(S)-Serine derived N-O and N-P oxazoline ligands for asymmetric catalysis

Article abstract of DOI:10.1016/j.tetasy.2003.11.030

(S)-Serine methyl ester and a range of carboxylic acids RCO₂H (a R=(η⁵-C₅H₄)Fe(η⁵-C ₅Ph₅), b (η⁵-C₅H ₄)Co(η⁴-C₄Ph₄

Full text of DOI:10.1016/j.tetasy.2003.11.030

Tetrahedron:
Asymmetry
Tetrahedron: Asymmetry 15 (2004) 653–664
(S)-Serine derived N–O and N–P oxazoline ligands for asymmetric
catalysis
Geraint Jones and Christopher J. Richards*
Department of Chemistry, Cardiff University, PO Box 912, Cardiff CF10 3TB, UK
Received 4 November 2003; accepted 25 November 2003
Abstract—(S)-Serine methyl ester and a range of carboxylic acids RCO2H (a R ¼ (g5-C5H4)Fe(g5-C5Ph5), b (g5-C5H4)Co(g4-
C4Ph4), c (g5-C5H4)Fe(g5-C5H5), d 1-adamantyl, e C6H5) were readily transformed in three steps into (R)-4-hydroxymethylox-
azoline N–O ligands 3a–e containing the R substituent at position 2. Two further N–O ligands (S)-4-(1-hydroxy-1-methylethyl)-
oxazoline 3f and (S)-4-(1-hydroxy-1,1-diphenylmethyl)oxazoline 3g both containing (g5-C5H4)Co(g4-C4Ph4) as a 2-substituent were
also generated. Use of 5 mol % of 3a–f promoted the synthesis of (R)-1-phenylpropan-1-ol from benzaldehyde and diethylzinc, 3a
resulting in a highest ee of 75%. In a two step synthesis via an intermediate mesylate, 3b was converted into the corresponding (S)-4-
(diphenylphosphinomethyl)oxazoline N–P ligand 19, and an X-ray crystal structure analysis was obtained of the palladium dichloride
adduct. Treatment of 3a–e with Ph2PCl under basic conditions resulted in the corresponding phosphinite–oxazoline N–P ligands 4a–
e. All the N–P ligands were screened to determine the most selective for the palladium-catalysed allylic alkylation with dimethyl
malonate of the following racemic substrates: (i) 1,3-diphenylprop-2-enyl acetate [96% ee (S) with 4e], (ii) 1,3-dimethylprop-2-enyl
pivalate [70% ee (S) with 4b] and (iii) 3-cyclohexenyl acetate [48% ee (R) with 4c].
ꢀ 2004 Elsevier Ltd. All rights reserved.
1. Introduction
locenes (R ¼ a, b) and we report in detail on the appli-
cation of ligands 3 and 4 to aldehyde alkylation and
allylic alkylation, respectively. Parts of this study have
been the subject of previous communications.3;4
Oxazolines are now firmly established as one of the most
popular and successful classes of ligand for application
in metal-catalysed asymmetric transformations.1 This is
at least in part to their ease of synthesis from readily
available amino acids, with (S)-valine in particular being
utilised as the basis of many highly enantioseletive metal–
ligand systems. Another recent approach to catalyst
discovery is the synthesis and analysis of ligand libraries
as an aid to the optimisation of enantioselectivity for a
specific application.2 Ideally many diverse structures are
obtainable from one or more readily available starting
materials. For oxazoline ligands, an attractive building
block in this context is (S)-serine methyl ester 1 due to
the presence of three contrasting functionalities. Herein
we report on the use of this enantiopure starting mate-
rial for the synthesis of oxazolines 2, precursors to N–O
ligands 3 and N–P ligands 4 potentially incorporating
up to three points of diversity (R, R0 and R00 ) (Scheme
1). In particular, use is made of air stable bulky metal-
HO
O
RCO2H
O
R
H2N
1
N
CO2Me
R
CO2Me
R
2
O
ClPR''2
R'
R'MgX
R'
R'
R'
OPR''2
N
or
N
4
LiAlH4
OH
3
Scheme 1.
2. Results and discussion
2.1. (S)-Serine derived N–O ligands
A range of carboxylic acids 5a–e were first converted to
their corresponding acid chlorides by reaction with
oxalyl chloride, followed by addition of (S)-serine
methyl ester 1 in the presence of triethylamine. Although
various methods have been reported for the dehydrative
* Corresponding author. Present address: Department of Chemistry,
Queen Mary, University of London, Mile End Road, London E1
4NS, UK. Tel.: +44-20-7882-3271; fax: +44-20-7882-7427; e-mail:
c.j.richards@qmul.ac.uk
0957-4166/$ - see front matter ꢀ 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2003.11.030

654
G. Jones, C. J. Richards / Tetrahedron: Asymmetry 15 (2004) 653–664
cyclisation of b-hydroxy amides, many are not com-
patible with serine derived systems because of competi-
tive formation of dehydroamino esters.5 A mild and
effective method for the cyclisation of serine derived
b-hydroxy amides has been reported using diethyl-
aminosulfur trifluoride (DAST).6 Application of this
procedure to amides 6a–e resulted in clean transforma-
tion into oxazolines 2a–e. Subsequent reduction with
LiAlH4 gave new N–O ligands 3a–e, also in good yield.
Alternatively, Grignard reagents may be added to the
intermediate oxazoline esters. This was exemplified with
the synthesis of ligands 3f and 3g from the addition of
methyl- and phenylmagnesium bromide, respectively, to
ester 2b (Scheme 2). The stereochemical integrity of 3e
was determined as >95% ee by examination of the
been widely explored. To the best of our knowledge
there are only two reports on the application of 4-(hy-
droxymethyl)oxazolines to this reaction with ligands 7a–
c and 8a–c (Fig. 1).8;9 With compounds 3a–g available
we sought to investigate further and ideally optimise the
influence of substituents R and R0 on the asymmetric
catalysis of aldehyde alkylation.
Ph
O
O
R'
R
R
R'
OH
N
N
OH
7a R = Me8a
8a R = Me, R' = Me8a
7b R = Ph8a
8b R = Me, R' = Ph8a
1
7c R = 2-thiophenyl8a
8c R = 2-biphenyl, R' = Me8b
400 MHz H NMR spectra of the esters obtained with
(S)- and (R)-MosherÕs acid chloride. From the former a
methyl singlet at 3.41 ppm was observed, from the latter
the corresponding peak was found at 3.40 ppm, and in
each case none of the other possible diastereoisomer was
observed.
Figure 1. Related 4-hydroxymethyloxazoline ligands.
Addition of 5 mol % of ligand 3a to a toluene solution of
benzaldehyde containing 1.5 equiv of diethylzinc, and
stirring at room temperature for 24 h, resulted in clean
conversion to (R)-1-phenylpropan-1-ol 9 in 75% ee
(Scheme 3, Table 1, entry 1). Changing the solvent to 1:1
toluene/hexane (entry 2), the reaction temperature (entry
3), or both (entry 4), did not lead to an improvement of
enantioselectivity. Thus ligands 3b–g were also
employed at room temperature in toluene, all of which
proved inferior to the pentaphenylferrocene derivative
3a (entries 5–8). Increasing the size of the R0 substituent
results in a severe decrease in enantioselectivity (entries 9
and 10). This trend, summarised in Figure 2, is also
apparent in the results obtained with ligands 7a–c and
8a–c for this same reaction. (S)-1-Phenylpropan-1-ol 9 is
Co
Fe
Ph
Fe
R =
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
a
b
c
d
e
O
CO2Me
OH
i) (COCl)2
RCO2H
5a-e
R
N
H
ii)
(S)-serine methyl
ester. HCl, NEt3,
CH2Cl2
6a 98%
6b 94%
6c 81%
6d 98%
6e 89%
OH
5 mol% lig.
PhCHO + Et2Zn
O
R
Ph
2a 97%
2b 99%
2c 95%
2d 92%
2e 94%
PhCH3
DAST
CH2Cl2
9
N
CO2Me
Scheme 3.
3a 95%
3b 96%
3c 88%
3d 64%
3e 88%
O
N
Table 1. Addition of diethylzinc to benzaldehydea
LiAlH4
Et2O
2a-e
R
R
R
Entry
Catalystb
Solvent
Temperature Ee 9
(ꢁC)
(config)c (%)
OH
1
2
3a
3a
Toluene
rt
75 (R)
61 (R)
O
N
MeMgI
Me
Me
50% Toluene/ rt
hexanes
2b
3f 94%
Et2O, THF
OH
3
4
3a
3a
Toluene
0 ꢁC
69 (R)
75 (R)
50% Toluene/ 0 ꢁC
hexanes
O
N
PhMgI
Ph
3g 99%
2b
Ph
Et2O, THF
5
3b
3c
3d
3e
3f
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
rt
rt
rt
rt
rt
rt
68 (R)
36 (R)
22 (R)
52 (R)
54 (R)
8 (R)
6
OH
7
8
Scheme 2.
9
10
3g
Chiral non-racemic ligands containing a b-hydroxy
nitrogen have been very widely applied to the asym-
metric alkylation of aldehydes with dialkylzincs.7 In
most cases the nitrogen based functionality is a tertiary
amine although 2-(hydroxymethyl)pyridines have also
a Reactions had proceeded to >95% conversion after 24 h.
b 5 mol %.
c Determined by GC with a Chrompack CP-Chirasil-DEX CB column.
Absolute configuration determined by comparison to commercial
(R)-1-phenylpropan-1-ol.

