Stereoselective functionalisation of SuperQuat enamides: asymmetric synthesis of homochiral 1,2-diols and α-benzyloxy carbonyl compounds

Article abstract of DOI:10.1016/j.tet.2008.07.012

Homochiral (E)- and (Z)-enamides derived from SuperQuat (S)-4-phenyl-5,5-dimethyl-oxazolidin-2-one undergo highly diastereoselective epoxidation upon treatment with dimethyldioxirane. Subsequent epoxide opening with meta-chlorobenzoic acid proceeds via a stereoselective S_N1-type process, with retention of configuration, to give the corresponding 1′-m-chlorobenzoyl-2′-hydroxy derivatives. Treatment of the SuperQuat enamides with mCPBA effects this two-step transformation in one pot. Reductive cleavage of the isolated 1′-m-chlorobenzoyl-2′-hydroxy derivatives (≥96% de) generates homochiral 1,2-diols in ≥96% ee. Alternatively, regioselective lithiation of the enamide at C(1′) with ^tBuLi followed by reaction with an aromatic aldehyde and in situ O-benzylation generates a 1′-(benzyloxy-aryl-methyl) substituted enamide with high diastereoselectivity. Subsequent oxidative cleavage of the enamide C{double bond, long}C bond with NaIO₄/RuCl₃ followed by methanolysis of the resultant N-acyl fragment furnishes an O-benzyl protected α-hydroxy methyl ester in high ee.

Full text of DOI:10.1016/j.tet.2008.07.012

Tetrahedron 64 (2008) 9320–9344
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Stereoselective functionalisation of SuperQuat enamides: asymmetric synthesis
of homochiral 1,2-diols and a-benzyloxy carbonyl compounds
*
Caroline Aciro, Stephen G. Davies , A. Christopher Garner, Yutaka Ishii, Min-Suk Key, Kenneth B. Ling,
R. Shyam Prasad, Paul M. Roberts, Humberto Rodriguez-Solla, Catherine O’Leary-Steele,
Angela J. Russell, Hitesh J. Sanganee, 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:
Homochiral (E)- and (Z)-enamides derived from SuperQuat (S)-4-phenyl-5,5-dimethyl-oxazolidin-2-one
undergo highly diastereoselective epoxidation upon treatment with dimethyldioxirane. Subsequent
epoxide opening with meta-chlorobenzoic acid proceeds via a stereoselective SN1-type process, with
retention of configuration, to give the corresponding 10-m-chlorobenzoyl-20-hydroxy derivatives.
Treatment of the SuperQuat enamides with mCPBA effects this two-step transformation in one pot.
Reductive cleavage of the isolated 10-m-chlorobenzoyl-20-hydroxy derivatives (ꢀ96% de) generates
homochiral 1,2-diols in ꢀ96% ee. Alternatively, regioselective lithiation of the enamide at C(10) with tBuLi
followed by reaction with an aromatic aldehyde and in situ O-benzylation generates a 10-(benzyloxy-
aryl-methyl) substituted enamide with high diastereoselectivity. Subsequent oxidative cleavage of the
enamide C]C bond with NaIO4/RuCl3 followed by methanolysis of the resultant N-acyl fragment
Received 16 April 2008
Received in revised form 16 June 2008
Accepted 3 July 2008
Available online 8 July 2008
Keywords:
Asymmetric synthesis
SuperQuat
Enamides
Oxidation
furnishes an O-benzyl protected
a
-hydroxy methyl ester in high ee.
Ó 2008 Elsevier Ltd. All rights reserved.
1,2-Diols
1. Introduction
of 1 in a highly selective manner on the face opposite to the ster-
eodirecting group of the auxiliary (Scheme 1). Subsequently, Adam
et al.5b,c investigated the oxidation of a range of enamides derived
from the Evans auxiliary with DMDO and mCPBA. For instance,
enamide 5 reacted with DMDO to give epoxide 6 in 84% de. Sub-
sequent acidic hydrolysis followed by reduction gave terminal 1,2-
diol 8 in 84% ee. Alternatively, treatment of 5 with mCPBA was
reported to generate 7 in 84% de, with the stereochemistry of 7
being assigned on the assumption of ring opening of epoxide
Homochiral 1,2-diols and
a-hydroxy carbonyl compounds are
valuable building blocks in the synthesis of biologically active
compounds and natural products; the motif occurs in numerous
synthetic intermediates1 and is readily amenable to manipulation.2
The utility of the 1,2-diol motif has ensured that a multitude of
methods have been developed for its synthesis in both racemic and
homochiral forms,3 with the oxidation of olefins having proven to
be a popular and versatile transformation.4 Synthetic investigations
concerning the oxidative functionalisation of enamines and
enamides5 with either dimethyldioxirane (DMDO) or mCPBA have
demonstrated that oxidation occurs selectively at the C]C bond
rather than at the nitrogen atom. Although isolation of the epoxides
formed upon oxidation of enamines is generally difficult due to
dimerisation,6 N-acylation has been shown to stabilise the corre-
sponding enamide epoxides, enabling their detection via spectro-
scopic methods.7 The oxidative functionalisation of enamides
derived from the Evans auxiliary was initially demonstrated by
Hsung et al.,5a whereupon treatment of 1 with mCPBA followed by
HCl in MeOH gave a 56:44 mixture of 3 and 4 in 80% yield. This
stereochemical outcome was proposed to be a result of epoxidation
O
O
O
O
Ar
(i), (ii)
Me
Me
O
N
O
N
OH
Ph
2
Ph
1
Crude product ratio
3:4 = 56:44
O
O
O
OMe
OMe
Me
Me
N
O
N
OH
OH
Ph
Ph
3
4
* Corresponding author.
Scheme 1. Reagents and conditions: (i) mCPBA, DCM, MeOH, NaHCO3; (ii) HCl, MeOH.
E-mail address: steve.davies@chem.ox.ac.uk (S.G. Davies).
0040-4020/$ – see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2008.07.012

C. Aciro et al. / Tetrahedron 64 (2008) 9320–9344
9321
intermediate 6 in an SN2-type process. Reduction of 7 with NaBH4
gave diol 8 in 84% ee (Scheme 2).
16–18 as single diastereoisomers in good yield. Attempted con-
densation of 13 with propanal, however, furnished a complex
mixture of products, presumably due to polymerisation of the al-
dehyde. Therefore, a copper-catalysed coupling14 of 13 with trans-
1-bromoprop-1-ene was employed, giving 15 in quantitative yield
(Scheme 4). The configurations of enamides 14–18 were initially
assigned on the basis of 1H NMR spectroscopic analysis, from the
O
O
O
Me
Me
(i)
O
N
O
N
Ph
Ph
Ph
Ph
5
6, quant, 84% de
0
0
diagnostic values of the olefinic coupling constants (J1 –2 14.4–
14.9 Hz), and in the case of 14, 15 and 17 were subsequently proven
unambiguously by single crystal X-ray analysis (vide infra).
(ii)
(iii), (iv)
O
O
O
Ar
Me
Me
HO
(v)
O
O
HO
Ph
O
N
R
(i) or (ii)
HO
Ph
Ph
O
NH
Ph
O
N
8, 84% ee
53% from 6
78% from 7
Ph
7, 67%, 84% de
13
(i). 14, R = Ph, 79%
(ii). 15, R = Me, quant
(i). 16, R = Bn, 71%
(i). 17, R = iPr, 71%
(i). 18, R = tBu, 67%
Scheme 2. Reagents and conditions: (i) DMDO, acetone, 20 ꢁC; (ii) mCBPA, CHCl3,
20 ꢁC; (iii) TsOH, acetone/H2O (3:1), 20 ꢁC, 30 min; (iv) NaBH4, DBU, THF/H2O (4:1),
20 ꢁC, 15 min; (v) NaBH4, EtOH, 20 ꢁC, 24 h.
Scheme 4. Reagents and conditions: (i) RCH2CHO, TsOH, PhMe, Dean–Stark reflux; (ii)
trans-1-bromoprop-1-ene, N,N0-dimethylethylenediamine, CuI, K2CO3, PhMe, reflux, 5
days.
As part of our ongoing research programme for the direct syn-
thesis of homochiral aldehydes and alcohols from N-acyl oxazoli-
dinones,8,9 through exploitation of their utility as latent aldehyde
equivalents,8 we have communicated10 that the stereoselective
epoxidation of (E)-enamides 9 (derived from SuperQuat 4-phenyl-
5,5-dimethyl-oxazolidin-2-one) with either DMDO or mCPBA,11
coupled with regio- and stereoselective SN1-type ring opening of
the intermediate epoxide 10 with meta-chlorobenzoic acid (mCBA),
gave 10-m-chlorobenzoyl-20-hydroxy derivatives 11 with excellent
levels of diastereoselectivity, and suggesting that the C(10)-config-
uration assigned by Adam is in error.5b,c Cleavage of the 10-m-
chlorobenzoyl-20-hydroxy derivatives 11 gave a range of homo-
chiral 1,2-diols 12 with very high levels of enantiomeric purity
(Scheme 3). In this manuscript, we delineate fully our investigations
within this area, and report the extension of this protocol to the
2.2. Oxidation of SuperQuat (E)-enamides with DMDO
The epoxidation of representative SuperQuat (E)-enamides, viz.
14 and 15, with DMDO was initially investigated. Oxidation of 14
(R¼Ph) with an acetone solution of DMDO15 gave epoxide 19 as
the major component of a mixture of products, which precluded
accurate determination of the epoxidation diastereoselectivity.
However, recrystallisation of the crude reaction mixture gave 19 in
84% isolated yield and >98% de (Scheme 5).16 Single crystal X-ray
analysis unambiguously established the relative configuration of
19, with the absolute (4S,10R,20S)-configuration assigned from the
known (S)-stereocentre within the oxazolidinone (Fig. 1). Treat-
ment of 15 (R¼Me) with DMDO gave epoxide 20 as a single di-
astereoisomer, the configuration of which was assigned by analogy
to that of 19 (Scheme 5). The regioselectivity of ring opening of
epoxides 19 and 20 upon treatment with mCBA was next estab-
lished. Addition of mCBA to either the crude or the isolated epoxide
19 (>98% de) resulted, in both cases, in the quantitative formation
of a 96:4 mixture of the C(10)-epimeric 10-m-chlorobenzoyl-20-hy-
droxy derivatives 21 and 22, respectively (Scheme 5). The
preparation of O-benzyl protected
a-hydroxy ketones and esters.
O
O
O
R
R
(i)
O
N
O
N
Ph
9
Ph
10
(iii)
(ii)
O
O
O
Ar
R
O
R
O
(iv)
O
HO
R
R
(i)
O
N
O
N
OH
12, ≥96% ee
O
N
OH
Ph
Ph
11, ≥96% de
Ph
19, R = Ph, quant
(ii)
19, R = Ph, 84%, >98% de
14, R = Ph
15, R = Me
20, R = Me, quant, >98% de
Scheme 3. Reagents and conditions: (i) DMDO, acetone, rt; (ii) mCBA, CHCl3, rt; (iii)
mCPBA, CHCl3, rt; (iv) NaBH4, MeOH, rt.
(iii)
O
O
O
O
O
Ar
R
O
Ar
R
2. Results and discussion
+
O
N
O
N
2.1. Synthesis of SuperQuat (E)-enamides
OH
OH
Ph
Ph
21, R = Ph
22, R = Ph
24, R = Me
Initial investigations were concerned with the preparation of
homochiral (E)-enamides derived from condensation of SuperQuat
(S)-4-phenyl-5,5-dimethyl-oxazolidin-2-one12 13 with an alde-
hyde. Treatment of 13 with phenylacetaldehyde under dehydrative
conditions13 generated (E)-14 as a single diastereoisomer in 79%
isolated yield. Extension of this protocol to condensation of
hydrocinnamaldehyde, 3-methylbutyraldehyde and 3,3-dime-
thylbutyraldehyde with 13 gave the corresponding (E)-enamides
23, R = Me
Conditions
(i) - (iii)
Enamide
R
Products dra
%
14
14
15
Ph
Ph
Me
21:22
21:22
96:4
96:4
(i) then (iii)
(i) then (iii)
23:24 >99:<1
Scheme 5. Reagents and conditions: (i) DMDO, acetone, 0 ꢁC to rt, 1 h; (ii) recrystal-
lisation; (iii) mCBA, CHCl3, 0 ꢁC to rt, 3 h. [aCrude product ratio of 10-m-chlorobenzoyl-
20-hydroxy derivatives 21/22 or 23/24; Ar¼m-ClC6H4.]

9322
C. Aciro et al. / Tetrahedron 64 (2008) 9320–9344
O
O
O
O
Ar
R
R
O
N
O
N
OH
Ph
(E)-enamide
Conformation A
DMDO then mCBA
Ph
Major diastereoisomer
(4S,1'R,2'S)
O
)
(
H
O
Ar
O
H
SN1
type
R'
OH
O
O
N
O
R
O
N
R
Ph
Major epoxide
Iminium intermediate
Figure 3. Postulated mechanism for oxidation of SuperQuat (E)-enamides [Ar¼
m-ClC6H4].
analogous oxidation of Evans oxazolidinone enamides,5b,c and
furthermore is inconsistent with a mechanism involving regiose-
lective SN2-type opening of the epoxide.18 The alternative mecha-
nism involving epoxide opening in an SN1-type process to give an
N-acyl iminium intermediate, which is trapped stereoselectively by
m-chlorobenzoate is consistent with the data herein. The selectivity
in this oxidation protocol therefore arises as a result of two distinct
mechanistic steps: enamide oxidation installs the C(20)-stereo-
centre whilst the selectivity of the iminium trap by mCBA installs
the C(10)-stereocentre. The stereochemistry within epoxides 19 and
20 is consistent with oxidation occurring with high diaster-
eoselectivity anti to the stereodirecting group of the oxazolidinone
with the enamide in conformation A. The subsequent selectivity
observed upon trapping of the corresponding iminium in-
termediate may be under the control of the oxazolidinone, with
addition of mCBA occurring anti to the stereodirecting group, al-
though hydrogen-bonded delivery by the C(20)-hydroxyl group
may also be involved (Fig. 3).
Figure 1. Chem 3D representation of the X-ray crystal structure of 19 (some H atoms
removed for clarity).
observation of identical product distributions from ring opening of
either the crude or the purified (>98% de) epoxide is consistent
with 19 being formed as a single diastereoisomer in the oxidation
with DMDO. The relative configuration within the major product 21
resulting from epoxide opening was unambiguously established by
single crystal X-ray analysis,17 with the absolute (4S,10R,20S)-con-
figuration being assigned from the known (S)-stereocentre of the
oxazolidinone. The assignment of the minor product 22 as a di-
astereoisomer (rather than regioisomer) of 21 was made on the
basis of 1H NMR analysis, which revealed signals at dH 6.24 and
6.07 ppm for C(10)H, and at dH 5.66 and 5.65 ppm for C(20)H of 21
and 22, respectively, characteristic of the m-chlorobenzoyl sub-
stituent being present at C(10), and consistent with observations
made by Hsung5a and Adam.5b,c Epoxide opening of 20 (R¼Me)
with mCBA gave 23 in >98% de quantitatively (Scheme 5). The
relative configuration within 23 was unambiguously established by
single crystal X-ray analysis, with the absolute (4S,10R,20S)-config-
uration being assigned from the known (S)-stereocentre of the
oxazolidinone (Fig. 2).
2.3. Oxidation of SuperQuat (E)-enamides with mCPBA
Investigations next turned to assessment of the reactivity of the
enamide functionality towards oxidation with mCPBA, in order to
prepare the 10-m-chlorobenzoyl-20-hydroxy derivatives in one step.
Thus, oxidation of enamide 14 (R¼Ph) with mCPBA proceeded to
give a 96:4 mixture of the C(10)-epimers 21/22 (i.e., with identical
selectivity to that observed upon sequential treatment with DMDO
then mCBA). Recrystallisation of the crude reaction mixture gave 21
in >98% de and 84% isolated yield. Analogous oxidation of enamide
15 (R¼Me) also proceeded with identical levels of selectivity as the
two-step process, giving 23 as a single diastereoisomer (dr >99:<1,
23/24), which was isolated in 95% yield after recrystallisation. Ap-
plication to the range of (E)-enamides 16–18 was next investigated
and proceeded, in each case, with excellent levels of diaster-
eoselectivity to give the corresponding (4S,10R,20S)-10-m-chloro-
benzoyl-20-hydroxy derivatives 25, 27 and 29 as the major
diastereoisomeric products. Recrystallisation of the crude reaction
mixture allowed the isolation of 25 and 27 as single di-
astereoisomers, although 29 was not amenable to recrystallisation
and proved extremely labile, fragmenting to a complex mixture of
products upon attempted purification by chromatography, and
was therefore characterised from the crude reaction mixture
(Scheme 6). The relative configuration within 25 (R¼Bn) was
unambiguously established by single crystal X-ray analysis, with
the absolute (4S,10R,20S)-configuration assigned from the
known (S)-stereocentre within the oxazolidinone (Fig. 4). The
The observed syn-selectivity in these epoxide opening reactions
is in contrast to the anti-selectivity assumed by Adam et al. upon
Figure 2. Chem 3D representation of the X-ray crystal structure of 23 (some H atoms
removed for clarity) [Ar¼m-ClC6H4].

