Investigations into the enantioselective C-protonation of prostereogenic enolate(s) derived from N,N′-diisopropyl-2-phenylpropanamide using suicide C-based proton sources

Article abstract of DOI:10.1016/j.tetlet.2004.10.090

The synthesis of enantiomerically enriched (-)-(R)-N, N′-diisopropyl- 2-phenylpropanamide was achieved in up to 69% enantiomeric excess by symmetrisation of the corresponding racemic amide by addition of sec-BuLi (to give the corresponding achiral lithium

Full text of DOI:10.1016/j.tetlet.2004.10.090

Tetrahedron
Letters
Tetrahedron Letters 45 (2004) 9469–9474
Investigations into the enantioselective C-protonation of
prostereogenic enolate(s) derived from N,N0-diisopropyl-2-
phenylpropanamide using suicide C-based proton sources
Gregory S. Coumbarides, Jason Eames,* Stephanos Ghilagaber and Michael J. Suggate
Department of Chemistry, Queen Mary, University of London, Mile End Road, London E1 4NS, UK
Received 9 August 2004; revised 6 October 2004; accepted 14 October 2004
Available online 6 November 2004
Abstract—The synthesis of enantiomerically enriched (À)-(R)-N, N0-diisopropyl-2-phenylpropanamide was achieved in up to 69%
enantiomeric excess by symmetrisation of the corresponding racemic amide by addition of sec-BuLi (to give the corresponding achi-
ral lithium enolate) and subsequent desymmetrisation by the addition of a chiral C-based proton source. We discuss potential fac-
tors that may be responsible for this observed enantioselectivity and comment on the role of the chiral acid.
ꢀ 2004 Elsevier Ltd. All rights reserved.
1. Introduction
slower carbon-to-carbon proton transfer.22 We now wish
to report our study into the use of C-based proton do-
nors as potential chelating proton donors for the enan-
tioselective C-protonation of prostereogenic enolates.
In an attempt to promote stereoselective C-protonation,
we chose to study an unusual class of stereogenic C-
based acids 7a–l in which the carbon bearing the pro
proton was stereogenic. To avoid problems associated
with racemisation of the parent proton source, we chose
to investigate the use of weakly acidic substituted esters
as our potential C-based proton sources. To ensure effi-
cient removal of the weakly acidic proton from these es-
ters 7a–l,21,25 we decided to use a prostereogenic lithium
enolate (Z)-23c [derived from VedejsÕ amide (rac)-1] as
our standard substrate as this is sufficiently basic to fully
deprotonate the parent acid (Scheme 1). In order to pre-
vent in situ racemisation of the required enantiomeri-
cally enriched amide (R) or (S)-1 by the intermediate
conjugate base (derived from the chiral proton source),
we needed to ensure that the conjugate base fragmented
to form a less basic species.25
The synthesis of optical active a-substituted carbonyl
compounds by enantioselective protonation of enolic
species derived from racemic carbonyl derivatives such
as ketones,1 esters,2 amides,3 lactones4 and carboxylic
acids5 is well documented.6,7 Within this area, there
are two main approaches, those that rely on the use of
an internal proton source6,7 (such as enantiomerically
pure chiral acids)6 and those that rely on an external
proton source6,7 (by coupling an achiral acid with a chi-
ral Lewis base) to control facial protonation.8 The
majority of these have used heteroatomic acids, such
as O-based carboxylic acids,9 phenols,10 alcohols4a,11
and water,12 N-based succinimides,13 amides,14 sulfon-
amides,15 oxazolidinones,16 anilines,17 ammonium
salts,18 and amines,19 and S-based thiols.20 The success
of these types of proton donors is largely due to their
mild acidity21 and efficient proton transfer.22
Over the last few years, we have been interested in the
use of C-based proton donors as potential proton
sources for the stereoselective C-protonation of eno-
lates.23 The use of C-based proton donors for enantiose-
lective C-protonation of prostereogenic enolates has
been limited.24 This may be in part due to their limited
availability, weakly acidic nature and intrinsically
The required racemic amide (rac)-1 for our study was
efficiently synthesised by refluxing 2-phenylpropanoic
acid (rac)-3 in thionyl chloride (SOCl2) to give 2-phenyl-
propanoyl chloride 4 in 94% yield, subsequent addition
of diisopropylamine (2equivalents) in dichloromethane
gave the required amide (rac)-1 in 95% yield (Scheme
2).3c Due to the near-identical nature of the starting
amide (rac)-1 and the required product, amide (R)- or
(S)-1; we focussed on the initial symmetrisation step to
*
Corresponding author. Tel./fax: +44-2078825251; e-mail: j.eames@
qmul.ac.uk
0040-4039/$ - see front matter ꢀ 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2004.10.090

9470
G. S. Coumbarides et al. / Tetrahedron Letters 45 (2004) 9469–9474
O
O
OLi
chiral proton
source
sec-BuLi
THF, 78 oC
Ph
Ph
Ph
N
N
N
H
Me
H
Me
Me
(Z)-2
(R)-1
(rac)-1
enantiomerically enriched
Scheme 1. Proposed synthetic route to enantiomerically enriched amide 1.
