The dienolate aldol reaction of (E)-N-crotonoyl C(4)-isopropyl SuperQuat: asymmetric synthesis of α-vinyl-β-hydroxycarboxylic acid derivatives and conversion to α-ethylidene-β-hydroxyesters (β-substituted Baylis-Hillman products)

Article abstract of DOI:10.1016/j.tet.2009.07.004

The synthesis of α-vinyl-β-hydroxyesters and α-ethylidene-β-hydroxyesters (β-substituted Baylis-Hillman products) via the dienolate aldol reaction of (E)-N-crotonoyl C(4)-isopropyl SuperQuat is described. High levels of syn-diastereoselectivity (up to >98

Full text of DOI:10.1016/j.tet.2009.07.004

Tetrahedron 65 (2009) 7837–7851
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
The dienolate aldol reaction of (E)-N-crotonoyl C(4)-isopropyl SuperQuat:
asymmetric synthesis of
a
-vinyl-
b
b
-hydroxycarboxylic acid derivatives and
-substituted Baylis–Hillman
conversion to
products)
a
-ethylidene- -hydroxyesters (b
*
Stephen G. Davies , Dirk L. Elend, Simon Jones, Paul M. Roberts, Edward D. Savory,
Andrew D. Smith, James E. Thomson
Department of Chemistry, Chemistry Research Laboratory, University of Oxford, Mansfield Road, Oxford OX1 3TA, UK
a r t i c l e i n f o
a b s t r a c t
Article history:
The synthesis of a-vinyl-b-hydroxyesters and a-ethylidene-b-hydroxyesters (b-substituted Baylis–Hill-
Received 19 March 2009
Received in revised form 18 June 2009
Accepted 2 July 2009
man products) via the dienolate aldol reaction of (E)-N-crotonoyl C(4)-isopropyl SuperQuat is described.
High levels of syn-diastereoselectivity (up to >98% de) are observed for the dienolate aldol reaction with
boron enolates, generated either directly with Bu2BOTf or by transmetalation of the potassium enolate
with B-bromocatecholborane. Cleavage of the resultant syn-aldol products from the auxiliary gives
Available online 7 July 2009
a
-vinyl-
conjugation provides
diastereo- and enantiopurity (ꢀ91:9 [(E):(Z)] and >98% ee).
b
-hydroxyesters in >98% de and >98% ee. Subsequent isomerisation of the double bond into
Keywords:
Asymmetric synthesis
SuperQuat
Dienolate aldol
Baylis–Hillman
a
-ethylidene- -hydroxyesters ( -substituted Baylis–Hillman products) in high
b
b
Ó 2009 Elsevier Ltd. All rights reserved.
1. Introduction
from
a
-silyl-alkenoates but with low levels of (E):(Z) stereocontrol,9
-propiolates in the presence of HMPA
whilst hydroalumination of
b
The Morita–Baylis–Hillman reaction has been used extensively
in organic synthesis as a key carbon–carbon bond forming re-
action.1 This reaction employs either tertiary amines2 or phos-
phines3 to catalyse the condensation of an aldehyde and an acrylate
and subsequent reaction with an aldehyde gives the desired
products with high (Z)-stereocontrol.10 Enantiomerically enriched
b
a
-substituted Baylis–Hillman products may be prepared by
-functionalisation of chiral -unsaturated sulfoxides with alde-
a,b
ester to give
a
-methylene-
b-hydroxy-esters. These compounds
hydes,11 and through the reaction of silyl allenolates with aldehydes
catalysed by a chiral oxazaborolidine,12 although the synthetic
generality of these procedures has yet to be demonstrated. In order
to address this structural limitation, we became interested in the
development of methodology that is capable of the stereoselective
have proven to be useful synthetic intermediates, often used to
provide practical synthons in stereoselective synthesis.4 As this
efficient reaction produces polyfunctional chiral molecules in
a single step, various endeavours seeking to develop asymmetric
versions of this reaction to afford allylic alcohols in enantiomeri-
cally enriched form have been reported: for example, chiral acry-
lates,5 chiral aldehydes,6 chiral amines7 and chiral phosphines8
have been used. Although efficient, these approaches are restricted
synthesis of enantiomerically pure
b-substituted Baylis–Hillman
products, and have recently reported an asymmetric protocol13 in
which the highly diastereoselective conjugate addition of a homo-
chiral lithium amide14 to an
a
,
b
-unsaturated ester was used as the
key step for the introduction of stereochemistry. For example, ad-
dition of lithium (R)-N-methyl-N-( -methylbenzyl)amide 2 to tert-
butyl crotonate 1 gave -aminoester 3 in 84% yield and >98% de.
to the use of acrylate components, generating
droxy compounds. Methods for the preparation of
hydroxycarboxylic acid derivatives ( -substituted Baylis–Hillman
products) have been reported, although examples are limited. Ra-
cemic -substituted Baylis–Hillman products may be prepared
a
-methylene-b-hy-
a
-alkylidene-
b
-
a
b
b
Subsequent asymmetric aldol reaction via deprotonation with LDA,
transmetallation with B(OMe)3, and addition of acetaldehyde gave
syn-aldol product 4 in good yield, which was isolated as a single
diastereoisomer (>98% de). Tandem N-oxidation and Cope elimi-
b
nation then gave the desired
b-substituted Baylis–Hillman product
* Corresponding author.
(S,E)-5 in good yield and high de and ee (Scheme 1).
E-mail address: steve.davies@chem.ox.ac.uk (S.G. Davies).
0040-4020/$ – see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2009.07.004

7838
S.G. Davies et al. / Tetrahedron 65 (2009) 7837–7851
with KHMDS for 1 h then satd aq NH4Cl was added to assess the
extent of dienolate formation. 1H NMR spectroscopic analysis of the
crude reaction mixture indicated that all starting material had been
consumed, and that the N-acyl fragment had been converted to the
Me
Ph
N
(i)
CO2tBu
Me
CO2tBu
Me
Me
corresponding
b,g-unsaturated isomer 12, consistent with dien-
1
3, 84%, >98% de
olate formation followed by regioselective (kinetic) protonation at
C(20).21,22 Non-acylated SuperQuat 11 was also detected as a minor
side product (w4%), which is consistent with a ketene de-
composition pathway occurring as a side reaction (Scheme 2).
(ii)
78:22 dr
Ph
N
Li
(R)-2
Me
O
O
O
O
O
Ph
N
H
CO2tBu
CO2tBu
Me
(iii)
O
N
Me
O
N
O
NH
Me
(i)
+
Me
OH
Me
OH
100% conv.
~96:4
5, 58%, >98% ee
4, 56%, >98% de
(12:11)
>99:1 [(E):(Z)]
6
12
11
Scheme 2. Reagents and conditions: (i) KHMDS, THF, ꢁ78 ꢂC, 1 h then NH4Cl (satd, aq).
Scheme 1. Reagents and conditions: (i) lithium (R)-N-methyl-N-(a-methyl-
benzyl)amide 2 (1.6 equiv), THF, ꢁ78 ꢂC then NH4Cl (satd aq); (ii) LDA (3.0 equiv), THF,
ꢁ78 to 0 ꢂC, then B(OMe)3, then CH3CHO; (iii) mCPBA, CHCl3, rt.
The level of diastereoselectivity in the asymmetric dienolate aldol
reactions of the potassium dienolate of (E)-N-crotonoyl SuperQuat 6
was next assessed by reaction with acetaldehyde. 1H NMR spectro-
scopic analysis of the crude reaction mixture indicated that a complex
mixture of products was obtained with poor conversion (w5%) to the
desired aldol products 13, with poor diastereoselectivity (20% de).
Protonation at C(20) of the dienolate (to give 12), ketene decomposition
(to give SuperQuat 11), and formation of dioxanone 14 (presumably by
reaction of the product alkoxide with excess acetaldehyde) were
identified as the major side reactions in this system (Scheme 3).5e
We also proposed that homochiral b-substituted Baylis–Hillman
products 9 could be accessed via a diastereoselective dienolate al-
dol reaction of (E)-N-crotonoyl oxazolidinone 6. Either cleavage of
the auxiliary from the aldol product 7 and subsequent isomer-
isation of the double bond within the corresponding
a-vinyl-b-
hydroxyester 8, or isomerisation of the double bond within 7
followed by cleavage of the auxiliary from 10, would then afford the
desired b-substituted Baylis–Hillman products 9 directly (Fig. 1).
The enhanced exocyclic cleavage capacity and the high levels of
diastereofacial control observed in reactions of N-acyl SuperQuat
O
O
derivatives made the L-valine derived SuperQuat auxiliary 11 an
O
ideal choice for this transformation.15,16 We delineate herein our
investigations within this area.
O
NH
SQ
(i)
Me
N
12
Me
SQ
6
4:49:18:5:24
(6:11:12:13:14)
11
2. Results and discussion
O
O
OH
O
O
2.1. Dienolate aldol reaction
SQ =
O
SQ
Me
O
Me
The reaction of enolates with electrophiles is a powerful strat-
egy for carbon–carbon bond formation,17 although lithium amide
bases such as LDA (which are commonly used for enolisation of
a
13
14
Scheme 3. Reagents and conditions: (i) KHMDS, THF, ꢁ78 ꢂC, 1 h then CH3CHO,
ꢁ78 ꢂC, 1 h [a20% de (only two diastereoisomers were detected)].
carbonyl compounds) are also known to add to
a,b-unsaturated
esters in a conjugate fashion unless carcinogenic additives such as
HMPA are used.18,19 Initial studies therefore focused on preparing
dienolates of (E)-N-crotonoyl SuperQuat 620 via deprotonation with
the non-nucleophilic base KHMDS. Thus, 6 was stirred at ꢁ78 ꢂC
Subsequent efforts to promote the dienolate aldol reaction fo-
cused on transmetallation of the potassium dienolate to give the
O
O
O
O
O
OH
O
OH
Me
Dienolate
Double bond
isomerisation
aldol reaction
Me
R
R
O
N
O
N
O
N
O
H
R
6
7
10
Auxiliary
cleavage
Auxiliary
cleavage
O
O
NH
O
OH
R
O
OH
R
Double bond
isomerisation
R'O
R'O
11
Me
9
8
Figure 1. Potential route to b-substituted Baylis–Hillman products 9.

S.G. Davies et al. / Tetrahedron 65 (2009) 7837–7851
7839
less reactive zinc dienolate. Transmetallation of the potassium
dienolate of (E)-N-crotonoyl SuperQuat 6 with ZnCl2 followed by
addition of acetaldehyde gave good conversion (80%) to aldol
products 15–18, with no traces of side products 11, 12 or 14 being
detected. 1H NMR spectroscopic analysis of the crude reaction
mixture revealed that all four aldol products had been formed in
a ratio of 33:27:22:18 for 15:16:17:18, respectively. Chromato-
graphic purification allowed separation of all the diastereoisomers,
which were individually isolated in 14–26% yield, and in >98% de in
each case (Scheme 4).23 The relative configurations within aldol
products 15–18 were initially assigned by 1H NMR 3J coupling
constant analyses: N-acyl oxazolidinone derived syn- and anti-aldol
products have been shown to display indicative coupling constants
between the C(20)H and C(30)H protons.24 The accepted model for
the explanation of this finding postulates that hydrogen bonding
between the C(30)-hydroxyl group and the C(10)-carbonyl group
forms a chair-like conformation with the largest possible number of
substituents in equatorial positions. The coupling constants then
follow from the Karplus equation, with diagnostic 3J coupling
constants of 2–4 Hz for the syn-diastereoisomers and 8–10 Hz for
the anti-diastereoisomers. Furthermore, the relative anti-configu-
ration of 17 was established via X-ray crystallographic analysis,
with the (4S,20S,30S)-absolute configuration assigned relative to the
known (S)-configuration of the C(4)-stereogenic centre (Fig. 2).25
The configurations within the two remaining syn-aldol products 15
and 16 were subsequently assigned by comparison with an au-
thentic sample of 15 (vide infra).
These data suggest that employing a less reactive enolate sup-
presses the formation of the undesired side products 11, 12 and 14,
although the diastereoselectivity was poor in the case of the zinc
dienolate. The corresponding boron dienolate was therefore in-
vestigated. Formation of the boron dienolate may either be achieved
by transmetallation of thepotassium dienolateor by directformation
by treatment of (E)-N-crotonoyl oxazolidinone 6 with Bu2BOTf in the
presence of Et3N. Evans et al. have shown that direct boron enoli-
sation with Bu2BOTf is applicable to (E)-N-crotonoyl oxazolidinones
giving b,g
-unsaturated aldol products in high de.26 Application of
this protocol to (E)-N-crotonoyl oxazolidinone 6 via addition of
Bu2BOTf and Et3N at ꢁ78 ꢂC, followed by warming to 0 ꢂC for 30 min,
and re-cooling to ꢁ78 ꢂC with subsequent addition of aldehyde
(1.0 equiv) led to a complex mixture of products, indicating
that (E)-N-crotonoyl SuperQuat 6 behaves somewhat differently to
(E)-N-crotonoyl Evans oxazolidinones. To confirm that dienolate
formation occurs at ꢁ78 ꢂC, without the need to warm the solution
to 0 ꢂC, Bu2BOTf and Et3N were added to (E)-N-crotonoyl oxazoli-
dinone 6 at ꢁ78 ꢂC followed by the addition of satd aq NH4Cl after
30 min which gave 12 in quantitative yield. This modified dienolate
formation protocol was therefore applied to the aldol reaction with
acetaldehyde: Bu2BOTf and Et3N were added to 6 in CH2Cl2 at
ꢁ78 ꢂC; after 30 min acetaldehyde was added and the reaction
mixture was stirred at ꢁ78 ꢂC for 1 h before the addition of satd aq
NH4Cl to give syn-aldol product 15 in 98% conversion and >93% de.
Purification via flash column chromatography gave 15 as a single
diastereoisomer (>98% de) in 91% isolated yield (Scheme 5). The
relative configuration within syn-15, which displayed a diagnostic 3J
coupling constant of 4.0 Hz between the C(20)H and C(30)H protons
(indicative of a syn-configuration), was assigned by analogy to the
well established aldol reaction of dienolates derived from N-acyl
oxazolidinones, presumably proceeding via chair-like transition
state 19.26,27 Within this transition state the dipole–dipole in-
teractions within the imide are minimised, with the stereodirecting
isopropyl group blocking the Si face of the dienolate; the aldehyde
then presents its Si face towards the dienolate, with the sterically
more demanding methyl group occupying an equatorial position
within the transition state, giving rise to syn-aldol product 15.
O
OH
O
OH
SQ
Me SQ
Me
O
15, 26%, >98% de 16, 22%, >98% de
(J2'-3' = 4.0 Hz) (J2'-3' = 4.1 Hz)
(i)
SQ
Me 33:27:22:18
O
OH
O
OH
(15:16:17:18)
6
SQ
Me SQ
Me
17, 18%, >98% de 18, 14%, >98% de
(J2'-3' = 8.5 Hz) (J2'-3' = 9.8 Hz)
Scheme 4. Reagents and conditions: (i) KHMDS, THF, ꢁ78 ꢂC, 30 min then ZnCl2, Et2O,
30 min then CH3CHO, ꢁ78 ꢂC, 1 h.
O
O
O
O
(i)
O
N
Me
O
N
6
12, quant
(ii)
O
O
O
OH
Me
O
98% conv.
>93% de
O
O
N
N
Bu
B
H
Bu
O
H
Me
R
19
15, 91%, >98% de
Scheme 5. Reagents and conditions: (i) Bu2BOTf, Et3N, CH2Cl2, ꢁ78 ꢂC, 30 min then
satd aq NH4Cl; (ii) Bu2BOTf, Et3N, CH2Cl2, ꢁ78 ꢂC, 1 h then CH3CHO, ꢁ78 ꢂC, 1 h
[R ¼ CH]CH2].
The generality of this aldol protocol was next established by
reaction with a range of aldehydes: treatment of the boron dien-
Figure 2. Chem3D representation of the single crystal X-ray structure of 17 (some H
atoms have been omitted for clarity).
olate derived from (E)-N-crotonoyl SuperQuat
6
with