C. Aciro et al. / Tetrahedron 64 (2008) 9320–9344
9323
O
O
chromatographic purification. Reaction of 32 with acetaldehyde
generated a complex mixture of unidentifiable products and
therefore copper-catalysed coupling14 of SuperQuat 13 with cis-1-
bromoprop-1-ene was utilised, which gave 34 in quantitative yield
(Scheme 7). The configurations of enamides 33 and 34 were ini-
tially assigned on the basis of the diagnostic olefinic coupling
O
O
O
O
Ar
R
O
Ar
R
R
(i)
+
O
N
O
N
O
N
OH
OH
Ph
14-18
Ph
major
diastereoisomer
Ph
minor
diastereoisomer
0
0
constants (J1 –2 7.1–9.6 Hz) and were subsequently proven un-
ambiguously by single crystal X-ray analysis (vide infra).
Yield (de) %b
dra
Enamide
R
Products
21:22
14
15
16
17
18
Ph
Me
Bn
iPr
tBu
84 (>98)
96:4
>99:<1
96:4
95 (>98)
23:24
60 (>98)
25:26
PPh3+Cl−
(i)
O
N
O
O
O
P(OCH2CF3)2
61 (>98)
27:28
96:4
quant (96)a
(ii)
29:30
98:2
O
N
O
N
O
Scheme 6. Reagents and conditions: (i) mCPBA, CHCl3, 0 ꢁC to rt, 2.5 h. [aCrude product
ratio; b purifieddisolated yield and de of major diastereoisomer; Ar¼m-ClC6H4.]
R
Ph
31
Ph
Ph
32
(i).33, R = Ph, 76%
(ii).33, R = Ph, quant
(i).34, R = Me, 63%
O
O
(iii)
O
NH
Ph
O
N
Me
Ph
34, quant
13
Scheme 7. Reagents and conditions: (i) KOtBu, THF, ꢂ78 ꢁC, 30 min, then RCHO,
ꢂ78 ꢁC, 24 h; (ii) BuLi, THF, ꢂ78 ꢁC, 30 min, then PhCHO, ꢂ78 ꢁC, 24 h; (iii) cis-1-
bromoprop-1-ene, N,N0-dimethylethylenediamine, CuI, K2CO3, PhMe, reflux, 5 days.
2.5. Oxidation of SuperQuat (Z)-enamides with DMDO
Investigations into the oxidation of (Z)-enamides with DMDO
revealed that treatment of 34 (R¼Me) with DMDO gave an 87:13
mixture (74% de) of diastereoisomeric epoxides 35/36. Subsequent
epoxide opening upon treatment with mCBA furnished a 5:8:84:3
mixture of diastereoisomers 23/24/37/38 (Scheme 8). The relative
stereochemistry within the major diastereoisomer 37 was un-
ambiguously established by single crystal X-ray analysis, with the
absolute (4S,10R,20R)-configuration assigned from the known
(S)-stereocentre within the oxazolidinone (Fig. 5). Since the
diastereoisomeric ratio of the epoxide also represents the
diastereoisomeric ratio at the C(20)-stereocentre within the 10-m-
chlorobenzoyl-20-hydroxy oxidation products, and the absolute
configurations of 23 and 37 had been unambiguously assigned via
single crystal X-ray analysis, the absolute configurations of minor
diastereoisomers 24 and 38 could thus be assigned, i.e., [23þ24]/
[37þ38]¼13:87 (Scheme 8).
Figure 4. Chem 3D representation of the X-ray crystal structure of 25 (some H atoms
removed for clarity) [Ar¼m-ClC6H4].
(4S,10R,20S)-configurations of major diastereoisomers 27 (R¼iPr)
and 29 (R¼tBu) were assigned by analogy to those unambiguously
established for 21, 23 and 25. These observations are entirely
consistent with the oxidation with mCPBA proceeding via the
intermediacy of the corresponding diastereoisomerically pure
epoxide.
O
O
O
O
O
(i)
+
O
N
O
N
O
N
Me
Me
Me
Ph
34
Ph
35
Ph
36
The effect of changing the geometry of the enamide system from
(E) to (Z) upon the diastereoselectivity of these processes was next
examined by the preparation and subsequent oxidation of Super-
Quat (Z)-enamides.
Crude product ratio
35:36 = 87:13
(ii)
O
O
O
O
O
O
O
O
O
Ar
Me
O
Ar
Me
O
Ar
Me
O
Ar
Me
2.4. Synthesis of SuperQuat (Z)-enamides
+
+
+
O
N
O
N
O
N
O
N
In order to access SuperQuat (Z)-enamides, olefination of
benzaldehyde and acetaldehyde with the ylide derived from the
novel precursor 3119 gave 9:91 and 20:80 (E)/(Z) mixtures, re-
spectively, from which (Z)-enamides 33 and 34 were isolated
as single diastereoisomers in 76 and 63% yield, respectively.20 In
order to improve both the selectivity and the yield of enamide
formation, olefination of benzaldehyde with the novel phospho-
nate ester 32 according to the Still–Gennari protocol21 was in-
vestigated and furnished exclusively 33, in quantitative yield after
OH
OH
OH
OH
Ph
23
Ph
24
Ph
37
Ph
38
Crude product ratio 23:24:37:38 = 5:8:84:3
Scheme 8. Reagents and conditions: (i) DMDO, acetone, 0 ꢁC to rt, 1 h; (ii) mCBA,
CHCl3, 0 ꢁC to rt, 3 h. [aCrude product ratio; Ar¼m-ClC6H4.]
Treatment of 33 (R¼Ph) with DMDO gave a mixture of products,
the two major components of which were identified as the epoxide
39 and diol 40 in a 93:7 ratio (Scheme 9). A minor diastereoisomeric

9324
C. Aciro et al. / Tetrahedron 64 (2008) 9320–9344
Figure 5. Chem 3D representation of the X-ray crystal structure of 37 (some H atoms
removed for clarity) [Ar¼m-ClC6H4].
Figure 6. Chem 3D representation of the X-ray crystal structure of 40 (some H atoms
removed for clarity).
(ii)
products also represents the epoxide diastereoisomeric ratio, this
can be inferred as 89:11 (78% de), i.e., [21þ22]/[41þ42]¼11:89.
Thus, whilst oxidation of (E)-enamides 14 and 15 gives
(4S,10R,20S)-21 and (4S,10R,20S)-23 as the major products, oxidation
of the corresponding (Z)-enamides 33 and 34 gives (4S,10R,20R)-41
and (4S,10R,20R)-37 as the major products, with the opposite con-
figuration at C(20) but the same configuration at C(10), which is
entirely consistent with our mechanistic rationale involving ster-
eoselective SN1-type ring opening of the epoxide intermediate
(Fig. 7).
O
O
O
OH
O
(i)
Ph
+
O
N
O
N
O
N
Ph
Ph
OH
Ph
33
Ph
39
Ph
40
Crude product ratio
39:40 = 93:7
(iii)
O
O
O
O
O
O
O
O
O
Ar
Ph
O
Ar
Ph
O
Ar
Ph
O
Ar
Ph
+
+
+
2.6. Oxidation of SuperQuat (Z)-enamides with mCPBA
O
N
O
N
O
N
O
N
OH
OH
OH
OH
Ph
21
Ph
22
Ph
41
Ph
42
Oxidation of 33 (R¼Ph) with mCPBA gave a 5:14:77:4 mixture of
diastereoisomers 21/22/41/42, respectively, from which the major
diastereoisomer 41 was isolated in 57% yield and >98% de after
recrystallisation. Oxidation of 34 (R¼Me) with mCPBA gave
a 7:10:81:2 mixture of 23/24/37/38 from which the major product
37 was isolated in >98% de and 41% yield after recrystallisation
(Scheme 10). In both cases, the product distribution is consistent
with that seen in the two-step (DMDO then mCBA) process and is
Crude product ratio 21:22:41:42 = 3:8:85:4
Scheme 9. Reagents and conditions: (i) DMDO, acetone, 0 ꢁC to rt, 1 h; (ii) recrystal-
lisation; (iii) mCBA, CHCl3, 0 ꢁC to rt, 3 h. [aCrude product ratio; Ar¼m-ClC6H4.]
epoxide could not be unambiguously identified in the 1H NMR
spectrum of the crude reaction mixture, precluding an assessment
of the epoxide diastereoisomeric ratio. Attempted recrystallisation
of the crude reaction mixture furnished diol 40 only. Single crystal
X-ray analysis unambiguously established the relative configura-
tion of 40, with the absolute (4S,10R,20R)-configuration assigned
from the known (S)-stereocentre of the oxazolidinone (Fig. 6). This
unambiguously confirmed the (20R)-configuration, and corrobo-
rates the (4S,10R,20R)-configuration, of the major epoxide 39. The
observed stereochemistry within diol 40 is in accordance with 40
arising from stereoselective SN1-type ring opening of epoxide 39 by
adventitious water. Treatment of the crude mixture of 39 and 40
with mCBA gave a 3:8:85:4 mixture of 21/22/41/42 (Scheme 9).
Diastereoisomers 21 and 22 were spectroscopically identical to the
products resulting from oxidation of the corresponding (E)-enam-
ide 14. The absolute configuration of the major diastereoisomeric
product 41 in this protocol was assigned by direct analogy to that
unambiguously proven for 37 (R¼Me). Therefore, the configuration
within the remaining diastereoisomer (4S,10S,20R)-42 could be
assigned. Given that the diastereoisomeric ratio at the C(20)-ster-
eocentre within the 10-m-chlorobenzoyl-20-hydroxy oxidation
O
O
O
O
Ar
R
O
N
O
N
R
OH
Ph
Ph
(Z)-enamide
Major diastereoisomer
Conformation A
(4S,1'R,2'R)
mCPBA
mCBA
O
)
(
H
O
Ar
O
H
SN1
type
R
O
O
N
O
R
OH
O
N
Ph
Iminium intermediate
Ph
Major epoxide
Figure 7. Postulated mechanism for oxidation of SuperQuat (Z)-enamides [Ar¼
m-ClC6H4].

C. Aciro et al. / Tetrahedron 64 (2008) 9320–9344
9325
O
O
O
O
O
O
O
O
O
O
Ar
R
O
Ar
R
O
Ar
R
O
Ar
R
(i)
+
+
+
O
N
O
N
O
N
O
N
O
N
R
OH
OH
OH
OH
Ph
Ph
21, R = Ph
23, R = Me
Ph
22, R = Ph
24, R = Me
Ph
Ph
42, R = Ph
38, R = Me
33, R = Ph
34, R = Me
41, R = Ph
37, R = Me
Yield (de) %b
57 (>98)
dra
Enamide
R
Products
33
34
Ph
Me
21:22:41:42 5:14:77:4
23:24:37:38 7:10:81:2
41 (>98)
Scheme 10. Reagents and conditions: (i) mCPBA, CHCl3, 0 ꢁC to rt, 2.5 h. [aCrude product ratio; bpurifieddisolated yield and de of major diastereoisomer; Ar¼m-ClC6H4.]
consistent with the reaction proceeding via the corresponding
epoxide intermediate.
C(20)H for (E)-enamides, or N(3)–C(10)–C(20)–C(20)R for (Z)-enam-
ides (42). For (Z)-enamides 33 and 34, significant deviation from
planarity is noted and is presumably the result of unfavourable
steric interactions between the C(20)-substituent and the oxazoli-
dinone framework. For all enamides 14, 15, 33 and 34, however,
s-trans conformation A is preferred over s-cis conformation B to
minimise steric interactions between the enamide system and the
oxazolidinone carbonyl group (Fig. 9). Similar solution-phase
enamide conformations were inferred from UV studies: lmax for 33
and 34 is shifted to lower wavelengths as compared to the corre-
sponding (E)-enamides 14 and 15, with a concomitant reduction in
the value of the molar extinction coefficient. These effects are more
2.7. Solid and solution-phase conformations of SuperQuat
enamides
In order to probe the origin of the lower levels of selectivity
observed upon the oxidative functionalisation of (Z)-enamides 33
and 34 as compared to their (E)-counterparts 14 and 15, re-
spectively, their preferred conformations were investigated. Single
crystal X-ray analysis of 14, 15, 33 and 34 confirmed the assigned
enamide configurations and allowed the solid state conformations
to be probed (Fig 8). For (E)-enamides 14 and 15, the enamide
system lies approximately planar as indicated by the values of the
dihedral angles C(2)–N(3)–C(10)–C(10)H (41), and N(3)–C(10)–C(20)–
pronounced in the
b-styryl-enamides: for 14, lmax 275.11 nm,
3
¼27103ꢃ103 cm2 molꢂ1
,
cf. 33, lmax 259.45 nm,
3
¼14864ꢃ
103 cm2 molꢂ1; for 15 lmax 240.65 nm,
3
¼2661ꢃ103 cm2 molꢂ1, cf.
Figure 8. Chem 3D representations of the single crystal X-ray structures of 14, 15, 33 and 34 (some H atoms removed for clarity).