O
O
O
SOCl2
HN(i-Pr)2
Ph
Ph
Ph
Cl
OH
N
CH2Cl2
H
Me
H
Me
H Me
(rac)-4; 94%
(rac)-3
(rac)-1; 95%
Scheme 2. Synthesis of N,N-diisopropyl-2-phenylpropanamide (rac)-1.
50%
1. (COCl)
ensure full deprotonation of the parent amide and sub-
sequent formation of the intermediate lithium enolate
2 (Scheme 1). Addition of an excess of sec-BuLi (2.5
equivalents)3 to a stirred solution of racemic amide
(rac)-1 at À78ꢁC was required for efficient deprotona-
tion. The resulting enolate 2 was trapped efficiently with
D2O26 to give the required deuterium labelled amide 1-
d1 ([D]:[H] = >98:2) in 60% yield (Scheme 3). It is inter-
esting to note that deprotonation of the parent amide
(rac)-1 and subsequent formation of the enolate 2 ac-
counts for at least 60% of the starting amide. As for
the remainder, it is presumably removed by competitive
nucleophilic addition of sec-BuLi to the carbonyl group
to give the corresponding substituted sec-butyl ketone
after aqueous work-up. This particular competitive
nucleophilic pathway is very well documented.27
O
O
2
Ph
Ph
N
OH
2. HN(i-Pr)
2
H Me
H Me
(S)-1; 87% ee; [α] = +92
(S)-3; 100% ee
D
52%
1. (COCl)
O
O
2
Ph
Ph
Me
(R)-3; 100% ee
N
OH
2. HN(i-Pr)
2
Me
H
H
(R)-1; 90% ee; [α] = -95
D
Chiralcel OD column: solvent = hexane:IPA [9:1]
flow rate = 0.5 ml/min, retention time 10 mins (S)- and 12 mins (R)-.
Scheme 4. Synthesis of enantiomerically enriched amide (S)-1 and
(R)-1.
We next studied a variety of structurally related chiral
proton sources 7a–l for the enantioselective protonation
of lithium enolate 2 to give the required enantiomeri-
cally enriched amide 1 (Scheme 1). The enantiomeric ex-
cesses were determined by analytical HPLC using a
chiralcel OD column eluting with hexane:isopropanol
(9:1) with a flow rate of 0.5ml per minute. The relative
configurations were determined by comparison with
authentic samples of enantiomerically enriched amides
(R)- and (S)-1 (Scheme 4). These were synthesised by
addition of diisopropylamine to the corresponding
enantiomerically pure acid chloride 4 (formed by addi-
tion of oxalyl chloride to the parent 2-phenylpropionic
acid 3) in a non-polar solvent,3c such as toluene, to pre-
vent in situ racemisation (Scheme 4).3c
(Scheme 5). The structural and electronic nature of the
sulfonamide groupings present within this skeleton 7
were found to be important with regard the stereochem-
ical outcome of enantioselective C-protonation of the
intermediate enolate 2. The highest level of enantioselecti-
vity was found to be 69% ee using the 4-isopropyl-sub-
stituted sulfonamide 7e as the chiral proton donor
(Scheme 6). For the simplest sulfonamide 7a, moderate
enantioselectivity was observed [(R)-45% ee]. Increasing
the sterically demanding nature at C(4) of the aryl ring
of this sulfonamide increased the levels of enantioselecti-
vity from (R)-45% ee (for 7a), to (R)-64% ee by addi-
tion of a methyl substituent (in 7b), and to (R)-69% ee
for a similarly sized isopropyl substituent (in 7e).