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S.G. Davies et al. / Tetrahedron 65 (2009) 7837–7851
propionaldehyde, isobutyraldehyde, pivalaldehyde, benzaldehyde
and phenylacetaldehyde was investigated. Extended reaction times
(2–4 h) were required for the reactions to proceed to good con-
version, with the increasing steric bulk having a marked effect on
both yield and diastereoselectivity of the reaction. syn-Aldol
products 20–24 were formed with moderate to good diastereo-
selectivity (52–98% de), with chromatographic purification giving
20–24 as single diastereoisomers (>98% de) in 40–95% isolated
yield (Scheme 6).28 Recrystallisation of the major diastereoisomers
arising from reaction with pivalaldehyde and benzaldehyde
allowed unambiguous assignment of the syn-relative configuration
of aldol products 22 and 23 by single crystal X-ray analysis, with the
absolute (4S,20S,30S)-configurations assigned from the known (S)-
configuration of the C(4)-stereogenic centre within the L-valine
derived SuperQuat auxiliary (Figs. 3 and 4).29 This stereochemical
outcome is consistent with the dienolate aldol reaction of sub-
strates 22 and 23 proceeding via a transition state analogous to 19,
and giving the expected syn-Evans aldol products. The configura-
tions within 20, 21, and 24 were thus assigned by analogy to those
of 22 and 23.
O
O
O
O
OH
Figure 4. Chem3D representation of the single crystal X-ray structure of 23 (some H
atoms have been omitted for clarity).
(i)
O
N
Me
O
N
R
25 in CH2Cl2, followed by the addition of acetaldehyde gave
a 39:61 mixture of
b,g-unsaturated N-acyl SuperQuat 12 and
6
20-24
syn-aldol product 15 in >98% de. Chromatographic purification
of this mixture gave 12 in 39% yield, and syn-15 in 61% yield and
>98% de (Scheme 7).
Conv. (%) Product de (%)a Yield (%)b J2'-3' (Hz)
92
88
53
95
95
86
76
52
98
92
86
88
40
95
95
3.7
4.0
4.4
9.0
3.2
20 R = Et
i
21 R = Pr
t
22 R = Bu
O
O
23 R = Ph
24 R = Bn
O
N
Me
Scheme 6. Reagents and conditions: (i) Bu2BOTf, Et3N, CH2Cl2, ꢁ78 ꢂC, 60 min then
RCHO, ꢁ78 ꢂC, 2–4 h [acrude; bisolated as single diastereoisomers (>98% de)].
O
O
B
Br
6
Transmetallation of the potassium dienolate of (E)-N-croto-
noyl SuperQuat 6 to the corresponding boron dienolate was
next investigated: treatment of the potassium dienolate with
B(OMe)3 followed by the addition of acetaldehyde gave a com-
plex mixture of products. However, treatment of the potassium
dienolate with a pre-made solution of B-bromocatechol borane
25
(i)
O
O
O
O
OH
O
N
O
N
Me
+
12, 39%
15, 61%, >98% de
Scheme 7. Reagents and conditions: (i) KHMDS, THF, ꢁ78 ꢂC, 30 min then 25, 30 min
then CH3CHO, ꢁ78 ꢂC, 1 h.
The generality of this highly diastereoselective trans-
metallation/boron enolisation protocol was next established by
application of these conditions to a range of aldehydes. Upon
treatment of the boron dienolate of (E)-N-crotonoyl SuperQuat
6 with propionaldehyde, isobutyraldehyde, benzaldehyde and
phenylacetaldehyde complete consumption of starting material
was observed with the major products being the desired syn-
aldol products 20, 21, 23 and 24 (>98% de in each case).30
Chromatographic purification gave syn-aldol products 20, 21,
23 and 24 in 57–78% isolated yield and in >98% de
(Scheme 8).31
With a range of syn-aldol products 15 and 20–24 (as single
diastereoisomers) in hand their conversion to the corresponding
a-vinyl-
b
-hydroxycarboxylic acid derivatives and
a
-ethylidene-
b-
hydroxyesters (
investigated.
b-substituted Baylis–Hillman products) was next
Figure 3. Chem3D representation of the single crystal X-ray structure of 22 (some H
atoms have been omitted for clarity).

S.G. Davies et al. / Tetrahedron 65 (2009) 7837–7851
7841
O
O
to the same cleavage conditions and cleanly gave carboxylic acids
37 and 38 (both in >98% de and >98% ee32) in 89 and 92% yield,
respectively (Scheme 11).
O
O
OH
(i)
Me
R
O
N
O
N
O
O
OTBDMS
(i)
O
OTBDMS
R
6
20, 21, 23, 24
Product de (%)a Yield (%)b J2' -3' (Hz)
O
N
R
HO
>98
>98
>98
66
57
78
64
3.7
4.0
9.0
3.2
20 R = Et
21 R = iPr
23 R = Ph
27, 28, 31, 32
33-36
Yield (%) de (%) ee (%)
24 R = Bn >98
27 R = Met
28 R = Et
31 R = Ph
32 R = Bn
33 R = Met
34 R = Et
35 R = Ph
36 R = Bn
73
85
92
90
>98
>98
>98
>98
>98
>98
>98
>98
Scheme 8. Reagents and conditions: (i) KHMDS, THF, ꢁ78 ꢂC, 30 min then 25, 30 min
then RCHO, ꢁ78 ꢂC, 1–4 h [acrude; bisolated as single diastereoisomers (>98% de)].
2.2. Synthesis of a-vinyl-b-hydroxycarboxylic acid derivatives
O
O
OH
Initial studies showed that treatment of 15 with lithium hy-
droperoxide (under the standard conditions for auxiliary cleav-
age)19 gave SuperQuat 11 in quantitative yield, and the desired
O
OH
(i)
O
N
R
HO
R
b
-hydroxy acid product 26, although 26 was found to be highly
water soluble (even at very low pH) and was isolated in only 42%
yield (in >98% de and >98% ee32) (Scheme 9).
21, 22
37, 38
Yield (%) de (%) ee (%)
O
O
O
OH
i
i
O
OH
Me
21 R = Pr
37 R = Pr
89
>98
>98
>98
>98
t
t
(i)
22 R = Bu
38 R = Bu 92
O
N
Me
O
NH
+
HO
Scheme 11. Reagents and conditions: (i) LiOH, H2O2, H2O, MeOH, 0 ꢂC to rt, 18 h.
Methanolysis of the syn-aldol products was also investigated as
it would afford synthetically more useful methyl esters directly and
11, quant
15
26, 42%, >98% de
>98% ee
potentially provide access to
b-methyl Baylis–Hillman products.
Scheme 9. Reagents and conditions: (i) LiOH, H2O2, H2O, MeOH, 0 ꢂC to rt, 18 h.
Thus, treatment of a solution of 15 in MeOH with BuLi at ꢁ78 ꢂC
gave, in addition to SuperQuat 11, an 87:13 mixture of 39 and 40
indicating that partial isomerisation of the double bond had oc-
curred under these conditions. Following chromatographic purifi-
cation of the mixture 39 was isolated in 87% yield (in >98% de and
>98% ee32), and 40 was isolated in 13% yield as a 92:8 [(E):(Z)]
mixture of geometric isomers (Scheme 12).
An alternative protocol employing O-silyl protection of the b-
hydroxy substituent was next investigated. Aldol products 15, 20,
23 and 24 were treated with TBDMSCl and imidazole in DMF to give
quantitative conversion to the desired O-TBDMS protected products
27, 28, 31 and 32, which were isolated in 40–98% yield; attempted
t
silylation of 21 and 22 (R¼iPr and Bu) failed to give the desired
products 29 and 30, even employing more forcing conditions
(TBDMSOTf and DMAP), and returned starting material in each case
presumably as a result of the steric bulk of the C(20)-alkyl sub-
stituent reducing the nucleophilicity of the alcohol (Scheme 10).
O
O
OH
O
N
Me
O
O
O
OH
O
OTBDMS
R
15
(i)
R
O
N
O
N
(i)
O
15, 20-24
27-32
Yield (%) de (%)
O
OH
Me
O
OH
Me
O
NH
+
+
MeO
MeO
Me
15 R = Me
20 R = Et
27 R = Me
28 R = Et
97
98
0
>98
>98
--
i
i
21 R = Pr
29 R = Pr
t
t
0
--
22 R = Bu
30 R = Bu
11, quant
39, 87%, >98% de
40, 13%,
92:8 [(E):(Z)]
>98% ee
40
96
>98
>98
23 R = Ph
24 R = Bn
31 R = Ph
32 R = Bn
Scheme 12. Reagents and conditions: (i) MeOH, BuLi, ꢁ78 ꢂC, 3 h.
Scheme 10. Reagents and conditions: (i) TBDMSCl, imidazole, DMF, rt, 12 h.
Further optimisation revealed that a reaction temperature of
ꢁ20 ꢂC proved advantageous for controlled methanolysis and this
protocol was successfully applied to syn-aldol products 15 and 20–
With O-silyl protected material 27, 28, 31 and 32 in hand,
cleavage to give the corresponding carboxylic acids was attempted.
Treatment of 27, 28, 31 and 32 with LiOOH in MeOH gave carboxylic
acids 33–36 in 73–92% yield (>98% de and >98% ee32 in each case).
24.
b,g-Unsaturated esters 39 and 41–44 were isolated in 79–91%
yield, and in >98% de and >98% ee32 in each case, although
Furthermore, the substrates with
a
-branched C(20)-substituents 21
45 could not be separated from its a,b-unsaturated isomer
and 22 (where O-silylation was not successful) were also subjected
(Scheme 13).

7842
S.G. Davies et al. / Tetrahedron 65 (2009) 7837–7851
O
material 49 (R¼Ph), the yield was greatly reduced as dehydration
O
OH
O
OH
competed with isomerisation (Scheme 15). The enantiopurity of a,b-
unsaturated compounds 40 and 46–50 was assessed by 1H NMR
analysis in the presence of chiral solvating agent Eu(hfc)3, and com-
(i) or (ii)
O
N
R
MeO
R
parison with authentic racemic samples. In each case, b-substituted
Baylis–Hillman products 40 and 46–50 were found to be >98% ee,
confirming that the stereochemical integrity of these substrates had
not been compromised during the deprotection protocol.
15, 20-24
39, 41-44
Yield (%) de (%) ee (%)
15 R = Me
20 R = Et
39 R = Me
41 R = Et
81
87
>98
>98
>98
>98
>98
--
>98
>98
>98
>98
>98
--
O
OH
O
OH
i
i
21 R = Pr
42 R = Pr
79
91
(i)
t
t
22 R = Bu
43 R = Bu
MeO
R
MeO
R
83
23 R = Ph
24 R = Bn
44 R = Ph
45 R = Bn
quanta
Me
40, 46-50
Scheme 13. Reagents and conditions: (i) MeOH, BuLi, ꢁ78 ꢂC, 3 h [a76:24 mixture of
39, 41-45
a,b- and b,g-unsaturated isomers].
Yield (%) (E):(Z) ee (%)
95
89
98
97
43
97b
92:8
92:8
92:8
91:9
94:6
92:8
>98
>98
>98
>98
>98
>98
39 R = Me
40 R = Me
46 R = Et
2.3. Synthesis of
Baylis–Hillman products)
a-ethylidene-b-hydroxyesters (b-substituted
41 R = Et
i
i
42 R = Pr
47 R = Pr
t
t
43 R = Bu
48 R = Bu
While there appear to be no reports concerning the direct iso-
merisation of -hydroxy- -unsaturated amides to their -un-
saturated derivatives, number of protocols exist for the
isomerisation of -branched- -unsaturated carbonyl compounds
44 R = Ph
49 R = Ph
50 R = Bn
45 R = Bn a
b
b
,g
a,b
a
Scheme 15. Reagents and conditions: (i) DBU, THF, ꢁ20 ꢂC, 48 h [a76:24 mixture of
a
b,g
a,b- and b,g
-unsaturated isomers; byield from 24 (two steps)].
by treatment with either Et3N or DBU.33,34 Thus, a solution of 15 in
THF was treated with Et3N and stirred for for 2 h, but returned only
starting material.22 Treatment of 15 with a number of different
bases including piperidine, DBU and DABCO was then attempted
with no reaction noted even upon extended reaction times (up to
24 h). Attempts to promote the isomerisation via heating under
more forcing conditions (KOtBu) also proved unsuccessful, resulting
in the formation of (E)-N-crotonoyl 6, presumably as a result of
a retro-aldol-type process under the basic conditions of the re-
action; similar reactivity was noted upon treatment with KOtBu at
rt (Scheme 14). Treatment of the O-TBDMS protected silyl ether 27
with either DBU or KOtBu at elevated temperatures was also un-
successful: in both cases no reaction was observed, with only
starting material returned. The use of acidic conditions was next
investigated, but treatment of a solution of 15 in CH2Cl2 or toluene
with acid (TFA, p-TsOH or CSA) was found to only result in the
return of staring material.
3. Conclusion
The aldol reaction of the boron dienolate derived from (E)-N-
crotonoyl C(4)-isopropyl SuperQuat (generated either directly
with Bu2BOTf or by transmetalation of the potassium enolate with
B-bromocatecholborane) with a range of aldehydes proceeds in
high yield and with excellent syn-diastereoselectivity (up to >98%
de). Cleavage of the resultant syn-aldol products from the auxiliary
gives
the double bond into conjugation provides a range of
-hydroxy-esters ( -substituted Baylis–Hillman products) in high
a
-vinyl-
b
-hydroxy-esters, and subsequent isomerisation of
a
-ethylidene-
b
b
diastereo- and enantiopurity (ꢀ91:9 [(E):(Z)] and >98% ee).
4. Experimental
4.1. General experimental
O
O
O
O
OH
Me
O
All reactions involving organometallic or other moisture-sensi-
tive reagents were carried out under a nitrogen or argon atmo-
sphere using standard vacuum line techniques and glassware that
was flame dried and cooled under nitrogen before use. Solvents
were dried according to the procedure outlined by Grubbs et al.35
Water was purified by a Millipore ElixÒ UV-10 system. All other
solvents were used as supplied (analytical or HPLC grade) without
prior purification. Organic layers were dried over MgSO4. Thin layer
chromatography was performed on aluminium plates coated with
60 F254 silica. Plates were visualised using UV light (254 nm), io-
dine, 1% aq KMnO4, or 10% ethanolic phosphomolybdic acid. Flash
column chromatography was performed on Kieselgel 60 silica.
Elemental analyses were recorded by the microanalysis service of
the Inorganic Chemistry Laboratory, University of Oxford, UK.
Melting points were recorded on a Gallenkamp Hot Stage apparatus
and are uncorrected. Optical rotations were recorded on a Perkin–
Elmer 241 polarimeter with a water-jacketed 10 cm cell. Specific
rotations are reported in 10ꢁ1 deg cm2 gꢁ1 and concentrations in
g/100 mL. IR spectra were recorded on a Bruker Tensor 27 FT-IR
spectrometer as either a thin film on NaCl plates (film) or a KBr disc
(i) or (ii)
Me
O
N
O
NH
+
O
N
15
11
6
(i). 44%; (ii). 18% (i). 56%; (ii). 82%
Scheme 14. Reagents and conditions: (i) KOtBu, THF, rt, 24 h; (ii) KOtBu, THF, reflux, 24 h.
Having previously shown that isomerisation of
methyl esters to -unsaturated methyl esters is possible under
b,g-unsaturated
a,b
basic conditions (vide supra), treatment of methyl ester 39 with DBU
at rt was investigated and found to isomerise the double bond into
conjugation at similar rate in THF, Et2O or CH2Cl2. After 1 h, 40 was
isolated in 88% yield as an inseparable 83:17 mixture of (E):(Z) iso-
mers. The major component was determined to be the (E)-isomer by
1H NMR NOE studies. While changing the solvent to Et2O, CH2Cl2 or
pentane had no effect on the (E):(Z) selectivity, lowering the tem-
perature to ꢁ20 ꢂC increased the (E):(Z) ratio to 92:8, with a con-
comitant increase in the reaction time to 48 h. Application of this
protocol to
b
,g
-unsaturated methyl esters 41–45 also proved suc-
(KBr), as stated. Selected characteristic peaks are reported in cmꢁ1
.
cessful and gave the desired
b
-substituted Baylis–Hillman products
NMR spectra were recorded on Bruker Avance spectrometers in the
deuterated solvent stated. The field was locked by external refer-
encing to the relevant deuteron resonance. Low-resolution mass
46–50 in excellent yield and high diastereoisomeric purity [ꢀ91:9
(E):(Z) ratio]. However, in the case of the benzaldehyde derived