G. Jones, C. J. Richards / Tetrahedron: Asymmetry 15 (2004) 653–664
655
e.e. decreased by size
O
O
R'
N
HO
R
N
R'
OH
OH
N
Fe
Fe
Ph
e.e. highest with R =
pentaphenylferrocene
Me
Me
Me
Me
Ph
Ph
N
Ph
This configuration gives
OH
13
3a
12 Me
(R)-1-phenyl-1-propanol
Figure 2. Ligand influences on the enantioselectivity of diethylzinc
addition to benzaldehyde promoted by 3.
(R)-9
(S)-9
(R)-9
Figure 4. The correlation between ligand stereochemistry and the
configuration of 1-phenyl-1-propanol 7.
obtained with 7a (50% ee) and 7b/c (both 57% ee); (R)-9
is obtained with 8a (30% ee), 8b (7% ee) and 8c (37% ee).
Calculations on the b-amino alcohol promoted alkyl-
ation of aldehydes by diethylzinc have revealed a pref-
erence for the tricyclic anti-trans transition state.10
Accordingly, the hydroxymethyl oxazolines of this study
can give rise to the two anti-trans transition states 10
and 11, with the former leading to the observed (R)-1-
phenylpropan-1-ol (Fig. 3).
[Pd]
[Pd]
N
N
O
N
Co
Co
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Cy
Me
H
Ph
14
15
O
Figure 5. Metallocenes 14 and 15 and the positions of palladation on
heating with Pd(OAc)2.13;14
O
Zn Et
N
H
Zn
O
Et
Fe
(R)-9
(S)-9
Ph
Ph
Ph
Ph
Et
Ph
from (S)-serine via a common intermediate 16, with the
variable R substituent being introduced in the final steps
of the synthesis (Scheme 4).
R2
N
Ph
10
Et
Et
Zn
O
H
O
Zn
Et
Et
O
Ph
Zn
O
BOC
N
O
Et
Ph
O
Zn
Et
N
(S)-serine
R
PPh2.BH3
anti-trans
Fe
N
Ph
Ph
Ph
Ph
H
O
16
17
PPh2
Ph
11
Scheme 4.
Figure 3. The two possible anti-trans transition states available from
ligand 3a.
These ligands have been applied to palladium-catalysed
allylic alkylation of 1,3-diphenylpropenyl acetate (up to
94% ee with R ¼ adamantyl)15b and dimethylpropenyl
pivalate (up to 75% ee with R ¼ 3,5-tBu–C6H3).15a In
light of the relative success of bulky metallocenes as R
substituents in the diethylzinc alkylation chemistry
described above, we sought to synthesis a related
example of ligand 17 and test it in palladium-catalysed
allylic alkylation chemistry. Thus 3b was first converted
to intermediate mesylate 18 and subsequent treatment
with potassium diphenylphosphine, generated in situ,
resulted in N–P ligand 19 in good overall yield (Scheme
5). This was then applied to the palladium-catalysed
allylic alkylation of three representative substrates 20, 22
and 24 (Scheme 6, Table 2).
b-Hydroxynitrogen functionalities are also present in
the planar chiral ligands 12 and 13, which give (S)-9
(58% ee)11 and (R)-9 (64% ee),12 respectively, from the
reaction between diethylzinc and benzaldehyde (Fig. 4).
The correlation between the sense of planar chirality
and the configuration of 9 may be extended to 3a with
one side of the 4-(hydroxymethyl)oxazoline covered by
the pentaphenylcyclopentadienyl moiety. This is con-
sistent with the orientation of this bulky group away
from the larger 4-oxazoline substituent. Thus the het-
erocycle is mimicking the related planar chiral systems
12 and 13, such that the oxazoline is in an environment
of virtual planar chirality. Related conformational
preferences in complexes 1413 and 1514 have been used to
account for their highly diastereoselective palladation at
the positions indicated (Fig. 5).
The enantioselectivities obtained were modest and var-
ied significantly on changing the solvent from THF to
CH2Cl2. A feature previously observed with ligands 17 is
the strong dependency of enantioselectivity on the
ligand/palladium ratio employed. For example, a 1:1
ratio of 17 (R ¼ 4-MeOC6H4) to palladium in CH2Cl2 is
reported to give (S)-21 in ꢀ82% ee, which dropped to
ꢀ20% ee of (R)-21 when a 2:1 ligand/metal ratio was
employed.15b These differences are suggested to arise
2.2. (S)-Serine derived N–P ligands
Nitrogen–phosphorus ligands 17 have been previously
reported by Burgess et al.15 These are also synthesised

656
G. Jones, C. J. Richards / Tetrahedron: Asymmetry 15 (2004) 653–664
enantiomers of 21 on the same type of HPLC column is
opposite to that previously reported.
O
N
MsCl, NEt3,
Co
Co
3b
OSO2Me
Ph
Ph
Ph
To investigate the coordination geometry of ligand 19,
the palladium dichloride complex 26 was synthesised as
outlined in Scheme 7 and an X-ray crystal structure
obtained (Fig. 6).19 Three points are noteworthy. Firstly,
the five-membered chelate results in a distortion in the
square–planar geometry about palladium, with the
N(1)–Pd(1)–P(1) angle only 83.1ꢁ. Secondly, the ring
formed by chelation is in an envelope conformation and
the phenyl substituents at phosphorus are not in dis-
tinctively axial or equatorial orientations (N(1)–Pd(1)–
DMAP, CH2Cl2
Ph 18 90%
O
N
Ph2PH, KOtBu,
THF
PPh2
Ph
Ph
Ph
Ph
19 76%
Scheme 5.
P(1)–C(38) ¼ 113.9ꢁ
and
N(1)–Pd(1)–P(1)–C(44) ¼
121.1ꢁ), and they display only a partial edge-to-face
orientation (30ꢁ). This contrasts markedly with the
structure of the palladium complex of phosphinoaryl-
oxazoline 2720 with which (S)-21 is obtained in 98.5% ee
from palladium-catalysed alkylation of substrate 20.21
MeO2C
Ph
MeO2C
Me
CO2Me
Ph
OAc
CH2(CO2Me)2
BSA, Pd/Lig.a
Ph
Ph
20
21
23
CO2Me
Me
tBuO C
O
2
CH2(CO2Me)2
a
Me
Me
O
N
BSA, Pd/Lig.
22
CO2Me
CO2Me
PPh2
PdCl2(NCMe)2
CH2Cl2
Pd
Cl
Cl
OAc
Co
19
CH2(CO2Me)2
BSA, Pd/Lig.a
Ph
Ph
Ph
24
25
26 70%
Ph
Scheme 6.
Scheme 7.
from a change in coordination mode from a P–N chelate
with a 1:1 ligand/metal ratio to a bisphosphine adduct
with a 2:1 ligand/metal ratio. It is possible that the sol-
vent also has a significant effect on the coordination
mode of the key p-allyl intermediate in the catalytic
cycle. It is of note that use of a 1:1 ratio of 17 (R ¼
4-MeOC6H4)/Pd in THF gives (S)-21 in only ꢀ18%
ee.15b The changes we observed on changing from
CH2Cl2 to THF with ligand 19 [(R)-21 to (S)-21] are
opposite to the changes reported for ligands 17 [(S)-21
to (R)-21]. We are unsure of the significance of this
though we note that the order of elution of the two
Table 2. Pd-catalysed reaction of allylic substrates 20, 22 and 24 with
dimethyl malonate mediated by ligand 19a;b
Ligand
Solvent Ee 21
(config)c (%)
Ee 23
Ee 25
(config)d (%) (config)e (%)
19
19
THF 43 (S)
CH2Cl2 24 (R)
36 (S)
6 (S)
5 (R)
25 (R)
a 6 mol % 19, 2.5 mol % [(g3-C3H5)PdCl]2.
b Reactions had proceeded to >95% conversion after 24 h.
c Determined by HPLC with a Diacel Chiralcel OD column (99:1
hexanes/propan-2-ol). Absolute configuration determined by com-
parison to (S)-21 obtained with (S)-2-[(S)-2-diphenylphosphino)ferro-
cenyl]-4-(1-methylethyl)oxazoline (94% ee).16
d Determined by GC with a Chrompack CP-Chirasil-DEX CB column.
Absolute configuration determined by comparison to (S)-23 obtained
with (S)-2-[(S)-2-diphenylphosphino)ferrocenyl]-4-(1-methylethyl)-
oxazoline (12% ee).17
e Determined by GC with a Chrompack CP-Chirasil-DEX CB column.
Absolute configuration determined by comparison of retention times
to reported literature values.18
Figure 6. Representations of the crystal structures of 26. Selected bond
ꢀ
distances (A) and angles (deg) are as follows: Pd(1)–N(1) ¼ 2.018(5),
Pd(1)–P(1) 2.221(2), Pd(1)–Cl(1) 2.370(2), Pd(1)–Cl(2) 2.290(2), N(1)–
Pd(1)–P(1) 83.1(2), P(1)–Pd(1)–Cl(2) 90.56, N(1)–Pd(1)–Cl(1) 96.1(2),
Cl(1)–Pd(1)–Cl(2) 90.41(6).