Whereas, for a more sterically demanding tert-butyl sub-
stituent (in the sulfonamide 7f), the level of enantioselecti-
vity was lowered to (R)-36% ee. By comparison, using a
fluoro-substituent at C(4) (in 7g) had little effect on the
The required esters 7a–l were synthesised by deprotona-
tion of the parent oxazolidinone 5 (with n-BuLi) and
addition of the corresponding sulfonyl chloride 6a–l
O
O
OLi
D2O
Ph
sec-BuLi
THF, 78 o
Ph
Ph
N
N
N
C
H
Me
D Me
Me
(rac)-1
(rac)-1-d1; 60%
2
([D]:[H] = >98:2)
Scheme 3. Synthesis of N,N-diisopropyl-2-phenylpropanamide (rac)-1-d1.

G. S. Coumbarides et al. / Tetrahedron Letters 45 (2004) 9469–9474
9471
R
O
O
H
1. n-BuLi
O
O
THF, -78 o
C
S
O
NH
CO2Et
O
N
2.
R
CO2Et
H
6a-l
O
O
S
7a-l
5
Cl
O
O
O
O
O
SO2
N
O
SO2
N
O
O
SO2 N
Pr
Br
SO2
N
O
EtO2C
7b; 40%
EtO2C
7a; 44%
EtO2C
7c; 59%
EtO2C
7d; 30%
O
O
O
O
F
SO2
N
O
SO2
EtO2C
7h; 51%
N
O
t-Bu
SO2
N
O
i-Pr
SO2
EtO2C
7e; 34%
N
EtO2C
EtO2C
7g; 26%
7f; 25%
i-Pr
O
O
O
O
SO2
N
O
i-Pr
SO2
i-Pr EtO2C
7k; 27%
N
O
SO2
EtO2C
7l; 37%
N
O
O2N
SO2
N
O
EtO2C
EtO2C
7j; 37%
7i; 60%
Scheme 5. Synthesis of ester-based chiral proton sources 7a–l.
chiral proton
source(s)
O
O
OLi
sec-BuLi
THF, 78 oC
Ph
Ph
Ph
N
N
N
7a-l
H
Me
H
Me
Me
1
(rac)-1
2
enantiomerically enriched
Amide 1
Chiral proton
source
Enantiomeric
Yield
58%
45%
excess
(R)-45% e.e.
(R)-64% e.e.
7a
7b
7c
(R)-18% e.e.
(R)-47% e.e.
38%
50%
7d
7e
7f
(R)-69% e.e.
(R)-36% e.e.
(R)-44% e.e.
42%
50%
7g
42%
7h
7i
(R)-4% e.e.
(R)-30% e.e.
(rac)-0% e.e.
(S)-20% e.e.
47%
50%
7j
31%
50%
7k
7l
50%
(S)-10% e.e.
Scheme 6. Enantioselective C-protonation of prostereogenic lithium enolate 2.

9472
G. S. Coumbarides et al. / Tetrahedron Letters 45 (2004) 9469–9474
level of stereocontrol [(R)-44% ee]. In addition, a nitro
group (in 7i) behaved similarly [(R)-30% ee], but a
slightly larger bromo-substituent (in 7h) gave little facial
control [(R)-4% ee]. The position of these substituents
was found to be important on the levels of enantioselec-
tivity. Positioning a methyl group at C(3) in 7c only
served to lower the level of enantioselectivity [(R)-18%
ee]. In all these cases, the facial preference of protona-
tion was the same, leading to the (R)-enantiomer of
the amide 1.
esters 7a–l can occur enantioselectively to give the cor-
responding enantiomerically enriched amide 1 with
moderate to good levels of enantiomeric excess (up to
69% ee). The structural nature of these proton donors
appear to play an important role on the overall level
of facial selectivity for the enantioselective protonation
of the lithium enolate 2. This overall strategy amounts
to an indirect resolution for carbonyl-based substrates
through symmetrisation (by deprotonation with sec-
BuLi) followed by desymmetrisation (by enantioselec-
tive protonation). The nearest analogy to this work
has been reported by Vedejs et al.3c He has elegantly
shown that lithium enolate 2 can be enantioselectively
protonated with near perfect facial control using a sub-
stituted chiral aniline, giving the required amide (R)-1
with greater than 97% ee.3c This approach has now been
extended towards the enantioselective protonation of re-
lated amide-based enolates using a substoichiometric
amount of this chiral aniline in the presence of a stoichio-
metric amount of achiral proton donor, such as tert-
butyl phenylacetate to give the corresponding amide
with superb levels of enantioselectivity (up to 94%
ee).28 It is interesting to note, that the rate of proton
transfer between the enolate and substoichiometric
chiral aniline must be significantly faster than that be-
tween the corresponding enolate and the stoichiometric
C-based acid for efficient enantioselective protonation.