S.G. Davies et al. / Tetrahedron 65 (2009) 7837–7851
7843
spectrawere recorded on either a VG MassLab 20-250 or a Micromass
4.7. General procedure 6 for double dond isomerisation
DBU (4.0 equiv) was added to a solution of the requisite
Platform 1 spectrometer. Accurate mass measurements were run on
either a Bruker MicroTOF internally calibrated with polyalanine, or
a Micromass GCT instrument fitted with a Scientific Glass In-
struments BPX5 column (15 mꢃ0.25 mm) using amyl acetate as
a lock mass.
a
-vinyl-
b-hydroxyester (1.0 equiv) in CH2Cl2 (2.0 M) and the resultant so-
lution was stirred at ꢁ20 ꢂC for 36 h. The reaction mixture was then
diluted with pentane and the organic layer was washed with satd
aq NH4Cl then dried, filtered and concentrated in vacuo.
4.2. General procedure 1 for dibutylborontriflate aldol
reaction
4.7.1. (4S,20E)-N(3)-But-2-enoyl-4-isopropyl-5,5-dimethyl-
oxazolidin-2-one 6
Bu2BOTf (1.3 equiv, 1.0 M in CH2Cl2) and Et3N (1.5 equiv) were
added to a solution of (E)-N-crotonoyl SuperQuat 6 (1.0 equiv) in
CH2Cl2 at ꢁ78 ꢂC and the resultant mixture was stirred at ꢁ78 ꢂC for
1 h. Freshly distilled aldehyde (1.5 equiv) was then added and the
reaction mixture was allowed to warm to rt and stirred for 1 h. Satd
aq NH4Cl (1 mL) solution was then added, the resultant mixture was
cooled to 0 ꢂC, and H2O2 (2 mL, 35% inwater) and MeOH (2 mL) were
added. The resultant mixture was allowed to warm to rt, stirred for
1 h, and then concentrated in vacuo. The residue was triturated with
40–60 ꢂC petrol, and the organic extracts were washed with satd aq
NaHCO3, then dried, filtered and concentrated in vacuo.
O
O
O
N
Me
BuLi (2.5 M in hexanes, 62 mL, 0.16 mol) was added dropwise
via syringe to a solution of SuperQuat 11 (20.0 g, 0.13 mol) in THF
(200 mL) at ꢁ78 ꢂC. The reaction mixture was stirred at ꢁ78 ꢂC for
10 min then trans-crotonoyl chloride (21.3 mL, 90%, 0.2 mol) was
added and the resultant mixture was allowed to warm to rt over
2 h. Satd aq NH4Cl (250 mL) was then added and the resultant
mixture was extracted with EtOAc (2ꢃ250 mL). The combined or-
ganic extracts were washed with satd aq NaHCO3 (300 mL), then
dried, filtered and concentrated in vacuo. The residue was recrys-
4.3. General procedure 2 for B-bromocatecholborane aldol
reaction
KHMDS (1.1 equiv, 0.5 M in toluene) was added to a solution of
(E)-N-crotonoyl SuperQuat 6 (1.0 equiv) in THF at ꢁ78 ꢂC and the
reaction mixture was stirred for 1 h at ꢁ78 ꢂC. A pre-made solution
of B-bromocatecholborane 25 (1.1 equiv) in THF (1.25 M) was then
added and the resultant mixture was stirred for 30 min before
freshly distilled aldehyde (1.5 equiv) was added. The reaction
mixture was then stirred at ꢁ78 ꢂC for 30 min before it was allowed
warm to rt and stirred for 1 h. Satd aq NH4Cl was then added and
the resultant mixture was partitioned between Et2O and brine. The
organic phase was then dried, filtered and concentrated in vacuo.
tallised from 40–60 ꢂC petrol/Et2O to give 6 as a white crystalline
23
solid (24.3 g, 85%);15b mp 69–70 ꢂC; {lit.15b mp 71–72 ꢂC}; [
a]
D
22
þ13.9 (c 0.85, CHCl3); {lit.15b
[
a
]
þ14.5 (c 1.0, CHCl3); dH (500 MHz,
D
CDCl3) 0.94 (3H, d, J 6.9, CH(CH3)A(CH3)B), 1.01 (3H, d, J 6.9,
CH(CH3)A(CH3)B), 1.37 (3H, s, C(CH3)A(CH3)B), 1.49 (3H, s,
C(CH3)A(CH3)B), 1.94 (3H, dd, J 6.9, 1.6, C(40)H3), 2.13 (1H, septd, J 6.9,
3.4, CH(CH3)2), 4.19 (1H, d, J 3.4, C(4)H), 7.13 (1H, qd, J 15.2, 6.9,
C(30)H), 7.30 (1H, qd, J 15.2, 1.6, C(20)H); dC (50 MHz, CDCl3) 16.9,
18.4, 21.2, 21.2 (C(CH3)2, CH(CH3)2), 28.7 (C(40)H3), 29.5 (CH(CH3)2),
66.3 (C(4)H), 82.8 (C(CH3)2), 122.1 (C(20)H), 146.8 (C(30)H), 153.8
(C(2)), 165.9 (C(10)); m/z (GC Tof CIþ) 226 ([MþH]þ, 37%), 158
([MꢁC4H3O]þ, 100).
4.4. General procedure 3 for O-silyl protection
TBDMSCl (1.5 equiv) and imidazole (2.0 equiv) were added to
a solution of the alcohol (1.0 equiv) in DMF (0.2 M) at rt and the
resultant solution was stirred at rt for 16 h. The reaction was
monitored by TLC and upon completion, the mixture was parti-
tioned between satd aq NH4Cl and pentane. The organic phase was
then dried, filtered and concentrated in vacuo.
4.7.2. (4S,20S,30R)-, (4S,20R,30S)-, (4S,20S,30S)- and (4S,20R,30R)-N(3)-
(20-Vinyl-30-hydroxybutanoyl)-4-isopropyl-5,5-dimethyl-oxazolidin-
2-one (4S,20S,30R)-15, (4S,20R,30S)-16, (4S,20S,30S)-17 and
(4S,20R,30R)-18
O
O
O
O
O
O
OH
OH
O
O
OH
4.5. General procedure 4 for lithium hydroperoxide auxiliary
cleavage
O
N
Me
Me
O
N
Me
Me
Satd aq LiOH in hydrogen peroxide (30% w/w) was added to a stirred
solution of the substrate (1.0 equiv) in methanol (2.0 M) at 0 ꢂC. The
resulting suspensionwas allowed to warm to rt and stirred for 18 h. The
mixture was then concentrated in vacuo and the residue was triturated
with Et2O. The combined organic extracts were acidified to pH 2 with
1.0 M aq HCl and extracted with CH2Cl2. The combined organic extracts
were then dried, filtered and concentrated in vacuo.
15
16
OH
O
N
O
N
17
18
4.6. General procedure 5 for lithium methoxide auxiliary
cleavage
A solution of 6 (3.00 g, 11.8 mmol) in THF (50 mL) was stirred at
ꢁ78 ꢂC for 5 min then KHMDS (23.6 mL, 13.0 mmol, 0.5 M in tolu-
ene) was added via syringe. The resultant mixture was stirred at
ꢁ78 ꢂC for 1 h then ZnCl2 (23.6 mL, 13.0 mmol, 0.5 M in THF) was
added and the reaction mixture was stirred for another 30 min
before freshly distilled acetaldehyde (1.00 mL, 17.7 mmol) was also
added. The resultant mixture was stirred for 30 min, allowed to
BuLi (1.0 equiv) was added to a solution of alcohol (1.0 equiv) in
MeOH (0.2 M) at ꢁ78 ꢂC over a period of 5 min. The resultant
mixture was allowed to warm to ꢁ20 ꢂC and was monitored by TLC
analysis. After completion, the mixture was partitioned between
satd aq NH4Cl and pentane, the organic phase was then dried, fil-
tered and concentrated in vacuo.

7844
S.G. Davies et al. / Tetrahedron 65 (2009) 7837–7851
warm to rt then stirred for a further 1 h. Satd aq NH4Cl (80 mL) was
then added and the resultant mixture was partitioned between
Et2O (300 mL) and brine (300 mL). The organic phase was sepa-
rated and then dried, filtered and concentrated in vacuo. The resi-
due was purified by flash column chromatography (eluent Et2O/
pentane, 3:7) to give (4S,20S,30R)-15 (823 mg, 26%, >98% de),
(4S,20R,30S)-16 (696 mg, 22%, >98% de) and (4S,20R,30R)-18 (443 mg,
14%, >98% de) as colourless oils, and (4S,20S,30S)-17 as a white
4.7.2.1. X-ray crystal structure determination for 17. Data were
collected using an Enraf-Nonius -CCD diffractometer with graph-
ite monochromated Mo K radiation using standard procedures at
190 K. The structure was solved by direct methods (SIR92); all non-
hydrogen atoms were refined with anisotropic thermal parameters.
Hydrogen atoms were added at idealised positions. The structure
was refined using CRYSTALS.36
k
a
X-ray crystal structure data for 17 [C14H23NO4]: M¼269.34, or-
crystalline solid (570 mg, 18%, >98% de).
thorhombic, space group P212121, a¼7.9067(2) Å, b¼12.5456(3) Å,
22
Data for (4S,20S,30R)-15. [
a
]
ꢁ43.5 (c 1.0, CHCl3); nmax (film)
c¼15.3428(3) Å, V¼1521.9(6) Å3, Z¼4,
m
¼0.085 mmꢁ1, colourless
D
1770 (C]O, exocyclic), 1702 (C]O, endocyclic), 1635 (C]C); dH
(500 MHz, CDCl3) 0.93 (3H, d, J 6.9, CH(CH3)A(CH3)B), 1.00 (3H, d, J
6.9, CH(CH3)A(CH3)B), 1.20 (3H, d, J 6.3, C(40)H3), 1.41 (3H, s,
C(CH3)A(CH3)B), 1.52 (3H, s, C(CH3)A(CH3)B), 2.13 (1H, septd, J 6.9,
3.2, CH(CH3)2), 3.06 (1H, s, OH), 4.13–4.19 (1H, m, C(30)H), 4.22 (1H,
d, J 3.2, C(4)H), 4.60 (1H, dd, J 9.1, 4.0, C(20)H), 5.40 (1H, app dd, J
10.1, 1.4, CH]CHAHB), 5.49 (1H, d, J 17.1, CH]CHAHB), 5.99 (1H, ddd,
J 17.1, 10.1, 9.1, CH]CH2); dC (50 MHz, CDCl3) 16.5, 19.6, 21.7, 28.6
(CH(CH3)2, C(CH3)2), 21.2 (C(40)H3), 29.7 (CH(CH3)2), 53.2 (C(20)H),
66.0 (C(4)H), 67.9 (C(30)H), 82.8 (C(CH3)2), 121.9 (CH]CH2), 131.9
(CH]CH2),153.4 (C(2)),175.1 (C(10)); m/z (GC Tof CIþ) 270 ([MþH]þ,
15%) 158 ([MꢁC6H7O2]þ, 100); HRMS (GC Tof CIþ) C14H24NOþ4
block, crystal dimensions¼0.4ꢃ0.4ꢃ0.4 mm3. A total of 3365
unique reflections were measured for 5<q<27 and 2930 reflections
were used in the refinement. The final parameters were wR2¼0.084
and R1¼0.036 [I>3.0
s(I)].
Crystallographic data (excluding structure factors) has been
deposited with the Cambridge Crystallographic Data Centre as
supplementary publication number CCDC 720350. Copies of the
data can be obtained, free of charge, on application to CCDC,
12 Union Road, Cambridge CB2 1EZ, UK [fax: þ44(0) 1223 336033
or e-mail: deposit@ccdc.cam.ac.uk].
4.7.3. (4S,20S,30R)-N(3)-(20-Vinyl-30-hydroxybutanoyl)-4-isopropyl-
5,5-dimethyl-oxazolidin-2-one 15
([MþH]þ) requires 270.1700; found 270.1698.
22
Data for (4S,20R,30S)-16. [
a
]
þ92.3 (c 1.5, CHCl3); nmax (film)
D
3516 (O–H), 1770 (C]O, exocyclic), 1694 (C]O, endocyclic), 1635
(C]C); dH (500 MHz, CDCl3) 0.98 (3H, d, J 6.9, CH(CH3)A(CH3)B), 1.06
(3H, d, J 6.9, CH(CH3)A(CH3)B), 1.23 (3H, d, J 6.4, C(40)H3), 1.35 (3H, s,
C(CH3)A(CH3)B), 1.52 (3H, s, C(CH3)A(CH3)B), 2.10 (1H, septd, J 6.9,
3.4, CH(CH3)2), 3.12 (1H, br s, OH), 4.13 (1H, d, J 3.4, C(4)H), 4.23 (1H,
dq, J 6.4, 4.1, C(30)H), 4.55 (1H, dd, J 9.1, 4.1, C(20)H), 5.30 (1H, d, J 17.2,
CH]CHAHB), 5.33 (1H, d, J 10.3, CH]CHAHB), 5.97 (1H, ddd, J 17.2,
10.3, 9.1, CH]CH2); dC (125 MHz, CDCl3) 16.8, 19.6, 21.5, 28.6
(C(CH3)2, CH(CH3)2), 21.2 (C(40)H3), 29.4 (CH(CH3)2), 53.0 (C(20)H),
66.6 (C(4)H), 68.3 (C(30)H), 83.1 (C(CH3)2), 121.0 (CH]CH2), 131.3
(CH]CH2),153.4 (C(2)),174.1 (C(10)); m/z (APCIþ) 270 ([MþH]þ, 4%),
252 ([MꢁOH]þ, 26), 158 ([SQþH]þ, 100); HRMS (CIþ) C14H24NOþ4
([MþH]þ) requires 270.1700; found 270.1700.
O
O
OH
O
N
Me
Method A. Following general procedure 1, 6 (500 mg, 2.22 mmol)
gave, after purification by flash column chromatography (eluent
Et22O2/pentane, 3:7), 15 as a colourless oil (539 mg, 91%, >98% de);
[a
]
ꢁ43 (c 1.0, CHCl3).
D
Method B. Following general procedure 2, 6 (500 mg, 2.22 mmol)
gave, after purification by flash column chromatography (eluent
Data for (4S,20S,30S)-17. Found: C, 62.4; H, 8.7; N, 5.2%;
Et22O2/pentane, 3:7), 15 as a colourless oil (385 mg, 65%, >98% de);
21
C14H25NO4 requires C, 62.4; H, 8.6; N, 5.2%; mp 99–100 ꢂC; [
a]
[a
]
ꢁ42 (c 1.0, CHCl3).
D
D
þ4.4 (c 1.0, CHCl3); nmax (KBr) 3466 (O–H), 1770 (C]O, exocyclic),
1680 (C]O, endocyclic),1633 (C]C); dH (400 MHz, CDCl3) 0.90 (3H,
d, J 6.8, CH(CH3)A(CH3)B), 0.98 (3H, d, J 6.8, CH(CH3)A(CH3)B), 1.23
(3H, d, J 6.6, C(40)H3), 1.34 (3H, s, C(CH3)A(CH3)B), 1.49 (3H, s,
C(CH3)A(CH3)B), 2.10 (1H, septd, J 6.8, 3.2, CH(CH3)2), 2.44 (1H, app
d, J 6.2, OH), 4.08 (1H, dq, J 8.5, 6.6, C(30)H), 4.20 (1H, d, J 3.2, C(4)H),
4.54 (1H, dd, J 9.7, 8.5, C(20)H), 5.24 (1H, d, J 9.8, CH]CHAHB), 5.37
(1H, d, J 17.3, CH]CHAHB), 5.89 (1H, app dd, J 17.3, 9.7, CH]CH2); dC
(100 MHz, CDCl3) 16.7, 20.9, 21.7, 28.6 (CH(CH3)2, C(CH3)2), 21.2
(C(40)H3), 29.8 (CH(CH3)2), 55.4 (C(20)H), 66.0 (C(4)H), 69.5 (C(30)H),
82.8 (C(CH3)2), 119.8 (CH]CH2), 133.7 (CH]CH2), 153.4 (C(2)), 174.2
(C(10)); m/z (GC Tof CIþ) 270 ([MþH]þ, 5%), 226 ([MꢁC2H3O]þ, 100),
158 ([SQþH]þ, 73).
4.7.4. (4S,20S,30R)- and (4S,20R,30S)-N(3)-(20-Vinyl-30-hydroxy-
pentanoyl)-4-isopropyl-5,5-dimethyl-oxazolidin-2-one (4S,20S,30R)-
20 and (4S,20R,30S)-51
O
O
O
OH
O
OH
O
N
Et
O
N
Et
20
51
Data for (4S,20R,30R)-18. nmax (KBr) 3466 (O–H), 1765 (C]O,
exocyclic), 1685 (C]O, endocyclic), 1635 (C]C); dH (400 MHz,
CDCl3) 0.95 (3H, d, J 6.9, CH(CH3)A(CH3)B), 1.03 (3H, d, J 6.9,
Method A. Following general procedure 1, 6 (3.00 g, 13.2 mmol)
gave, after purification by flash column chromatography (eluent
Et2O/pentane, 4:6), (4S,20S,30R)-20 (3.20 g, 86%, >98% de) and
CH(CH3)A(CH3)B), 1.25 (3H, d,
J
6.8, C(40)H3), 1.38 (3H, s,
(4S,20R,30S)-51 (342 mg, 9%, >98% de) as colourless oils.
24
C(CH3)A(CH3)B),1.51 (3H, s, C(CH3)A(CH3)B),1.97 (1H, app s, OH), 2.14
(1H, septd, J 6.9, 3.2, CH(CH3)2), 3.73 (1H, dq, J 9.8, 6.8, C(30)H), 3.81
(1H, dd, J 9.8, 9.3, C(20)H), 4.15 (1H, d, J 3.2, C(4)H), 5.24 (1H, d, J 10.1,
CH]CHAHB), 5.29 (1H, d, J 17.0, CH]CHAHB), 6.00 (1H, ddd, J 17.0,
10.1, 9.3, CH]CH2); dC (100 MHz, CDCl3) 20.1, 21.0, 21.6, 29.3
(CH(CH3)2, C(CH3)2), 22.9 (C(40)H3), 30.3 (CH(CH3)2), 50.0 (C(20)H),
65.6 (C(4)H), 69.7 (C(30)H), 85.5 (C(CH3)2), 134.2 (CH]CH2), 146.8
(CH]CH2), 153.2 (C(2)), 174.5 (C(10)); m/z (APCIþ) 270 ([MþH]þ,
10%), 252 ([MꢁOH]þ, 32), 158 ([SQþH]þ, 100); HRMS (CIþ)
C14H24NOþ4 ([MþH]þ) requires 270.1700; found 270.1703.
Data for (4S,20S,30R)-20. [
a]
ꢁ44 (c 1.0, CHCl3); nmax (film) 3518
D
(O–H), 1775 (C]O, exocyclic), 1692 (C]O, endocyclic), 1635 (C]C);
dH (400 MHz, CDCl3) 0.92 (3H, d, J 6.9, CH(CH3)A(CH3)B), 0.97 (3H, d,
J 7.6, C(50)H3), 0.99 (3H, d, J 6.9, CH(CH3)A(CH3)B), 1.40 (3H, s,
C(CH3)A(CH3)B),1.43–1.59 (2H, m, C(40)H2),1.51 (3H, s, C(CH3)A(CH3)B),
2.13 (1H, septd, J 6.9, 3.1, CH(CH3)2), 3.11 (1H, br s, OH), 3.83–3.89 (1H,
m, C(30)H), 4.21 (1H, d, J 3.1, C(4)H), 4.66 (1H, dd, J 9.1, 3.7, C(20)H), 5.38
(1H, dd, J 10.2, 1.4, CH]CHAHB), 5.48 (1H, dd, J 17.3, 1.4, CH]CHAHB),
5.98 (1H, ddd, J 17.3, 10.2, 9.1, CH]CH2); dC (100 MHz, CDCl3) 10.1
(C(50)H3),16.6, 21.3, 21.5, 28.8 (C(CH3)2, CH(CH3)2), 26.9(C(40)H2), 29.8