G. Jones, C. J. Richards / Tetrahedron: Asymmetry 15 (2004) 653–664
657
Here the axial and equatorial orientations of the two
O
4a 68%
4b 58%
4c 94%
4d 99%
4e 70%
ClPPh2, NEt3,
DMAP,CH2Cl2
3a-e
R
phosphorus phenyl substituents are pronounced, with
selective interaction between the latter and the p-allyl
intermediate accounting, in part, for the high selectivity
observed with this ligand. Thirdly, the position of ligand
Cl(1), resulting from the square–planar geometry about
palladium, forces the cobalt metallocene to lie on the
same side as the larger 4-oxazoline substituent. The
C@N bond of the oxazoline is at an angle of 25ꢁ to
the plane of the cyclopentadienyl ring so that one side of
the heterocycle is shielded by the large cyclobutadiene
moiety. Here the sense of virtual planar chirality is
opposite to that speculated to arise from the reaction
between 3a/b and diethylzinc.
N
OPPh2
Scheme 8.
Table 3. Pd-catalysed reaction of 20 into 21 mediated by ligands
4a–ea;b
Entry
Ligand
Solvent
Temperature
(ꢁC)
Ee of 21
(config)c (%)
1
2
3
4
5
6
7
4a
4a
4b
4c
4d
4e
4e
THF
20
20
20
20
20
20
0
53 (S)
80 (S)
52 (S)
90 (S)
67 (S)
90 (S)
96 (S)
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
The results obtained with ligand 19, taken together with
the earlier work of Burgess, reveal that five-membered
chelates of this type are not well suited as P–N ligands
for allylic alkylation due to: (i) the instability of the
chelate itself, and (ii) the lack of differentiation in the
orientation of the two phosphorus aryl substituents. As
already discussed, six-membered P–N derived chelates
such as 27 have been applied with success to metal-
catalysed allylic alkylation, as have related 2-ferrocenyl
and 2-alkyl substituted ligands 2822 and 29.23 Structures
30, homologues of ligands 17, have been synthesised
from (S)-aspartic acid and have been applied to palla-
dium-catalysed allylic alkylation and iridium-catalysed
hydrogenation.24 With N–O ligands 3a–e available we
sought to generate new N–P ligands in one step with the
formation of phosphinite–oxazolines 4.25 Structurally
related phosphinite–oxazolines 31 have been previously
a 6 mol % 4, 2.5 mol % [(g3-C3H5)PdCl]2.
b Reactions had proceeded to >95% conversion after 24 h.
c Determined by HPLC with a Diacel Chiralcel OD column (99:1
hexanes/propan-2-ol). Absolute configuration determined by com-
parison to (S)-15 obtained with (S)-2-[(S)-2-diphenylphosphino)ferro-
cenyl]-4-(1-methylethyl)oxazoline (94% ee).16
Again the choice of solvent was found to be important
with CH2Cl2 resulting in a significantly higher ee than
THF (entry 2 vs 1). Thus continuing with CH2Cl2, the
other ligands were tested under the same conditions with
the smaller R substituents of ligands 4c and 4e both
resulting in 90% ee (entries 4 and 6), the larger R sub-
stituents leading to reduced enantioselectivies (entries 3
and 5). Use of 4e at 0 ꢁC improved the ee further to 96%
(entry 7). This result is very similar to those obtained
with 30 (R ¼ Ph) and 31 (R ¼ Ph), also obtained at 0 ꢁC.
The former led to the generation of (R)-21 in 98% ee,24a;b
the latter gave (S)-21 in 94% enantiomeric excess.26a;b As
orientation of the oxazoline 4-substituents are opposite
in ligands 30 and 4e (as a consequence of the CIP rules
their configurations are both S), changing from a
alkyldiarylphosphine (i.e., 30) to a diarylphosphinite
does not change the sense of asymmetric induction. It
also has very little effect on the selectivity, which is high.
Furthermore, the conformationally locked phosphinite
31 is not required for high enantioselectivity.
reported derived from
D
-glucosamine (Fig. 7).26
O
O
O
N
R
N
N
R
R
R'
PPh2
Fe
PPh2
PPh2
27
28
29
O
O
O
O
Ph
R
R
O
N
N
OPPh2
Ph2P
30
31
In view of the similarity of the results obtained with 30
(R ¼ Ph) and 4e, the X-ray crystal structure analysis of
3224b may also be used to account for the observed
selectivity of the phosphinite–oxazoline ligands. Further
to the discussion of structure 26 above two points are
noteworthy. Firstly, the N–Pd–P bond angle of 90.5ꢁ is
close to ideal for a square–planar complex, thus these
six-membered ring chelates are expected to be signifi-
cantly more stable than those arising from 19 and
related structures. Secondly, as the chelate gives rise to a
chair conformation, the two phosphorus phenyl sub-
stituents adopt distinctively axial and equatorial orien-
tations. This environment, which is very similar to that
arising from phosphinoaryloxazoline 27, favours exo-33
over the alternative syn–syn arrangement endo-33, as the
latter displays an unfavourable interaction between the
Figure 7. Oxazoline based N–P ligands.
Phosphinites 4a–e were synthesised by simply adding
chlorodiphenylphosphine to alcohols 3a–e in the pres-
ence of triethylamine and a catalytic amount of DMAP,
followed by filtration through a plug of Al2O3 (Scheme
8). In all cases a single peak was observed in the 31P
NMR spectra of the product at ꢀ115 ppm indicating
that the phosphinites had been successfully synthesised.
They are however moderately air sensitive and in this
study were prepared shortly before use, in the first in-
stance as ligands for the allylic alkylation of 20 (Scheme
6, Table 3).

658
G. Jones, C. J. Richards / Tetrahedron: Asymmetry 15 (2004) 653–664
Table 5. Pd-catalysed reaction of 24 into 25 mediated by ligands 4a–
ea;b
equatorial phenyl and an allyl phenyl substituent.
Attack trans to phosphorus in exo-33 rather than trans to
nitrogen then leads to (S)-21. This selectivity is deter-
mined by the relative trans effect of these heteroatom
containing substituents, with the phosphinite expected
to be similar to a phosphine in its superior ability to
labilise a trans substituent compared to the nitrogen of
an oxazoline. Finally, this model accounts for the ero-
sion of enantioselectivity observed with larger R sub-
stituents, these resulting either a greater abundance of
endo-33 or the alternative exo-anti-configuration at the
carbon trans to phosphorus, both of which lead to (R)-
21 (Fig. 8).
Entry
Ligand
Solvent
Temperature
(ꢁC)
Ee of 25
(config)c (%)
1
2
3
4
5
6
4a
4b
4b
4c
4d
4e
CH2Cl2
THF
20
20
20
20
20
20
3 (R)
0
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
7 (R)
48 (R)
6 (R)
5 (R)
a 6 mol % 4, 2.5 mol % [(g3-C3H5)PdCl]2.
b Reactions had proceeded to >95% conversion after 24 h.
c Determined by GC with a Chrompack CP-Chirasil-DEX CB column.
Absolute configuration determined by comparison of retention times
to reported literature values.18
_
+
PF6
3. Conclusions
R
O
Ph
Ph
N
P
In conclusion, we have demonstrated that (S)-serine
may be readily transformed into N–O ligands 3 and N–P
ligands 4 containing, respectively, up to two and three
points of diversity. This methodology may of course be
applied to (R)-serine, which is also readily available and
relatively inexpensive. Using a small library of N–O
ligands we quickly identified the influences of R and R0
leading to enhanced enantioselectivity for the diethyl-
zinc addition to benzaldehyde. The synthetic method-
ology was extended to the synthesis of an
alkyldiarylphosphine oxazoline based upon a bulky
cobalt metallocene R substituent. The limitations of the
resulting five-membered palladium chelate in asymmet-
ric allylic alkylation resulted in the synthesis of phos-
phinite–oxazoline ligands. Analysis of a small library of
these quickly lead to the identification of a highly
enantioselective catalyst for the allylic alkylation of 1,3-
diphenylprop-2-enyl acetate (96% ee). In view of the
very large number of structures 3 and 4 potentially
available, we anticipate the methodology described in
this work will be applicable to the discovery of ligands
for a large number of metal-catalysed asymmetric
transformations.25
Pd
Ph
Ph
MeO2C
CO2Me (S)-21
32
R
R
O
O
N
N
P
P
O
Pd
Pd
O
Ph
Ph
Ph
Ph
exo-33
endo-33
Figure 8. The origin of enantioselection in allylic alkylation of 20 with
N–P ligand 4e.
We next examined the more demanding substrates 22
and 24 (Scheme 6) and in both cases CH2Cl2 again
proved superior to THF (entry 3 vs 2, Tables 4 and 5).
Encouraging results were obtained for 4b with dimeth-
ylpropenyl pivalate 22 (85:15 selectivity––Table 4, entry
3), and for 4c with cyclohexenyl acetate 24 (74:26
selectivity––Table 5, entry 4). However, in both sets of
results no clear correlation emerged between ee and the
nature of the R substituent. Unlike 1,3-diphenylprop-2-
enyl acetate 20 few ligands have been successfully
applied (i.e., >90% ee) to the palladium-catalysed
transformation of 22 and 24.27
4. Experimental
4.1. General considerations
Table 4. Pd-catalysed reaction of 22 into 23 mediated by ligands
4a–ea;b
Dichloromethane was distilled from calcium hydride,
THF and Et2O were distilled from sodium benzophe-
none ketyl and toluene was distilled from sodium, all
under an atmosphere of nitrogen. Petroleum ether refers
to that fraction boiling in the range 40–60 ꢁC. Column
chromatography was performed on SiO2 (40–63 lm).
Entry
Ligand
Solvent
Temperature
(ꢁC)
Ee of 23
(config)c (%)
1
2
3
4
5
6
4a
4b
4b
4c
4d
4e
CH2Cl2
THF
20
20
20
20
20
20
0
30 (S)
70 (S)
50 (S)
11 (S)
43 (S)
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
4.2. General procedure A
a 6 mol % 4, 2.5 mol % [(g3-C3H5)PdCl]2.
b Reactions had proceeded to >95% conversion after 24 h.
c Determined by GC with a Chrompack CP-Chirasil-DEX CB column.
Absolute configuration determined by comparison to (S)-21 obtained
with (S)-2-[(S)-2-diphenylphosphino)ferrocenyl]-4-(1-methylethyl)ox-
azoline (12% ee).17
Oxalyl chloride (2 equiv) was added to a solution of the
acid 5 (1 equiv) in CH2Cl2 (20 mL/g of acid) and the
resulting solution stirred at room temperature for
20 min. The solvent and excess oxalyl chloride were