These results into the use of C-based proton donors
should be of use for future design of potential chiral
C-based proton donors and may aid mechanistic inter-
pretation of related reactions, work towards this is
currently in progress within our laboratory.
Whereas, increasing the sterically demanding nature of
the sulfonamide group, by altering the substituent(s) at
the C(2) position of the sulfonamide aryl ring (which
are presumably positioned nearer the acidic proton of
the ester) in the sulfonamides 7k and 7l, not only low-
ered the overall level of enantioselectivity, but also chan-
ged the facial preference in favour of the (S)-enantiomer
of the amide 1. The presence of the sulfonamide group
in 7 was also found to be important; without it, the lev-
els of enantioselectivity were found to be lower when
using a related ester 8 (Scheme 7). This tentatively sug-
gests that the sulfonamide motif in 7 binds to the lithium
of the enolate (in 9) to assist in the discrimination (on
protonation) of the faces of the lithium enolate 2
(Scheme 8).
From these studies, it is evident that the subtle changes in
the structural nature of the chiral proton source can cause
a substantial change in level and facial selectivity of pro-
tonation. This may be due to structural subtleties within
the lithium enolate aggregate prior to proton transfer.
Deprotonation of these chiral proton donors (e.g., 7a)
has been shown to give the corresponding enamide 13 pre-
sumably via E1cb fragmentation25 of the intermediate
lithium enolate 10, decarboxylation of 11 and protona-
tion of 12 during aqueous work-up (Scheme 9).
2. Representative experimental procedures
2.1. Synthesis of ethyl 3-(4-isopropylphenylsulfonyl)
oxazolidinon-2-on-(4S)-4-carboxylate 7e
In conclusion, we have shown that C-protonation of
an amide-based enolate 2 using enantiomerically pure
n-BuLi (2.52ml, 2.5M in hexanes, 6.29mmol) was added
to a solution of oxazolidin-2-one 5 (1.00g, 6.29mmol) in
THF (10ml) at À78ꢁC. The solution was stirred for 1h.
A solution of 4-isopropylphenylsulfonyl chloride (1.38g,
6.32mmol) in THF (10ml) was added at À78ꢁC. The
resulting solution was stirred for a further 3h. Water
(20ml) was added, and the resulting solution was ex-
tracted with ether (2 · 50ml). The combined organic
layers were dried (MgSO4) and evaporated under re-
duced pressure. The residue was purified by flash col-
umn chromatography on silica gel eluting with ether
to give ethyl 3-(4-isopropylphenylsulfonyl) oxazolidi-
non-2-on-(4S)-4-carboxylate 7e (0.72g, 34%) as a white
O
O
enolate 2
O
N
Me
O
Ph
N
H
Me
H
EtO
(R)-1; 36% e.e.; 62%
8
Scheme 7. Enantioselective C-protonation of enolate 2.
Me
O
N(i-Pr)2
O
Ph
(i) sec-BuLi
O
-78oC
(rac)-1
O
H
N
(R)-1
S
(ii) 7e
69% e.e.; 42%
Li
-78oC
EtO
O
O
9
Scheme 8. Enantioselective protonation of enolate 2 using proton donor 7e.

G. S. Coumbarides et al. / Tetrahedron Letters 45 (2004) 9469–9474
9473
O
H
O
O
+ 2
- (R)-1
O
N
S
O
N
S
LiO
N S
O
O
O
O
O
O
O
O
O
Li
EtO
11
EtO
7a
EtO
10
-CO2
H2O
LiN
S
O
HN
S
O
on aqueous
work-up
O
O
O
O
EtO
12
EtO
13
Scheme 9. Fragmentation of chiral proton source 7a.