S.G. Davies et al. / Tetrahedron 65 (2009) 7837–7851
7845
(CH(CH3)2), 51.6 (C(20)H), 66.0 (C(4)H), 73.0 (C(30)H), 82.7 (C(CH3)2),
121.6 (CH]CH2), 131.6 (CH]CH2), 153.0 (C(2)), 175.0 (C(10)); m/z
(APCIþ) 284 ([MþH]þ, 5%), 266 ([MꢁOH]þ, 20), 158 ([SQþH]þ,
100); HRMS (CIþ) C15H26NO4þ ([MþH]þ) requires 284.1856; found
284.1856.
16.9, 19.9, 21.2, 21.6, 28.6 (C(CH3)2, C(4)CH(CH3)2, C(40)H(CH3)2),
29.6, 30.4 (C(4)CH(CH3)2, C(40)H), 50.9 (C(20)H), 66.9 (C(4)H), 77.9
(C(30)H), 83.1 (C(CH3)2), 119.0 (CH]CH2), 133.9 (CH]CH2), 153.9
(C(2)), 174.4 (C(10)); m/z (APCIþ) 298 ([MþH]þ, 10%), 280 ([MꢁOH]þ,
34), 158 ([SQþH]þ, 100).
Data for (4S,20R,30S)-51. nmax (film) 3515 (O–H), 1775 (C]O,
exocyclic), 1693 (C]O, endocyclic), 1635 (C]C); dH (400 MHz,
CDCl3) 0.98 (3H, d, J 7.0, CH(CH3)A(CH3)B), 1.00 (3H, t, J 7.4, C(50)H3),
1.05 (3H, d, J 7.0, CH(CH3)A(CH3)B), 1.34 (3H, s, C(CH3)A(CH3)B),
1.43–1.59 (2H, m, C(40)H2), 1.51 (3H, s, C(CH3)A(CH3)B), 2.16 (1H,
septd, J 7.0, 3.3, CH(CH3)2), 3.05 (1H, d, J 2.7, OH), 3.92–3.97 (1H, m,
C(30)H), 4.13 (1H, d, J 3.3, C(4)H), 4.63 (1H, dd, J 9.3, 3.6, C(20)H),
5.30 (1H, d, J 17.2, CH]CHAHB), 5.32 (1H, d, J 10.2, CH]CHAHB),
5.97 (1H, ddd, J 17.2, 10.2, 9.3, CH]CH2); dC (100 MHz, CDCl3) 10.0
(C(50)H3), 17.0, 21.3, 21.5, 21.5 (C(CH3)2, CH(CH3)2), 27.0 (C(40)H2),
29.5 (CH(CH3)2), 51.6 (C(20)H), 66.7 (C(4)H), 73.4 (C(30)H), 83.1
(C(CH3)2), 121.1 (CH]CH2), 131.2 (CH]CH2), 153.3 (C(2)), 174.6
(C(10)); m/z (APCIþ) 284 ([MþH]þ, 7%), 266 ([MꢁOH]þ, 23), 158
([SQþH]þ, 100); HRMS (CIþ) C15H26NOþ4 ([MþH]þ) requires
284.1856; found 284.1858.
Method B. Following general procedure 2, 6 (500 mg, 2.22 mmol)
gave, after purification by flash column chromatography (eluent
Et2O/pentane, 3:7), 21 as a white solid (372 mg, 57%, >98% de); mp
26
46–47 ꢂC; [
a
]
ꢁ54.8 (c 1.0, CHCl3).
D
4.7.5.1. X-ray crystal structure determination for 52. Data were
collected using an Enraf-Nonius -CCD diffractometer with graph-
ite monochromated Mo K radiation using standard procedures at
k
a
190 K. The structure was solved by direct methods (SIR92); all non-
hydrogen atoms were refined with anisotropic thermal parameters.
Hydrogen atoms were added at idealised positions. The structure
was refined using CRYSTALS.36
X-ray crystal structure data for 52 [C16H27NO4]: M¼297.39, or-
thorhombic, space group P212121, a¼7.9367(1) Å, b¼11.1016(2) Å,
c¼19.1260(5) Å, V¼1685.2(12) Å3, Z¼4,
m
¼0.083 mmꢁ1, colourless
Method B. Following general procedure 2, 6 (500 mg, 1.95 mmol)
plate, crystal dimensions¼0.2ꢃ0.2ꢃ0.2 mm3.
A total of 2205
gave, after purification by flash column chromatography (eluent
unique reflections were measured for 5<q<27 and 1936 reflections
24
Et2O/pentane, 4:6), 20 as colourless oil (348 g, 66%, >98% de); [
ꢁ44 (c 1.0, CHCl3).
a]
were used in the refinement. The final parameters were wR2¼0.025
D
and R1¼0.031 [I>3.0
s(I)].
Crystallographic data (excluding structure factors) has been
deposited with the Cambridge Crystallographic Data Centre as
supplementary publication number CCDC 720191. Copies of the
data can be obtained, free of charge, on application to CCDC,
12 Union Road, Cambridge CB2 1EZ, UK [fax: þ44(0) 1223 336033
or e-mail: deposit@ccdc.cam.ac.uk].
4.7.5. (4S,20S,30R)- and (4S,20R,30S)-N(3)-(20-Vinyl-30-hydroxy-40-
methylpentanoyl)-4-isopropyl-5,5-dimethyl-oxazolidin-2-one
(4S,20S,30R)-21 and (4S,20R,30S)-52
O
O
O
OH
iPr
O
OH
iPr
O
N
O
N
4.7.6. (4S,20R,30S)-N(3)-(20-Vinyl-30-hydroxy-40,40-dimethyl-
pentanoyl)-4-isopropyl-5,5-dimethyl-oxazolidin-2-one 22
21
52
O
O
OH
tBu
Method A. Following general procedure 1, 6 (500 mg, 2.22 mmol)
gave, after purification by flash column chromatography (eluent
Et2O/pentane, 3:7), (4S,20S,30R)-21 (575 mg, 88%, >98% de) and
(4S,20R,30S)-52 (31 mg, 5%, >98% de) as white crystalline solids.
O
N
Data for (4S,20S,30R)-21. Found: C, 64.6; H, 9.4; N, 4.8%; C16H27NO4
26
requires C, 64.6, H, 9.15, N, 4.7%; mp 46–47 ꢂC; [
a
]
ꢁ53.2 (c 1.0,
Following general procedure 1, 6 (500 mg, 2.22 mmol) gave, after
purification by flash column chromatography (eluent Et2O/pen-
tane, 3:7) 22 as a white crystalline solid (274 mg, 40%, >98% de);
D
CHCl3); nmax (KBr disc) 3510 (O–H), 1762 (C]O, endocyclic), 1686
(C]O, exocyclic),1631 (C]C); dH (400 MHz, CDCl3) 0.90 (6H, app t, J
6.7, C(4)H(CH3)2), 0.96 (6H, app d, J 7.0, C(40)H(CH3)2), 1.37 (3H, s,
C(CH3)A(CH3)B),1.49 (3H, s, C(CH3)A(CH3)B),1.68 (1H, app octet, J 6.7,
C(4)CH(CH3)2), 2.10 (1H, septd, J 7.0, 3.1, C(40)H), 3.14 (1H, d, J 2.3, OH),
3.58–3.62 (1H, m, C(30)H), 4.18 (1H, d, J 3.1, C(4)H), 4.82 (1H, dd, J 9.1,
4.0, C(20)H), 5.35 (1H, dd, J 10.2,1.4, CH]CHAHB), 5.48 (1H, dd, J 17.3,
1.4, CH]CHAHB), 5.97 (1H, ddd, J 17.3, 10.2, 9.1, CH]CH2); dC
(100 MHz, CDCl3) 14.0, 16.6, 19.0, 21.0, 21.3, 28.7, (C(CH3)2,
C(4)CH(CH3)2, C(40)H(CH3)2), 30.0, 30.9 (C(4)CH(CH3)2, C(40)H), 49.6
(C(20)H), 65.9 (C(4)H), 76.3 (C(30)H), 82.7 (C(CH3)2),121.3 (CH]CH2),
131.9 (CH]CH2), 152.9 (C(2)), 175.1 (C(10)); m/z (GC Tof CIþ) 298
([MþH]þ, 11%), 280 ([MꢁOH]þ, 76).
Found: C, 65.6; H, 9.4; N, 4.55%; C17H29NO4 requires C, 65.6, H, 9.4,
27
N, 4.5%; mp 64–66 ꢂC; [
a
]
ꢁ75.0 (c 1.0, CHCl3); nmax (film) 3523
D
(O–H), 1774 (C]O, exocyclic), 1693 (C]O, endocyclic), 1632 (C]C);
dH (400 MHz, CDCl3) 0.92 (3H, d, J 6.9, CH(CH3)A(CH3)B), 0.95 (9H, s,
C(CH3)3), 0.97 (3H, d,
J 6.9, CH(CH3)A(CH3)B), 1.39 (3H, s,
C(CH3)A(CH3)B), 1.51 (3H, s, C(CH3)A(CH3)B), 2.12 (1H, septd, J 6.9,
3.0, CH(CH3)2), 2.82 (1H, d, J 3.2, OH), 3.73 (1H, dd, J 4.4, 3.2, C(30)H),
4.21 (1H, d, J 3.0, C(4)H), 5.07 (1H, dd, J 9.4, 4.4, C(20)H), 5.34 (1H, d, J
9.4, CH]CHAHB), 5.54 (1H, d, J 17.2, CH]CHAHB), 6.04 (1H, app dt,
J, 9.4, 17.2, CH]CH2); dC (100 MHz, CDCl3) 16.5, 21.3, 21.4, 28.8
(C(CH3)2, CH(CH3)2), 26.5 (C(CH3)3), 30.0 (CH(CH3)2), 35.6 (C(CH3)3),
48.5 (C(20)H), 65.8 (C(4)H), 77.7 (C(30)H), 82.5 (C(CH3)2), 120.8
(CH]CH2), 133.7 (CH]CH2), 153.0 (C(2)), 175.2 (C(10)); m/z (APCIþ)
312 ([MþH]þ, 3%), 158 ([SQþH]þ, 100).
Data for (4S,20R,30S)-52. Found: C, 64.6; H, 9.15; N, 4.7%;
22
C16H27NO4 requires C, 64.6, H, 9.15, N, 4.7%; mp 102–103 ꢂC; [
a]
D
þ115 (c 1.0, CHCl3); nmax (KBr disc) 3579 (O–H), 1770 (C]O, endo-
cyclic), 1686 (C]O, exocyclic), 1646 (C]C); dH (400 MHz, CDCl3)
0.94–1.00 (9H, m, C(4)CH(CH3)A, C(40)H(CH3)2), 1.04 (3H, d, J
6.9, C(4)CH(CH3)B), 1.32 (3H, s, C(CH3)A(CH3)B), 1.50 (3H, s,
CH(CH3)A(CH3)B), 1.80 (1H, septd, J 7.3, 4.0, C(40)H), 2.14 (1H, septd, J
6.9, 3.2, C(4)CH(CH3)2), 2.75 (1H, d, J 2.3, OH), 3.68 (1H, td, J 8.6, 4.0,
C(30)H), 4.11 (1H, d, J 3.2, C(4)H), 4.75 (1H, app t, J 8.6, C(20)H), 5.18
(1H, dd, J 9.9, 1.1, CH]CHAHB), 5.23 (1H, dd, J 17.2, 1.1, CH]CHAHB),
5.89 (1H, ddd, J 17.2, 9.9, 8.6, CH]CH2); dC (100 MHz, CDCl3) 15.3,
4.7.6.1. X-ray crystal structure determination for 22. Data were
collected using an Enraf-Nonius
ite monochromated Mo K radiation using standard procedures at
190 K. The structure was solved by direct methods (SIR92); all non-
hydrogen atoms were refined with anisotropic thermal parameters.
Hydrogen atoms were added at idealised positions. The structure
was refined using CRYSTALS.36
k-CCD diffractometer with graph-
a