G. Jones, C. J. Richards / Tetrahedron: Asymmetry 15 (2004) 653–664
659
removed in vacuo and the crude acid chloride was dis-
solved in CH2Cl2 (30 mL/g) and serine methyl ester
hydrochloride (1 equiv) added in one portion to this
solution. Triethylamine (2 equiv) and additional CH2Cl2
(10 mL/g) were added with ice bath cooling of the
reaction mixture. This was then stirred at room tem-
perature for 3 h, the solvent removed in vacuo, and the
residue column chromatographed to give the appropri-
ate amide 6.
4.2.4.
(S)-N-1-(1-Carbomethoxy-2-hydroxyethyl)ada-
mantyl-1-carboxamide 6d. General procedure A used––
5d (1.278 g, 7.09 mmol) gave 6d as a colourless crystal-
line solid (1.96 g, 98%). dH (CDCl3) 1.64–1.81 (6H, m),
1.85–1.92 (6H, m), 2.00–2.09 (3H, m), 3.76 (3H, s, CH3),
3.83 (1H, dd, J 11.0, 3.3, CHHO), 3.98 (1H, dd, J 11.0,
3.8, CHHO), 4.61 (1H, dt, J 7.7, 3.3, CHN), 6.74 (1H, d,
J 7.4, NH); dC (CDCl3){1H} 28.00 (CH), 36.39 (CH2),
38.91 (CH2), 40.63 (CCO), 52.51 (CH3), 54.42 (CHN),
62.82 (OCH2), 171.23 (C@O), 178.76 (C@O).
4.2.1. (g5-(S)-N-1-(1-Carbomethoxy-2-hydroxyethyl)carb-
oxamidecyclopentadienyl)(g5-pentaphenylcyclopentadi-
enyl)-iron 6a. General procedure A used––5a (1.073 g,
4.2.5. (S)-N-1-(1-Carbomethoxy-2-hydroxyethyl)benzene-
carboxamide 6e. Benzoyl chloride (0.72 mL, 6.2 mmol)
was reacted with (S)-serine methyl ester hydrochloride
as described in general procedure A to give 6e as a
colourless crystalline solid (1.24 g, 90%). dH (CDCl3)
3.60 (1H, br s, NH), 3.75 (1H, s, CH3), 3.96 (1H, dd,
J 11.6, 3.2, CHHO), 4.05 (1H, dd, J 11.1, 3.7, CHHO),
4.82 (1H, dt, J 7.7, 3.2, CHN), 7.37 (2H, t, J 7.9, Ph),
7.48 (1H, t, J 7.4, Ph), 7.81 (2H, d, J 7.8, Ph); dC
(CDCl3){1H} 52.87 (CH3), 55.27 (CHN), 63.20 (CH2),
127.35 (Ph), 128.71 (Ph), 132.08 (para-Ph), 133.57 (ipso-
Ph), 167.99 (C@O), 171.23 (C@O).
1.76 mmol) gave 6a as a red solid (1.226 g, 98%). Mp
20
D
137–139 ꢁC; ½aꢁ ¼ þ98 (c 0.23, CHCl3); mmax/cmꢂ1
(CH2Cl2) 1658 (amide), 1738 (ester); dH (CD2Cl2) 2.12
(1H, br s, OH), 3.61–3.68 (5H, m, OCH2+CO2CH3),
4.29 (1H, dt, J 6.3, 3.4, CHN), 4.34 (2H, br s, Cp), 4.63
(2H, br s, Cp), 6.48 (1H, d, J 6.2, NH), 6.92–6.99 (20H,
m, Ph), 7.03–7.10 (5H, m, Ph); dC (CD2Cl2){1H} 53.5
(CH3), 56.3 (CHN), 64.0 (CH2), 74.2 (Cp), 74.9 (Cp),
78.5 (Cp), 78.8 (Cp), 81.4 (ipso-Cp), 89.0 (C5Ph5), 127.2
(para-Ph), 127.9 (meta-Ph), 133.0 (ortho-Ph), 135.8
(ipso-Ph), 168.9 (C@O), 171.8 (C@O); m=z (APCI) 712
(MHþ, 100). HRMS (FAB) m=z found for Mþ,
711.2060; calcd for C45H37FeNO4, 711.2067.
4.3. General procedure B
Diethylaminosulfur trifluoride (1.1 equiv) was added
drop wise to a solution of 6 (1 equiv) in CH2Cl2 (20 mL/g
of amide) cooled to )78 ꢁC. This solution was then
stirred at this temperature for 1 h. Anhydrous K2CO3
(1.5 equiv) was added in one portion and the reaction
mixture allowed to warm to room temperature. Satu-
rated NaHCO3ðaqÞ (40 mL/g) was then added and the
organic layer separated, dried (Na2SO4), filtered and the
solvent removed in vacuo. The residue was column
chromatographed to give the desired oxazoline 2.
4.2.2. (g5-(S)-N-1-(1-Carbomethoxy-2-hydroxyethyl)carb-
oxamidecyclopentadienyl)(g4-tetraphenylcyclobutadiene)-
cobalt 6b. General procedure A used––5b (0.560 g,
1.07 mmol) gave 6b as an orange crystalline solid
20
(0.628 g, 94%). Mp 207–209 ꢁC; ½aꢁ ¼ ꢂ14 (c 0.25,
D
CH2Cl2); mmax/cmꢂ1 (CH2Cl2) 1643 (amide), 1744 (ester);
dH (CDCl3) 2.71 (1H, br s, OH), 3.51–3.69 (2H, br m,
OCH2), 3.70 (3H, s, CO2CH3), 3.96–3.98 (1H, m, CHN),
4.68 (1H, br s, Cp), 4.71 (1H, br s, Cp), 4.99 (1H, br s,
Cp), 5.04 (1H, br s, Cp), 6.15 (1H, d, J 5.7, NH), 7.12–
7.21 (12H, m, Ph), 7.36–7.38 (8H, m, Ph); dC
(CDCl3){1H} 53.1 (CH3), 56.0 (CHN), 64.3 (CH2), 76.7
(C4Ph4), 82.0 (Cp), 83.8 (Cp), 86.3 (Cp), 87.2 (Cp), 89.6
(ipso-Cp), 126.3 (para-Ph), 127.1 (meta-Ph), 129.2 (or-
tho-Ph), 135.5 (ipso-Ph), 166.2 (C@O), 171.1 (C ¼ O);
m=z (APCI) 626 (MHþ, 100). HRMS (FAB) m=z found
for MHþ, 626.1740; calcd for C38H33CoNO4, 626.1741.
4.3.1. (g5-(S)-2-(4-Carbomethoxy)oxazolinylcyclopenta-
dienyl)(g5-pentaphenylcyclopentadienyl) iron 2a. General
procedure B used––6a (0.758 g, 1.07 mmol) gave 2a as a
20
red solid (0.713 g, 97%). Mp 132–134 ꢁC; ½aꢁ ¼ þ18 (c
D
0.26, CHCl3); mmax/cmꢂ1 (CH2Cl2) 1645 (C@N), 1738
(C@O); dH (CD2Cl2) 3.53 (3H, s, CO2CH3), 3.90 (1H,
dd, J 10.6, 8.4, 1H, OCHH), 4.21 (1H, t, J 8.2, CHN),
4.27–4.37 (3H, m, Cp · 2+OCHH), 4.69 (2H, br s, Cp),
6.94–6.99 (20H, m, Ph) 7.01–7.09 (5H, m, Ph); dC
(CD2Cl2){1H} 51.5 (CH3), 67.8 (CHN), 68.0 (CH2), 73.6
(Cp), 74.0 (Cp), 74.2 (Cp), 76.7 (Cp), 77.2 (Cp), 87.5
(C5Ph5), 125.1 (Ph), 126.3 (Ph), 131.6 (Ph), 134.3 (ipso-
Ph), 165.1 (C@N), 170.5 (C@O); m=z (ES) 694 (MHþ,
100). HRMS (FAB) m=z found for MHþ, 694.2041;
calcd for C45H36FeNO3, 694.2044.
4.2.3. (S)-N-1-(1-Carbomethoxy-2-hydroxyethyl)ferro-
cenecarboxamide 6c. General procedure A used––5c
(1.459 g, 6.34 mmol) gave 6c as an orange crystalline
20
solid (1.699 g, 81%). Mp 131–133 ꢁC; ½aꢁ ¼ ꢂ15 (c 0.25,
D
CH2Cl2); mmax/cmꢂ1 (CH2Cl2) 1657 (amide), 1742 (ester);
dH (CDCl3) 3.23 (1H, br s, OH), 3.57 (3H, s, CO2CH3),
3.90–4.01 (2H, br m, OCH2), 4.30 (5H, s, Cp), 4.31 (2H,
br s, Cp), 4.65 (1H, br s, Cp), 4.65 (1H, br s, Cp), 4.74–
4.78 (1H, m, CHN), 6.70 (1H, d, J 7.5, NH); dC
(CDCl3){1H} 51.8 (CH3), 53.6 (CHN), 62.5 (CH2), 67.1
(Cp), 67.6 (Cp), 68.9 (Cp · 5), 69.8 (Cp), 69.9 (Cp), 73.6
(ipso-Cp), 170.2 (C@O), 170.3 (C@O); m=z (ES) 331
(MHþ, 100), 213 (45) 147 (33). HRMS (ES) m=z found
for MHþ, 332.0585; calcd for C15H18FeNO4, 332.0585.
4.3.2. (g5-(S)-2-(4-Carbomethoxy)oxazolinylcyclopenta-
dienyl)(g4-tetraphenylcyclobutadiene)cobalt 2b. General
procedure B used––6b (0.382 g, 0.61 mmol) gave 2b as an
orange crystalline solid (0.367 g, 99%). Mp 83–85 ꢁC;
20
½aꢁ ¼ ꢂ6 (c 0.31, CHCl3); mmax/cmꢂ1 (CH2Cl2) 1646
D
(C@N), 1740 (C@O); dH (CDCl3) 3.48 (1H, dd, J 10.6,