22
D
solid; RF (ether) 0.56; ½aŠ À 35:2 (c = 4.2, chloroform);
6.7, CH3), 1.13 (3H, d, J 6.7, CH3) and 0.58 (3H, d, J
6.6, CH3); dC (62.5MHz, CDCl3) 172.2, 143.1, 128.2,
127.2, 126.6, 48.4, 45.8, 44.9, 21.1, 20.1 and 19.2, found
MH+, 234.1861. C15H24NO requires 233.1782.
mp 99–101ꢁC; mmax (film) 3057–2874cmÀ1 (CH),
1793cmÀ1 (C@O) and 1751cmÀ1 (C@O); dH
(250MHz, CDCl3) 8.03 (2H, d, J 8.5, 2 · CH; 2,6-CH;
Ar), 7.41 (2H, d, J 8.5, 2 · CH; 3,5-CH; Ar), 5.03–5.00
(1H, dd, J 9.4 and 4.3, NCH), 4.59 (1H, t, J 9.4,
OCHAHB), 4.33–4.22 (3H, m, OCHAHB and CH3CH2),
3.09–2.92 (1H, septet, J 6.9, CH(CH3)2), 1.28 (3H, t, J
7.1, CH3) and 1.27 (6H, d, J 6.9, 2 · CH3; i-Pr); dC
(62.5MHz, CDCl3) 160.7, 148.9, 143.6, 126.9, 121.7,
119.4, 57.7, 55.2, 49.5, 26.7, 15.9 and 6.3, found
MNH4 þ, 359.1273. C15H23N2O6S requires 359.1271.
Acknowledgements
We are grateful to the EPSRC for a studentship (to
S.G.), The Royal Society and The University of London
Central Research Fund for their financial support (to
J.E.) and the EPRSC National Mass Spectrometry Serv-
ice (Swansea) for accurate mass determinations.
2.2. Desymmetrisation of amide (rac)-1 via symmetrisa-
tion with sec-BuLi and enantioselective C-protonation
with ester 7e
References and notes
A solution of sec-butyllithium (0.54ml, 1.4M in cyclo-
hexanes, 0.75mmol) was added to (rac)-amide 1
(0.10g, 0.43mmol) in THF (3ml) at À78ꢁC under nitro-
gen. The solution was stirred for 1h. A solution of ethyl
3-(4-isopropylphenylsulfonyl) oxazolidinon-2-on-(4S)-
4-carboxylate 7e (0.29g, 0.86mmol) in THF (2ml) was
added and the resulting solution was stirred for a further
30min. The mixture was quenched with chlorotrimeth-
ylsilane (Me3SiCl) (86mg, 0.10ml, 0.79mmol) and stir-
red for 1h. Water (10ml) was added, and the resulting
solution was extracted with ether (2 · 50ml). The com-
bined organic layers were dried (MgSO4) and evapo-
rated under reduced pressure. The residue was purified
by flash column chromatography on silica gel eluting
with light petroleum:ether (7:3) to give the enantiomeri-
cally enriched amide (R)-1 (42mg, 42%); 69% ee [enan-
tiomeric excess determined using analytical hplc
(CHIRALCEL OD, 25cm · 0.46cm I.D.), eluting with
hexane/isopropanol (9:1), 0.5ml/min]; RF [light petro-
leum:ether (7:3)] 0.36; mp 39–40ꢁC; mmax (KBr) 3057–
2872cmÀ1 (aromatic, C–H) and 1638cmÀ1 (C@O); dH
(250MHz, CDCl3) 7.34–7.18 (5H, m, 5 · CH; Ph),
4.10–3.95 (1H, m, NCH), 3.83–3.75 (1H, q, J 6.8,
C(2)H), 3.32–3.25 (1H, m, NCH), 1.45 (3H, d, J 6.8,
C(2)HCH3), 1.41 (3H, d, J 6.8, CH3), 1.38 (3H, d, J
1. (a) Fehr, C.; Galindo, J. Angew. Chem., Int. Ed. Engl.
1994, 33, 1888; (b) Fehr, C.; Galindo, J. J. Am. Chem. Soc.
1988, 110, 6909; (c) Potin, D.; Williams, K.; Rebek, J.