7846
S.G. Davies et al. / Tetrahedron 65 (2009) 7837–7851
X-ray crystal structure data for 22 [C34H58N2O8]: M¼622.84, or-
12 Union Road, Cambridge CB2 1EZ, UK [fax: þ44(0) 1223 336033
thorhombic, space group P212121, a¼10.4670(1) Å, b¼11.0940(1) Å,
or e-mail: deposit@ccdc.cam.ac.uk].
c¼31.2650(4) Å, V¼3630.5(12) Å3, Z¼4,
m
¼0.080 mmꢁ1, colourless
plate, crystal dimensions¼0.3ꢃ0.4ꢃ0.5 mm3. A total of 4380 unique
4.7.8. (4S,20R,30S)-N(3)-(20-Vinyl-30-hydroxy-40-phenylbutanoyl)-
4-isopropyl-5,5-dimethyl-oxazolidin-2-one 24
reflections were measured for 5<q<27 and 3352 reflections were
used in the refinement. The final parameters were wR2¼0.033 and
O
O
OH
R1¼0.030 [I>3.0
s
(I)].
Crystallographic data (excluding structure factors) has been
deposited with the Cambridge Crystallographic Data Centre as
supplementary publication number CCDC 720190. Copies of the
data can be obtained, free of charge, on application to CCDC,
12 Union Road, Cambridge CB2 1EZ, UK [fax: þ44(0) 1223 336033
or e-mail: deposit@ccdc.cam.ac.uk].
O
N
Bn
Method A. Following general procedure 1, 6 (3.00 g, 13.2 mmol)
gave, after purification by flash column chromatography (eluent
Et22O4/pentane, 1:1), 24 as a colourless oil (4.24 g, 95%, >98% de);
4.7.7. (4S,20R,30S)-N(3)-(20-Vinyl-30-hydroxy-30-phenyl-
propanoyl)-4-isopropyl-5,5-dimethyl-oxazolidin-2-one 23
[a
]
ꢁ21.6 (c 1.0, CHCl3); nmax (film) 3520 (O–H), 1770 (C]O,
D
exocyclic), 1694 (C]O, endocyclic), 1633 (C]C); dH (400 MHz,
CDCl3) 0.92 (3H, d, J 6.8, CH(CH3)A(CH3)B), 1.00 (3H, d, J 6.8,
CH(CH3)A(CH3)B), 1.39 (3H, s, C(CH3)A(CH3)B), 1.52 (3H, s,
C(CH3)A(CH3)B), 1.70–1.73 (1H, m, C(40)HA), 1.83–1.87 (1H, m,
C(40)HB), 2.13 (1H, septd, J 6.8, 3.0, CH(CH3)2), 3.30 (1H, s, OH), 3.97–
4.01 (1H, m, C(30)H), 4.21 (1H, d, J 3.0, C(4)H), 4.65 (1H, dd, J 8.9, 3.2,
C(20)H), 5.40 (1H, dd, J 10.3, 1.4, CH]CHAHB), 5.50 (1H, dd, J 17.3, 1.4,
CH]CHAHB), 6.00 (1H, ddd, J 17.3, 10.3, 8.9, CH]CH2), 7.23–7.35
(5H, m, Ph); dC (50 MHz, CDCl3) 16.7, 21.3, 21.5, 28.8 (C(CH3)2,
CH(CH3)2), 29.9 (CH(CH3)2), 35.6 (C(40)H2), 52.0 (C(20)H), 66.0
(C(4)H), 70.7 (C(30)H), 82.8 (C(CH3)2), 121.8 (CH]CH2), 125.8 (p-Ph),
128.3, 128.5 (o,m-Ph), 131.4 (i-Ph), 141.8 (CH]CH2), 153.0 (C(2)),
175.0 (C(10)); m/z (ESIþ) 382 ([MþNa]þ, 100%); HRMS (ESIþ)
C20H27NNaOþ4 ([MþNa]þ) requires 368.1832; found 368.1843.
Method B. Following general procedure 2, 6 (500 mg, 2.22 mmol)
gave, after purification by flash column chromatography (eluent
Et22O4/pentane, 1:1), 24 as a colourless oil (487 mg, 64%, >98% de);
O
O
OH
O
N
Ph
Method A. Following general procedure 1, 6 (3.00 g, 13.2 mmol)
gave, after purification by flash column chromatography (eluent
Et2O/pentane, 1:1), 23 as a white crystalline solid (4.14 g, 95%,
>98% de); Found: C, 68.9; H, 7.6; N, 4.2%; C19H25NO4 requires C,
68.9, H, 7.6, N, 4.2%; mp 99–101 ꢂC; [
27
a
]
ꢁ41 (c 1.0, CHCl3); nmax
D
(film) 3487 (O–H), 1779 (C]O, exocyclic), 1667 (C]O, endocyclic),
1639 (C]C); dH (400 MHz, CDCl3) 0.86 (3H, s, C(CH3)A(CH3)B), 0.87
(3H, d, J 7.0, CH(CH3)A(CH3)B), 0.96 (3H, d, J 7.0, CH(CH3)A(CH3)B),
1.41 (3H, s, C(CH3)A(CH3)B), 2.05 (1H, dsept, J 7.0, 3.4, CH(CH3)2),
2.78 (1H, d, J 2.3, OH), 3.94 (1H, d, J 3.4, C(4)H), 5.01 (1H, d, J 7.5,
2.3, C(30)H), 5.09 (1H, dd, J 9.0, 7.5, C(20)H), 5.40 (1H, dd, J 10.0,
CH]CHAHB), 5.51 (1H, dd, J 17.4, CH]CHAHB), 6.03 (1H, ddd, J 17.4,
10.0, 9.0, CH]CH2), 7.24–7.40 (5H, m, Ph); dC (100 MHz, CDCl3)
16.7, 21.2, 21.4, 27.8 (C(CH3)2, CH(CH3)2), 29.6 (CH(CH3)2), 55.1
(C(20)H), 65.9 (C(4)H), 74.5 (C(30)H), 82.6 (C(CH3)2), 121.9
(CH]CH2), 127.1 (p-Ph), 128.0, 128.4 (o,m-Ph), 133.1 (i-Ph), 140.7
(CH]CH2), 152.9 (C(2)), 172.9 (C(10)); m/z (APCIþ) 331 ([M]þ, 3%);
HRMS (CIþ) C19H25NNaOþ4 ([MþNa]þ) requires 354.1676; found
354.1681.
[a
]
ꢁ22 (c 1.0, CHCl3).
D
4.7.9. (2S,3R)-2-Vinyl-3-hydroxybutanoic acid 26
O
OH
HO
Me
Following general procedure 4, 15 (200 mg, 0.52 mmol) gave,
after purification by flash column chromatography (eluent CHCl3/
MeOH, 1:10), 26 as a colourless oil (39 mg, 42%, >98% de, >98%
Method B. Following general procedure 2, 6 (500 mg, 2.22 mmol)
gave, after purification by flash column chromatography (eluent
Et2O/pentane, 1:1), 23 as a white crystalline solid (571 mg, 78%,
24
ee);37
[a
]
ꢁ2.2 (c 0.2, MeOH); dH (400 MHz, CDCl3) 1.23 (3H, d, J
27
>98% de); mp 99–101 ꢂC; [
a
]
ꢁ41 (c 1.0, CHCl3).
D
D
6.4, C(4)H3), 3.07 (1H, dd, J 9.2, 4.5, C(2)H), 4.14–4.19 (1H, m, C(3)H),
5.30 (1H, d, J 17.2, CH]CHAHB), 5.37 (1H, d, J 9.9, CH]CHAHB), 5.95
(1H, app dt, J 17.2, 9.9, CH]CH2); dC (100 MHz, CDCl3) 19.9 (C(4)H3),
56.7 (C(2)H), 67.6 (C(3)H), 121.0 (CH]CH2), 131.1 (CH]CH2), 177.4
(C(1)); m/z (ESIꢁ) 129 ([MꢁH]ꢁ, 100%); HRMS (ESIꢁ) C6H9O3ꢁ
([MꢁH]ꢁ) requires 129.0557; found 129.0554.
4.7.7.1. X-ray crystal structure determination for 23. Data were
collected using an Enraf-Nonius -CCD diffractometer with graph-
ite monochromated Mo K radiation using standard procedures at
k
a
190 K. The structure was solved by direct methods (SIR92); all non-
hydrogen atoms were refined with anisotropic thermal parameters.
Hydrogen atoms were added at idealised positions. The structure
was refined using CRYSTALS.36
4.7.10. (4S,20R,30S)-N(3)-[20-Vinyl-30-(tert-butyldimethylsilyloxy)-
butanoyl]-4-iso-propyl-5,5-dimethyl-oxazolidin-2-one 27
X-ray crystal structure data for 23 [C19H25NO4]: M¼331.41,
tetragonal, space group P41212, a¼8.8433(1) Å, b¼8.8433(1) Å,
O
OTBDMS
Me
O
c¼46.7682(4) Å, V¼3657.46(7) Å3, Z¼8,
m
¼0.084 mmꢁ1, colourless
plate, crystal dimensions¼0.2ꢃ0.2ꢃ0.2 mm3.
A total of 2528
O
N
unique reflections were measured for 5<q<27 and 1796 reflections
were used in the refinement. The final parameters were wR2¼0.034
and R1¼0.030 [I>3.0
s
(I)].
Crystallographic data (excluding structure factors) has been
deposited with the Cambridge Crystallographic Data Centre as
supplementary publication number CCDC 720193. Copies of the
data can be obtained, free of charge, on application to CCDC,
Following general procedure 3, 15 (2.00 g, 7.42 mmol) gave 27 as
23
a pale yellow oil (2.76 g, 97%, >98% de); [
a
]
ꢁ3.5 (c 1.0, CHCl3);
D
nmax (film) 1778 (C]O, exocyclic), 1694 (C]O, endocyclic), 1638