9326
C. Aciro et al. / Tetrahedron 64 (2008) 9320–9344
Y
(
)
X
phenylethane-1,2-diol (S)-49, which, after separation from the
SuperQuat auxiliary 13 by chromatography, was isolated in 81%
O
O
X
22
20
O
N
N
O
yield and >98% ee {[
a
]
þ64.0 (c 0.25, CHCl3); lit.26
[
a]
þ60.5 (c
D
D
1.15, CHCl3)}. Analogous treatment of (4S,10R,20R)-41 gave (R)-1-
Y
Ph
Conformation A
19
Ph
Conformation B
max nm
103cm2mol-1
phenylethane-1,2-diol (R)-49 in 60% yield and >98% ee {[
a
]
ꢂ54.1
D
(c 0.9, CHCl3)}. Reduction of (4S,10R,20S)-23 with NaBH4 allowed the
isolation of (S)-propane-1,2-diol (S)-50 in 37% yield and >98% ee
Enamide
14
X,Y
ε
X = Ph,Y = H 275.11
27103
2661
14864
1944
23
31
after distillation {[
a
]
þ18.1 (c 0.15, H2O); lit.27
[a
]
þ20.7 (c 7.5,
D
D
15 X = Me,Y = H 240.65
33
H2O)}. Similarly, reduction of (4S,10R,20R)-37 gave (R)-propane-1,2-
X = H,Y = Ph 259.45
23
34 X = H,Y = Me 240.06
diol (R)-50 in 40% yield and >98% ee {[
Meanwhile, reduction of 25 (>98% de) with NaBH4 gave (S)-3-
phenylpropane-1,2-diol (S)-51 {[
a
]
ꢂ19.6 (c 1.6, H2O)}.
D
Figure 9. UV data and conformations of SuperQuat enamides.
24
20
a]
ꢂ33.5 (c 0.9, EtOH), lit.28
[a]
D
D
ꢂ36 (c 1.0, EtOH)} in 93% yield and >98% ee. Although similar
reduction of 27 (>98% de) with NaBH4 led to low isolated yields of
the corresponding diol, treatment with LiAlH4 allowed the direct
isolation of diol (S)-52 in 56% yield and in 96% ee. Application of this
reduction protocol to a freshly prepared sample of crude enamide
29 (96% de) with LiAlH4 allowed the isolation of diol (S)-53 in 51%
yield and 96% ee (Scheme 12).
34, lmax 240.06 nm,
3
¼1944ꢃ103 cm2 molꢂ1 (Fig. 9). These results
are therefore suggestive that, as a result of the distortion from
planarity of the enamide system, the C(4)-phenyl stereodirecting
group is less well able to shield one face of the (Z)-enamide when
compared to the corresponding (E)-enamide, resulting in a lower-
ing of the diastereofacial selectivity upon epoxidation, which is
consistent with our experimental observations.
O
2.8. Synthesis of homochiral 1,2-diols
O
O
O
Ar
R
R
(i)
HO
+
O
NH
Ph
With single diastereoisomers of 10-m-chlorobenzoyl-20-hydroxy
derivatives available, their hydrolysis to furnish
O
N
OH
a-hydroxy alde-
OH
Ph
hydes was investigated. It is known that -hydroxy aldehydes
a
13
49-53
Yield diol % ee %a
readily undergo dimerisation22 or rearrangement to
a-hydroxy
ketones,23 and are therefore usually obtained in protected forms.24
Diol
R
Yield 13 %
(4S,1'R,2'S)-21
(4S,1'R,2'R)-41
(4S,1'R,2'S)-23
(4S,1'R,2'R)-37
(4S,1'R,2'S)-25
(4S,1'R,2'S)-27
(4S,1'R,2'S)-29
(S)-49
(R)-49
(S)-50
(R)-50
(S)-51
(S)-52
(S)-53
Ph
Ph
Me
Me
Bn
iPr
78
90
99
90
99
81
84
81
60
37
40
93
56
51
>98
>98
>98
>98
>98
96
Unfortunately, attempted methanolysis of 21 gave a 62:38 mixture
of diastereoisomeric
a-methoxy compounds 43/44, which was
stable even upon prolonged heating, whilst all attempts to protect
the hydroxyl group of 21 (to facilitate subsequent acidic hydroly-
sis)8 gave a complex mixture of products, of which SuperQuat 13
and ketone 48 were the only identifiable components; treatment of
21 with Et3N and DMAP gave 13 and 48 as the only products. This
may be explained by decomposition of 21 via acyl transfer to the
C(20)-hydroxyl group followed by cleavage to SuperQuat 13 and
tBu
96
Scheme 12. Reagents and conditions: (i) NaBH4, MeOH, rt; (ii) LiAlH4, THF, rt.
[aEnantiomeric excess values were determined by chiral GC analysis of diol 49, the
diacetyl derivatives of diols 50, 52 and 53, and the bis-trifluoroacetyl derivative of 51;
Ar¼m-ClC6H4.]
a
-hydroxyaldehyde 45, which subsequently isomerises under the
basic reaction conditions25 to give 48 (Scheme 11).
2.9. Oxidative functionalisation of SuperQuat enamides
derived from a ketone
O
Following the successful application of this enamide oxidation
protocol to the synthesis of 1,2-diols, extension to incorporate the
synthesis of a-hydroxy ketones was examined. Initial studies pro-
O
OMe
O
O
Ar
Ph
(i)
Ph
O
N
N
O
bed the oxidation of cyclohexenyl enamide 54, derived from con-
densation of SuperQuat 13 with cyclohexanone. Treatment of 54
with mCPBA gave a 78:22 mixture of SuperQuat 13 and aldehyde
58. Repetition of this protocol omitting aqueous work-up gave
predominantly 58 (>90%), although attempted purification of the
crude reaction mixture returned only SuperQuat 13. These results
suggest that epoxidation was occurring, followed by ring opening
and trapping of the resultant N-acyl iminium intermediate 56 by
mCPBA to generate 57.29 Collapse of 57 liberates aldehyde 58, which
upon hydrolysis regenerates SuperQuat 13. Although this oxidation
pathway contrasts with the oxidation of the aldehyde derived
systems, a plausible rationale for the addition of mCPBA to the
cyclohexenyl system may be due to the greater inductive stability of
the ketone derived N-acyl iminium intermediate as compared to
the aldehyde derived system (Scheme 13).
To address the problem of oxidative ring cleavage, it was en-
visaged that epoxidation in a nucleophilic alcohol solvent such as
methanol may suppress the unwanted fragmentation by competi-
tive trapping of the N-acyl iminium intermediate 56. Treatment
of 54 with mCPBA in anhydrous MeOH at 0 ꢁC gave a 66:30:3:1 ratio
of 59/60/61/62. The effect of temperature on the diaster-
eoselectivity was next investigated, with the optimum conversion
OH
OH
Ph
Ph
21
43 and 44, dr 62:38, 88%
(ii)
O
O
Ph
Ph
HO
H
+
O
NH
Ph
O
Ar
O
Ar
O
O
13, 90%
45
46
acyl
migration
Ph
Ph
O
O
O
OH
O
Ar
O
Ar
47
48, quant
Scheme 11. Reagents and conditions: (i) MeOH, TsOH, reflux; (ii) Et3N, DMAP [Ar¼
m-ClC6H4].
Following the recalcitrance of 21 towards hydrolysis, reduction
to the corresponding homochiral 1,2-diol was investigated. Treat-
ment of (4S,10R,20S)-21 with NaBH4 in MeOH furnished (S)-1-

C. Aciro et al. / Tetrahedron 64 (2008) 9320–9344
9327
O
O
O
(i)
NH
Ph
O
O
O
N
Ph
54
13
(ii)
O
O
N
N
O
OH
Ph
56
Ph
55
CHO
O
O
Ar
O
O
O
O
+
O
O
N
O
NH
Ph
O
N
OH
Ph
57
Ph
58
13
(iii)
Scheme 13. Reagents and conditions: (i) cyclohexanone, TsOH, PhMe, Dean–Stark
reflux; (ii) mCPBA, DCM, 0 ꢁC, molecular sieves, 12 h; (iii) chromatography on SiO2.
Figure 10. Chem 3D representation of the X-ray crystal structure of 59 (some H atoms
removed for clarity).
and diastereocontrol observed at ꢂ20 ꢁC, giving a 67:30:2:1 ratio of
59/60/61/62; subsequent chromatography gave 59, 60 and 61 in 50,
26 and (higher than expected) 11% yield, respectively, and in >98%
de in each case (Scheme 14).
The relative configurations within 59–61 were determined from
1H NMR NOESY experiments, with those of 59 and 61 being con-
firmed unambiguously by single crystal X-ray analysis (Figs. 10 and
11). The absolute configurations (4S,10R,20S)-59, (4S,10S,20R)-60 and
(4S,10S,20S)-61 were thus assigned from the known (S)-stereocentre
within the oxazolidinone.
The isolated yield of 61 (11%) was significantly higher than the
proportion indicated by analysis of the crude reaction mixture, and
most likely originates from interconversion of 59 and 61 during
chromatography. In support of this hypothesis, a pure sample of 59
(>98% de) was treated with a catalytic amount of sulfuric acid in
MeOH-d4, and the reaction was monitored over time by 1H NMR
spectroscopy: complete epimerisation of 59-d3 to 61-d3 (>98% de)
was observed, demonstrating that 61 is the thermodynamically
more stable isomer (Scheme 15). These results are in accordance
with observations made by Zefirov et al. in studies on 1,1,2-tri-
substituted cyclohexanes in which the 2-substituent preferentially
lies axial due to minimisation of syn-pentane interactions.30
In contrast to the high diastereocontrol observed in the oxida-
tive functionalisation of aldehyde derived SuperQuat enamides,
only modest stereoselectivity is seen in the cyclohexenyl system.
The selectivity in the oxidation of the cyclohexenyl system is as-
sumed to be controlled by similar factors to the aldehyde derived
enamide system, with the oxidation occurring anti to the phenyl
Figure 11. Chem 3D representation of the X-ray crystal structure of 61 (some H atoms
removed for clarity).
substituent on the oxazolidinone ring. The selectivity of the epoxi-
dation is represented by the ratio of the (S) to (R) configurations at
the C(20) position; hence, under the optimum reaction conditions,
Me
O
Me
O
Me
O
Me
O
O
O
O
O
O
(i)
+
+
+
O
N
O
N
O
N
O
N
O
N
OH
OH
OH
OH
Ph
54
Ph
Ph
Ph
Ph
(4S,1'R,2'S)-59 (4S,1'S,2'R)-60 (4S,1'S,2'S)-61
(4S,1'R,2'R)-62
Ratio
Temperature °C
Time h Conversion %
59:60:61:62
80:17:2:1
67:30:2:1
66:30:3:1
64:30:5:1
−40
−20
0
2
2
1
1
35
100
100
100
20
Scheme 14. Reagents and conditions: (i) mCPBA, MeOH, T ꢁC, X h (see table).

9328
C. Aciro et al. / Tetrahedron 64 (2008) 9320–9344
Me
O
CD3
O
CD3
O
O
O
O
O
(i)
O
N
N
N
N
O
O
O
OH
OH
OH
OH
Ph
56
Ph
Ph
(4S,1'R,2'S)-59-d
Ph
(4S,1'R,2'S)-59
3
(4S,1'S,2'S)-61-d
3
>98% de
>98% de
Scheme 15. Reagents and conditions: (i) MeOH-d4, H2SO4 (cat).
H
N
the epoxide diastereoisomeric ratio is 69:31 ([59þ61]/[60þ62]).
Stereoselective oxidation of 54 in conformation C, anti to the ster-
eodirecting group of the oxazolidinone generates epoxide 55 from
which 59 and 61 are subsequently derived. Diastereoisomers 60
and 62 originate from either non-stereoselective epoxidation of 54
in conformation C or stereoselective epoxidation of 54 in confor-
mation D, followed by regioselective epoxide opening by MeOH,
although single crystal X-ray analysis of 54 indicates that in the
solid state the cyclohexene ring exclusively adopts conformation C,
which places the enamide double bond in the plane of the oxazo-
lidinone ring system with the methylene group straddling the
carbonyl group to minimise steric interactions (Fig. 12). The 67:2
ratio of C(10) epimers 59 and 61, and 30:1 ratio of C(10) epimers 60
and 62 show that the trapping of the corresponding N-acyl iminium
intermediates by MeOH (under kinetic control) occurs with high
syn-selectivity with respect to the C(20)-hydroxyl group for both
epoxide diastereoisomers (Fig. 13).
O
O
N
O
O
Ph
54
Ph
54
Conformation C
mCPBA
Conformation D
Me
O
O
O
O
O
N
O
N
O
N
O
OH
OH
Ph
Major epoxide 55
Ph
Iminium 56
Ph
Major diastereoisomer
(4S,1'R,2'S)-59
Figure 13. Postulated mechanism for oxidation of enamide 54.
The hydrolytic cleavage of 59 and 61 to
a-hydroxycyclohex-
Me
O
N
Me
O
N
O
O
O
anone 63 was next examined. Treatment of 59 with HCl in THF
gave a mixture of 63 and SuperQuat 13, from which 63 was iso-
lated by chromatography in 55% yield (Scheme 16). The specific
rotation of 63 was considerably lower than the literature values
(i)
(ii), (iii)
HO
O
O
OH
OBn
Ph
Ph
64
(4S,1'R,2'S)-59
63, 55%
20
20
{[a
]
ꢂ1.5 (c 1.0, CHCl3); lit.31 for 90% ee [
a
]
ꢂ13.3 (c 0.5, CHCl3);
D
lit.32D for enantiomer, 96% ee [
a]
þ23.3 (c 0.6, CHCl3)}, suggesting
18
D
Me
O
Me
O
that extensive racemisation had occurred33 and therefore pro-
tection of the hydroxyl group prior to hydrolysis was probed.
Benzylation of (4S,10R,20S)-59 was followed by chromatography,
O
O
N
O
(i)
(ii)
BnO
O
O
N
OH
OBn
Ph
Ph
(4S,1'S,2'S)-65, 95%
giving (S)-a-benzyloxycyclohexanone (S)-66 in 9% yield and in-
(S)-66
(4S,1'S,2'S)-61
9% from 59
dicating that 64 is unstable towards hydrolysis. Benzylation of the
thermodynamically more stable diastereoisomer (4S,10S,20S)-61
gave 65 in 95% isolated yield with subsequent hydrolysis giving
69% from 65
Scheme 16. Reagents and conditions: (i) HCl (10% aq), THF, 2 h; (ii) NaH, BnBr, DMF;
(iii) chromatography on SiO2.
23
21
(S)-66 in 69% yield {[
a
]
ꢂ103.0 (c 0.8, CHCl3); lit.34
[
a
]
ꢂ108.1
D
D
(c 1.2, CHCl3)} (Scheme 16).
2.10. Stereoselective functionalisation of SuperQuat
enamides via C(10)-lithiation
In order to extend the utility of this methodology for the syn-
thesis of a-hydroxy carbonyl compounds, the ability of SuperQuat
enamides to function as acyl anion equivalents through lithiation,
subsequent reaction with an aldehyde, and hydrolysis was in-
vestigated. It was anticipated that regioselective lithiation of
SuperQuat enamides 67 followed by stereoselective aldol reaction35
would generate
to hydrolytic cleavage to
cleavage followed by alcoholysis to
Initial investigations focused on the functionalisation of enam-
ides 14 and 72,36 which lack the capacity for -deprotonation.37
a
-substituted enamides 69 that would be amenable
-hydroxy ketones 70, or oxidative C]C
-hydroxy esters 71 (Fig. 14).
a
a
g
Regioselective C(10)-lithiation of 14 with tBuLi followed by addition
of benzaldehyde gave a 92.5:7.5 mixture of alcohols 75 and 76 (85%
de) from which the major diastereoisomer 75 was isolated in 60%
yield and >98% de after sequential chromatography and recrys-
tallisation. Meanwhile, analogous treatment of enamide 72 gave
alcohols 77 and 78 as a 67:33 mixture, indicating that the presence
of the (E)-b-phenyl group has a beneficial effect on the selectivity in
this protocol. Further studies in this area therefore centred upon
Figure 12. Chem 3D representation of the X-ray crystal structure of 54 (some H atoms
removed for clarity).
enamide 14 (Scheme 17).

C. Aciro et al. / Tetrahedron 64 (2008) 9320–9344
9329
chromatography, however, resulted in an intramolecular rear-
rangement via endocyclic cleavage to afford tertiary alcohol 81 as
the sole product. In order to suppress this rearrangement, an in situ
O-benzyl protection strategy was investigated. Thus, sequential
treatment of 14 with tBuLi and acetaldehyde, and subsequent
addition of benzyl bromide afforded a complex mixture containing
82 and 83. Chromatography furnished the major diastereoisomer
82 in 51% yield and >98% de (Scheme 18).
With higher levels of reactivity and diastereocontrol displayed
in reaction of 14 with benzaldehyde compared to the aliphatic al-
dehydes, further additions to aromatic aldehydes were pursued,
with in situ benzylation being preferred. Treatment of 14 with tBuLi
and benzaldehyde, and subsequent addition of benzyl bromide
afforded a 92:8 mixture of 84 and 85. Purification via chromatog-
raphy furnished 84 in 83% yield and >98% de. Analogous reactions
employing p-anisaldehyde and m-trifluoromethylbenzaldehyde
gave chromatographically separable 78:22 and 94:6 mixtures of the
corresponding benzyl ethers 86/87 and 88/89, respectively
(Scheme 19).
The relative configurations within 84 and 88 were un-
ambiguously established by single crystal X-ray analysis (Figs. 15
and 16), with the absolute (4S,100R)-configurations assigned from
the known (S)-stereocentre of the oxazolidinone. The absolute
configurations of the other major diastereoisomers 75, 77, 79, 82
and 86 were therefore assigned as (4S,100R) by analogy.
Schmidt et al. have represented the addition of a vinyl lithium
species to a carbonyl compound as a centre–face interaction, where
the C–Li bond, centre, attacks the face of the carbonyl double bond
in the aldehyde.38 The intermediate vinyl lithium species 73 is
expected to have a defined five-membered ring chelate structure
due to the stabilisation of the carbanion by complexation of the
lithium by the carbonyl group and whilst the origin of stereocontrol
in the approach of an aldehyde to a monomeric organolithium is
unclear, a simplistic model may be proposed to account for the
observed stereocontrol.38 Initial co-ordination of the aldehyde to
O
O
Li
regioselective
lithiation
R
R
O
N
O
N
Ph
67
Ph
68
stereoselective
aldol reaction
HO
R'
O
C=C oxidation
HO
O
R'
HO
O
R'
hydrolysis
and alcoholysis
R
O
N
R
OR''
Ph
69
70
71
Figure 14. Proposed synthesis of
SuperQuat enamides 67.
a
-hydroxy carbonyl compounds 70 and 71 from
HO
HO
Ph
Ph
O
O
Li
O
O
R
R
(ii)
(i)
R
+
O
R
O
N
O
N
O
N
N
Ph
Ph
Ph
Ph
14, R = Ph
73, R = Ph
75, R = Ph
77, R = H
76, R = Ph
78, R = H
72, R = H
74, R = H
R
Ph
H
Products
75:76 92.5:7.5
77:78
dra
Yield (de) %b
60 (>98)
Enamide
14
72
60 (34)
67:33
Scheme 17. Reagents and conditions: (i) tBuLi, THF, ꢂ78 ꢁC; (ii) PhCHO. [aCrude
product ratio; bpurifieddisolated yield and de of major diastereoisomer.]
The scope of other aldehydes that could be tolerated in the
reaction protocol was next examined. Although treatment of 14
with tBuLi followed by isobutyraldehyde or pivalaldehyde fur-
nished a complex mixture of products in both cases, with no evi-
dence of the desired addition products, reaction with acetaldehyde
gave an 83:17 mixture of 79 and 80. Attempted separation by
HO
HO
Me
Ph
Me
Ph
Me
Ph
O
O
N
O
O
O
HO
Ph
(i), (ii)
(iii)
O
O
N
+
O
O
N
N
Ph
14
Ph
81
Ph
79
Ph
80
79:80 83:17, 57% yield
(i), (iv)
BnO
O
BnO
O
Me
Ph
Me
Ph
+
N
O
N
Ph
Ph
83
82, 51%
>98% de
t
Scheme 18. Reagents and conditions: (i) BuLi, THF, ꢂ78 ꢁC; (ii) MeCHO; (iii) SiO2; (iv) MeCHO, then BnBr.
BnO
O
BnO
O
Ar
Ar
O
O
Li
Ph
Ph
(ii)
(i)
Ph
Ph
O
N
O
N
+
O
O
N
N
Ph
14
Ph
73
Ph
84, Ar = Ph
Ph
85, Ar = Ph
86, Ar = p-MeOC6H4 87, Ar = p-MeOC6H4
88, Ar = m-CF3C6H4 89, Ar = m-CF3C6H4
Yield (de) %b
83 (>98)
dra
Ar
Products
84:85
Ph
92:8
78:22
94:6
p-MeOC6H4
m-CF3C6H4
72 (>98)
86:87
88:89
62 (>98)
t
Scheme 19. Reagents and conditions: (i) BuLi, THF, ꢂ78 ꢁC; (ii) ArCHO, then BnBr. [aCrude product ratio; bpurifieddisolated yield and de of major diastereoisomer.]