Angew. Chem., Int. Ed. Engl. 1990, 29, 1420; (d) Fuji, K.;
Tanaka, K.; Miyamoto, H. Tetrahedron: Asymmetry 1993,
4, 247; (e) Yasukata, T.; Koga, K. Tetrahedron: Asymme-
try 1993, 4, 35; (f) Ishihara, K.; Kaneeda, M.; Yamamoto,
H. J. Am. Chem. Soc. 1994, 116, 11179; (g) Vedejs, E.;
Garcia-Rivas, J. A. J. Org. Chem. 1994, 59, 6517; (h)
Yangagisawa, A.; Kikuchi, T.; Kuribayashi, T.; Yama-
moto, H. Tetrahedron 1998, 54, 10253; (i) Yangagisawa,
A.; Kikuchi, T.; Yamamoto, H. Synlett 1998, 174; (j)
Nakamura, Y.; Takeuchi, S.; Ohgo, Y.; Yamaoka, M.;
Yoshida, A.; Mikami, K. Tetrahedron Lett. 1997, 38, 2709;
(k) Aboulhoda, S. J.; Reiners, I.; Wilken, J.; Henin, F.;
Martens, J.; Muzart, J. Tetrahedron: Asymmetry 1998, 9,
1847; (l) Takahashi, M.; Ogasawara, K. Tetrahedron:
Asymmetry 1997, 8, 3125; (m) Fuji, K.; Kawabata, T.;
Kuroda, A. J. Org. Chem. 1995, 60, 1914; (n) Riviere, P.;
Koga, K. Tetrahedron Lett. 1997, 38, 7859.
2. (a) Duhamel, L.; Plaquevent, J.-C. J. Am. Chem. Soc.
1978, 100, 7415; (b) Duhamel, L.; Plaquevent, J.-C. Bull.
Soc. Chim. Fr. 1982, II-75; (c) Duhamel, L.; Duhamel, P.;
Fouquay, S.; Eddine, J. J.; Peschard, O.; Plaquevent, J.-C.;
Ravard, A.; Solliard, R.; Valnot, J. Y.; Vincens, H.
Tetrahedron 1998, 44, 5495; (d) Pacejus, H.; Wilcke,
F.-W.; Hanemann, K. J. Prakt. Chem. 1977, 319, 219;

9474
G. S. Coumbarides et al. / Tetrahedron Letters 45 (2004) 9469–9474
(e) Toke, L.; Bako, P.; Keseru, G. M.; Albert, M.;
Fenichel, L. Tetrahedron Lett. 1998, 54, 213.
12. Hogeveen, H.; Zwart, L. Tetrahedron Lett. 1982, 23, 105.
For an additional example see Ref. 9b.
3. (a) Vedejs, E.; Lee, N. J. Am. Chem. Soc. 1991, 113, 5483;
(b) Vedejs, E.; Lee, N.; Sakata, S. T. J. Am. Chem. Soc.
1994, 116, 2175; (c) Vedejs, E.; Kruger, A. W.; Lee, N.;
Sakata, S. T.; Stec, M.; Suna, E. J. Am. Chem. Soc. 2000,
122, 4602; (d) Vedejs, E.; Kruger, A. W.; Suna, E. J. Org.
Chem. 1999, 64, 7863; (e) Vedejs, E.; Lee, N. J. Am. Chem.
Soc. 1995, 117, 891.
13. (a) Yanagisawa, A.; Kuribayashi, T.; Kikuchi, T.; Yama-
moto, H. Angew. Chem., Int. Ed. Engl. 1994, 33, 107; (b)
Yanagisawa, A.; Kikuchi, T.; Watanabe, T.; Kuribayashi,
T.; Yamamoto, H. Synlett 1995, 372. For an additional
example see Ref. 1h.
14. Fujihara, H.; Tomioka, K. J. Chem. Soc., Perkin Trans. 1
1999, 2377.
4. (a) Haubenreich, T.; Hunig, S.; Schulz, H.-J. Angew.
Chem., Int. Ed. Engl. 1993, 32, 398; (b) Gerlach, U.;
Hunig, S. Angew. Chem., Int. Ed. Engl. 1987, 26, 1283.
15. Xu, M.-H.; Wang, W.; Lin, G.-Q. Org. Lett. 2000, 2, 2229,
For additional examples see Refs. 4a,b.
16. (a) Fehr, C. Chimia 1991, 45, 253; (b) Carbery, D. R.;
Donohoe, T. J. Chem. Commun. 2004, 722. For an
additional example see Ref. 15.
´
´
5. Henin, F.; Letinois, S.; Muzart, J. Tetrahedron: Asymme-
try 2000, 11, 2037.
6. Fehr, C. Angew. Chem., Int. Ed. Engl. 1996, 35, 2566, and
references therein.
7. Eames, J.; Weerasooriya, N. Tetrahedron: Asymmetry
2001, 12, 1, and references therein.