S.G. Davies et al. / Tetrahedron 65 (2009) 7837–7851
7847
(C]C); dH (400 MHz, CDCl3) 0.03 (3H, s, Si(CH3)A), 0.05 (3H, s,
Si(CH3)B), 0.85 (9H, s, C(CH3)3), 0.92 (3H, d, J 7.0, CH(CH3)A(CH3)B),
1.00 (3H, d, J 7.0, CH(CH3)A(CH3)B), 1.18 (3H, d, J 6.5, C(40)H3), 1.34
(3H, s, C(CH3)A(CH3)B), 1.50 (3H, s, C(CH3)A(CH3)B), 2.13 (1H, septd, J
7.0, 3.2, CH(CH3)2), 4.13 (1H, app quintet, J 6.5, C(30)H), 4.17 (1H, d, J
3.2, C(4)H), 4.65 (1H, dd, J 8.8, 6.5, C(20)H), 5.23 (1H, dd, J 10.2, 1.4,
CH]CHAHB), 5.31 (1H, app d, J 17.2, CH]CHAHB), 5.94 (1H, ddd, J
17.2, 10.2, 8.8, CH]CH2); dC (100 MHz, CDCl3) ꢁ4.7, ꢁ4.5 (Si(CH3)2),
16.8, 21.3, 21.4, 28.7 (C(CH3)2, CH(CH3)2), 21.8 (C(40)H3), 25.8
(C(CH3)3), 29.7 (CH(CH3)2), 55.1 (C(20)H), 66.2 (C(4)H), 70.1 (C(30)H),
82.4 (C(CH3)2), 119.2 (CH]CH2), 134.8 (CH]CH2), 153.1 (C(2)), 173.1
(C(10)); m/z (GC Tof CIþ) 384 ([MþH]þ, 32%), 252 ([MꢁC6H15OSi]þ,
34), 158 ([SQþH]þ, 85); HRMS (GC Tof CIþ) C20H38NO4Siþ ([MþH]þ)
requires 384.2565; found 384.2579.
142.7 (CH]CH2), 152.8 (C(2)), 172.4 (C(10)); m/z (ESIþ) 446
([MþH]þ, 100%); HRMS (ESIþ) C25H39NNaO4Siþ ([MþNa]þ) requires
468.2541; found 468.2563.
4.7.13. (4S,20R,30S)-N(3)-[20-Vinyl-30-(tert-butyldimethylsilyloxy)-
40-phenylbutanoyl]-4-isopropyl-5,5-dimethyl-oxazolidin-2-one 32
O
OTBDMS
Bn
O
O
N
Following general procedure 3, 24 (200 mg, 0.56 mmol) gave 32
24
4.7.11. (4S,20R,30S)-N(3)-[20-Vinyl-30-(tert-butyldimethylsilyloxy)-
pentanoyl]-4-isopropyl-5,5-dimethyl-oxazolidin-2-one 28
as a colourless wax (253 mg, 96%, >98% de); [
a]
ꢁ20.0 (c 1.0,
D
CHCl3); nmax (film) 1770 (C]O, exocyclic), 1694 (C]O, endocyclic),
1635 (C]C); dH (400 MHz, CDCl3) 0.06 (3H, s, Si(CH3)A), 0.08 (3H, s,
Si(CH3)B), 0.91 (9H, s, C(CH3)3), 0.93 (3H, d, J 6.9, CH(CH3)A(CH3)B),
1.01 (3H, d, J 6.9, CH(CH3)A(CH3)B), 1.36 (3H, s, C(CH3)A(CH3)B), 1.51
(3H, s, C(CH3)A(CH3)B), 1.75–1.95 (2H, m, C(40)H2), 2.14 (1H, septd, J
6.9, 3.0, CH(CH3)2), 4.18 (1H, d, J 3.0, C(4)H), 4.22 (1H, dt 7.1, 5.1,
C(30)H), 4.84 (1H, dd, J 9.0, 7.1, C(20)H), 5.28 (1H, dd, J 10.1, 1.4,
CH]CHAHB), 5.39 (1H, dd, J 17.3, 1.4, CH]CHAHB), 5.96 (1H, ddd, J
17.3, 10.1, 9.0, CH]CH2), 7.23–7.34 (5H, m, Ph); dC (50 MHz, CDCl3)
ꢁ4.15, ꢁ4.1 (Si(CH3)2), 16.8, 21.4, 21.5, 28.8 (C(CH3)2, CH(CH3)2), 18.1
(C(CH3)3), 25.7 (C(CH3)3), 29.8 (CH(CH3)2), 37.6 (C(40)H2), 53.0
(C(20)H), 66.1 (C(4)H), 72.7 (C(30)H), 82.4 (C(CH3)2), 119.7
(CH]CH2), 125.7 (p-Ph), 128.3, 128.4 (o,m-Ph), 135.0 (i-Ph), 142.4
(CH]CH2), 153.0 (C(2)), 173.0 (C(10)); m/z (APCIþ) 460 ([MþH]þ,
6%), 228 ([MꢁC6H15OSi]þ, 100); HRMS (CIþ) C26H42NO4Siþ
([MþH]þ) requires 460.2878; found 460.2880.
O
O
OTBDMS
Et
O
N
Following general procedure 3, 20 (200 mg, 0.74 mmol) gave 28 as
21
a colourless wax (288 mg, 98%, >98% de); [
a]
ꢁ7.6 (c 1.0, CHCl3);
D
nmax (film) 1778 (C]O, exocyclic), 1695 (C]O, endocyclic), 1636
(C]C); dH (400 MHz, CDCl3) 0.03 (3H, s, Si(CH3)A), 0.05 (3H, s,
Si(CH3)B), 0.88 (9H, s, C(CH3)3), 0.89 (3H, t, J 7.5, C(50)H3), 0.92 (3H, d, J
7.0, CH(CH3)A(CH3)B), 1.01 (3H, d, J 7.0, CH(CH3)A(CH3)B), 1.39 (3H, s,
C(CH3)A(CH3)B), 1.51 (3H, s, C(CH3)A(CH3)B), 1.54–1.65 (2H, m,
C(40)H2), 2.14 (1H, septd, J 7.0, 3.2, CH(CH3)2), 4.08 (1H, dt, J 7.3, 5.0,
C(30)H), 4.16 (1H, d, J 3.2, C(4)H), 4.71 (1H, dd, J 8.9, 7.3, C(20)H), 5.24
(1H, dd, J 10.2,1.6, CH]CHAHB), 5.38 (1H, dd, J 17.2,1.6, CH]CHAHB),
5.97 (1H, ddd, J 17.2, 10.2, 8.9, CH]CH2); dC (100 MHz, CDCl3) ꢁ4.2,
ꢁ4.2 (Si(CH3)2), 8.6 (C(50)H3), 16.8, 21.4, 21.4, 28.7 (C(CH3)2,
CH(CH3)2), 18.1 (C(CH3)3), 25.9 (C(CH3)3), 28.2 (C(40)H2), 29.8
(CH(CH3)2), 52.6 (C(20)H), 66.2 (C(4)H), 73.7 (C(30)H), 82.4 (C(CH3)2),
119.4 (CH]CH2),135.1 (CH]CH2),153.0 (C(2)),175.2 (C(10)); m/z (GC
Tof CIþ) 398 ([MþH]þ, 100%), 266 ([MꢁC6H15OSi]þ, 90); HRMS (GC
Tof CIþ) C21H40NO4Siþ ([MþH]þ) requires398.2721; found 398.2740.
4.7.14. (2S,3R)-2-Vinyl-3-(tert-butyldimethylsilyloxy)butanoic
acid 33
O
OTBDMS
Me
HO
Following general procedure 4, 27 (200 mg, 0.52 mmol) gave,
after purification by flash column chromatography (eluent Et2O), 33
21
4.7.12. (4S,20R,30S)-N(3)-[20-Vinyl-30-(tert-butyldimethylsilyloxy)-
30-phenylpropanoyl]-4-isopropyl-5,5-dimethyl-oxazolidin-2-one 31
as a colourless oil (92 mg, 73%, >98% de, >98% ee); [
a
]
þ1.7 (c 1.1,
D
CHCl3); nmax (film) 3300–2500 (O–H), 1712 (C]O), 1643 (C]C); dH
(400 MHz, CDCl3) 0.07 (3H, s, Si(CH3)A), 0.08 (3H, s, Si(CH3)B), 0.88
(9H, s, C(CH3)3), 1.18 (3H, d, J 6.3, C(4)H3), 3.04 (1H, dd, J 9.4, 4.8,
C(2)H), 4.23 (1H, dq, J 6.3, 4.8, C(3)H), 5.15 (1H, br d, J 17.4,
CH]CHAHB), 5.28 (1H, dd, J 10.4, 1.5, CH]CHAHB), 5.94 (1H, ddd, J
17.4, 10.4, 9.4, CH]CH2); dC (100 MHz, CDCl3) ꢁ4.5, ꢁ4.1 (Si(CH3)2),
17.9 (C(4)H3), 21.1 (C(CH3)3), 25.6 (C(CH3)3), 57.6 (C(2)H), 69.6
(C(3)H), 119.5 (CH]CH2), 132.2 (CH]CH2), 177.3 (C(1)); m/z (APCIꢁ)
243 ([MꢁH]ꢁ, 6%), 129 ([MꢁC6H14Si]ꢁ, 100); HRMS (ESIꢁ)
C12H23O3Siꢁ ([MꢁH]ꢁ) requires 243.1422; found 243.1417.
O
O
OTBDMS
Ph
O
N
Following general procedure 3, 23 (100 mg, 0.35 mmol) gave 31
21
as a colourless wax (56 mg, 40%, >98% de); [
a
]
ꢁ22.1 (c 0.9,
D
CHCl3); nmax (film) 1781 (C]O, exocyclic), 1694 (C]O, endocyclic);
dH (400 MHz, CDCl3) ꢁ0.25 (3H, s, Si(CH3)A), 0.01 (3H, s, Si(CH3)B),
0.59 (3H, s, C(CH3)A(CH3)B), 0.81 (9H, s, C(CH3)3), 0.85 (3H, d, J 6.9,
CH(CH3)A(CH3)B), 0.94 (3H, d, J 6.9, CH(CH3)A(CH3)B), 1.34 (3H, s,
C(CH3)A(CH3)B), 2.00 (1H, septd, J 6.9, 3.4, CH(CH3)2), 3.80 (1H, d, J
3.4, C(4)H), 4.92 (1H, d, J 9.2, C(30)H), 5.09 (1H, app t, J 8.5, C(20)H),
5.29 (1H, dd, J 10.1, 1.5, CH]CHAHB), 5.43 (1H, dd, J 17.3, 1.5,
CH]CHAHB), 6.02 (1H, ddd, J 17.3,10.1, 8.5, CH]CH2), 7.15–7.35 (5H,
m, Ph); dC (100 MHz, CDCl3) ꢁ4.9, ꢁ4.7 (Si(CH3)2), 16.8, 21.1, 21.4,
27.3 (C(CH3)2, CH(CH3)2), 18.3 (C(CH3)3), 25.6 (C(CH3)3), 29.5
(CH(CH3)2), 56.4 (C(20)H), 65.8 (C(4)H), 76.4 (C(30)H), 82.2 (C(CH3)2),
119.6 (CH]CH2), 127.5 (p-Ph), 127.6, 128.0 (o,m-Ph), 135.1 (i-Ph),
4.7.15. (2S,3R)-2-Vinyl-3-(tert-butyldimethylsilyloxy)pentanoic
acid 34
O
OTBDMS
Et
HO
Following general procedure 4, 28 (150 mg, 0.38 mmol) gave,
after purification by flash column chromatography (eluent Et2O),
24
34 as a colourless oil (83 mg, 85%, >98% de, >98% ee); [
a]
þ4.2 (c
D

7848
S.G. Davies et al. / Tetrahedron 65 (2009) 7837–7851
1.3, CHCl3); nmax (film) 3300–2500 (O–H), 1710 (C]O), 1642 (C]C);
dH (400 MHz, CDCl3) 0.07 (3H, t, J 5.0, C(5)H3), 0.08 (3H, s, Si(CH3)A),
0.89 (9H, s, C(CH3)3), 0.90 (3H, s, Si(CH3)B), 1.53–1.56 (2H, m,
C(4)H2), 3.17 (1H, dd, J 9.2, 4.5, C(2)H), 4.01 (1H, dt, J 6.2, 4.5, C(3)H),
5.15 (1H, br d, J 17.3, CH]CHAHB), 5.27 (1H, dd, J 10.3, 1.6,
CH]CHAHB), 5.96 (1H, ddd, J 17.3, 10.3, 9.2, CH]CH2); dC (100 MHz,
CDCl3) ꢁ4.8, ꢁ4.4 (Si(CH3)2), 9.6 (C(5)H3), 18.0 (C(CH3)3), 25.7
(C(CH3)3), 29.7 (C(4)H2), 54.9 (C(2)H), 74.8 (C(3)H), 119.4 (CH]H2),
132.1 (CH]CH2), 177.3 (C(1)); m/z (APCIþ) 259 ([MþH]þ, 12%), 114
([C6H14Si]þ, 100); HRMS (CIþ) C13H27O3Siþ ([MþH]þ) requires
259.1724; found 259.1719.
1.0, CHCl3); nmax (film) 3420 (O–H), 3500–2500 (O–H), 1713 (C]O),
1637 (C]O); dH (400 MHz, CDCl3) 0.93 (3H, d, 7.0,
J
CH(CH3)A(CH3)B), 1.01 (3H, d, J 7.0, CH(CH3)A(CH3)B), 1.73 (1H, app
octet, J 6.8, CH(CH3)2), 3.28 (1H, dd, J 9.3, 4.5, C(2)H), 3.68 (1H, dd, J
7.0, 4.5, C(3)H), 5.31 (1H, dd, J 17.2, 1.3, CH]CHAHB), 5.36 (1H, dd, J
10.3, 1.3, CH]CHAHB), 5.97 (1H, ddd, J 17.2, 10.3, 9.3, CH]CH2); dC
(100 MHz, CDCl3) 17.8, 19.0 (CH(CH3)2), 30.8 (C(4)H), 53.3 (C(2)H),
76.3 (C(3)H), 120.8 (CH]CH2), 131.1 (CH]CH2), 178.8 (C(1)); m/z
(ESIꢁ) 157 ([MꢁH]ꢁ, 100%); HRMS (ESIꢁ) C8H13Oꢁ3 ([MꢁH]ꢁ) re-
quires 157.0870; found 157.0862.
4.7.19. (2S,3R)-2-Vinyl-3-hydroxy-4,4-dimethylpentanoic acid 38
4.7.16. (2S,10S)-2-Vinyl-3-(tert-butyldimethylsilyloxy)-3-phenyl-
propanoic acid 35
O
OH
tBu
O
OTBDMS
Ph
HO
HO
Following general procedure 4, 22 (100 mg, 0.32 mmol) gave,
after purification by flash column chromatography (eluent
Et22O4), 38 as a colourless oil (50 mg, 92%, >98% de, >98% ee);
Following general procedure 4, 31 (100 mg, 0.32 mmol) gave,
after purification by flash column chromatography (eluent Et2O), 35
24
as a colourless oil (50 mg, 92%, >98% de, >98% ee); [
a]
þ33.6 (c
D
[
a
]
ꢁ0.7 (c 0.9, CHCl3); nmax (film) 3700–3000 (O–H), 1682
1.0, CHCl3); nmax (film) 2600–3200 (O–H), 1710 (C]O), 1641 (C]C);
dH (400 MHz, CDCl3) ꢁ0.20 (3H, s, Si(CH3)A), 0.03 (3H, s, Si(CH3)B),
0.87 (9H, s, C(CH3)3), 3.26 (1H, dd, J 9.2, 5.7, C(2)H), 4.96 (1H, d, J
17.4, CH]CHAHB), 5.11 (1H, d, J 5.7, C(3)H), 5.18 (1H, app dd, J 10.3,
1.3, CH]CHAHB), 5.98 (1H, ddd, J 17.4, 10.3, 9.2, CH]CH2), 7.24–7.30
(5H, m, Ph); dC (100 MHz, CDCl3) ꢁ5.3, ꢁ4.7 (Si(CH3)2), 18.1
(C(CH3)3), 25.7 (C(CH3)3), 59.5 (C(2)H), 75.7 (CH]CH2), 119.8
(CH]CH2), 126.6 (p-Ph), 127.6, 127.9 (o,m-Ph), 128.0 (p-Ph), 141.8
(CH]CH2), 177.7 (C(1)); m/z (ESIꢁ) 305 ([MꢁH]ꢁ, 100%); HRMS
(ESIꢁ) C17H25O3Siꢁ ([MꢁH]ꢁ) requires 305.1578; found 305.1564.
D
(C]O), 1633 (C]C); dH (400 MHz, CDCl3) 0.97 (9H, s, C(CH3)3),
3.36 (1H, dd, J 9.5, 4.4, C(2)H), 3.74 (1H, d, J 4.4, C(3)H), 5.29–
5.33 (1H, m, CH]CHAHB), 5.34 (1H, d, J 6.0, CH]CHAHB), 6.05
(1H, dt,
J 17.4, 9.5, CH]CH2); dC (100 MHz, CDCl3) 25.4
(C(CH3)3), 34.6 (C(CH3)3), 52.3 (C(2)H), 77.8 (C(3)H), 120.4
(CH]CH2), 132.4 (CH]CH2), 177.9 (C(1)); m/z (ESIꢁ) 171
([MꢁH]ꢁ, 100%); HRMS (ESIꢁ) C9H15Oꢁ3 ([MꢁH]ꢁ) requires
171.1027; found 171.1024.
4.7.20. Methyl (2S,3R)-2-vinyl-3-hydroxybutanoate 39
4.7.17. (2S,3R)-2-Vinyl-3-(tert-butyldimethylsilyloxy)-4-
phenylbutanoic acid 36
O
OH
O
OTBDMS
Bn
MeO
Me
HO
Following general procedure 5, 15 (500 mg, 1.86 mmol) gave,
after purification by flash column chromatography (eluent Et2O),
Following general procedure 4, 32 (200 mg, 0.56 mmol) gave,
25
39 as a colourless oil (217 mg, 81%, >98% de, >98% ee); [
a
]
D
ꢁ110 (c
after purification by flash column chromatography (eluent Et2O),
1.0, CHCl3); nmax (film) 3444 (O–H), 1732 (C]O), 1641 (C]C); dH
(400 MHz, CDCl3) 1.18 (3H, d, J 6.2, C(4)H3), 2.64 (1H, br s, OH), 3.02
(1H, dd, J 9.1, 4.9, C(2)H), 3.72 (3H, s, OCH3), 4.10 (1H, app quintet, J
5.8, C(3)H), 5.25 (1H, dd, J 17.2, 1.4, CH]CHAHB), 5.33 (1H, dd, J 10.2,
1.4, CH]CHAHB), 5.93 (1H, ddd, J 17.2, 10.2, 9.1, CH]CH2); dC
(100 MHz, CDCl3) 20.0 (C(4)H3), 52.1 (OCH3), 57.1 (C(2)H), 67.6
(C(3)H), 120.7 (C(20)H2), 131.7 (C(10)H), 173.6 (C(1)); m/z (GC Tof CIþ)
145 ([MþH]þ, 100%); HRMS (GC Tof CIþ) C7H13Oþ3 ([MþH]þ) re-
quires 145.0859; found 145.0867.
23
36 as a colourless oil (167 mg, 90%, >98% de, >98% ee); [
a]
þ4.1 (c
D
1.0, CHCl3); nmax (film) 2500–3400 (O–H), 1709 (C]O), 1642 (C]C);
dH (400 MHz, CDCl3) 0.06 (3H, s, Si(CH3)A), 0.09 (3H, s, Si(CH3)B),
0.90 (9H, s, C(CH3)3), 1.83–1.88 (2H, m, C(4)H2), 3.23 (1H, dd, J 9.4,
4.4, C(2)H), 4.17 (1H, dt, J 6.0, 4.4, C(3)H), 5.19 (1H, br d, J 17.4,
CH]CHAHB), 5.32 (1H, dd, J 10.3, 1.3, CH]HAHB), 6.00 (1H, ddd, J
17.4, 10.3, 9.4, CH]CH2), 7.16–7.31 (5H, m, Ph); dC (100 MHz, CDCl3)
ꢁ4.7, ꢁ4.4 (Si(CH3)2), 18.0 (C(CH3)3), 25.8 (C(CH3)3), 31.6 (C(4)H2),
55.4 (C(2)H), 73.2 (C(3)H), 119.7 (CH]CH2), 125.9 (p-Ph), 128.3,
128.4 (o,m-Ph), 128.4 (i-Ph), 141.6 (C(10)H), 177.8 (C(1)); m/z (APCIꢁ)
333 ([MꢁH]ꢁ, 5%), 131 ([C6H15OSi]ꢁ, 100%); HRMS (ESIþ)
C18H29O3Siþ ([MþH]þ) requires 321.1880; found 321.1882.
4.7.21. Methyl (2S,3R)-2-vinyl-3-hydroxypentanoate 41
O
OH
4.7.18. (2S,3R)-2-Vinyl-3-hydroxy-4-methylpentanoic acid 37
MeO
Et
O
OH
Following general procedure 5, 20 (500 mg, 1.77 mmol) gave,
after purification by flash column chromatography (eluent Et2O),
i
HO
Pr
24
41 as a colourless oil (243 mg, 87%, >98% de, >98% ee); [
a
]
ꢁ96.8
D
(c 1.0, CHCl3); nmax (film) 3454 (O–H), 1732 (C]O), 1640 (C]C); dH
(400 MHz, CDCl3) 0.93 (3H, t, J 7.4, C(5)H3), 1.41–1.46 (2H, m,
C(4)H2), 2.70 (1H, br s, OH), 3.06 (1H, dd, J 9.3, 4.8, C(2)H), 3.69
(3H, s, OCH3), 3.82 (1H, dt, J 7.6, 4.8, C(3)H), 5.20 (1H, dd, J 17.2, 1.5,
Following general procedure 4, 21 (200 mg, 0.67 mmol) gave,
after purification by flash column chromatography (eluent Et2O), 37
as a colourless oil (95 mg, 89%, >98% de, >98% ee); [
24
a]
ꢁ78.0 (c
D