9330
C. Aciro et al. / Tetrahedron 64 (2008) 9320–9344
Ph
O
Ph
Ph
N
O
O
H
O
Li
O
Ph
N
O
O
H
Li
H
Ph
73
90
Ar
Ph
O
O
H
Ph
H
Ph
N
N
Li
O
OH
H
H
Ar
91
Major diastereoisomer
Si face attack Ar
(4S,1''R)-92
FAVOURED
Figure 17. Plausible model for the approach of an aldehyde to lithiated enamide 73.
The cleavage of the addition products to the corresponding
a
-hydroxy ketones was probed, although treatment of 84 with HCl
at rt returned the starting material and subjecting 84 to similar
conditions under reflux led to decomposition. Sequential C]C
oxidation followed by alcoholysis of the resultant N-acyl oxazoli-
dinone was therefore examined. Treatment of 84 (90% de) with
39
sodium periodate and a catalytic amount of RuCl3 gave the N-
acyl product 94 in 92% isolated yield and 90% de. Methanolysis of
23
94 gave
a
-benzyloxyester 95 in 79% yield and 90% ee {[
a
]
ꢂ84.9
D
Figure 15. Chem 3D representation of the X-ray crystal structure of 84 (some H atoms
removed for clarity).
20
(c 1.15, CHCl3); lit.40 for >99% ee [
a]
ꢂ95.9 (c 1.1, CHCl3)} in-
D
dicating that no racemisation occurs during the cleavage process
(Scheme 20).
BnO
O
Ph
HO
O
Ph
(i) or (ii)
Ph
O
N
Ph
Ph
84, 90% de
93
(iii)
BnO
O
Ph
O
BnO
MeO
Ph
O
(iv)
O
N
Ph
94, 92%
95, 79%
90% ee
90% de
Scheme 20. Reagents and conditions: (i) HCl (10% aq), THF, rt, 12 h; (ii) HCl (10% aq),
THF, reflux, 12 h; (iii) NaIO4, RuCl3, CCl4/MeCN/H2O (2:2:3); (iv) MeMgBr, MeOH.
3. Conclusion
In conclusion, the oxidation of SuperQuat enamides via epoxi-
dation with DMDO and subsequent SN1-type regio- and stereo-
selective epoxide opening with m-chlorobenzoic acid generates the
corresponding 10-m-chlorobenzoyl-20-hydroxy derivatives in good
to excellent de, which can be recrystallised to single di-
astereoisomers (>98% de). Enamide oxidation with mCPBA gener-
ates the 10-m-chlorobenzoyl-20-hydroxy derivatives in one pot.
Subsequent reductive cleavage enables access to 1,2-diols with high
enantiomeric purity. The SuperQuat enamides are available with
either (E)- or (Z)-geometry of the double bond, and therefore this
protocol represents a stereodivergent strategy to either enantiomer
of the corresponding 1,2-diol from a single enantiomer of the
SuperQuat auxiliary. Alternatively, addition of a C(10)-lithiated
SuperQuat enamide to an aromatic aldehyde proceeds with high
levels of diastereoselectivity. Sequential O-benzylation, enamide
oxidation with NaIO4/RuCl3 and methanolysis give a homochiral
Figure 16. Chem 3D representation of the X-ray crystal structure of 88 (some H atoms
removed for clarity).
the lithium atom anti to the stereodirecting phenyl group of the
oxazolidinone and to the more sterically available lone pair of
the aldehyde 90 also serves to minimise interactions between the
oxazolidinone ring and the b-phenyl group of the enamide, pre-
senting the Si face of the aldehyde to the enamide. Subsequent
attack of the lithiated enamide on the Si face of the aldehyde 91
gives rise to the observed major diastereoisomer 92. This simple
model is thus able to rationalise the beneficial effect of the b-phenyl
substituent in 73 (as compared to unsubstituted 74), and the higher
stereoselectivity observed on the addition to an aryl aldehyde (as
compared to acetaldehyde), as potential steric interactions in these
cases are likely to be more severe (Fig. 17).
O-benzyl protected a-hydroxy methyl ester in high ee.

C. Aciro et al. / Tetrahedron 64 (2008) 9320–9344
9331
4. Experimental
4.4. General procedure 3 for addition of lithiated SuperQuat
enamides to an aldehyde
4.1. General experimental
tBuLi (1.7 M in pentane, 2.0 equiv) was added dropwise via sy-
ringe to a solution of SuperQuat enamide 14 (1.0 equiv) in anhy-
drous THF at ꢂ78 ꢁC and stirred for 45 min. The requisite aldehyde
(2.2 equiv) was added and the reaction mixture was stirred for
a further 1 h at ꢂ78 ꢁC before the addition of BnBr (2.0 equiv), after
which it was allowed to warm to rt over 12 h. The reaction mixture
was quenched with satd aq NH4Cl, diluted with H2O and extracted
three times with EtOAc. The combined organic extracts were dried
and concentrated in vacuo. The residue was purified via flash
column chromatography.
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.41
Water was purified by an ElixÒ UV-10 system. All other solvents
were used as supplied (analytical or HPLC grade) without prior
purification. mCPBA was used as a 70–77% suspension in water
(Aldrich). Solutions of DMDO in acetone were prepared15a and
titrated15b according to the procedures of Adam et al. 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), iodine, 1% aq KMnO4 or 10%
ethanolic phosphomolybdic acid. Flash column chromatography
was performed on Kieselgel 60 silica.
4.4.1. (S,E)-N(3)-(20-Phenylethenyl)-4-phenyl-5,5-dimethyl-
oxazolidin-2-one 14
O
Ph
O
N
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 10ꢂ1 deg cm2 gꢂ1 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
Ph
Following General Procedure 1, TsOH (ca. 500 mg), phenyl-
acetaldehyde (1.47 mL, 12.6 mmol) and 13 (2.0 g, 10.5 mmol) in
PhMe (150 mL) gave the crude reaction mixture. Purification via
flash column chromatography (eluent 30–40 ꢁC petrol/Et2O, 19:1)
gave 14 as a white solid (2.43 g, 79%). Found C, 78.0; H, 6.5; N, 4.65%.
19H19NO2 requires C, 77.8; H, 6.5; N, 4.8%. Mp 144 ꢁC; [
1.0, DCM); nmax (DCM) 1752 (C]O); dH (200 MHz, CDCl3) 1.00 (3H,
s, C(5)MeA), 1.66 (3H, s, C(5)MeB), 4.81 (1H, s, C(4)H), 5.51 (1H, d, J
14.9, C(20)H), 7.12–7.50 (11H, m, C(10)H, Ph); dC (50 MHz, CDCl3) 24.1,
29.2, 68.1, 82.6, 113.0, 123.4, 125.6, 126.8, 128.8, 129.1, 129.3, 135.0,
136.2, 155.2; m/z (APCIþ) 294 ([MþH]þ).
23
C
a
]
þ7.8 (c
D
(KBr), as stated. Selected characteristic peaks are reported in cmꢂ1
.
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
spectra were recorded on either a VG MassLab 20–250 or a Micro-
mass Platform
1
spectrometer. The ion [Mþ59]þ refers to
[MþMeCNþNH4]þ. Accurate mass measurements were run on ei-
ther 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. Chiral gas chromatography was performed on a CE
instruments Trace GC (Thermoquest) machine with an SGE Cydex-
4.4.1.1. X-ray crystal structure determination for 14. Data were col-
k-CCD diffractometer with graphite
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.42
lected using an Enraf–Nonius
a
b
stationary phase (25 mꢃ0.22 mm) with helium as the carrier gas,
using an FID detector.
X-ray crystal structure data for 14 [C19H19NO2]: M¼293.37,
monoclinic, space group P1211, a¼6.1034(2) Å, b¼7.9182(3) Å,
4.2. General procedure 1 for the preparation of SuperQuat
(E)-enamides
c¼17.0391(7) Å,
0.077 mmꢂ1
b
¼92.994(2)ꢁ,
V¼822.34(5) Å3,
Z¼2,
m
¼
,
colourless plate, crystal dimensions¼0.1ꢃ0.1ꢃ
0.2 mm3. A total of 1970 unique reflections were measured for
5< <27 and 1629 reflections were used in the refinement. The final
parameters were wR2¼0.056 and R1¼0.047 [I>1.0 (I)]. Crystallo-
TsOH (ca. 25 mol %) and the requisite aldehyde (1.2 equiv) were
added sequentially to a stirred solution of SuperQuat 13 (1.0 equiv)
in PhMe. The reaction mixture was heated at 120 ꢁC under Dean–
Stark conditions for 12 h and then concentrated in vacuo. The
residue was purified via flash column chromatography.
q
s
graphic data (excluding structure factors) have been deposited with
the Cambridge Crystallographic Data Centre as supplementary
publication number CCDC 653128. 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].
4.3. General procedure 2 for oxidation of SuperQuat
enamides with mCPBA
4.4.2. (S,E)-N(3)-(Prop-10-en-10-yl)-4-phenyl-5,5-dimethyl-
oxazolidin-2-one 15
mCPBA (1.5 equiv) was added to a stirred solution of the
requisite SuperQuat enamide (1.0 equiv) in CHCl3 at 0 ꢁC and the
resultant suspension stirred for 30 min before warming to rt over
a further 2 h. After this time, satd aq Na2SO3 was added until
starch–iodide paper indicated that no mCPBA remained. The
mixture was then partitioned between DCM and satd aq NH4Cl,
and the organic layer was separated. The aqueous layer was then
extracted twice with DCM and the combined organic extracts
were washed twice with brine, dried and concentrated in vacuo.
The residue was purified via recrystallisation from DCM/heptane
(1:1).
O
Me
O
N
Ph
trans-1-Bromoprop-1-ene (0.81 mL, 9.40 mmol) was added to
a suspension of 13 (360 mg, 1.88 mmol), CuI (30 mg, 0.156 mmol),
K2CO3 (434 mg, 3.14 mmol) and N,N0-dimethylethylenediamine
(17 mL, 0.156 mmol) in PhMe (3 mL). The suspension was stirred at

9332
C. Aciro et al. / Tetrahedron 64 (2008) 9320–9344
110 ꢁC for 5 days then allowed to cool to rt, filtered through Celite
(eluent EtOAc) and concentrated in vacuo. Purification via flash
column chromatography (eluent 30–40 ꢁC petrol/Et2O, 19:1) gave
PhMe (25 mL) gave the crude reaction mixture. Purification via flash
column chromatography (eluent 40–60 ꢁC petrol/EtOAc/Et3N,
75:25:1) gave 17 as a white solid (290 mg, 71%). Found C, 74.6; H,
15 as a white solid (432 mg, quant). Found C, 72.5; H, 7.3; N, 5.8%.
8.45; N, 5.15%. C16H21NO2 requires C, 74.7; H, 8.5; N, 5.1%. Mp 96–
23
21
C
14H17NO2 requires C, 72.7; H, 7.4; N, 6.1%. Mp 78–79 ꢁC; [
a
]
97 ꢁC; [
a]
þ91.7 (c 0.9, CHCl3); nmax (KBr) 1735 (C]O),1669 (C]C);
D
D
þ93.3 (c 0.2, CHCl3); nmax (KBr) 1734 (C]O); dH (400 MHz, CDCl3)
0.93 (3H, s, C(5)MeA), 1.54 (3H, app ddd, J 6.8, 1.0, 0.8, C(30)H3), 1.59
(3H, s, C(5)MeB), 4.46–4.56 (1H, m, C(20)H), 4.58 (1H, s, C(4)H),
6.61–6.68 (1H, m, C(10)H), 7.11–7.16 (2H, m, Ph), 7.32–7.42 (3H, m,
Ph); dC (100 MHz, CDCl3) 15.2, 24.1, 29.3, 68.3, 82.0, 107.8,
123.7, 128.6, 128.9, 135.2; m/z (ESIþ) 290 ([Mþ59]þ, 100%);
HRMS (ESIþ) found 254.1157, C14H17NNaOþ2 ([MþNa]þ) requires
254.1151.
dH (400 MHz, CDCl3) 0.80 (3H, d, J 6.7, CH3CHCH3), 0.85 (3H, d, J 6.7,
CH3CHCH3), 0.94 (3H, s, C(5)MeA), 1.60 (3H, s, C(5)MeB), 2.17 (1H,
J 6.9, 6.7,1.2, CH3CHCH3), 4.46 (1H, dd, J 14.6, 6.9, C(20)H), 4.60 (1H, s,
C(4)H), 6.60 (1H, dd, J 14.6, 1.2, C(10)H), 7.40–7.11 (5H, m, Ph); dC
(100 MHz, CDCl3) 22.6, 22.8, 24.2, 29.0, 29.3, 68.2, 81.9, 120.8, 128.5,
128.7, 135.1, 155.0; m/z (CIþ) 260 ([MþH]þ, 6%), 216 (100).
4.4.4.1. X-ray crystal structure determination for 17. Data were
collected using an Enraf–Nonius
k-CCD diffractometer with
4.4.2.1. X-ray crystal structure determination for 15. Data were
graphite monochromated Mo K radiation using standard pro-
a
collected using an Enraf–Nonius
k
-CCD diffractometer with
cedures 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.42
graphite monochromated Mo K radiation using standard pro-
a
cedures 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.42
X-ray crystal structure data for 17 [C16H21NO2]: M¼259.35, or-
thorhombic, space group P212121, a¼9.8502(2) Å, b¼10.3090(2) Å,
X-ray crystal structure data for 15 [C14H17NO2]: M¼231.29, or-
c¼14.3867(3) Å, V¼1460.91(5) Å3, Z¼4,
m
¼0.077 mmꢂ1, colourless
thorhombic, space group P212121, a¼7.7201(2) Å, b¼9.8983(3) Å,
plate, crystal dimensions¼0.3ꢃ0.4ꢃ0.5 mm3.
A total of 1895
c¼17.1370(5) Å, V¼1309.54(6) Å3, Z¼4,
m
¼0.078 mmꢂ1, colourless
unique reflections were measured for 5<q<27 and 1660 re-
plate, crystal dimensions¼0.05ꢃ0.1ꢃ0.1 mm3. A total of 1703
flections were used in the refinement. The final parameters were
(I)]. Crystallographic data (ex-
unique reflections were measured for 5<
q<27 and 1316 reflections
wR2¼0.039 and R1¼0.033 [I>3.0
s
were used in the refinement. The final parameters were
(I)]. Crystallographic data (ex-
cluding structure factors) have been deposited with the Cambridge
Crystallographic Data Centre as supplementary publication num-
ber CCDC 653136. 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].
wR2¼0.051 and R1¼0.043 [I>3.0
s
cluding structure factors) have been deposited with the Cambridge
Crystallographic Data Centre as supplementary publication num-
ber CCDC 653129. 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].
4.4.5. (S,E)-N(3)-(30,30-Dimethyl-but-10-enyl)-4-phenyl-
5,5-dimethyl-oxazolidin-2-one 18.
4.4.3. (S,E)-N(3)-(30-Phenyl-prop-10-enyl)-4-phenyl-
5,5-dimethyl-oxazolidin-2-one 16.
O
tBu
O
N
O
Bn
Ph
O
N
Following General Procedure 1, TsOH (ca. 100 mg), 3,3-dime-
thylbutyraldehyde (0.31 mL, 2.51 mmol) and 13 (400 mg,
2.09 mmol) in PhMe (40 mL) gave the crude reaction mixture. Pu-
rification via flash column chromatography (eluent 40–60 ꢁC pet-
rol/EtOAc/Et3N, 100:10:1) gave 18 as a white solid (382 mg, 67%).
Ph
Following General Procedure 1, TsOH (ca. 125 mg), 3-phenyl-
propionaldehyde (1.47 mL, 12.6 mmol) and 13 (500 mg, 2.62 mmol)
in PhMe (35 mL) gave the crude reaction mixture. Purification via
flash column chromatography (eluent 40–60 ꢁC petrol/EtOAc, 15:1)
Found C, 74.0; H, 8.1; N, 5.45%. C17H23NO2 requires C, 74.1; H, 8.2; N,
25
22
gave 16 as a white solid (570 mg, 71%); [
a
]
þ38.4 (c 1.5, CHCl3);
5.4%. Mp 105–107 ꢁC; [
a
]
þ83.5 (c 1.05, CHCl3); nmax (KBr) 1733
D
D
nmax (KBr) 1751 (C]O), 1670 (C]C); dH (400 MHz, CDCl3) 0.95 (3H,
s, C(5)MeA), 1.61 (3H, s, C(5)MeB), 3.18–3.31 (2H, m, C(3)H2), 4.60–
4.71 (2H, m, C(4)H, C(20)H), 6.77 (1H, d, J 14.4, C(10)H), 6.92–7.41
(10H, m, Ph); dC (100 MHz, CDCl3) 24.2, 29.3, 35.6, 68.2, 82.0, 111.8,
124.1 (2C), 125.8, 126.0, 126.1, 128.1, 128.2, 128.4, 128.5, 128.6, 128.7,
128.9, 129.2, 134.9, 140.4, 154.8; m/z (APCIþ) 308 ([MþH]þ, 20%),
264 (100), 192 (100); HRMS (ESIþ) found 308.1651, C20H22NOþ2
([MþH]þ) requires 308.1645.
(C]O),1669 (C]C); dH (400 MHz, CDCl3) 0.85 (3H, s, C(5)MeA), 0.94
(9H, s, CMe3), 1.60 (3H, s, C(5)MeB), 4.49 (1H, d, J 14.8, C(20)H), 4.61
(1H, s, C(4)H), 6.56 (1H, d, J 14.8, C(10)H), 7.38–7.10 (5H, m, Ph); dC
(100 MHz, CDCl3) 24.2, 29.3, 29.8, 31.9, 68.2, 81.9,119.4,125.3,128.4,
128.6, 135.0, 155.1; m/z (CIþ) 274 ([MþH]þ, 42%), 230 (100).
4.4.6. (4S,20R,30S)-N(3)-(30-Phenyloxiran-20-yl)-4-phenyl-
5,5-dimethyl-oxazolidin-2-one 19.
O
4.4.4. (S,E)-N(3)-(30-Methyl-but-10-enyl)-4-phenyl-
O
Ph
O
N
5,5-dimethyl-oxazolidin-2-one 17.
O
Ph
iPr
O
N
A solution of DMDO (0.116 M in acetone, 6.1 mL, 0.71 mmol) at
0 ꢁC was added to 14 (100 mg, 0.34 mmol) and the reaction mixture
allowed to warm to rt over 1 h (with stirring) before being con-
centrated in vacuo to give a mixture of products (105 mg) of which
19 was the major component. Recrystallisation from DCM/heptane
Ph
Following General Procedure 1, TsOH (ca. 100 mg), 3-methyl-
butyraldehyde (0.40 mL, 3.77 mmol) and 13 (300 mg, 1.57 mmol) in