660
G. Jones, C. J. Richards / Tetrahedron: Asymmetry 15 (2004) 653–664
20
D
8.1, OCHH), 3.66 (3H, s, CO2CH3), 4.02 (1H, t, J 8.1,
CHN), 4.15 (1H, dd, J 10.6, 8.1, OCHH), 4.69 (1H, br s,
Cp), 4.75 (1H, br s, Cp), 5.02 (1H, br s, Cp), 5.18 (1H, br
s, Cp), 7.10–7.16 (8H, m, meta-Ph), 7.17–7.24 (4H, m,
para-Ph), 7.31–7.38 (8H, m, ortho-Ph); dC (CDCl3){1H}
51.5 (CH3), 67.3 (CH2), 67.4 (CHN), 75.1 (C4Ph4), 81.7
(Cp), 83.0 (ipso-Cp), 83.7 (Cp), 84.1 (Cp), 85.1 (Cp),
125.5 (para-Ph), 126.9 (meta-Ph), 127.8 (ortho-Ph), 134.1
(ipso-Ph), 161.9 (C@N), 170.8 (C@O); m=z (APCI) 608
(MHþ, 100). HRMS (FAB) m=z found for MHþ,
608.1637; calcd for C38H31CoNO3, 608.1636.
red solid (2.077 g, 95%). Mp 119–120 ꢁC; ½aꢁ ¼ þ96 (c
0.31, CHCl3); mmax/cmꢂ1 (CH2Cl2) 1649 (C@N); dH
(CDCl3) 3.30 (1H, dd, J 11.2, 4.2, OCHH), 3.43–3.49
(1H, m, OCHH), 3.92–3.99 (3H, m, OCH2+CHN), 4.37
(1H, br s, Cp), 4.40 (1H, br s, Cp), 4.71 (1H, br s, Cp),
4.78 (1H, br s, Cp), 7.08–7.12 (20H, m, Ph), 7.15–7.20
(5H, m, Ph); dC (CDCl3){1H} 64.2 (CH2), 68.7 (CHN),
68.9 (CH2), 74.8 (Cp), 75.0 (Cp), 75.8 (ipso-Cp), 77.6
(Cp), 78.0 (Cp), 88.6 (C5Ph5), 126.7 (Ph), 127.4 (Ph),
132.7 (Ph), 135.6 (Ph), 165.4 (C@N); m=z (APCI) 666
(MHþ, 100). HRMS (FAB) m=z found for MHþ,
666.2099; calcd for C44H36FeNO2, 666.2095.
4.3.3. (S)-4-Carbomethoxy-2-ferrocenyloxazoline 2c.
General procedure B used––6c (1.046 g, 3.16 mmol) gave
2c as an orange crystalline solid (0.940 g, 95%). Mp 93–
4.4.2. (g5-(R)-2-(4-Hydroxymethyl)oxazolinylcyclopenta-
dienyl)(g4-tetraphenylcyclobutadiene) cobalt 3b. General
procedure C used––2b (0.495 g, 0.81 mmol) gave 3b as
20
95 ꢁC; ½aꢁ ¼ þ224 (c 0.05, CH2Cl2);
m
max/cmꢂ1
D
(CH2Cl2) 1646 (C@N), 1741 (C@O); dH (CDCl3) 3.75
(3H, s, CO2CH3), 4.15 (5H, s, Cp), 4.30 (2H, br s, Cp),
4.40 (1H, dd, J 10.0, 8.8, OCHH), 4.53 (1H, t, J 7.3,
CHN), 4.70–4.74 (2H, m, OCHH+Cp), 4.77 (1H, br s,
Cp); dC (CDCl3){1H} 51.7 (CH3), 67.4 (CHN), 67.6
(ipso-Cp), 68.27 (CH2), 68.35 (Cp · 2), 68.8 (Cp · 5), 69.6
(Cp), 69.8 (Cp), 168.6 (C@N), 170.9 (C@O); m=z (ES)
313 (MHþ, 100), 254 (14). HRMS (FAB) m=z found for
MHþ, 314.0485; calcd for C15H16FeNO3, 314.0479.
an orange crystalline solid (0.453 g, 96%). Mp 109–
20
D
110 ꢁC; ½aꢁ ¼ ꢂ192 (c 0.36, CHCl3);
m
max/cmꢂ1
(CH2Cl2) 1650 (C@N); dH (CDCl3) 3.39 (1H, dd, J 12.4,
4.3, OCHH), 3.56–3.73 (2H, m, OCH2+CHN), 3.77
(1H, t, J 9.1, OCHH), 4.82 (1H, br s, Cp), 4.90 (1H, br s,
Cp), 5.18 (1H, br s, Cp), 5.64 (1H, br s, Cp), 7.02–7.24
(12H, m, meta-Ph+para-Ph), 7.27–7.36 (8H, m, ortho-
Ph); dC (CDCl3){1H} 62.3 (CH2), 68.4 (CHN), 71.9
(CH2), 78.0 (C4Ph4), 78.4 (ipso-Cp), 84.2 (Cp), 85.7
(Cp), 88.6 (Cp), 89.3 (Cp), 127.6 (para-Ph), 128.7 (meta-
Ph), 129.2 (ortho-Ph), 134.6 (ipso-Ph), 167.2 (C@N); m=z
(APCI) 580 (MHþ, 100). HRMS (FAB) m=z found for
MHþ, 580.1681; calcd for C37H31CoNO2, 580.1687.
4.3.4. (S)-4-Carbomethoxy-2-(1-adamantyl)oxazoline 2d.
General procedure B used––6d (1.75 g, 6.2 mmol) gave
2d as a colourless crystalline solid (1.50 g, 92%). dH
(CDCl3) 1.63–1.80 (6H, m), 1.80–1.95 (6H, m), 1.95–
2.10 (3H, m), 3.79 (3H, s, CH3), 3.94 (1H, d, J 4.2,
CHN), 4.23–4.42 (2H, m, OCH2); dC (CDCl3){1H}
28.03 (CH), 36.62 (CH2), 38.81 (CH2), 39.23 (CC@N),
52.94 (–CH3), 54.86 (CHN), 63.75 (OCH2), (C@O and
C@N not observed).
4.4.3. (R)-4-Hydroxymethyl-2-ferrocenyloxazoline 3c.
General procedure C used––2c (0.366 g, 1.17 mmol) gave
3c as an orange crystalline solid (0.293 g, 88%). Mp 117–
20
119 ꢁC; ½aꢁ ¼ þ96 (c 0.05, CH2Cl2);
m
max/cmꢂ1
D
(CH2Cl2) 1650 (C@N); dH (CDCl3) 3.55 (1H, dd, J 11.6,
3.4, OCHH), 3.84 (1H, dd, J 11.6, 2.5, OCHH), 4.09
(5H, s, Cp), 4.12–4.38 (5H, m, OCH2+CHN+Cp · 2),
4.56 (1H, br s, Cp), 4.70 (1H, br s, Cp); dC (CDCl3){1H}
62.6 (CH2) 66.8 (CHN), 67.9 (Cp), 67.9 (CH2), 68.2
(Cp), 68.3 (ipso-Cp), 68.6 (Cp · 5), 69.4 (Cp), 69.5 (Cp),
167.5 (C@N); m=z (ES) 286 (MHþ, 100). HRMS (FAB)
m=z found for MHþ, 286.0528; calcd for C14H16FeNO2,
286.0530.
4.3.5. (S)-4-Carbomethoxy-2-phenyloxazoline 2e. Gen-
eral procedure B used––6e (1.020 g, 4.57 mmol) gave 2e
as a colourless crystalline solid (0.88 g, 94%). dH
(CDCl3) 3.82 (3H, s, CH3), 4.59 (1H, t, J 10, OCHH),
4.69 (1H, t, J 8, CHN), 4.95 (1H, dd, J 11, 8, OCHH),
7.38–7.52 (3H, m, Ph), 7.98 (2H, d, J 8, ortho-Ph); dC
(CDCl3){1H} 52.87 (CH3), 68.78 (CHN or OCH2), 69.71
(CHN or OCH2), 127.09 (ipso-Ph), 128.51 (Ph), 128.75
(Ph), 132.04 (para-Ph), 166.46 (C@N), 171.80 (C@O).
4.4. General procedure C
4.4.4.
(R)-4-Hydroxymethyl-2-(1-adamantyl)oxazoline
3d. General procedure C used––2d (1.43 g, 5.4 mmol)
gave 3d as a colourless crystalline solid that was
recrystallised from EtOAc/petroleum ether 40:60 (0.82 g,
LiAlH4 (1.1 equiv) was added in five portions over
10min to a solution of 2 (1equiv) in Et2O (30 mL/g) cooled
to 0 ꢁC. After stirring for 15 min, EtOAc (50 mL/g) was
added then H2O (75 mL/g), the organic layer was then
separated, dried (MgSO4), filtered and the solvent
removed in vacuo to give alcohols 3.
20
64%). Mp 81–83 ꢁC; ½aꢁ ¼ þ100 (c 0.1, CH2Cl2); mmax
/
D
cmꢂ1 (CH2Cl2) 1651 (C@N); dH (CDCl3) 1.65–1.80 (6H,
m), 1.85–1.92 (6H, m), 1.95–2.08 (3H, m), 3.54 (1H, dd,
J 11.4, 4.5, OCHH), 3.78 (1H, br d, J 12, OCHH), 4.06
(1H, t, J 6, CHN), 4.15–4.32 (2H, m, OCH2); dC
(CDCl3){1H} 28.07 (CH), 35.64 (CC@N), 36.71 (CH2),
39.81 (CH2), 64.53 (CH2), 67.24 (CHN), 69.22 (CH2),
(C@N not observed). HRMS (ES) m=z found for MHþ,
236.1645; calcd for C14H22NO2, 236.1651.
4.4.1. (g5-(R)-2-(4-Hydroxymethyl)oxazolinylcyclopenta-
dienyl)(g5-pentaphenylcyclopentadienyl) iron 3a. General
procedure C used––2a (2.278 g, 3.28 mmol) gave 3a as a