S.G. Davies et al. / Tetrahedron 65 (2009) 7837–7851
7849
CH]CHAHB), 5.27 (1H, dd, J 10.3, 1.5, CH]CHAHB), 5.91 (1H, ddd, J
17.2, 10.3, 9.3, CH]CH2); dC (100 MHz, CDCl3) 9.9 (C(5)H3), 27.0
(C(4)H2), 52.0 (OCH3), 55.3 (C(2)H), 72.7 (C(3)H), 120.2 (CH]CH2),
131.7 (CH]CH2), 173.8 (C(1)); m/z (GC Tof CIþ) 176 ([MþNH4]þ,
100%), 159 ([MþH]þ, 92); HRMS (GC Tof CIþ) C8H15Oþ3 ([MþH]þ)
requires 159.1016; found 159.1020.
5.92 (1H, ddd, J 17.3, 10.2, 8.9, CH]CH2), 7.26–7.33 (5H, m, Ph); dC
(100 MHz, CDCl3) 52.4 (OCH3), 58.2 (C(2)H), 73.8 (C(3)H), 120.7
(C(20)H2), 126.3 (p-Ph), 127.9, 128.2 (o,m-Ph), 131.7 (i-Ph), 140.7
(C(10)H), 172.9 (C(1)); m/z (GC Tof CIþ) 207 ([MþH]þ, 11%), 189
([MꢁOH]þ, 76).
4.7.25. Methyl (2E,3R)-2-ethylidene-3-hydroxybutanoate 40
4.7.22. Methyl (2S,3R)-2-vinyl-3-hydroxy-4-methylpentanoate 42
O
OH
Me
O
OH
iPr
MeO
Me
MeO
Following general procedure 5, 21 (200 mg, 0.67 mmol) gave,
Following general procedure 5, 39 (200 mg, 1.39 mmol) gave,
after purification by flash column chromatography (eluent Et2O),
after purification by flash column chromatography (eluent Et2O),
24
40 as a colourless oil (188 mg, 95%, 92:8 [(E):(Z)], >98% ee);13b,37
42 as a colourless oil (92 mg, 79%, >98% de, >98% ee); [
a
]
ꢁ99.9
D
24
(c 0.95, CHCl3); nmax (film) 3452 (O–H), 1731 (C]O), 1642 (C]C);
dH (400 MHz, CDCl3) 0.93 (3H, d, J 6.8, CH(CH3)A(CH3)B), 0.98 (3H,
d, J 6.8, CH(CH3)A(CH3)B), 1.81–1.85 (1H, m, C(4)H), 2.64 (1H, d, J
3.3, OH), 3.25 (1H, dd, J 9.3, 4.5, C(2)H), 3.60–3.64 (1H, m, C(3)H),
3.72 (3H, s, OCH3), 5.26 (1H, br dd, J 17.3, 1.4, CH]CHAHB), 5.31
(1H, dd, J 10.2, 1.4, CH]CHAHB), 5.96 (1H, ddd, J 17.3, 10.2, 9.3,
CH]CH2); dC (100 MHz, CDCl3) 17.4, 19.5 (CH(CH3)2), 29.2 (C(4)H),
51.8 (OCH3), 56.4 (C(2)H), 76.4 (C(3)H), 120.1 (CH]CH2), 131.6
(CH]CH2), 173.0 (C(1)); m/z (GC Tof CIþ) 173 ([MþH]þ, 100);
HRMS (GC Tof CIþ) C9H17O3þ ([MþH]þ) requires 173.1172; found
173.1169.
[a
]
þ36.6 (c 1.0, CHCl3); nmax (film) 3430 (O–H), 1706 (C]O),
D
1653 (C]C); dH (400 MHz, CDCl3) 1.39 (3H, d, J 6.7, C(4)H3), 1.83
(1H, d, J 7.3, C(20)H3), 3.75 (3H, s, OCH3), 4.75 (1H, q, J 6.7, C(3)H),
6.81 (1H, q, J 7.3, C(10)H); dC (100 MHz, CDCl3) 13.7 (C(4)H3), 21.0
(C(20)H3), 51.7 (OCH3), 64.6 (C(3)H), 134.6 (C(10)H), 138.1 (C(2)),
167.6 (C(1)); m/z (APCIþ) 145 ([MþH]þ, 100%), 127 ([MꢁOH]þ, 32);
HRMS (CIþ) C7H13Oþ3 ([MþH]þ) requires 145.0859; found
145.0869.
4.7.26. Methyl (2E,3R)-2-ethylidene-3-hydroxypentanoate 46
O
OH
Me
4.7.23. Methyl (2S,3R)-2-vinyl-3-hydroxy-4,4-dimethyl-
pentanoate 43
MeO
Et
O
OH
tBu
Following general procedure 5, 41 (200 mg, 1.27 mmol) gave,
MeO
after purification by flash column chromatography (eluent Et2O),
46 as a colourless oil (178 mg, 89%, 92:8 [(E):(Z)], >98% ee);38
[a]
24
D
þ22.4 (c 1.0, CHCl3); nmax (film) 3516 (O–H), 1697 (C]O), 1644
(C]C); dH (400 MHz, CDCl3) 0.90 (3H, t, J 7.4, C(5)H3),1.60–1.65 (1H,
m, C(4)HA),1.81–1.84 (1H, m, C(4)HB),1.84 (1H, d, J 7.3, C(20)H3), 3.51
(1H, br d, J 7.4, OH), 3.74 (3H, s, OCH3), 4.44 (1H, app t, J 7.3, C(3)H),
6.90 (1H, q, J 7.3, C(10)H); dC (100 MHz, CDCl3) 10.4 (C(4)H2), 14.0
(C(5)H3), 29.9 (C(20)H3), 51.6 (OCH3), 70.1 (C(3)H), 133.5 (C(10)H),
139.1 (C(2)), 167.8 (C(1)); m/z (GC Tof CIþ) 159 ([MþH]þ, 82%), 141
([MꢁOH]þ, 100); HRMS (CIþ) C8H18NO3þ ([MþNH4]þ) requires
176.1281; found 176.1293.
Following general procedure 5, 22 (400 mg, 1.29 mmol) gave,
after purification by flash column chromatography (eluent Et2O),
25
43 as a colourless oil (218 mg, 91%, >98% de, >98% ee); [
a]
ꢁ121 (c
D
1.0, CHCl3); nmax (film) 3534 (O–H), 1738 (C]O), 1636 (C]C); dH
(400 MHz, CDCl3) 0.94 (9H, s, C(CH3)3), 2.49 (1H, d, J 3.6, OH), 3.31
(1H, dd, J 9.6, 4.5, C(2)H), 3.68 (1H, dd, J 4.5, 3.6, C(3)H), 3.70 (3H, s,
OCH3), 5.22–5.27 (1H, m, CH]CHAHB), 5.28–5.31 (1H, m,
CH]CHAHB), 6.02 (1H, app dt, J 17.6, 9.6, CH]CH2); dC (100 MHz,
CDCl3) 26.3 (C(CH3)3), 35.5 (C(CH3)3), 52.1 (OCH3), 52.6 (C(2)H), 77.8
(C(3)H), 119.8 (CH]CH2), 133.2 (CH]CH2), 174.3 (C(1)); m/z (GC Tof
CIþ) 204 ([MþNH4]þ, 96%), 187 ([MþH]þ, 100), 169 ([MꢁOH]þ, 45);
HRMS (GC Tof CIþ) C10H22NO3þ ([MþNH4]þ) requires 204.1594;
found 204.1597.
4.7.27. Methyl (2E,3R)-2-ethylidene-3-hydroxy-4-
methylpentanoate 47
O
OH
Me
4.7.24. Methyl (2S,10R)-2-vinyl-3-hydroxyl-3-phenyl-
propanoate 44
MeO
iPr
O
OH
Following general procedure 5, 42 (200 mg, 1.16 mmol) gave,
MeO
Ph
after purification by flash column chromatography (eluent Et2O),
21
47 as colourless oil (197 mg, 98%, 92:8 [(E):(Z)], >98% ee); [a]
D
þ15.5 (c 1.0, CHCl3); nmax (film) 3520 (O–H), 1697 (C]O), 1644
(C]C); dH (400 MHz, CDCl3) 0.78 (3H, d, J 6.6, CH(CH3)A(CH3)B),
1.10 (3H, d, J 6.6, CH(CH3)A(CH3)B), 1.86 (3H, d, J 7.3, C(20)H3), 1.98
(1H, septd, J 9.3, 6.6, C(4)H) 3.48 (1H, d, J 11.0, OH), 3.76 (3H, s,
OCH3), 4.10 (1H, dd, J 11.0, 9.3, C(3)H), 6.97 (1H, app qd, J 7.3, 0.5,
C(10)H); dC (100 MHz, CDCl3) 14.4, 19.2 (CH(CH3)2), 19.5 (C(20)H3),
33.8 (C(4)H), 51.7 (OCH3), 74.4 (C(3)H), 132.9 (C(10)H), 139.9 (C(2)),
168.1 (C(1)); m/z (GC Tof CIþ) 173 ([MþH]þ, 42%), 155 ([MꢁOH]þ,
Following general procedure 5, 23 (500 mg,1.41 mmol) gave, after
purification by flash column chromatography (eluent Et2O), 44 as
22
a colourless oil (241 mg, 83%, >98% de, >98% ee);38
[
a
]
ꢁ87.5 (c 0.5,
D
CHCl3); nmax (film) 3480 (O–H), 1732 (C]O), 1639 (C]C); dH
(400 MHz, CDCl3) 2.99 (1H, d, J 2.8, OH), 3.35 (1H, dd, J 8.9, 6.0,
C(2)H), 3.61 (3H, s, OCH3), 5.03 (1H, dd, J 6.0, 2.8, C(3)H), 5.16 (1H, br
dt, J 17.3, 1.3, CH]CHAHB), 5.27 (1H, br dd, J 10.2, 1.3, CH]CHAHB),