C. Aciro et al. / Tetrahedron 64 (2008) 9320–9344
9333
(1:1) gave 19 as a white solid (88 mg, 84%, >98% de). Found C, 74.0;
4.4.8. (4S,10R,20S)-N(3)-[10-(m-Chlorobenzoyl)-20-hydroxy-
H, 5.8; N, 4.3%. C19H19NO3 requires C, 73.8; H, 6.2; N, 4.5%. Mp 92 ꢁC;
20-phenyl-ethan-10-yl]-4-phenyl-5,5-dimethyl-oxazolidin-2-one 21
21
[
a]
ꢂ7.2 (c 0.5, CHCl3); nmax (KBr) 1773 (C]O); dH (400 MHz,
D
Cl
CDCl3) 0.81 (3H, s, C(5)MeA), 1.56 (3H, s, C(5)MeB), 3.55 (1H, s,
C(30)H), 4.49 (1H, s, C(4)H), 4.65 (1H, s, C(20)H), 6.75–7.49 (10H, m,
Ph); dC (100 MHz, CDCl3) 24.1, 28.8, 57.2, 65.6, 66.0, 82.5, 125.2,
126.8, 128.4, 128.6, 129.0, 129.2, 134.7, 136.4, 137.5; m/z (CIþ) 310
([MþH]þ, 100%).
O
O
O
Ph
O
N
Epoxide opening. mCBA (80 mg, 0.51 mmol) was added to a so-
lution of 19 (105 mg, ca. 0.34 mmol) in acetone (2 mL) at 0 ꢁC, the
resultant solution stirred for 30 min and then allowed to warm to
rt over a further 2.5 h. The reaction mixture was concentrated in
vacuo and the residue was partitioned between satd aq NH4Cl
(10 mL) and CHCl3 (10 mL). The organic layer was separated and
the aqueous layer was extracted with CHCl3 (2ꢃ10 mL). The com-
bined organic extracts were washed with brine (20 mL), dried and
concentrated in vacuo to give a 96:4 mixture of 21/22 (159 mg,
quant).
OH
Ph
Following General Procedure 2, mCPBA (221 mg, 1.28 mmol) and
14 (150 mg, 0.51 mmol) in CHCl3 (10 mL) gave a 96:4 mixture of
21/22. Purification via recrystallisation from DCM/heptane (1:1)
gave 21 as a white crystalline solid (200 mg, 84%, >98% de); mp
21
104–105 ꢁC; [
a]
þ94.0 (c 1.0, CHCl3); nmax (KBr) 1757 (C]O), 1736
D
(C]O); dH (400 MHz, CDCl3) 0.82 (3H, s, C(5)MeA), 0.98 (3H, s,
C(5)MeB), 2.64 (1H, br s, OH), 3.94 (1H, s, C(4)H), 5.66 (1H, d, J 7.7,
C(20)H), 6.24 (1H, d, J 7.7, C(10)H), 6.84–8.03 (14H, m, Ar, Ph); dC
(100 MHz, CDCl3) 23.4, 27.9, 71.4, 72.7, 82.3, 82.7, 127.3, 128.3,
128.4, 128.7, 129.0, 129.2, 129.5, 130.0, 130.4, 131.2, 133.7, 134.7,
135.5, 139.4, 156.7, 164.0; m/z (ESIþ) 488 ([MþNa]þ, 100%); HRMS
(ESIþ) found 488.1232, C26H24ClNNaOþ5 ([MþNa]þ) requires
488.1235.
4.4.6.1. X-ray crystal structure determination for 19. Data were
collected using an Enraf–Nonius
k-CCD diffractometer with
graphite monochromated Mo K radiation using standard pro-
a
cedures 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.42
4.4.9. (4S,10R,20S)-N(3)-[10-(m-Chlorobenzoyl)-20-hydroxy-propan-
10-yl]-4-phenyl-5,5-dimethyl-oxazolidin-2-one 23
X-ray crystal structure data for 19 [C19H19NO3]: M¼309.36,
monoclinic, space group P1211, a¼8.241(1) Å, b¼6.1420(7) Å,
c¼17.030(2) Å, V¼860.8(2) Å3, Z¼2,
m
¼0.67 mmꢂ1, colourless plate,
Cl
crystal dimensions¼0.1ꢃ0.5ꢃ0.5 mm3. A total of 2781 unique re-
flections were measured for 5<q<27 and 1590 reflections were
used in the refinement. The final parameters were wR2¼0.057 and
O
O
O
Me
R1¼0.045 [I>3.0
s
(I)]. Crystallographic data (excluding structure
factors) have been deposited with the Cambridge Crystallographic
Data Centre as supplementary publication number CCDC 653144.
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
OH
Ph
Following General Procedure 2, mCPBA (204 mg, 1.19 mmol) and
15 (153 mg, 0.66 mmol) in CHCl3 (10 mL) gave a >99:<1 mixture of
23/24. Purification via recrystallisation from DCM/heptane (1:1)
4.4.7. (4S,20R,30S)-N(3)-(30-Methyloxiran-20-yl)-4-phenyl-5,5-
dimethyl-oxazolidin-2-one 20
gave 23 as a white crystalline solid (254 mg, 95%, >98% de); mp 72–
17
73 ꢁC; [
a
]
þ76.9 (c 0.7, CHCl3); nmax (KBr) 3441 (O–H), 1748
D
(C]O); dH (400 MHz, CDCl3) 0.97 (3H, s, C(5)MeA), 1.23 (3H, d, J 6.6,
C(30)H3), 1.53 (3H, s, C(5)MeB), 2.65 (1H, br s, OH), 4.16–4.22 (1H, m,
C(20)H), 4.52 (1H, s, C(4)H), 6.27 (1H, d, J 5.1, C(10)H), 7.15–7.90 (9H,
m, Ar); dC (100 MHz, CDCl3) 19.3, 23.5, 28.7, 67.1, 69.3, 82.4, 83.1,
128.0, 128.8, 128.9, 129.7, 129.8, 130.7, 133.5, 134.5, 136.3, 157.0,
163.8; m/z (ESIþ) 462 ([Mþ59]þ, 100%); HRMS (ESIþ) found
426.1077, C21H22ClNNaO5þ ([MþNa]þ) requires 426.1079.
O
O
Me
O
N
Ph
A solution of DMDO (0.046 M in acetone, 19 mL, 0.87 mmol) at
0 ꢁC was added to 15 (100 mg, 0.433 mmol) and the reaction mix-
ture allowed to warm to rt over 1 h (with stirring) before being
concentrated in vacuo to give 20 as a white solid (107 mg, quant,
>98 % de) that was used without purification; dH (400 MHz, CDCl3)
0.92 (3H, s, C(5)MeA), 0.95 (3H, J 5.2, C(30)Me), 1.56 (3H, s, C(5)MeB),
2.77–2.78 (1H, m, C(30)H), 4.40 (1H, s, C(4)H), 4.74 (1H, d, J 1.4,
C(20)H), 7.16–7.17 (2H, m, Ph), 7.35–7.43 (3H, m, Ph).
Epoxide opening. mCBA (102 mg, 0.65 mmol) was added to a so-
lution of 20 (107 mg, 0.43 mmol, >98% de) in acetone (2.0 mL) at
0 ꢁC, the resultant solution stirred for 30 min and then allowed to
warm to rt over a further 2.5 h. The reaction mixture was concen-
trated in vacuo and the residue was partitioned between satd aq
NH4Cl (10 mL) and CHCl3 (10 mL). The organic layer was separated
and the aqueous layer was extracted with CHCl3 (2ꢃ10 mL). The
combined organic extracts were washed with brine (20 mL), dried
and concentrated in vacuo to give 23 as a white solid (175 mg,
quant, >98% de).
4.4.9.1. X-ray crystal structure determination for 23. Data were
collected using an Enraf–Nonius
k-CCD diffractometer with
graphite monochromated Mo K radiation using standard pro-
a
cedures 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 po-
sitions. The structure was refined using CRYSTALS.42
X-ray crystal structure data for 23 [C21H21ClNO5]: M¼402.85,
orthorhombic, space group P212121, a¼7.22210(10) Å, b¼
11.8317(2) Å, c¼24.1532(4) Å, V¼2063.88(6) Å3, Z¼4,
m
¼0.22 mmꢂ1
,
colourless block, crystal dimensions¼0.3ꢃ0.3ꢃ0.3 mm3. A total of
4442 unique reflections were measured for 5<q<27 and 3864 re-
flections were used in the refinement. The final parameters were
(I)]. Crystallographic data (ex-
wR2¼0.077 and R1¼0.064 [I>3.0
s
cluding structure factors) have been deposited with the Cambridge
Crystallographic Data Centre as supplementary publication number

9334
C. Aciro et al. / Tetrahedron 64 (2008) 9320–9344
CCDC 653133. 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].
0.96 (3H, d, J 6.8, CH3CHCH3), 0.97 (3H, s, C(5)MeA), 1.51 (3H, s,
C(5)MeB),1.78 (1H, m, CH3CHCH3), 2.58 (1H, br s, OH), 3.81 (1H, dd, J
6.8, 5.8, C(20)H), 4.53 (1H, s, C(4)H), 6.49 (1H, d, J 5.8, C(10)H), 8.13–
7.16 (9H, m, Ar, Ph); dC (100 MHz, CDCl3) 16.1, 19.4, 23.4, 28.8, 29.5,
68.8, 74.9, 80.2, 83.0, 127.3, 128.1, 128.9, 129.7, 130.2, 130.9, 133.5,
134.4, 134.6, 136.5, 157.0, 163.8; m/z (ESIþ) 454 ([MþNa]þ, 100%);
HRMS (ESIþ) found 454.1396, C23H26ClNNaOþ5 ([MþNa]þ) requires
454.1392.
4.4.10. (4S,10R,20S)-N(3)-(10-m-Chlorobenzoyl-20-hydroxy-
30-phenyl-prop-10-yl-)-4-phenyl-5,5-dimethyl-oxazolidin-2-one 25
Cl
4.4.12. (4S,10R,20S)-N(3)-(10-m-Chlorobenzoyl-20-hydroxy-30,30-di-
methyl-but-10-yl)-4-phenyl-5,5-dimethyl-oxazolidin-2-one 29.
O
O
O
Bn
O
N
Cl
OH
Ph
O
Following General Procedure 2, mCPBA (471 mg, 2.83 mmol) and
16 (300 mg, 0.98 mmol) in CHCl3 (40 mL) gave a 96:4 mixture of 25/
26. Recrystallisation from DCM/heptane (1:1) gave 25 as a white
crystalline solid (280 mg, 60%, >98% de). Found C, 67.8; H, 5.4; N,
O
O
tBu
O
N
OH
Ph
2.7%. C27H26ClNO5 requires C, 67.6; H, 5.4; N, 2.9%. Mp 109–110 ꢁC;
25
Following General Procedure 2, mCPBA (317 mg, 1.84 mmol) and
18 (200 mg, 0.73 mmol) in CHCl3 (10 mL) gave a 98:2 mixture of 29/
30 as a yellow oil (359 mg, quant, 96% de) that was used without
purification; nmax (film) 3433 (O–H), 1730 (C]O); dH (400 MHz,
CDCl3) 0.92 (9H, s, CMe3), 0.93 (3H, s, C(5)MeA), 1.51 (3H, s,
C(5)MeB), 3.63 (1H, d, J 1.1, C(20)H), 4.53 (1H, s, C(4)H), 6.57 (1H, d, J
1.1, C(10)H), 7.15–8.09 (9H, m, Ar, Ph); dC (100 MHz, CDCl3) 23.3, 26.0,
28.6, 34.6, 69.5, 77.3, 78.7, 83.2,128.0,128.7,129.0,129.7,129.8,130.1,
133.4, 134.5, 136.4, 157.3, 163.3; m/z (ESIþ) 468 ([MþNa]þ, 100%).
[
a]
þ68.6 (c 1.0, CHCl3); nmax (KBr) 3455 (O–H), 1736 (C]O); dH
D
(400 MHz, CDCl3) 0.97 (3H, s, C(5)MeA), 1.53 (3H, s, C(5)MeB), 2.72
(1H, dd, J 13.9, 8.9, C(30)HA), 2.89 (1H, dd, J 13.9, 4.1, C(30)HB), 4.20
(1H, br m, C(20)H), 4.50 (1H, s, C(4)H), 6.44 (1H, d, J 5.3, C(10)H),
7.92–7.01 (14H, m, Ar, Ph); dC (100 MHz, CDCl3) 23.4, 28.8, 39.3, 68.7,
71.9, 81.1, 83.2, 126.7, 128.0, 128.5, 128.9, 129.3, 129.7, 129.8, 130.7,
133.5, 134.5, 136.5, 136.8, 157.1, 163.7; m/z (ESIþ) 502 ([MþNa]þ,
100%); HRMS (ESIþ) found 502.1389, C27H26ClNNaO5þ ([MþNa]þ)
requires 502.1392.
4.4.13. (S)-N(3)-Chloromethyl-4-phenyl-5,5-dimethyl-
4.4.10.1. X-ray crystal structure determination for 25. Data were
oxazolidin-2-one.
collected using an Enraf–Nonius
k-CCD diffractometer with
O
graphite monochromated Mo K radiation using standard pro-
a
O
N
Cl
cedures 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.42
Ph
A suspension of 13 (1.06 g, 5.55 mmol) and paraformaldehyde
(1.16 g, 6.09 mmol) in TMSCl (8.9 mL) was refluxed at 60 ꢁC for 2 h.
The volatile materials were then removed in vacuo to give the title
X-ray crystal structure data for 25 [C27H26ClNO5]: M¼479.96,
triclinic, space group P1, a¼6.1400(2) Å, b¼8.1370(2) Å, c¼
12.9972(5) Å,
a
¼104.1148(11)ꢁ,
b
¼102.6525(11)ꢁ,
g
¼94.8880(15)ꢁ,
compound as a yellow solid (1.33 g, quant) that was used without
V¼607.83(3) Å3, Z¼1,
m
¼0.20 mmꢂ1
, colourless block, crystal
22
purification; mp 161–162 ꢁC; [
a
]
þ135.7 (c 0.9, CHCl3); nmax (film)
D
dimensions¼0.2ꢃ0.2ꢃ0.2 mm3. A total of 5047 unique reflections
1766 (C]O); dH (400 MHz, CDCl3) 1.00 (3H, s, C(5)MeA), 1.60 (3H, s,
C(5)MeB), 4.67 (1H, d, J 10.3, C(10)HA), 4.75 (1H, s, C(4)H), 5.75 (1H, d,
J 10.3, C(10)HB), 7.20–7.25 (2H, m, Ph), 7.40–7.49 (3H, m, Ph); dC
(100 MHz, CDCl3) 23.8, 27.9, 55.0, 67.0, 82.6, 127.0, 129.2, 129.3,
133.3, 156.5; m/z (ESIþ) 204 ([MꢂCl]þ, 100%).
were measured for 1<q<27 and 3965 reflections were used in the
refinement. The final parameters were wR2¼0.019 and R1¼0.034
[I>3.0 (I)]. Crystallographic data (excluding structure factors) have
s
been deposited with the Cambridge Crystallographic Data Centre as
supplementary publication number CCDC 653137. 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].
4.4.14. (S)-N(3)-[(Triphenylphosphonium)methyl]-4-phenyl-
5,5-dimethyl-oxazolidin-2-one chloride 31.
O
4.4.11. (4S,10R,20S)-N(3)-(10-m-Chlorobenzoyl-20-hydroxy-
O
N
PPh3+Cl−
30-methyl-but-10-yl)-4-phenyl-5,5-dimethyl-oxazolidin-2-one 27.
Ph
Cl
PPh3 (26.9 g, 103 mmol) was added to a stirred suspension of
freshly prepared (S)-N(3)-chloromethyl-4-phenyl-5,5-dimethyl-
oxazolidin-2-one (12.5 g, 521 mmol) in MeCN (192 mL) and the
suspension stirred at rt for 24 h. The reaction mixture was then
concentrated in vacuo and the residue was purified via flash col-
O
O
O
iPr
O
N
umn chromatography (eluent 30–40 ꢁC petrol/Et2O, 9:1) to give 31
OH
Ph
20
as a white solid (19.4 g, 74%); mp 143–144 ꢁC; [
a]
þ30.4 (c 0.8,
D
Following General Procedure 2, mCPBA (62 mg, 0.36 mmol) and
17 (37 mg, 0.14 mmol) in CHCl3 (7 mL) gave a 96:4 mixture of 27/28.
Recrystallisation from DCM/heptane (1:1) gave 27 as a white
crystalline solid (200 mg, 61%, >98% de); nmax (KBr) 3447 (O–H),
1750 (C]O); dH (400 MHz, CDCl3) 0.81 (3H, d, J 6.8, CH3CHCH3);
CHCl3); nmax (KBr) 1744 (C]O); dH (400 MHz, CDCl3) 0.85 (3H, s,
C(5)MeA), 1.37 (3H, s, C(5)MeB), 5.31 (1H, s, C(4)H), 5.59 (1H, dd, J
12.1, 6.1, C(10)HA), 5.68 (1H, dd, J 12.1, 3.5, C(10)HB), 7.14 (2H, s, Ph),
7.28–7.32 (3H, m, Ph), 7.64–7.90 (15H, m, Ph); dC (125 MHz, CDCl3)
23.8, 28.3, 41.0 (d, J 60.1), 69.6, 84.3, 117.2, 117.9, 129.1, 129.1, 130.3,

