.59 (s, 3H,
CH3), 3.09–4.18 (m, 8H, oxazolineþ2ꢁCH2-4þ-8þCH),
6.76–7.25 (m, 5H, HAr); 13C NMR (75.5 MHz, CDCl3): d¼
25.7, 26.1 (CH2), 26.2 [C(CH3)3], 28.0, 28.8 [C(CH3)2], 31.7
(CH2), 33.8 [C(CH3)3], 48.2 (CH), 52.8(CH2), 62.7 [C(CH3)2],
68.8 (H2C5’), 75.6 (HC4’), 115.8, 116.0, 118.8, 128.8 (HCAr),
Rhodium Complex 52
Ligand 30a (579 mg, 0.77 mmol) and [Rh(COD)Cl]2 (189 mg,
0.38 mmol) were dissolved in CH2Cl2 (2 mL) and heated at
76
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asc.wiley-vch.de
Adv. Synth. Catal. 2005, 347, 61–77

Bis(N-sulfonylamino)phosphine- and TADDOL-Phosphite-Oxazoline Ligands
508C for 2 h. After cooling to room temperature NH4PF6
FULL PAPERS
References and Notes
(175 mg, 1.07 mmol) was added and the reaction mixture was stir-
red overnight. Some water was added, the phases separated and
the solvent evaporated. Crystals suitable for X-ray analysis
were obtained by slow recrystallization from ethyl acetate/cyclo-
hexane at ꢀ188C. [a]2D0: 31.2 (c 1.11, CHCl3); 1H NMR
(400 MHz, CDCl3): d¼1.45–3.21 [m, 8H, 4ꢁH2C(COD)], 2.18
(s, 3H, CH3), 2.26 (s, 3H, CH3), 2.36 (s, 6H, 2ꢁC6H5-CH3), 4.23
[br m, 1 H, HC(COD)], 4.46 (m, 2H, H2C5’), 4.55 (m, 1H, H2
C4’), 4.65 [br m, 1H, HC(COD)], 4.81 (s, 1H, CH), 4.84 (s, 1H,
CH), 5.31 [br m, 1 H, HC(COD)], 6.14 [br m, 1H, HC(COD)],
6.60–7.73 (m, 23H, HAr); 31P NMR (121.5 MHz, CDCl3): d¼
ꢀ159.6, ꢀ156.1, ꢀ151.6, ꢀ147.5, ꢀ142.0, ꢀ138.1, ꢀ133.9,
102.1, 103.7; MS (FAB): m/z¼964; IR (NaCl): n¼3649 w, 3585
w, 3342 w, 3064 w, 2924 w, 2835 w, 2360 w, 1624 s, 1597 m,
1540 m, 1495 m, 1456 m, 1395 w, 1350 s, 1294 w, 1267 w, 1229 w,
1162 s, 1087 m, 1025 m, 948 m, 843 s, 784 w, 766 w, 733 w, 701 m,
672 m, 614 w, 600 w, 588 w, 557 w cmꢀ1; anal. calcd.: C 51.94, H
4.72, N 3.79; found: C 52.07, H 4.83, N 3.85. For the crystal data
of rhodium complex 52, see the Supporting Information.
[1] Comprehensive Asymmetric Catalysis, (Eds.: E. N. Jacob-
sen, A. Pfaltz, H. Yamamoto), Springer, Berlin, 1999.
[2] G. Helmchen, A. Pfaltz, Acc. Chem. Res. 2000, 33, 336–
345.
´ ˆ
[3] a) R. Pretot, A. Pfaltz, Angew. Chem. 1998, 110, 337–339;
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Angew. Chem. Int. Ed. 1998, 37, 323–325; b) R. Pretot,
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[4] a) A. K. H. Knçbel, I. H. Escher, A. Pfaltz, Synlett 1997,
1429–1431; b) I. H. Escher, A. Pfaltz, Tetrahedron 2000,
56, 2879–2888.
[5] R. Hilgraf, A. Pfaltz, Synlett 1999, 1814–1816.
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rahedron 1994, 50, 11827–11838.
[7] S. Roland, P. Mangeney, A. Alexakis, Synthesis 1999,
228–230.
[8] J. M. Brunel, T. Constantieux, G. Buono, J. Org. Chem.