7850
S.G. Davies et al. / Tetrahedron 65 (2009) 7837–7851
100); HRMS (GC Tof CIþ) C9H17Oþ3 ([MþH]þ) requires 173.1172;
(o,m-Ph), 133.6 (i-Ph), 139.0 (C(10)H), 141.6 (C(2)), 167.8 (C(1)); m/z
(APCIþ) 221 ([MþH]þ, 90%); HRMS (CIþ) C13H20NO3þ ([MþNH4]þ)
requires 238.1438; found 238.1440.
found 173.1180.
4.7.28. Methyl (2E,3R)-2-ethylidene-3-hydroxy-4,4-
dimethylpentanoate 48
Acknowledgements
O
OH
Me
The authors would like to thank the Oxford Chemical Crystal-
lography Service for the use of their X-ray diffractometers.
MeO
tBu
References and notes
1. For selected reviews, see: (a) Basavaiah, D.; Rao, A. J.; Satanarayana, T. Chem.
Rev. 2003, 103, 811; (b) Drewes, S. E.; Roos, G. H. P. Tetrahedron 1988, 44, 4653.
2. Baylis, A. B.; Hillman, M. E. D. German Patent 2155113, 1972.
3. Morita, K.; Suzuki, Z.; Hirose, H. Bull. Chem. Soc. Jpn. 1968, 41, 2815.
4. Hoffmann, H. M. R.; Rabe, J. Angew. Chem., Int. Ed. Engl. 1985, 24, 94.
5. For examples of menthyl derived auxiliaries, see: (a) Gilbert, A.; Heritage, T. W.;
Isaacs, N. S. Tetrahedron: Asymmetry 1991, 2, 969; (b) Drewes, S. E.; Emslie, N. D.;
Kahn, A. A. Synth. Commun. 1993, 23, 1215; For examples of carbohydrate de-
rived auxiliaries, see: (c) Krishna, R.; Kannan, V.; Ilanogovan, A.; Sharma, G. V.
M. Tetrahedron: Asymmetry 2001, 12, 829; For examples of pyrazolidinone de-
rived auxiliaries, see: (d) Yang, K. S.; Chen, K. Org. Lett. 2000, 2, 729; For ex-
amples employing Oppolzer0s camphor sultam auxiliary, see: (e) Brezezinski, L.
J.; Rafel, S.; Leahy, J. W. J. Am. Chem. Soc. 1997, 119, 4317; (f) Brezezinski, L. J.;
Rafel, S.; Leahy, J. W. Tetrahedron 1997, 53, 16423; (g) Piber, M.; Leahy, J. W.
Tetrahedron Lett. 1998, 39, 2043.
6. (a) Drewes, S. E.; Njamela, O. L.; Roos, G. H. P. Synth. Commun. 1988, 18, 1065;
(b) Manickum, T.; Roos, G. H. P. Synth. Commun. 1991, 21, 2269; (c) Drewes, S.
E.; Khan, A. A.; Rowland, K. Synth. Commun. 1993, 23, 183; (d) Ku¨ ndig, E. P.;
Xu, L. H.; Romanens, P.; Bernardinelli, G. Tetrahedron Lett. 1993, 34, 7049; (e)
Alcaida, B.; Almendros, P.; Aragoncillo, C. Chem. Commun. 1999, 1913; (f) Al-
caida, B.; Almendros, P.; Aragoncillo, C. J. Org. Chem. 2001, 66, 1612; For re-
lated studies, see: (g) Alcaida, B.; Almendros, P.; Aragoncillo, C. Tetrahedron
Lett. 1999, 40, 7537.
Following general procedure 5, 43 (200 mg, 1.07 mmol) gave,
after purification by flash column chromatography (eluent Et2O),
23
48 as a colourless oil (193 mg, 97%, 91:9 [(E):(Z)], >98% ee); [a]
D
þ28.5 (c 1.1, CHCl3); nmax (film) 3479 (O–H), 1694 (C]O), 1649
(C]C); dH (400 MHz, CDCl3) 0.90 (9H, s, C(CH3)3), 1.85 (3H, d, J
7.3, C(20)H3), 3.75 (3H, s, OCH3), 4.30 (1H, dd, J 10.0, 0.5, C(3)H),
4.70 (1H, br d, J 10.0, OH), 6.95 (1H, qd, J 7.3, 0.5, C(10)H); dC
(100 MHz, CDCl3) 15.0 (C(20)H3), 26.3 (C(CH3)3), 37.5 (C(4)),
51.9 (OCH3), 76.4 (C(3)H), 130.9 (C(10)H), 140.8 (C(2)), 169.8
(C(1)); m/z (GC Tof CIþ) 187 ([MþH]þ, 54%), 169 ([MꢁOH]þ, 100);
HRMS (GC Tof CIþ) C10H19O3þ ([MþH]þ) requires 187.1329; found
187.1340.
4.7.29. Methyl (2E,10R)-2-hydroxybenzyl-but-2-enoate 49
O
OH
Me
7. (a) Oishi, T.; Oguri, H.; Hirama, M. Tetrahedron: Asymmetry 1995, 6, 1241; (b)
Barrett, A. G. M.; Cook, A. S.; Kaminura, A. Chem. Commun. 1998, 2533; (c)
Barrett, A. G. M.; Dozzo, P.; White, A. J. P.; Williams, D. J. Tetrahedron 2002, 58,
7303; (d) Marko, I. E.; Giles, P. R.; Hindley, N. J. Tetrahedron 1997, 53, 1015; (e)
Iwabuchi, Y.; Nakatani, M.; Yokoyama, N.; Hatakeyama, S. J. Am. Chem. Soc.
1999, 121, 10219; (f) Iwabuchi, Y.; Hatakeyama, S. J. Synth. Org. Chem. Jpn.
2002, 60, 1; (g) Iwabuchi, Y.; Furukawa, M.; Esumi, T.; Hatakeyama, S. Chem.
Commun. 2001, 2030.
MeO
Ph
Following general procedure 6, 44 (300 mg, 0.91 mmol) gave,
after purification by flash column chromatography (eluent Et2O),
49 as a colourless oil (86 mg, 43%, 94:6 [(E):(Z)], >98% ee);13b,39
8. (a) Hayase, T.; Shibata, T.; Soai, K.; Wakatsuki, Y. Chem. Commun. 1998, 1271; (b)
Li, W.; Zhang, Z.; Xiao, D.; Zhang, X. J. Org. Chem. 2000, 65, 3489.
9. Sato, Y.; Takeuchi, S. Synthesis 1983, 734.
21
[
a]
þ38.5 (c 1.0, CHCl3); nmax (film) 3492 (O–H), 1698 (C]O), 1645
D
(C]C); dH (400 MHz, CDCl3) 2.00 (3H, d, J 7.4, C(20)H3), 3.69 (3H, s,
OCH3), 4.23 (1H, br d, J 9.4, OH), 5.74 (1H, d, J 9.4, C(3)H), 7.11 (1H, q,
J 7.4, C(10)H), 7.23–7.40 (5H, m, Ph); dC (100 MHz, CDCl3) 14.3
(C(20)H3), 51.8 (OCH3), 69.2 (C(3)H), 125.2 (p-Ph), 127.1, 128.3 (o,m-
Ph), 133.3 (i-Ph), 140.0 (C(10)H), 143.7 (C(2)), 167.6 (C(1)); m/z
(APCIþ) 224 ([MþNa]þ, 4%); HRMS (CIþ) C12H18NO3þ ([MþNH4]þ)
requires 224.1281; found 224.1291.
10. Li, G.; Wei, H.-X.; Willis, S. Tetrahedron Lett. 1998, 39, 4607.
11. (a) Marino, J. P.; Viso, A.; Lee, J.-D.; de la Pradilla, R. F.; Fernandez, P.; Rubio, M. B.
J. Org. Chem. 1997, 62, 645; (b) Satoh, T.; Kuramochi, Y.; Inoue, Y. Tetrahedron
Lett. 1999, 40, 8815.
12. Li, G.; Wei, H.-X.; Phelps, B. S.; Purkiss, D. W.; Kim, S. H. Org. Lett. 2001, 3, 823.
13. (a) Davies, S. G.; Smethurst, C. A. P.; Smith, A. D.; Smyth, G. D. Tetrahedron:
Asymmetry 2000, 11, 2437; (b) Chernega, A.; Davies, S. G.; Elend, D. L.;
Smethurst, C. A. P.; Roberts, P. M.; Smith, A. D.; Smyth, G. D. Tetrahedron
2007, 63, 7036.
14. For a review in this area, see: Davies, S. G.; Smith, A. D.; Price, P. D. Tetrahedron:
Asymmetry 2005, 16, 2833.
15. (a) Bull, S. D.; Davies, S. G.; Key, M.-S.; Nicholson, R. L.; Savory, E. D. Chem.
Commun. 2000, 1721; (b) Bull, S. D.; Davies, S. G.; Garner, A. C.; Kruchinin, D.;
Key, M.-S.; Roberts, P. M.; Savory, E. D.; Smith, A. D.; Thomson, J. E. Org. Biomol.
Chem. 2006, 4, 2945.
16. For a related example utilising the titanium enolate of an N-acyl SuperQuat,
see: Sakaguchi, H.; Tokuyama, H.; Fukuyama, T. Org. Lett. 2007, 9, 1635.
17. (a) Heathcock, C. H. In Comprehensive Organic Synthesis; Trost, B. M., Flem-
ing, I., Eds.; Pergamon: New York, NY, 1991; Vol. 2, pp 133–238; (b) Kim, B.
M.; Williams, S. F.; Masamune, S. In Comprehensive Organic Synthesis; Trost,
B. M., Fleming, I., Eds.; Pergamon: New York, NY, 1991; Vol. 2, pp 239–275;
(c) Paterson, I. In Comprehensive Organic Synthesis; Trost, B. M., Fleming, I.,
Eds.; Pergamon: New York, NY, 1991; Vol. 2, pp 301–319; (d) Zimmerman,
H. E.; Traxler, M. D. J. Am. Chem. Soc. 1957, 79, 1920; (e) Dubois, J. E.; Fell-
man, P. Tetrahedron Lett. 1975, 1225; (f) Heathcock, C. H.; Buse, C. T.;
Kleschnick, W. A.; Pirrung, M. C.; Sohn, J. E.; Lampe, J. J. Org. Chem. 1980, 45,
1066.
4.7.30. Methyl (2E,3R)-2-ethylidene-3-hydroxy-4-phenyl-
butanoate 50
O
OH
Me
MeO
Bn
Following general procedure 5, 24 (400 mg, 1.16 mmol) gave
a 76:24 mixture of 45 and 50, respectively (225 mg, quant). This
mixture was treated with DBU (0.7 mL, 4.64 mmol) according to
general procedure 6 to give, after purification by flash column
18. Ma, Y.; Collum, D. B. J. Am. Chem. Soc. 2007, 129, 14818.
19. For examples of secondary lithium amides undergoing conjugate addition re-
chromatography (eluent Et2O), 50 as a colourless oil (194 mg, 97%
25
actions to a,b-unsaturated N-acyl oxazolidinones, see: (a) Davies, S. G.; Her-
(two steps), 92:8 [(E):(Z)], >98% ee); [
a
]
D
þ64.0 (c 1.0, CHCl3); nmax
mann, G. J.; Sweet, M. J.; Smith, A. D. Chem. Commun. 2004, 1128; (b) Beddow,
J. E.; Davies, S. G.; Ling, K. B.; Roberts, P. M.; Russell, A. J.; Smith, A. D.;
Thomson, J. E. Org. Biomol. Chem. 2007, 5, 2812.
(film) 3515 (O–H), 1694 (C]O), 1644 (C]O), 1603 (C]C); dH
(400 MHz, CDCl3) 1.74 (3H, d, J 7.3, C(20)H3), 1.82–1.86 (1H, m,
C(4)HA), 2.00 (1H, m, C(4)HB), 3.59 (1H, d, J 10.8, OH), 3.77 (3H, s,
OCH3), 4.55 (1H, ddd, J 10.8, 8.8, 5.4, C(3)H), 6.88 (1H, q, J 7.3,
C(10)H), 7.23–7.35 (5H, m, Ph); dC (100 MHz, CDCl3) 13.9 (C(20)H3),
32.1 (C(4)H2), 51.7 (OCH3), 67.9 (C(3)H), 125.8 (p-Ph), 128.3, 128.4
20. Bull, S. D.; Davies, S. G.; Jones, S.; Sanganee, H. J. J. Chem. Soc., Perkin Trans. 1
1999, 387.
21. (a) Rathke, M. W.; Sullivan, D. Tetrahedron Lett. 1972, 13, 4249; (b) Herrmann,
J. L.; Kieczykowski, G. R.; Schessinger, R. H. Tetrahedron Lett. 1973, 26, 2433; (c)
Zimmerman, M. P. Synth. Commun. 1977, 7, 189; (d) von Rague Schleyer, P.;

S.G. Davies et al. / Tetrahedron 65 (2009) 7837–7851
Dill, J. D.; Pople, J. A.; Hehre, W. J. Tetrahedron 1977, 33, 2497; (e) Krebs, E.-P.
7851
Helv. Chim. Acta 1981, 64, 1023; (f) Kende, A. S.; Toder, B. H. J. Org. Chem. 1982,
47, 167; (g) Harris, F. L.; Weiler, L. Tetrahedron Lett. 1984, 25, 1333; (h) Alcock,
S. G.; Baldwin, J. E.; Bohlmann, R.; Harwood, L. M.; Seeman, J. I. J. Org. Chem.
1985, 50, 3526; (i) Gelatis, P.; Manwell, J. J.; Millan, S. D. Tetrahedron Lett. 1996,
37, 5261; (j) Tomooka, K.; Nagasawa, A.; Wei, S.-Y.; Nakai, T. Tetrahedron Lett.
1996, 37, 8895; (k) Tomooka, K.; Nagasawa, A.; Nakai, T. Chem. Lett. 1998,
1049; (l) Guha, S. K.; Shibayama, A.; Abe, D.; Ukaji, Y.; Inomata, K. Chem. Lett.
2003, 32, 778; (m) Guha, S. K.; Shibayama, A.; Abe, D.; Sakaguchi, M.; Ukaji,
Y.; Inomata, K. Bull. Chem. Soc. Jpn. 2004, 77, 2147.
22. Isomerisation of b,g-unsaturated N-acyl SuperQuat 12 to give N-crotonoyl Su-
perQuat 6 with either Et3N or DBU rapidly promoted full conversion to the
desired product as a single geometric isomer [(E):(Z) ratio >99:1], with chro-
matographic purification giving 6 in quantitative yield.
O
O
O
O
(i) or (ii)
O
N
O
N
Me
Chem3D representation of the single crystal X-ray structure of 52 (some H
atoms have been omitted for clarity).
12
6, quant
Reagents and conditions: (i) Et3N, THF, rt, 2 h; (ii) DBU, THF, rt, 2 h.
29. Within the crystal lattice for compound 22 intermolecular hydrogen bonding is
observed between the C(30)-hydroxyl groups and the C(2)-carbonyl groups,
whereas for compound 23 intermolecular hydrogen bonding is observed be-
tween the C(30)-hydroxyl groups and the C(10)-carbonyl groups.
30. No aldol products were isolated upon reaction with pivalaldehyde, presumably
due to its steric bulk precluding reaction.
23. SuperQuat 11 was also isolated in 9% yield.
24. House, H. O.; Crumrine, D. S.; Teranishi, A. Y.; Olmstead, H. D. J. Am. Chem. Soc.
1973, 95, 3310.
25. Within the crystal lattice for compound 17 intermolecular hydrogen bonding
is observed between the C(30)-hydroxyl groups and the C(10)-carbonyl
groups.
31. In each case, b,g-unsaturated 12 was isolated (typically in w20% yield), along
with small amounts (<5%) of SuperQuat auxiliary 11.
26. (a) Evans, D. A.; Sjorgen, E. B.; Bartroli, J.; Dow, R. L. Tetrahedron Lett. 1986, 27,
4957; (b) Evans, D. A.; Sjorgen, E. B. Tetrahedron Lett. 1986, 27, 4961.
27. Evans, D. A.; Bartroli, J.; Shih, T. J. Am. Chem. Soc. 1981, 103, 2127.
28. In the case of the C(30)-ethyl and C(30)-isopropyl substrates 20 and 21 the
corresponding non-Evans syn-aldol products 51 and 52 were isolated as
the minor diastereoisomers in 9 and 5% yield, respectively (in >98% de in
each case); no minor diastereoisomers were isolated from reaction of
substrates 22–24. The relative configurations within 51 and 52 were ini-
tially based on 3J 1H NMR coupling constant analysis with 51 and 52
displaying diagnostic coupling constants of 3.6 and 4.0 Hz, respectively
between the C(20)H and C(30)H protons, indicative of a syn-configuration.
Furthermore, recrystallisation of the minor diastereoisomeric product of
the reaction with isobutyraldehyde allowed the syn-relative configuration
of the minor aldol product 52 to be unambiguously determined by X-ray
crystallographic analysis, with the absolute (4S,20R,30S)-configuration as-
signed relative to the known (S)-configuration of the C(4)-stereogenic
centre. Within the crystal lattice for compound 52 intermolecular hydro-
gen bonding is observed between the C(30)-hydroxyl groups and the C(10)-
carbonyl groups.
32. Given the known enantiomeric purity (i.e., >98% ee) of the SuperQuat chiral
auxiliary (S)-11, the enantiomeric purity of 26, 33–39 and 41–45 was assigned
from the diastereoisomeric purity (determined by peak integration of the 1H
NMR spectrum of the crude reaction mixture and the pure product).
33. For examples of base-catalysed processes, see: (a) Ruano, G. J. L.; Fernandez, I.;
del Prado, C. M.; Hermoso, J. A.; Sanz-Aparicio, J.; Martinez-Ripoll, M. J. Org.
Chem. 1998, 21, 7157; (b) Fish, P. V.; Johnson, W. S. J. Org. Chem. 1994, 9, 2324;
(c) Weyerstahl, P.; Schneider, K. Liebigs Ann. Chem. 1992, 10, 1049.
34. For examples of acid-catalysed processes, see: Hayakawa, S.; Michiue, T.;
Okamoto, M.; Hatakeyama, S.; Ohta, S. Heterocycles 1998, 2, 457.
35. Pangborn, A. B.; Giardello, M. A.; Grubbs, R. H.; Rosen, R. K.; Timmers, F. J.
Organometallics 1996, 15, 1518.
36. Betteridge, P. W.; Carruthers, J. R.; Cooper, R. I.; Prout, C. K.; Watkin, D. J.
Crystals; Department of Chemical Crystallography, Chemistry Research Labo-
ratory, University of Oxford: Oxford, UK, 2001.
37. Calderon, A.; Font, J.; March, P. Tetrahedron 1992, 48, 5347.
38. Barluenga, J.; Fernandez, J. R.; Yus, M. J. Chem. Soc., Perkin Trans. 1 1985, 447.
39. (a) Nozaki, H.; Hitosi, O.; Koichiro, T.; Ozawa, S. Chem. Lett. 1979, 4, 379; (b)
Kamimura, A.; Mitsudera, H. Tetrahedron Lett. 2001, 42, 7457.