G. Jones, C. J. Richards / Tetrahedron: Asymmetry 15 (2004) 653–664
661
4.4.5. (R)-4-Hydroxymethyl-2-phenyloxazoline 3e. Gen-
eral procedure C used––2e (0.84 g, 4.1 mmol) gave 3e as
a colourless crystalline solid (0.64 g, 88%) that was
135.7 (ipso-Ph), 146.9 (C@N); m=z (APCI) 732 (MHþ,
100). HRMS (FAB) m=z found for MHþ, 732.2320;
calcd for C49H39CoNO2, 732.2313.
recrystallised from EtOAc/petroleum ether 40:60 (0.41 g,
20
57%). Mp 97–99 ꢁC; ½aꢁ ¼ þ82 (c 0.1, CH2Cl2); mmax
/
D
cmꢂ1 (CH2Cl2) 1643 (C@N); dH (CDCl3) 3.66 (1H, br d,
J 12, CHHOH), 4.00 (1H, br d, J 12, CHHOH), 4.31–
4.50 (3H, m, CHN and OCH2), 7.28 (2H, t, J 8, Ph),
7.40 (1H, t, J 8, Ph), 7.74, (2H, d, J 8, Ph); dC
(CDCl3){1H} 63.63 (CH2), 68.26 (CHN), 69.28 (CH2),
127.20 (ipso-Ph), 128.33 (Ph), 128.39 (Ph), 131.55 (para-
Ph), 165.69 (C@N). HRMS (ES) m=z found for MHþ,
178.0865; calcd for C10H12NO2, 178.0863.
4.6. General procedure E
The alkylation of benzaldehyde by Et2Zn. To a solution
of diethylzinc in hexanes (1.0 M, 1.5 equiv) was added to
a solution of ligand (5 mol %) in toluene (5 mL/25 mg)
and the mixture stirred for 20 min. Benzaldehyde was
then added (1 equiv) and this solution allowed to stir for
24 h. After this time, 0.5 mL of the reaction mixture was
removed and diluted with 1 mL of CH2Cl2. Following
filtration through a small pad of SiO2, this was then
analysed by GC (Chrompack CP-Chirasil-DEX CB
analytical column; 80 ꢁC, isothermal 30 min, ramp 8 ꢁC/
min, t1 ¼ 44:41 min for R-9, t2 ¼ 46:13 min for S-9).
4.5. General procedure D
A solution of Grignard reagent in THF (3 equiv) was
added dropwise to 2b in Et2O (20 mL/g) and THF
(20 mL/g) cooled to 0 ꢁC. The mixture was then stirred
for 3 h, allowed to warm to room temperature and
stirred overnight. The reaction was quenched with sat-
4.6.1. (g5-(S)-2-(4-Methylsulfonylatomethyl)oxazolinyl-
cyclopentadienyl)(g4-tetraphenylcyclobutadiene)cobalt
18. Methanesulfonyl chloride (0.65 mL, 8.4 mmol) was
added drop wise to a solution of 3b (4.41 g, 7.6 mmol),
triethylamine (1.27 mL, 9.1 mmol) and DMAP (5 mol%)
in CH2Cl2 (50 mL) cooled to 0 ꢁC. The solution was then
warmed to room temperature and stirred for 3 h. The
solvent was removed in vacuo and the residue column
urated NH4Cl
and followed by the addition of
ðaqÞ
additional Et2O and H2O. The organic layer was sepa-
rated, washed with H2O, dried (MgSO4), filtered and the
solvent removed in vacuo. Column chromatography
gave the desired tertiary alcohol.
chromatographed (75% EtOAc/40–60) to give 18 as an
20
D
orange solid (4.51 g, 90%). Mp 102–104 ꢁC; ½aꢁ ¼ ꢂ29
4.5.1. (g5-(S)-2-(4-Dimethylhydroxymethyl)oxazolinyl-
cyclopentadienyl)(g4- tetraphenylcyclobutadiene)cobalt 3f.
General procedure D used––2b (1.021 g, 1.68 mmol) and
(c 0.28, CHCl3); dH (CDCl3) 2.92 (1H, t, J 8.8, OCHH),
3.73 (1H, d, J 6.1, OCHH), 3.85–3.88 (2H, m,
OCHH+CHN), 4.02–4.08 (1H, m, OCHH), 4.71 (1H, br
s, Cp), 4.76 (1H, br s, Cp), 5.02 (1H, br s, Cp), 5.10 (1H,
m, br s, Cp), 6.92–7.23 (14H, m, Ph), 7.34–7.36 (16H, m,
Ph); dC (CDCl3){1H} 36.5 (CH3), 64.0 (CHN), 68.1
(OCH2), 69.6 (OCH2), 75.1 (C4Ph4), 81.4 (Cp), 82.8
(ipso-Cp), 83.9 (2 · Cp), 85.3 (Cp), 125.6 (para-Ph),
127.0 (meta-Ph), 127.8 (ortho-Ph), 134.0 (ipso-Ph), 162.8
(C@N); m=z (APCI) 658 (MHþ, 100). HRMS (FAB)
m=z found for Mþ, 657.1388; calcd for C38H32CoNO4S,
657.1379.
3 M MeMgI (1.68 mL, 5.04 mmol) gave 3f as an orange
20
D
solid (0.960 g, 94%). Mp 160–162 ꢁC; ½aꢁ ¼ ꢂ2 (c 0.13,
CHCl3); dH (CDCl3) 0.95 (3H, s, CH3), 1.13 (3H, s,
CH3), 3.38 (1H, dd, J 10.0, 7.6, OCHH), 3.46 (1H, dd, J
10.0, 7.8, CHN), 3.80 (1H, t, J 7.7, OCHH), 4.68 (1H, br
s, Cp), 4.71 (1H, br s, Cp), 5.00 (1H, br s, Cp), 5.12 (1H,
br s, Cp), 7.12–7.22 (12H, m, meta-Ph+para-Ph), 7.35–
7.37 (8H, m, ortho-Ph); dC (CDCl3){1H} 23.9 (CH3),
25.9 (CH3), 66.8 (CH2), 70.1 (CMe2), 74.4 (CHN), 75.0
(C4Ph4), 81.4 (Cp), 83.4 (Cp), 83.6 (ipso-Cp), 84.0 (Cp),
85.1 (Cp), 125.5 (para-Ph), 126.9 (meta-Ph), 127.8 (or-
tho-Ph), 134.2 (ipso-Ph), 161.1 (C@N); m=z (APCI) 608
(MHþ, 100). HRMS (FAB) m=z found for MHþ,
608.1995; calcd for C39H35CoNO2, 608.2000.
4.6.2. (g5-(S)-2-(4-Diphenylphosphinylmethyl)oxazolinyl-
cyclopentadienyl)(g4-tetraphenylcyclobutadiene)cobalt
19. Potassium tert-butoxide (0.216 g, 1.92 mmol) was
added in one portion to a solution of diphenylphosphine
(0.134 mL, 0.77 mmol) in THF (5 mL) cooled to )10 ꢁC.
The mixture was then stirred at this temperature for
30 min to give a deep orange/red solution and added to a
solution of 19 (0.506 g, 0.77 mmol) in THF (20 mL)
cooled to )10 ꢁC. The orange reaction mixture was then
allowed to warm to room temperature and then heated
under reflux overnight. On cooling to room temperature
the reaction was quenched with H2O (50 mL) and
quickly separated, dried (MgSO4), filtered and solvent
removed in vacuo. The residue was then flash chroma-
tographed (75% EtOAc/40–60) to give 19 as an air
4.5.2. (g5-(S)-2-(4-Diphenylhydroxymethyl)oxazolinylcy-
clopentadienyl)(g4-tetraphenylcyclobutadiene)cobalt 3g.
General procedure D used––2b (0.264 g, 0.43 mmol)
and 3 M PhMgBr (0.43 mL, 1.29 mmol) gave 3g as an
20
orange solid (0.315 g, 99%). Mp >220 ꢁC; ½aꢁ ¼ ꢂ166 (c
D
0.39, CHCl3); mmax/cmꢂ1 (CH2Cl2) 1644 (C@N); dH
(CDCl3) 3.27 (1H, dd, J 9.7, 8.4, OCHH), 3.67 (1H, dd,
J 9.4, 8.6, OCHH), 4.36 (1H, t, J 9.9, CHN), 4.66 (1H,
br s, Cp), 4.69 (1H, br s, Cp), 4.98 (1H, br s, Cp), 5.07
(1H, br s, Cp), 7.11–7.46 (30H, m, Ph); dC (CH2Cl2){1H}
68.5 (CH2), 73.0 (CHN), 76.4 (C4Ph4), 83.4 (Cp), 85.0
(ipso-Cp), 85.1 (Cp), 85.5 (Cp), 86.4 (Cp), 125.8 (Ph),
126.9 (para-Ph), 127.0 (Ph), 127.3 (Ph), 127.7 (Ph), 128.4
(meta-Ph), 128.4 (Ph), 128.6 (Ph), 129.3 (ortho-Ph),
sensitive orange solid, which was immediately stored
20
D
under nitrogen (0.437 g, 76%). Mp 89-90 ꢁC; ½aꢁ ¼ þ17
(c 0.29, CHCl3); dH (CDCl3) 1.45–1.63 (1H, m, OCHH),
2.43 (1H, d, J 13.0, OCHH), 3.40–3.54 (3H, m,