8. (a) Eames, J.; Weerasooriya, N. Tetrahedron Lett. 2000,
41, 521; (b) Eames, J.; Weerasooriya, N. Chirality 1999,
787.
9. (a) Duhamel, L.; Launay, J.-C. Tetrahedron Lett. 1983, 24,
4209; (b) Yamashita, Y.; Emura, Y.; Odashima, K.; Koga,
K. Tetrahedron Lett. 2000, 41, 209, For additional
examples see Refs. 1e,n,2a,b,c,4a.
10. (a) Ishihara, K.; Nakamura, S.; Kaneeda, M.; Yamamoto,
H. J. Am. Chem. Soc. 1996, 118, 12854; (b) Yamamoto,
H.; Yanagisawa, A.; Ishihara, K.; Saito, S. Pure Appl.
Chem. 1998, 70, 1507; (c) Nakamura, S.; Kaneeda, M.;
Ishihara, K.; Yamamoto, H. J. Am. Chem. Soc. 2000, 122,
8120. For an additional example see Ref. 1f.
11. (a) Curran, D. P.; Totleben, M. J. J. Am. Chem. Soc. 1992,
114, 6050; (b) Takeuchi, S.; Miyoshi, N.; Ohgo, Y. Chem.
Lett. 1992, 551; (c) Takeuchi, S.; Ohira, A.; Miyoshi, N.;
Mashio, H.; Ohgo, Y. Tetrahedron: Asymmetry 1994, 5,
1763; (d) Kosugi, H.; Hoshino, K.; Uda, H. Phosphorus,
Sulfur, Silicon Relat. Elem. 1994, 95–96, 401; (e) Kosugi,
H.; Hoshino, K.; Uga, H. Tetrahedron Lett. 1997, 38,
6861; (f) Takahashi, T.; Nakao, N.; Koizumi, T. Tetra-
hedron: Asymmetry 1997, 8, 3293; (g) Nakamura, Y.;
Takeuchi, S.; Ohgo, Y.; Yamaoka, M.; Yoshida, A.;
Mikami, K. Tetrahedron 1999, 55, 4595; (h) Nakamura,
Y.; Takeuchi, S.; Ohgo, Y.; Curran, D. Tetrahedron Lett.
1998, 39, 8691, For additional examples see Refs. 1j,4b.
17. For representative examples see Refs. 3b,c,d.
18. For a representative example see Ref. 1d.
19. For representative examples see Refs. 3a,e.
20. (a) Emori, E.; Arai, H.; Sasai, H.; Shibasaki, M. J. Am.
Chem. Soc. 1998, 120, 4043; (b) Asensio, G.; Gavina, P.;
Cuenca, A.; de Arellano, M. C. R.; Domingo, L. R.;
´
Medio-Simon, M. Tetrahedron: Asymmetry 2000, 11,
3481.
21. For further information see: (a) Bordwell, F. G.; Algrim,
D. J. Org. Chem. 1976, 41, 2507; (b) Bordwell, F. G.;
Fried, H. E.; Hughes, D. L.; Lynch, T.-Y.; Satish, A. V.;
Whang, Y. E. J. Org. Chem. 1990, 55, 3300; (c) Bordwell,
F. G.; Fried, H. E. J. Org. Chem. 1991, 56, 4218, and
references therein.
22. Eigen, M. Angew. Chem., Int. Ed. Engl. 1964, 3, 1, and
references therein.
23. (a) Eames, J. Tetrahedron Lett. 1999, 40, 5787;
(b) Eames, J.; Coumbarides, G. S.; Weerasooriya, N.
Can. J. Chem. 2000, 935–941. For further information see
Ref. 8a.
24. For representative examples see Refs. 1g,8a.
25. Falb, E.; Nudelman, A.; Gottlieb, H. E.; Hassner, A. Eur.
J. Org. Chem. 2000, 645.
26. Eames, J.; Coumbarides, G. S.; Ghilagaber, S. J. Labelled
Compd. Radiopharm. 2003, 75, 1033.
27. (a) Alonso, E.; Ramon, D. J.; Yus, M. Tetrahedron 1998,
54, 13629; (b) Kimachi, T.; Takemoto, Y. J. Org. Chem.
2001, 66, 2700.
28. Vedejs, E.; Kruger, A. W.; Suna, E. J. Org. Chem. 1998,
63, 2792.