C. Aciro et al. / Tetrahedron 64 (2008) 9320–9344
9335
130.4, 134.2, 134.3, 134.6, 135.1, 135.1, 158.5; m/z (ESIþ) 466
([MꢂCl]þ, 100%); HRMS (ESIþ) found 466.1931, C30H29NO2Pþ
([MꢂCl]þ) requires 466.1930.
concentrated in vacuo to give a 9:91 mixture of 14/33. Purification
via flash column chromatography (eluent 30–40 ꢁC petrol/Et2O,
19:1) gave 33 as a white solid (22 mg, 76%, >98% de). Found C, 77.7;
H, 6.6; N, 4.7%. C19H19NO2 requires C, 77.8; H, 6.5; N, 4.8%. Mp 105–
24
4.4.14.1. X-ray crystal structure determination for 31. Data were
106 ꢁC; [
a]
þ40.0 (c 0.8, CHCl3); nmax (KBr) 1745 (C]O); dH
D
collected using an Enraf–Nonius
k
-CCD diffractometer with
(400 MHz, CDCl3) 0.86 (3H, s, C(5)MeA), 1.55 (3H, s, C(5)MeB), 4.43
(1H, s, C(4)H), 5.85 (1H, d, J 9.6, C(20)H), 6.55 (2H, m, Ph), 6.62 (1H, d, J
9.6, C(10)H), 6.95–6.99 (2H, m, Ph), 7.11–7.30 (6H, m, Ph); dC
(100 MHz, CDCl3) 23.8, 28.8, 68.8, 82.4, 115.5, 123.1, 125.4, 127.1,
127.8,128.3,128.6,129.2,135.3,135.7,156.6; m/z (ESIþ) 294 ([MþH]þ,
38%); HRMS (ESIþ) found 294.1500; C19H20NOþ2 ([MþH]þ) requires
294.1489.
graphite monochromated Mo K radiation using standard pro-
a
cedures 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 po-
sitions. The structure was refined using CRYSTALS.42
X-ray crystal structure data for 31 [C61H60Cl4N2O4P2]:
M¼1088.92, orthorhombic, space group P212121, a¼15.9103(2) Å,
Wittig olefinations employing 31 were found to be highly sen-
sitive to the presence of adventitious water, with (S)-N(3)-methyl-
4-phenyl-5,5-dimethyl-oxazolidin-2-one (N-methyl SuperQuat)
being isolated as a side product on several occasions; mp 90–91 ꢁC;
b¼18.3528(3) Å, c¼18.9501(2) Å, V¼5533.40(13) Å3, Z¼8,
m
¼
0.32 mmꢂ1
,
colourless block, crystal dimensions¼0.2ꢃ0.2ꢃ
0.2 mm3. A total of 12,429 unique reflections were measured for
5< <27 and 8956 reflections were used in the refinement. The final
parameters were wR2¼0.041 and R1¼0.042 [I>3.0 (I)]. Crystallo-
24
q
[a
]
þ78.2 (c 0.3, CHCl3); nmax (KBr) 1735 (C]O); dH (400 MHz,
D
s
CDCl3) 0.92 (3H, s, C(5)MeA), 1.57 (3H, s, C(5)MeB), 2.79 (3H, s, NMe),
4.37 (1H, s, C(4)H), 7.15–7.19 (2H, m, Ph), 7.35–7.44 (3H, m, Ph); dC
(100 MHz, CDCl3) 24.8, 29.3, 31.3, 72.2, 83.6, 130.1, 130.2, 131.4,
157.8; m/z (ESIþ) 264 ([Mþ59]þ, 100%); HRMS (ESIþ) found
206.1186, C12H16NO2þ ([MþH]þ) requires 206.1176.
graphic data (excluding structure factors) has been deposited with
the Cambridge Crystallographic Data Centre as supplementary
publication number CCDC 653130. 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].
Still–Gennari olefination. BuLi (2.5 M in hexanes, 0.19 mL,
0.48 mmol) was added to a stirred suspension of 32 (100 mg,
0.24 mmol) in THF (2 mL) at ꢂ78 ꢁC. After stirring for 30 min,
4.4.15. (S)-N(3)-[(Bis-200,200,200-trifluoroethoxyphosphoryl)methyl]-
PhCHO (24 mL, 0.24 mmol) was added and stirring continued at
4-phenyl-5,5-dimethyl-oxazolidin-2-one 32
ꢂ78 ꢁC for 24 h. The reaction mixture was then allowed to warm to
rt, quenched with H2O (1 mL) and extracted with DCM (3ꢃ10 mL).
The combined organic extracts were then washed with brine
(2ꢃ20 mL), dried and concentrated in vacuo. Purification of the
residue via flash column chromatography (eluent 30–40 ꢁC petrol/
Et2O, 19:1) gave 33 as a white solid (70 mg, quant).
O
O
N
P(OCH2CF3)
O
Ph
A
mixture of tris-(2,2,2-trifluoroethyl)phosphite (627 mL,
4.4.16.1. X-ray crystal structure determination for 33. Data were
2.40 mmol) and freshly prepared (S)-N(3)-chloromethyl-4-phenyl-
5,5-dimethyl-oxazolidin-2-one (480 mg, 2.00 mmol) was heated at
140 ꢁC for 72 h. The reaction mixture was then allowed to cool to rt
and concentrated in vacuo. The residue was purified via flash col-
umn chromatography (eluent 30–40 ꢁC petrol and then 30–40 ꢁC
petrol/Et2O, 5:1) to give 32 as a colourless oil (533 mg, 64%). Found
collected using an Enraf–Nonius
k-CCD diffractometer with
graphite monochromated Mo K radiation using standard pro-
a
cedures 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.42
C, 42.7; H, 4.3; N, 3.1%. C16H18F6NO5P requires C, 42.8; H, 4.0; N,
3.1%. [
X-ray crystal structure data for 33 [C19H19NO2]: M¼293.37, or-
24
a
]
þ49.9 (c 1.0, CHCl3); nmax (film) 1749 (C]O); dH
D
thorhombic, space group P212121, a¼6.9994(2) Å, b¼9.6521(3) Å,
(400 MHz, CDCl3) 0.97 (3H, s, C(5)MeA), 1.59 (3H, s, C(5)MeB), 3.19
(1H, dd, J 16.4, 6.3, C(10)HA), 4.22 (1H, dd, J 16.4, 12.1, C(10)HB), 4.35–
4.50 (4H, m, 2ꢃOCH2), 4.64 (1H, app d, J 2.0, C(4)H), 7.10–7.14 (2H,
m, Ph), 7.37–7.45 (3H, m, Ph); dC (100 MHz, CDCl3) 23.8, 28.5, 39.0,
62.3 (quintet, P(OCH2CF3)2), 69.6, 82.6, 121.0–121.1 (m, (CF3)A),
123.7–123.8 (m, (CF3)B), 129.2, 129.4, 133.8, 157.3; m/z (ESIþ) 472
([MþNa]þ, 24%); HRMS (FIþ) found 449.0827, C16H18F6NO5Pþ
([M]þ) requires 449.0821.
c¼23.7351(6) Å, V¼1603.52(8) Å3, Z¼4,
m
¼0.079 mmꢂ1, colourless
plate, crystal dimensions¼0.05ꢃ0.1ꢃ0.2 mm3. A total of 2046
unique reflections were measured for 5<q<27 and 1666 reflections
were used in the refinement. The final parameters were wR2¼0.045
and R1¼0.042 [I>1.5
s
(I)]. Crystallographic data (excluding structure
factors) have been deposited with the Cambridge Crystallographic
Data Centre as supplementary publication number CCDC 653131.
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].
4.4.16. (S,Z)-N(3)-(20-Phenyl-ethenyl)-4-phenyl-5,5-dimethyl-
oxazolidin-2-one 33
4.4.17. (S,Z)-N(3)-(Prop-10-en-10-yl)-4-phenyl-5,5-dimethyl-
oxazolidin-2-one 34
O
O
N
Ph
O
Ph
O
N
Wittig olefination. A suspension of KOtBu (14 mg, 0.13 mmol) in
THF (1 mL) was added to a stirred suspension of 31 (50 mg,
Me
Ph
0.1 mmol) in THF (1 mL) at ꢂ78 ꢁC. After 30 min, PhCHO (50
mL,
0.5 mmol) was added and stirring continued for a further 24 h at
ꢂ78 ꢁC. The reaction mixture was quenched with satd aq NH4Cl
(1 mL) and allowed to warm to rt. The organic layer was separated
and the aqueous layer extracted with DCM (2ꢃ5 mL). The combined
organic extracts were washed with brine (5 mL), dried and
Wittig olefination. A suspension of KOtBu (28 mg, 0.25 mmol) in
THF (2 mL) was added to a stirred suspension of 31 (100 mg,
0.2 mmol) in THF (2 mL) at ꢂ78 ꢁC. After 30 min, MeCHO (56
mL,
1.0 mmol) was added and stirring continued for a further 24 h at
ꢂ78 ꢁC. The reaction mixture was quenched with satd aq NH4Cl