662
G. Jones, C. J. Richards / Tetrahedron: Asymmetry 15 (2004) 653–664
OCH2+CHN), 4.46 (1H, br s, Cp), 4.57 (1H, br s, Cp),
4.94 (1H, br s, Cp), 4.99 (1H, br s, Cp), 6.94–7.12 (14H,
m, Ph), 7.13–7.31 (16H, m, Ph); dC (CDCl3){1H} 35.5,
64.1 (d, J 17), 72.5 (d, J 10), 76.3 (C4Ph4), 82.2 (ipso-
Cp), 82.6 (Cp), 85.0 (Cp), 85.1 (Cp), 86.7 (Cp), 126.8
(para-Ph), 128.4 (meta-Ph), 128.8 (Ph), 128.9 (Ph), 129.0
(Ph), 129.2 (Ph), 129.3 (Ph), 129.5 (Ph), 132.9 (d, J 18,
Ph), 133.6 (d, J 19, Ph), 135.6 (ipso-Ph), 161.4 (C@N);
m=z (APCI) 748 (MHþ, 100). HRMS (FAB) m=z found
for MHþ, 748.2189; calcd for C49H40CoNOP, 748.2179.
tion solvent (1 equiv, 1 mL/100 mg) was then added and
stirred for an additional 5 min. Dimethylmalonate
(2 equiv), N,O-bis(trimethylsilyl)acetamide (2 equiv) and
potassium acetate (5 mol %) were then added in this
order. The reaction mixture was stirred for 24 h after
which time 0.5 mL of the reaction mixture was removed
and filtered through a pipette containing cotton wool
and a pad of silica (diethyl ether as eluent). The solvent
was removed in vacuo and a solution of the resultant oil
analysed via GC (Chrompack CP-Chirasil-DEX CB
analytical column; 110 ꢁC isothermal, t1 ¼ 29:91 min for
S-25, t2 ¼ 30:57 min for R-25).
4.7. General procedure F
The allylic alkylation of 1,3-diphenylprop-2-enyl acetate
20. A solution of the appropriate ligand (6 mol %) in the
reaction solvent (1 mL/10 mg) was added to allyl palla-
dium chloride dimer (2.5 mol %) and the resulting solu-
tion stirred for 20 min. A solution of 1,3-diphenylprop-
2-enyl acetate in the reaction solvent (1 equiv, 1 mL/
100 mg) was then added and the mixture stirred for an
additional 5 min followed by the addition in the fol-
lowing order of dimethylmalonate (2 equiv), N,O-
bis(trimethylsilyl)acetamide (2 equiv) and potassium
acetate (5 mol %). The reaction mixture was stirred for
24 h after which time a 0.5 mL portion was removed and
filtered through a pipette containing cotton wool and a
pad of silica (diethyl ether as eluent). The solvent was
removed in vacuo and a solution of the resultant oil
analysed via HPLC (Chiralcel OD analytical column
cooled to 11 ꢁC using a column jacket; eluting with 99:1
hexanes/2-propanol, flow rate 0.5 mL/min, 254 nm
t1 ¼ 36:8 min for R-21, t2 ¼ 39:6 min for S-21).
4.9.1. PdCl2 complex of (g5-(S)-2-(4-diphenylphosphinyl-
methyl)-oxazolinylcyclopentadienyl)(g4-tetraphenylcyclo-
butadiene)cobalt 26. PdCl2 (CH3CN)2 (0.098 g,
0.38 mmol) was added in one portion to a solution of 19
(0.281 g, 0.38 mmol) in CH2Cl2 (10 mL). This solution
was stirred for 1 h then the solvent was removed in
vacuo to give an orange solid. This sample was recrystal-
lised from hexanes/CH2Cl2 to give an orange crystalline
solid (0.243 g, 70%). Mp >220 ꢁC; mmax/cmꢂ1 (CH2Cl2)
1604 (C@N); dH (CDCl3) 1.92–2.06 (br m), 3.39–3.47 (br
m), 4.36 (br s), 4.74 (br s), 4.76 (br s), 5.23 (br s), 6.43 (br
s), 6.84–7.84 (br m); dP (CDCl3){1H} 35.8 (PPh2).
HRMS (ES) m=z found for (M)Cl)þ, 888.0828; calcd for
C49H39ClCoNOPPd, 888.0825.
4.10. General Procedure I
Chlorodiphenylphosphine (1.1 equiv) was added to a
solution of alcohol 3 (1 equiv), triethylamine (1.2 equiv)
and DMAP (0.1 equiv) in CH2Cl2 (5 mL/100mg of
alcohol) cooled to )10 ꢁC. The resulting solution was
stirred for 30 min, allowed to warm to room tempera-
ture and stirred for a further 10 min. The reaction mix-
ture was then filtered through a plug of alumina
(2.5 cm · 5 cm) using 50% EtOAc/40–60 as eluent and
the solvent removed in vacuo to give 4.
4.8. General procedure G
The allylic alkylation of 1,3-dimethylprop-2-enyl piva-
late 22. A solution of appropriate ligand (6 mol %) in the
reaction solvent (1 mL/10 mg) was added to allyl palla-
dium chloride dimer (2.5 mol %) and the solution stirred
for 20 min. A solution of 1,3-dimethylprop-2-enyl piva-
late in the reaction solvent (1 equiv, 1 mL/100 mg) was
then added and stirred for an additional 5 min. Di-
methylmalonate (2 equiv), N,O-bis(trimethylsilyl)acet-
amide (2 equiv) and potassium acetate (5 mol %) were
then added in this order. The reaction mixture was
stirred for 24 h after which time a 0.5 mL portion was
removed and filtered through a pipette containing
cotton wool and a pad of silica (diethyl ether as eluent).
The solvent was removed in vacuo and a solution of the
resultant oil analysed via GC (Chrompack CP-Chirasil-
DEX CB analytical column; 90 ꢁC isothermal,
t1 ¼ 16:62 min for S-23, t2 ¼ 17:00 min for R-23).
4.10.1. (g5-(S)-2-(4-Diphenylphosphinoxymethyl)oxazoli-
nylcyclopentadienyl)(g5-pentaphenylcyclopentadienyl)iron
4a. General procedure I used––3a (0.104 g, 0.16 mmol)
gave 4a as an air sensitive red/orange waxy solid
(0.090 g, 68%). mmax/cmꢂ1 (CH2Cl2) 1648 (C@N); dH
(CDCl3) 3.11 (1H, q, J 8.90, OCHH), 3.69–3.78 (1H, m,
OCHH), 3.82 (1H, t, J 8.93, OCHH), 3.89–4.07 (2H, m,
OCHH and CHN), 4.28 (2H, s, Cp), 4.63 (1H, s, Cp),
4.66 (1H, s, Cp), 6.87–7.09 (25H, m, Ph), 7.12–7.29 (6H,
m, Ph), 7.30–7.39 (4H, m, Ph); dC (CDCl3){1H} 66.8 (d,
J 8, CHN), 69.1 (OCH2), 70.8 (d, J 18.2, O CH2), 73.5
(Cp), 73.9 (Cp), 74.9 (ipso-Cp), 76.4 (Cp), 76.8 (Cp),
87.4 (C5Ph5), 125.5 (para-Ph), 126.3 (meta-Ph), 127.40
(Ph), 127.45 (Ph), 127.50 (Ph), 127.55 (Ph), 128.5 (d, J 4,
Ph), 129.2 (d, J 6, Ph), 129.4 (d, J 6, Ph), 131.6 (ortho-
Ph), 134.4 (ipso-Ph), 164.0 (C@N); dP {1H} 115.5
(OPPh2); m=z (FAB) 850 (MHþ, 100%). HRMS (ES)
m=z found for MHþ, 850.2527; calcd for
C56H45FeNO2P, 850.2537.
4.9. General procedure H
The allylic alkylation of 3-cyclohexenyl acetate 24. A
solution of appropriate ligand (6 mol %) in the reaction
solvent (1 mL/10 mg) was added to allyl palladium
chloride dimer (2.5 mol %) and the solution stirred for
20 min. A solution of cyclohexenyl acetate in the reac-