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[10] A. K. Beck, B. Bastani, D. A. Plattner, W. Petter, S. See-
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General Procedure for Pd-Catalyzed Allylic
Alkylations
A solution of [Pd(C3H5)Cl]2 (1 mol %) and chiral ligand
(2.5 mol %) in CH2Cl2 (1.2 mL/mmol substrate) in a Young
tube was degassed four times by freeze-thaw cycles. The reac-
tion mixture was stirred for 2 h at 488C. After cooling to room
temperature a solution of the substrate (1 equiv.) in CH2Cl2
(4 mL/mmol substrate) was added, followed by dimethyl mal-
onate (3 equivs.), BSA (3 equivs.) and catalytic amounts of dry
KOAc. Stirring was continued for 20 h at room temperature af-
ter four additional freeze-thaw cycles. The reaction mixture
was filtered over silica and washed with hexanes/EtOAc
(2:1, 200 mL). The solvent was evaporated and the residue
was analyzed by GC to determine the conversion and regiose-
lectivity. Enantiomeric excesses were determined after column
chromatography over silica.[18]
[11] D. Seebach, M. Hayakawa, J. Sakaki, W. B. Schweizer,
Tetrahedron 1993, 49, 1711–1724.
[12] Crystallographic data for complexes 51 and 52 have been
deposited with the Cambridge Crystallographic Data
Centre as supplementary publication numbers CCDC-
238429 (Rh-52) and CCDC-238430 (Ir-51). Copies of
the data can be obtained free of charge on application
to CCDC, 12 Union Road, Cambridge CB2 1EZ, UK
[Fax: int. codeþ44(1223)336–033; e-mail deposit@ccdc.-
cam.ac.uk].
[13] a) P. von Matt, A. Pfaltz, Angew. Chem. 1993, 105, 614–
616; Angew. Chem. Int. Ed. Engl. 1993, 32, 566–568; b) J.
Sbrinz, G. Helmchen, Tetrahedron Lett. 1993, 34, 1769–
1772; c) G. J. Dawson, C. G. Frost, J. M. J. Williams, S. J.
Coote, Tetrahedron Lett. 1993, 34, 3149–3150.
[14] S.-L. You, X.-Z. Zhu, Y.-M. Luo, X.-L. Hou, L.-X. Dai, J.
Am. Chem. Soc. 2001, 123, 7471–7472.
[15] C. Markert, A. Pfaltz, Angew. Chem. 2004, 116, 2552–
2554; Angew. Chem. Int. Ed. Engl. 2004, 43, 2498–2500.
[16] D. G. Blackmond, A. Lightfoot, A. Pfaltz, T. Rosner, P.
Schnider, N. Zimmermann, Chirality 2000, 12, 442–449.
[17] A. Pfaltz, J. Blankenstein, R. Hilgraf, E. Hçrmann, S.
McIntyre, F. Menges, M. Schçnleber, S. P. Smidt, B. Wꢂs-
tenberg, N. Zimmermann, Adv. Synth. Catal. 2003, 345,
33–43.
General Procedure for Ir-Catalyzed Hydrogenations
The alkene (1 equiv.) and Ir complex (4 mol %) were dissolved
in CH2Cl2 (10 mL/mmol substrate for TADDOL-derived li-
gands and 2.5 mL/mmol for N-sulfonyl-derived ligands) in a
high-pressure autoclave without exclusion of oxygen and pres-
surized to 100 bar for 2 h. The solvent was removed and the res-
idue was suspended in heptanes, filtered through a syringe fil-
ter and the filtrate was directly used for GC and chiral HPLC
analysis to determine the conversion and ee.[19]
Acknowledgements
[18] P. von Matt, G. C. Lloyd-Jones, A. B. E. Minidis, A.
Pfaltz, L. Macko, M. Neuburger, M. Zehnder, H. Rꢂeg-
ger, P. S. Pregosin, Helv. Chim. Acta 1995, 78, 265–284.
[19] F. Menges, A. Pfaltz, Adv. Synth. Catal. 2002, 344, 40–44.
We thank Markus Neuburger, Universityof Basel, for X-ray crys-
tallographic analyses. Financial support by the Swiss National
Science Foundation is gratefully acknowledged. R. H. thanks
´
the Fonds der Chemischen Industrie for a Kekule fellowship.
Adv. Synth. Catal. 2005, 347, 61–77
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