9336
C. Aciro et al. / Tetrahedron 64 (2008) 9320–9344
(1 mL) and allowed to warm to rt. The organic layer was separated
and the aqueous layer extracted with DCM (2ꢃ10 mL). The com-
bined organic extracts were washed with brine (10 mL), dried and
concentrated in vacuo to give a 20:80 mixture of 15/34. Purifica-
tion via flash column chromatography (eluent 30–40 ꢁC petrol/
30 min and then allowed to warm to rt over a further 2.5 h. The
reaction mixture was concentrated in vacuo and the residue was
partitioned between satd aq NH4Cl (10 mL) and CHCl3 (10 mL). The
organic layer was separated and the aqueous layer was extracted
with CHCl3 (2ꢃ10 mL). The combined organic extracts were washed
with brine (20 mL), dried and concentrated in vacuo to give to give
a 5:8:84:3 mixture of 23/24/37/38 (175 mg, quant).
Et2O, 19:1) gave 34 as a white solid (28 mg, 63%, >98% de); mp 82–
24
83 ꢁC; [
a]
þ39.9 (c 0.9, CHCl3); nmax (KBr) 1753 (C]O); dH
D
(400 MHz, CDCl3) 0.96 (3H, s, C(5)MeA), 1.61 (3H, dd, J 5.6, 1.8,
C(30)H3), 1.64 (3H, s, C(5)MeB), 4.73 (1H, s, C(4)H), 5.08 (1H, m,
C(20)H), 5.97 (1H, dq, J 7.1, 1.8, C(10)H), 7.12–7.15 (2H, m, Ph), 7.34–
7.41 (3H, m, Ph); dC (100 MHz, CDCl3) 12.9, 23.9, 28.7, 70.7, 81.9,
116.2, 122.9, 128.7, 128.8, 135.8, 155.9; m/z (ESIþ) 232 ([MþH]þ,
65%); HRMS (ESIþ) found 232.1338, C14H18NO2 ([MþH]þ) requires
232.1332.
Buchwald–Hartwig coupling. cis-1-Bromo-prop-1-ene (0.92 mL,
10.9 mmol) was added to a suspension of 13 (500 mg, 2.61 mmol),
CuI (41 mg, 0.22 mmol), K2CO3 (600 mg, 4.35 mmol) and N,N0-
4.4.19. (4S,10R,20R)-3-[10-(m-Chlorobenzoyl)-20-hydroxy-propan-
10-yl)-4-phenyl-5,5-dimethyl-oxazolidin-2-one 37
Cl
O
O
O
Me
O
N
OH
dimethylethylenediamine (23 mL, 0.22 mmol) in PhMe (5 mL). The
Ph
suspension was stirred at 110 ꢁC for 5 days. The reaction mixture
was then allowed to cool to rt and filtered through Celite (eluent
EtOAc). The filtrate was concentrated in vacuo and the residue was
purified via flash column chromatography (eluent 30–40 ꢁC petrol/
Et2O, 19:1) to give 34 as a white solid (603 mg, quant).
Following General Procedure 2, mCPBA (1.21 g, 5.41 mmol) and
34 (1.0 g, 4.33 mmol) in CHCl3 (45 mL) gave a 7:10:81:2 mixture of
23/24/37/38. Purification via recrystallisation from DCM/heptane
(1:1) gave 37 as a white crystalline solid (718 mg, 41%, >98% de);
21
mp 103–104 ꢁC; [
a
]
D
þ64.6 (c 0.4 in CHCl3); nmax (KBr) 3406 (O–H),
1742 (C]O); dH (400 MHz, CDCl3) 0.99 (3H, s, C(5)MeA),1.21 (3H, d, J
6.6, C(30)H3), 1.55 (3H, s, C(5)MeB), 4.16–4.24 (1H, m, C(20)H), 4.48
(1H, s, C(4)H), 6.11 (1H, d, J 7.6, C(10)H), 7.11–8.09 (9H, m, Ar, Ph); dC
(100 MHz, CDCl3) 19.3, 23.5, 29.0, 66.2, 69.6, 82.9, 83.2, 125.8, 128.0,
129.0, 129.1, 129.7, 129.8, 133.6, 134.6, 136.3, 145.7, 163.3; m/z (ESIþ)
462 ([Mþ59]þ, 100%); HRMS (ESIþ) found 426.1084,
4.4.17.1. X-ray crystal structure determination for 34. Data were
collected using an Enraf–Nonius
k-CCD diffractometer with
graphite monochromated Mo K radiation using standard pro-
a
cedures 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.42
C
21H22ClNNaOþ5 ([MþNa]þ) requires 426.1079.
X-ray crystal structure data for 34 [C14H17NO2]: M¼231.29,
4.4.19.1. X-ray crystal structure determination for 37. Data were
collected using an Enraf–Nonius -CCD diffractometer with
graphite monochromated Mo K radiation using standard pro-
monoclinic, space group P1211, a¼7.8226(2) Å, b¼8.5396(2) Å, c¼
¼95.1000(10)ꢁ, V¼648.16(3) Å3, Z¼2,
m
¼0.079 mmꢂ1
,
k
9.7413(4) Å,
b
colourless plate, crystal dimensions¼0.1ꢃ0.3ꢃ0.3 mm3. A total of
a
cedures 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 po-
sitions. The structure was refined using CRYSTALS.42
1523 unique reflections were measured for 5<q<27 and 1401
reflections were used in the refinement. The final parameters were
(I)]. Crystallographic data (ex-
wR2¼0.041 and R1¼0.041 [I>3.0
s
cluding structure factors) have been deposited with the Cam-
bridge Crystallographic Data Centre as supplementary publication
number CCDC 653132. 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].
X-ray crystal structure data for 37 [C21H22ClNO5]: M¼403.86,
orthorhombic, space group P212121, a¼5.5331(1) Å, b¼
10.7791(2) Å, c¼33.3743(8) Å, V¼1990.50(7) Å3, Z¼4,
m
¼0.22 mmꢂ1
,
colourless plate, crystal dimensions¼0.05ꢃ0.1ꢃ0.2 mm3. A total of
4293 unique reflections were measured for 5<q<27 and 2707 re-
flections were used in the refinement. The final parameters were
(I)]. Crystallographic data (ex-
4.4.18. (4S,20R,30R)- and (4S,20S,30S)-N(3)-(30-Methyloxiran-20-yl)-
4-phenyl-5,5-dimethyl-oxazolidin-2-one (4S,20R,30R)-35 and
(4S,20S,30S)-36
wR2¼0.041 and R1¼0.039 [I>3.0
s
cluding structure factors) has been deposited with the Cambridge
Crystallographic Data Centre as supplementary publication number
CCDC 653134. 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
O
O
O
+
O
N
O
N
Me
Me
4.4.20. (4S,20R,30R)-N(3)-(30-Phenyloxiran-20-yl)-4-phenyl-
5,5-dimethyl-oxazolidin-2-one 39 and (4S,20R,30R)-N(3)-(10,20-
dihydroxy-20-phenylethyl)-4-phenyl-5,5-dimethyl-oxazolidin-
2-one 40
Ph
35
Ph
36
A solution of DMDO (0.046 M in acetone, 19 mL, 0.87 mmol) at
0 ꢁC was added to 34 (42 mg, 0.18 mmol) and the reaction mixture
allowed to warm to rt over 1 h (with stirring) before being con-
centrated in vacuo to give an 87:13 mixture of 35/36 (107 mg,
quant) that was used without purification.
O
O
OH
O
Ph
+
O
N
O
N
Ph
OH
Data for 35: dH (400 MHz, CDCl3) 0.97 (3H, s, C(5)MeA),1.41 (3H, J
5.6, C(30)H3), 1.57 (3H, s, C(5)MeB), 3.04–3.09 (1H, m, C(30)H), 4.36
(1H, d, J 3.4, C(20)H), 4.71 (1H, s, C(4)H), 7.16–7.24 (2H, m, Ph), 7.35–
7.45 (3H, m, Ph).
Epoxide opening. mCBA (100 mg, 0.65 mmol) was added to a so-
lution of the crude mixture of 35 and 36 (92 mg, 0.43 mmol, 87:13
dr) in acetone (2 mL) at 0 ꢁC, and the resultant solution stirred for
Ph
39
Ph
40
A solution of DMDO (0.046 M in acetone, 15 mL, 0.69 mmol) at
0 ꢁC was added to 33 (100 mg, 0.34 mmol) and the reaction mixture
allowed to warm to rt over 1 h (with stirring) before being con-
centrated in vacuo to give a mixture of products (105 mg) of which

C. Aciro et al. / Tetrahedron 64 (2008) 9320–9344
9337
39 and 40 were the major components, in a 93:7 ratio. Recrystal-
lisation of an aliquot from DCM/heptane (1:1) gave 40 as a white
solid.
28.4, 65.8, 71.8, 82.1, 83.4, 126.0, 127.9, 128.2, 128.6, 128.8, 129.1,
129.7, 129.7, 130.6, 133.4, 134.5, 135.2, 139.4, 158.0, 163.0; m/z (ESIþ)
524 ([Mþ59]þ, 100%); HRMS (ESIþ) found 488.1236,
Data for 39: dH (400 MHz, CDCl3) 0.75 (3H, s, C(5)MeA), 1.25 (3H,
C
26H24ClNNaOþ5 ([MþNa]þ) requires 488.1235.
s, C(5)MeB), 3.40 (1H, s, C(4)H), 3.97 (1H, d, J 3.4, C(30)H), 4.76 (1H, d,
J 5.5, C(20)H), 7.21–7.49 (10H, m, Ph).
4.4.22. (4S,10R,20S)- and (4S,10S,20S)-N(3)-(10-Methoxy-20-hydroxy-
20-phenylethan-10-yl)-4-phenyl-5,5-dimethyl-oxazolidin-2-one 43
and 44
17
Data for 40: mp 135–136 ꢁC; [
a]
þ58.0 (c 0.3, CHCl3); nmax
D
(KBr) 3417 (O–H), 1723 (C]O); dH (400 MHz, CDCl3) 0.83 (3H, s,
C(5)MeA),1.15 (3H, s, C(5)MeB), 3.94 (1H, s, C(4)H), 4.41 (1H, d, J 10.4,
OH), 4.60–4.72 (2H, m, C(20)H, OH), 5.02 (1H, dd, J 8.6, 5.8, C(10)H),
6.85–7.63 (10H, m, Ph); dC (100 MHz, CDCl3) 23.9, 28.5, 70.0, 71.8,
82.0, 83.5, 126.1, 127.6, 128.2, 128.4, 129.1, 135.1, 139.9, 165.7; m/z
(ESIþ) 328 ([MþH]þ, 62%); HRMS (ESIþ) found 328.1543, C19H22NOþ4
([MþH]þ) requires 328.1543.
O
OMe
Ph
O
N
OH
Ph
Epoxide opening. mCBA (100 mg, 0.64 mmol) was added to
a solution of the crude mixture of 39 and 40 (105 mg, ca.
0.34 mmol) in acetone (2 mL) at 0 ꢁC, and the resultant solution
stirred for 30 min and then allowed to warm to rt over a further
2.5 h. The reaction mixture was concentrated in vacuo and the
residue was partitioned between satd aq NH4Cl (10 mL) and CHCl3
(10 mL). The organic layer was separated and the aqueous layer was
extracted with CHCl3 (2ꢃ10 mL). The combined organic extracts
were washed with brine (20 mL), dried and concentrated in vacuo
to give a 3:8:85:4 mixture of 21/22/41/42 (209 mg, quant).
CSA (w5 mg) was added to a stirred solution of 21 (300 mg,
0.64 mmol) in MeOH (4 mL) and heated at reflux for 1 h. The re-
action mixture was allowed to cool to rt and concentrated in vacuo.
The residue was partitioned between DCM (5 mL) and H2O (5 mL).
The organic layer was separated and washed sequentially with satd
aq NaHCO3 (5 mL) and brine (5 mL), dried and concentrated in
vacuo to give a 62:38 mixture of 43/44 (194 mg, 88%). Recrystalli-
sation of an aliquot from EtOAc/pentane (1:1) gave the major di-
astereoisomer 43 of unknown configuration (>95% de) as a white
solid. Found C, 70.4; H, 6.8; N, 4.1%. C20H23NO4 requires C, 70.0; H,
6.7; N, 3.8%. Mp 92 ꢁC; nmax (CHCl3) 1736 (C]O); dH (200 MHz,
CDCl3) 0.91 (3H, s, C(5)MeA), 1.18 (3H, s, C(5)MeB), 3.19 (3H, s, OMe),
3.32 (1H, br s, OH), 4.72 (1H, s, C(4)H), 4.92 (1H, d, J 6.4, C(20)H), 5.15
(1H, d, J 6.4, C(10)H), 7.19–7.45 (10H, m, Ph); dC (125 MHz, CDCl3)
23.6, 28.1, 56.9, 67.1, 72.8, 82.4, 87.9, 126.4, 127.2, 127.8, 128.2, 128.4,
128.6, 137.2, 139.6, 158.8; m/z (APCIþ) 364 ([MþNa]þ, 100%).
4.4.20.1. X-ray crystal structure determination for 40. Data were
collected using an Enraf–Nonius
k-CCD diffractometer with
graphite monochromated Mo K radiation using standard pro-
a
cedures 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 po-
sitions. The structure was refined using CRYSTALS.42
4.4.23. 2-Oxo-2-phenylethyl m-chlorobenzoate 48
X-ray crystal structure data for 40 [C19H21NO4]: M¼327.38,
monoclinic, space group P1211, a¼10.6588(4) Å, b¼6.2394(3) Å,
c¼12.6433(5) Å,
0.092 mmꢂ1
b
¼99.781(3)ꢁ, V¼828.62(6) Å3, Z¼2,
m
¼
O
,
colourless plate, crystal dimensions¼0.1ꢃ0.1ꢃ
Ph
Cl
0.2 mm3. A total of 2017 unique reflections were measured for
5< <27 and 2017 reflections were used in the refinement. The final
parameters were wR2¼0.073 and R1¼0.053 [I>ꢂ3.0 (I)]. Crystal-
O
O
q
s
Et3N (cat) and DMAP (cat) were added sequentially to a stirred
solution of 21 (41 mg, 0.09 mmol) in DCM (2 mL) at rt. After 12 h,
the reaction mixture was concentrated in vacuo. Purification via
flash column chromatography (eluent 40–60 ꢁC petrol/EtOAc, 7:3)
gave SuperQuat 13 (15 mg, 90%) as a white solid and 48 (24 mg,
quant) as a colourless oil.
lographic data (excluding structure factors) have been deposited
with the Cambridge Crystallographic Data Centre as supplementary
publication number CCDC 679091. 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].
Data for 48:43 dH (200 MHz, CDCl3) 5.61 (2H, s, C(1)H2), 7.27–8.14
(9H, m, Ar, Ph); dC (125 MHz, CDCl3) 66.7 (C(1)), 127.8, 128.1, 129.0,
129.8, 130.1, 131.2, 133.4, 134.0, 134.2, 134.7 (Ar, Ph), 164.9 (OCOAr),
191.7 (C(2)); m/z (CIþ) 275 ([MþH]þ, 100%).
4.4.21. (4S,10R,20R)-N(3)-[10-(m-Chlorobenzoyl)-20-hydroxy-
20-phenylethan-10-yl]-4-phenyl-5,5-dimethyl-oxazolidin-2-one 41
Cl
4.4.24. (S)-Phenylethane-1,2-diol (S)-49
Ph
O
O
O
HO
Ph
OH
O
N
OH
Ph
NaBH4 (64 mg, 1.68 mmol) was added to a solution of 21
(100 mg, 0.22 mmol) in MeOH (2 mL) and the resultant solution
was stirred for 10 min before concentration in vacuo. The mixture
was then partitioned between DCM (2 mL) and 1.0 M aq HCl (2 mL),
the organic layer separated and the aqueous layer extracted with
DCM (3ꢃ5 mL). The combined organic layers were dried and con-
centrated in vacuo. Purification via flash column chromatography
(eluent EtOAc/40–60 ꢁC petrol, 2:1, and then increased to EtOAc)
gave SuperQuat 13 as a white solid (32 mg, 78%) and (S)-49 as
a white amorphous solid (24 mg, 81%, >98% ee).
Following General Procedure 2, mCPBA (279 mg, 1.62 mmol) and
33 (230 mg, 1.37 mmol) in CHCl3 (14 mL) gave a 5:14:77:4 mixture
of 21/22/41/42. Purification via recrystallisation from DCM/heptane
(1:1) gave 41 as a white crystalline solid (207 mg, 57%, >98% de);
17
mp 63–64 ꢁC; [
a
]
þ44.7 (c 1.0, CHCl3); nmax (KBr) 1733 (C]O); dH
D
(400 MHz, CDCl3) 0.90 (3H, s, C(5)MeA), 1.23 (3H, s, C(5)MeB), 4.11
(1H, s, C(4)H), 4.54 (1H, d, J 7.9, OH), 5.24 (1H, m, C(20)H), 6.16 (1H, d,
J 6.6, C(10)H), 7.06–7.81 (14H, m, Ar, Ph); dC (100 MHz, CDCl3) 23.5,