G. Jones, C. J. Richards / Tetrahedron: Asymmetry 15 (2004) 653–664
663
4.10.2. (g5-(S)-2-(4-Diphenylphosphinoxymethyl)oxazoli-
Acknowledgements
nylcyclopentadienyl)(g4-tetraphenylcyclobutadiene)cobalt
4b. General procedure I used––3b (0.204 g, 0.35 mmol)
gave 4b as an air sensitive orange solid (0.156 g, 58%).
Mp 130–132 ꢁC; dH (CDCl3) 3.41 (2H, t, J 9.01, OCH-
H+OCHH), 3.70–3.76 (1H, m, 1H, OCHH), 3.80–3.99
(2H, m, OCH H and CHN), 4.65 (1H, br s, Cp), 4.72
(1H, br s, Cp), 4.96 (1H, br s, Cp), 5.08 (1H, br s, Cp),
7.01–7.41 (30H, m, Ph); dC (CDCl3){1H} 66.0 (CHN),
68.8 (OCH2), 70.9 (OCH2), 75.0 (C4Ph4), 81.4 (Cp), 83.8
(2 · Cp), 85.0 (Cp), 125.5 (para-Ph), 126.9 (meta-Ph),
127.2, 127.3 (Ph), 127.6 (Ph), 127.8 (ortho-Ph), 128.3 (d,
J 7, Ph), 129.2 (d, J 4, Ph), 129.4 (d, J 3, Ph), 134.2
(ipso-Ph); dP {1H} 115.7 (OPPh2); m=z (FAB) 764
(MHþ, 53%). HRMS (EI) m=z found for Mþ, 763.2041;
calcd for C49H39CoNO2P, 763.2050.
We thank the EPSRC for a studentship (G.J.) and the
EPRSC National Mass Spectrometry Service Centre,
University of Wales, Swansea. We are also indebted to
Abdul Malik for the X-ray structure determination, and
to Francesc X. Roca and Huy V. Nguyen (both Queen
Mary) for assistance with the preparation of this man-
uscript.
References and notes
€
1. Recent reviews: (a) Jonsson, C.; Hallman, K.; Andersson,
H.; Stemme, G.; Malkoch, M.; Malmstrom, E.; Hult, A.;
€
Moberg, C. Bioorg. Med. Chem. Lett. 2002, 12, 1857; (b)
Ghosh, A. K.; Mathivanan, P.; Cappiello, J. Tetrahedron:
Asymmetry 1998, 9, 1.
4.10.3. (S)-2-(4-Diphenylphosphinoxymethyl)oxazolinyl-
ferrocene 4c. General procedure I used––3c (0.128 g,
0.45 mmol) gave 4c as an air sensitive orange oil (0.198 g,
94%). dH (CDCl3) 3.77–3.82 (1H, m, OCHH), 3.95–4.00
(m, 1H, OCHH), 4.06 (5H, s, C5H5), 4.22–4.34 (3H, m,
OCH2 and CHN), 4.24 (2H, s, Cp), 4.64 (2H, s, Cp),
7.20–7.30 (6H, m, Ph), 7.37–7.43 (4H, m, Ph); dC
(CDCl3){1H} 66.2 (d, J 8, CHN), 68.0 (2 · Cp), 68.7
(5 · Cp), 69.3 (2 · Cp), 70.2 (d, J 17, OCH2), 127.26
(Ph), 127.29 (Ph), 127.33 (Ph), 127.36 (Ph), 128.4 (d, J 5,
Ph), 129.3 (d, J 6, Ph), 129.6 (d, J 6, Ph), 166.8 (C@N);
dP (CDCl3){1H} 115.3 (OPPh2).
2. See, for example: (a) Yao, S.; Meng, J.-C.; Siuzdak, G.;
Finn, M. G. J. Org. Chem. 2003, 68, 2540; (b) Gardiner,
J. M.; Crewe, P. D.; Smith, G. E.; Veal, K. T. Chem.
Commun. 2003, 618; (c) Blume, F.; Zemolka, S.; Fey, T.;
Kranich, R.; Schmalz, H. G. Adv. Synth. Catal. 2002, 868;
ꢁ
ꢂ
(d) Jimeno, C.; Pasto, M.; Riera, A.; Pericas, M. A. J. Org.
Chem. 2003, 68, 3131.
3. Jones, G.; Butler, D. C. D.; Richards, C. J. Tetrahedron
Lett. 2000, 41, 9351.
4. Jones, G.; Richards, C. J. Tetrahedron Lett. 2001, 42,
5553.
5. Gant, T. G.; Meyers, A. I. Tetrahedron 1994, 50, 2297.
6. Phillips, A. J.; Uto, Y.; Wipf, P.; Reno, M. J.; Williams,
D. R. Org. Lett. 2000, 2, 1165.
7. Pu, L.; Yu, H.-B. Chem. Rev. 2001, 101, 757.
8. (a) Allen, J. V.; Williams, J. M. J. Tetrahedron: Asymmetry
1994, 5, 277; (b) Imai, Y.; Matsuo, S.; Zhang, W.;
Nakatsuji, Y.; Ikeda, I. Synlett 2000, 239.
9. An ee of 93% has been obtained with a C2-symmetric
bis(4-hydroxymethyloxazoline) ligand: Schinnerl, M.;
Seitz, M.; Kaiser, A.; Reiser, O. Org. Lett. 2001, 3, 4259.
10. (a) Yamakawa, M.; Noyori, R. J. Am. Chem. Soc. 1995,
117, 6327; (b) Rasmussen, T.; Norrby, P.-O. J. Am. Chem.
Soc. 2001, 123, 2464.
11. Dosa, P. I.; Ruble, J. C.; Fu, G. C. J. Org. Chem. 1997, 62,
444; The absolute configuration of the azaferrocene used
in this study has been determined, see: Hansen, J. G.;
Søtofte, I.; Johannsen, M. Org. Lett. 2001, 3, 499.
12. Ruzziconi, R.; Piermatti, O.; Ricci, G.; Vinci, D. Synlett
2002, 747.
4.10.4. (S)-2-(4-Diphenylphosphinoxymethyl)oxazolinyl-
adamantane 4d. General procedure I used––3d (0.106 g,
0.45 mmol) gave 4d as an air sensitive colourless oil
(0.187 g, 99%). dH (CDCl3) 1.59 (6H, br s, 3 · CH2), 1.78
(6H, br s, 3 · CH2), 1.97 (3H, br s, 3 · CH), 3.76–3.80
(1H, m, OCHH), 3.86–4.25 (4H, m, 3 · OCH H+CHN),
7.21–7.33 (4H, m, Ph), 7.34–7.50 (4H, m, Ph), 7.61–7.78
(2H, m, Ph); dC (CDCl3){1H} 26.9 (3 · CH), 35.5
(3 · CH2), 38.5 (3 · CH2), 65.4 (OCH2), 68.4 (CHN),
70.0 (d, J 18, OCH2), 127.25 (Ph), 127.3 (Ph), 127.45
(Ph), 127.5 (Ph), 128.3 (d, J 11, Ph), 129.2 (d, J 10, Ph),
129.4 (d, J 11, Ph), 174.0 (C@N); dP (CDCl3){1H} 115.0
(OPPh2).
13. Stevens, A. M.; Richards, C. J. Organometallics 1999, 18,
1346.
14. Jones, G.; Richards, C. J. Organometallics 2001, 20, 1251.
15. (a) Burgess, K.; Porte, A. M. Tetrahedron: Asymmetry
1998, 9, 2465; (b) Porte, A. M.; Reibenspies, J.; Burgess,
K. J. Am. Chem. Soc. 1998, 120, 9180.
16. Zhang, W.; Hirao, T.; Ikeda, I. Tetrahedron Lett. 1996, 37,
4545.
17. Ahn, K. H.; Cho, C.-W.; Park, J.; Lee, S. Tetrahedron:
Asymmetry 1997, 8, 1179.
18. Kudis, S.; Helmchen, G. Angew. Chem., Int. Ed. 1998, 37,
3047.
19. Crystallographic data (excluding structure factors) for the
structure in this paper, have been deposited with the
Cambridge Crystallographic Data Centre as supplemen-
tary publication number CCDC 221592. Copies of the
data can be obtained, free of charge, on application to
4.10.5. (S)-2-(4-Diphenylphosphinoxymethyl)oxazolinyl-
benzene 4e. General procedure I used––3e (0.109 g,
0.62 mmol) gave 4e as an air sensitive colourless oil,
which solidified on standing (0.156 g, 70%). Mp 68–
70 ꢁC; dH (CDCl3) 3.87–3.93 (1H, m, OCHH), 4.05 (1H,
m, OCHH), 4.36 (2H, dd, J 7.93 3.05, OCH2), 4.43–4.51
(1H, m, CHN), 7.15–7.42 (13H, m, Ph), 7.82–7.84 (2H,
m, Ph); dC (CDCl3){1H} 67.7 (OCH2), 70.6 (CHN), 71.8
(d, J 18, OCH2), 126.3 (Ph), 128.6 (Ph), 128.7 (Ph),
128.8 (Ph), 129.7 (d, J 12, Ph), 130.6 (d, J 7, Ph) 130.8
(d, J 7, Ph), 131.8 (Ph), 165.6 (C@N); dP (CDCl3){1H}
116.4 (–OPPh2).

664
G. Jones, C. J. Richards / Tetrahedron: Asymmetry 15 (2004) 653–664
CCDC, 12 Union Road, Cambridge CB2 1EZ, UK (Fax:
+44(0)-1223-336033 or e-mail: deposit@ccdc.com.ac.uk).
25. Following our preliminary communication of these
results, reports appeared on the synthesis of related (S)-
serine derived phosphinite–oxazoline ligands and their
application to iridium catalysed hydrogenation. Blanken-
stein, J.; Pfaltz, A. Angew. Chem., Int. Ed. 2001, 40,
4445.
26. (a) Yonehara, K.; Hashizume, T.; Mori, K.; Ohe, K.;
Uemura, S. Chem. Commun. 1999, 415; (b) Yonehara, K.;
Hashizume, T.; Mori, K.; Ohe, K.; Uemura, S. J. Org.
Chem. 1999, 64, 9374; (c) Hashizume, T.; Yonehara, K.;
Ohe, K.; Uemura, S. J. Org. Chem. 2000, 65, 5197; (d)
Yonehara, K.; Mori, K.; Hashizume, T.; Chung, K.-O.;
Ohe, K.; Uemura, S. J. Organomet. Chem. 2000, 603, 40.
27. For notable exceptions with substrate 22 see: (a) Trost, B.
M.; Krueger, A. C.; Bunt, R. C.; Zambrano, J. J. Am.
Chem. Soc. 1996, 118, 6520; (b) Wiese, B.; Helmchen, G.
Tetrahedron Lett. 1998, 39, 5727, With substrate 24 see
Ref. 18.
20. (a) Helmchen, G. J. Organomet. Chem. 1999, 576, 203; (b)
Helmchen, G.; Pfaltz, A. Acc. Chem. Res. 2000, 33, 336.
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1993, 32, 566; (b) Helmchen, G.; Sprinz, J. Tetrahedron
Lett. 1993, 34, 1769; (c) Dawson, G. J.; Frost, C. G.;
Williams, J. M. J.; Coote, S. J. Tetrahedron Lett. 1993, 34,
3149.
22. (a) Richards, C. J.; Damalidis, T.; Hibbs, D. E.; Hurst-
house, M. B. Synlett 1995, 74; (b) Nishibayashi, Y.;
Uemura, S. Synlett 1995, 79.
23. Gilbertson, S. R.; Chang, C.-W. T. J. Org. Chem. 1998,
63, 8424.
24. (a) Hou, D.-R.; Burgess, K. Org. Lett. 1999, 1, 1745; (b)
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