9338
C. Aciro et al. / Tetrahedron 64 (2008) 9320–9344
22
20
Data for (S)-49: [
a
]
þ64.0 (c 0.25, CHCl3) {lit.26
[
a]
þ60.5 (c
4.4.27. (R)-Propane-1,2-diol (R)-50
D
D
1.15, CHCl3)}; dH (200 MHz, CDCl3) 2.48 (1H, br s, OH), 2.88 (1H, br s,
OH), 3.67–3.75 (2H, m, C(2)H2), 4.82 (1H, dd, J 7.9, 3.8, C(1)H),
7.27–7.38 (5H, m, Ph).
The ee of (S)-phenylethane-1,2-diol was determined by Chir-
alGC analysis [flow rate 1.5 mL/min; 40 ꢁC isotherm for 120 min;
4 ꢁC/min ramp to 140 ꢁC; 140 ꢁC isotherm for 120 min; retention
times: tR (S)¼159.25 min; tR (R)¼159.87 min] and comparison with
an authentic racemic sample.
Me
OH
HO
NaBH4 (1.47 g, 38.9 mmol) was added to a solution of 37 (2.02 g,
4.99 mmol) in MeOH (20 mL) and the resultant solution was stirred
for 10 min before concentration in vacuo. H2O (10 mL) was added
and the resultant slurry was filtered through cotton wool followed
by Celite (eluent H2O). The filtrate was distilled twice and the dis-
4.4.25. (R)-Phenylethane-1,2-diol (R)-49
tillate dried in a dessicator (over P2O5) to give (R)-50 as a colourless
23
oil (151 mg, 40%); [
a
]
D
ꢂ19.6 (c 1.6, H2O).
The filter cake was washed with CHCl3 (50 mL) and the filtrate
was dried and concentrated in vacuo. Purification via flash column
chromatography (eluent EtOAc/40–60 ꢁC petrol, 2:1) gave Super-
Quat 13 as a white solid (861 mg, 90%).
Ph
HO
OH
(R)-Propane-1,2-diol (R)-50 (20 mg, 0.26 mmol) was dissolved
in pyridine (0.5 mL), and DMAP (7 mg) and Ac2O (124 mL) were
NaBH4 (64 mg, 1.68 mmol) was added to a solution of 41
(100 mg, 0.22 mmol) in MeOH (2 mL) and the resultant solution
was stirred for 10 min before concentration in vacuo. The mixture
was then partitioned between DCM (2 mL) and 1.0 M aq HCl (2 mL),
the organic layer separated and the aqueous layer extracted with
DCM (3ꢃ5 mL). The combined organic layers were dried and con-
centrated in vacuo. Purification via flash column chromatography
(eluent EtOAc/40–60 ꢁC petrol, 2:1, and then increased to EtOAc)
gave SuperQuat 13 as a white solid (37 mg, 90%) and (R)-49 as
added sequentially. The reaction mixture was stirred at rt for 24 h,
after which it was cooled to 0 ꢁC and H2O (1 mL) was added. After
warming to rt, the mixture was extracted with Et2O (3ꢃ10 mL) and
the combined organic extracts were washed sequentially with satd
aq CuSO4 (2ꢃ20 mL), H2O (2ꢃ20 mL) and satd aq NaHCO3 (20 mL),
then dried, and concentrated in vacuo to give (R)-propane-1,2-diol
19
diacetate as a colourless oil (16 mg, 38%, >98% ee); [
2.2, MeOH).
a]
þ13.2 (c
D
a white amorphous solid (18 mg, 60%, >98% ee).
19
The ee of (R)-propane-1,2-diol diacetate was determined by
ChiralGC analysis [flow rate 3 mL/min; 70 ꢁC isotherm for 15 min;
retention times: tR (S)¼13.24 min; tR (R)¼14.35 min] and compar-
ison with an authentic racemic sample.
Data for (R)-49: [
a
]
ꢂ54.1 (c 0.9, CHCl3).
D
4.4.26. (S)-Propane-1,2-diol (S)-50
Me
OH
4.4.28. (S)-3-Phenyl-propane-1,2-diol (S)-51
HO
HO
Ph
OH
NaBH4 (658 mg, 17.4 mmol) was added to a solution of 23
(900 mg, 2.23 mmol) in MeOH (10 mL) and the resultant solution
was stirred for 10 min before concentration in vacuo. H2O (5 mL)
was added and the resultant slurry was filtered through cotton
wool, followed by Celite (eluent H2O). The filtrate was distilled
NaBH4 (112 mg, 2.96 mmol) was added to a solution of 25
(177 mg, 0.37 mmol) in MeOH (6 mL) and the resultant solution
was stirred for 10 min before concentration in vacuo. The mixture
was then partitioned between DCM (2 mL) and 1.0 M aq HCl (2 mL),
the organic layer was separated and the aqueous layer was
extracted with DCM (3ꢃ5 mL). The combined organic layers were
dried and concentrated in vacuo. Purification via column chroma-
tography (eluent EtOAc/40–60 ꢁC petrol, 2:1, and then increased to
EtOAc) gave SuperQuat 13 as a white solid (70 mg, 99%) and (S)-51
as a white amorphous solid (52 mg, 93%).
twice and the distillate was dried in a dessicator (over P2O5) to give
23
(S)-50 as a colourless oil (61 mg, 37%); [
a]
þ18.1 (c 0.15, H2O)
D
31
{lit.27
[
a]
þ20.7 (c 7.5, H2O)}; dH (400 MHz, D2O) 1.01 (3H, d, J 6.4,
D
CH3CHCH2), 3.31 (1H, dd, J 6.8, 11.6, CH3CHCH2), 3.42 (1H, dd, J 4.1,
11.6, CH3CHCH2), 3.70–3.78 (1H, m, CH3CHCH2).
The filter cake was washed with CHCl3 (50 mL), the filtrate was
dried and concentration in vacuo. Purification via flash column
chromatography (eluent EtOAc/40–60 ꢁC petrol, 2:1) gave Super-
Quat 13 as a white solid (422 mg, 99%).
(S)-Propane-1,2-diol (S)-50 (42 mg, 0.552 mmol) was dissolved
in pyridine (0.5 mL), and DMAP (7 mg) and Ac2O (261 mL) were
24
20
Data for (S)-51: [
a
]
ꢂ33.5 (c 0.9, EtOH) {lit.28,45
[a
]
ꢂ36 (c 1.0,
D
D
EtOH)}; dH (400 MHz, CDCl3) 2.23 (2H, br s, OH), 2.78 (2H, m, C(3)H2),
3.53 (1H, dd, J 11.2, 7.0, C(1)HA), 3.69 (1H, dd, J 11.2, 3.1, C(1)HB), 3.95
(1H, m, C(2)H), 7.20–7.56 (5H, m, Ph); dC (100 MHz, CDCl3) 39.8, 66.0,
73.3, 126.6, 128.6, 129.3, 137.7; m/z (CIþ) 152 ([M]þ, 100%); HRMS
(CIþ) found 152.0836, C9H12Oþ2 ([M]þ) requires 152.0832.
added sequentially. The reaction mixture was stirred at rt for 24 h,
after which it was cooled to 0 ꢁC and H2O (1 mL) was added. After
warming to rt, the mixture was extracted with Et2O (3ꢃ10 mL) and
the combined organic extracts were washed sequentially with satd
aq CuSO4 (2ꢃ20 mL), H2O (2ꢃ20 mL) and satd aq NaHCO3 (20 mL),
The ee of (S)-3-phenyl-propane-1,2-diol bis-trifluoroacetate was
determined by ChiralGC analysis [flow rate 2 mL/min; 50 ꢁC iso-
therm for 120 min; 4 ꢁC/min ramp to 110 ꢁC; 110 ꢁC isotherm for
60 min; retention times: tR (S)¼139.38 min; tR (R)¼139.89 min] and
comparison with an authentic racemic sample.
then dried, and concentrated in vacuo to give (S)-propane-1,2-diol
23
diacetate as a colourless oil (35 mg, 40%, >98% ee); [
a
]
D
ꢂ13.0 (c
25
0.8, MeOH) {lit.44
[a
]
ꢂ14.7 (c 0.15, MeOH)}; dH (400 MHz, CDCl3)
D
4.4.29. (S)-3-Methylbutane-1,2-diol (S)-52
1.26 (3H, d, J 6.5, C(3)H3), 2.06 (3H, s, COMe), 2.07 (3H, s, COMe),
4.04 (1H, dd, J 11.8, 6.6, C(1)HA), 4.16 (1H, dd, J 11.8, 3.5, C(1)HB),
5.10–5.15 (1H, m, C(2)H).
iPr
HO
The ee of (S)-propane-1,2-diol diacetate was determined by
ChiralGC analysis [flow rate 3 mL/min; 70 ꢁC isotherm for 15 min;
retention times: tR (S)¼13.24 min; tR (R)¼14.35 min] and compar-
ison with an authentic racemic sample.
OH
LiAlH4 (75 mg, 1.91 mmol) was added to a solution of 27
(310 mg, 0.72 mmol) in THF (10 mL) and the resultant solution was

C. Aciro et al. / Tetrahedron 64 (2008) 9320–9344
9339
stirred for 1 h before being quenched with satd aq NH4Cl (1 mL).
The mixture was diluted with brine (10 mL), the organic layer was
separated and the aqueous layer was extracted with EtOAc
(3ꢃ10 mL). The combined organic extracts were dried and con-
centrated in vacuo. Purification via flash column chromatography
(eluent 40–60 ꢁC petrol/Et2O, 3:1, and then increased to Et2O) gave
SuperQuat 13 as a white solid (107 mg, 81%) and (S)-52 as a
as a colourless oil (22 mg, 65%, 96% ee); dH (400 MHz, CDCl3) 0.95
(9H, s, CMe3), 2.02 (3H, s, COMe), 2.09 (3H, s, COMe), 4.00 (1H, dd, J
11.7, 9.0, C(1)HA), 4.95 (1H, dd, J 9.0, 2.4, C(2)H), 4.38 (1H, dd, J 11.7,
2.4, C(1)HB).
The ee of (S)-3,3-dimethyl-butane-1,2-diol diacetate was de-
termined by ChiralGC analysis [flow rate 1 mL/min; 40 ꢁC isotherm
for 30 min; 5 ꢁC/min ramp to 60 ꢁC; 60 ꢁC isotherm for 30 min;
20 ꢁC/min ramp to 190 ꢁC; 190 ꢁC isotherm for 2 min; retention
times: tR (R)¼51.00 min; tR (S)¼51.07 min] and comparison with an
authentic racemic sample.
colourless oil (42 mg, 56%).
25
Data for (S)-52: [
a
]
þ15.2 (c 0.9, CHCl3) {lit.46 for enantiomer
D
20
[
a]
ꢂ11.0 (c 1.0, CHCl3)}; nmax (film) 3442 (O–H); dH (400 MHz,
D
CDCl3) 0.93 (3H, d, J 6.8, CH3CHCH3), 0.98 (3H, d, J 6.8, CH3CHCH3),
1.72 (1H, octet, J 6.8, C(3)H), 2.20 (2H, br s, OH), 3.44 (1H, ddd, J 8.2,
6.8, 2.8, C(2)H), 3.52 (1H, dd, J 10.8, 8.2, C(1)HA), 3.72 (1H, dd, J 10.8,
2.8, C(1)HB); dC (100 MHz, CDCl3) 18.2, 18.7, 30.9, 63.9, 77.2; m/z
(ESIþ) 122 ([MþNH4]þ, 100%); HRMS (ESIþ) found 122.1183,
C5H16NOþ2 ([MþNH4]þ) requires 122.1176.
4.4.31. (S)-N(3)-(Cyclohex-10-en-10-yl)-4-phenyl-5,5-dimethyl-
oxazolidin-2-one 54
O
Diol (S)-52 (20 mg) was dissolved in pyridine (0.5 mL), and
DMAP (2 mg) and Ac2O (0.1 mL) were added sequentially. The re-
action mixture was stirred at rt for 24 h, after which it was cooled to
0 ꢁC and H2O (1 mL) was added. After warming to rt, the mixture
was extracted with Et2O (3ꢃ10 mL) and the combined organic ex-
tracts were washed sequentially with satd aq CuSO4 (2ꢃ20 mL),
H2O (2ꢃ20 mL) and satd aq NaHCO3 (20 mL), then dried, and
concentrated in vacuo to give (S)-3-methyl-butane-1,2-diol diac-
etate as a colourless oil (30 mg, 78%, 96% ee); dH (400 MHz, CDCl3)
0.94 (3H, d, J 2.3, C(3)MeA), 0.95 (3H, d, J 2.3, C(3)MeB), 1.98–1.90
(1H, m, C(3)H), 2.06 (3H, s, COMe), 2.11 (3H, s, COMe), 4.06 (1H, dd, J
12.0, 7.2, C(1)HA), 4.28 (1H, dd, J 12.0, 3.0, C(1)HB), 4.91 (1H, dt, J 7.2,
3.0, C(2)H).
The ee of (S)-3-methyl-butane-1,2-diol diacetate was de-
termined by ChiralGC analysis [flow rate 1 mL/min; 40 ꢁC isotherm
for 30 min; 5 ꢁC/min ramp to 60 ꢁC; 60 ꢁC isotherm for 30 min;
20 ꢁC/min ramp to 190 ꢁC; 190 ꢁC isotherm for 2 min; retention
times: tR (S)¼69.41 min; tR (R)¼69.45 min] and comparison with an
authentic racemic sample.
O
N
Ph
Following General Procedure 1, TsOH (ca. 100 mg), cyclohexa-
none (7.70 g, 78.6 mmol) and 13 (5.0 g, 26.2 mmol) in PhMe
(120 mL) gave the crude reaction mixture. Purification via flash
column chromatography (eluent 30–40 ꢁC petrol/Et2O, 3:1) gave 54
as a white solid (4.48 g, 63%). Found C, 75.2; H, 8.0; N, 4.9%.
C
17H21NO2 requires C, 75.25; H, 7.8; N, 4.9%. Mp 110–112 ꢁC (Et2O);
24
[a
]
þ36.6 (c 0.8, CHCl3); nmax (KBr) 1725; dH (400 MHz, CDCl3)
D
0.96 (3H, s, C(5)MeA), 1.41–1.65 (4H, m, C(40)HA, C(50)HA, C(60)H2),
overlapping 1.59 (3H, s, C(5)MeB), 1.96–2.02 (2H, m, C(30)H2), 2.23–
2.28 (1H, m, C(40)HB), 2.29–2.38 (1H, m, C(50)HB), 4.67 (1H, s, C(4)H),
5.44 (1H, app dq, J 3.7, 2.0, C(20)H), 7.26 (5H, m, Ph); dC (100 MHz,
CDCl3) 21.6, 22.5, 23.0, 24.2, 26.4, 28.6, 70.0, 80.7, 117.9, 127.4, 127.5,
128.0, 133.6, 136.3, 155.5.
4.4.31.1. X-ray crystal structure determination for 54. Data were
collected using an Enraf–Nonius
k-CCD diffractometer with
graphite monochromated Mo K radiation using standard pro-
a
4.4.30. (S)-3,3-Dimethyl-butane-1,2-diol (S)-53
cedures 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.42
tBu
HO
OH
X-ray crystal structure data for 54 [C17H21NO2]: M¼271.36, or-
thorhombic, space group Pbca, a¼9.9633(1) Å, b¼10.7233(1) Å,
LiAlH4 (90 mg, 2.3 mmol) was added to a solution of 29 (370 mg,
0.83 mmol) in THF (10 mL) and the resultant solution was stirred
for 1 h before being quenched with satd aq NH4Cl (1 mL). The
mixture was diluted with brine (10 mL), the organic layer was
separated and the aqueous layer was extracted with EtOAc
(3ꢃ10 mL). The combined organic extracts were dried and con-
centrated in vacuo. Purification via flash column chromatography
(eluent 40–60 ꢁC petrol/Et2O, 3:1, and then increased to Et2O)
gave SuperQuat 13 as a white solid (133 mg, 84%) and (S)-53 as
c¼26.7595(4) Å, V¼2858.97(6) Å3, Z¼8,
m
¼0.082 mmꢂ1, colourless
block, crystal dimensions¼0.2ꢃ0.2ꢃ0.2 mm3. A total of 3149
unique reflections were measured for 5<q<27 and 2502 reflections
were used in the refinement. The final parameters were wR2¼0.049
and R1¼0.039 [I>3.0
s
(I)]. Crystallographic data (excluding struc-
ture factors) have been deposited with the Cambridge Crystallo-
graphic Data Centre as supplementary publication number CCDC
653138. Copies of the data can be obtained, free of charge, on ap-
plication to CCDC, 12 Union Road, Cambridge CB2 1EZ, UK [fax: þ44
(0) 1223 336033 or e-mail: deposit@ccdc.cam.ac.uk].
a colourless oil (50 mg, 51%).
25
Data for (S)-53: [
a]
þ31.9 (c 1.0, CHCl3); nmax (film) 3279 (O–
D
H); dH (400 MHz, CDCl3) 0.90 (9H, s, CMe3), 2.65 (2H, br s, OH),
3.36 (1H, dd, J 9.5, 2.6, C(2)H), 3.46 (1H, t, J 9.5, C(1)HA), 3.71 (1H,
dd, J 9.5, 2.6, C(1)HB); dC (100 MHz, CDCl3) 25.9, 33.5, 63.3, 79.6;
HRMS (CIþ) found 136.1338, C6H18NO2þ ([MþNH4]þ) requires
136.1332.
4.4.32. (4S,10R,20S)-, (4S,10S,20R)- and (4S,10S,20S)-N(3)-(10-
Methoxy-20-hydroxy-cyclohex-10-yl)-4-phenyl-5,5-dimethyl-
oxazolidin-2-one (4S,10R,20S)-59, (4S,10S,20R)-60 and (4S,10S,20S)-61
Me
O
Me
O
Me
O
Diol (S)-53 (20 mg) was dissolved in pyridine (0.5 mL), and
DMAP (2 mg) and Ac2O (0.1 mL) were added sequentially. The re-
action mixture was stirred at rt for 24 h, after which it was cooled to
0 ꢁC and H2O (1 mL) added. After warming to rt, the mixture was
extracted with Et2O (3ꢃ10 mL) and the combined organic extracts
were washed sequentially with satd aq CuSO4 (2ꢃ20 mL), H2O
(2ꢃ20 mL) and satd aq NaHCO3 (20 mL), then dried and concen-
trated in vacuo to give (S)-3,3-dimethyl-butane-1,2-diol diacetate
O
O
O
+
+
N
N
N
O
O
O
OH
OH
OH
Ph
Ph
Ph
(4S,1'R,2'S)-59
(4S,1'S,2'R)-60
(4S,1'S,2'S)-61
A solution of mCPBA (1.27 g, 7.37 mmol) in MeOH (10 mL) was
dried over Na2SO4 and subsequently added to a solution of 54

9340
C. Aciro et al. / Tetrahedron 64 (2008) 9320–9344
(500 mg, 1.84 mmol) in MeOH (10 mL) at ꢂ20 ꢁC. After stirring for
4 h, DCM was added (20 mL) and the organic layer was washed
successively with satd aq Na2CO3 (5ꢃ20 mL) and brine (20 mL),
then dried over Na2SO4 and concentrated in vacuo to give
a 67:30:2:1 mixture of 59/60/61/62. Purification via flash column
chromatography (eluent 30–40 ꢁC petrol/Et2O, 4:1) gave 61 as
a white solid (first to elute, 125 mg, 11%), 60 as a colourless oil
(second to elute, 314 mg, 26%) and 59 as a white solid (third to
(SIR92); all non-hydrogen atoms were refined with anisotropic
thermal parameters. Hydrogen atoms were added at idealised
positions. The structure was refined using CRYSTALS.42
X-ray crystal structure data for 61 [C18H25NO4]: M¼319.40, te-
tragonal, space group P41, a¼12.8576(3) Å, b¼12.8576(3) Å,
c¼10.3348(3) Å, V¼1708.53(7) Å3, Z¼4,
m
¼0.087 mmꢂ1, colourless
block, crystal dimensions¼0.2ꢃ0.2ꢃ0.2 mm3. A total of 2052
unique reflections were measured for 5<q<27 and 1711 reflections
elute, 590 mg, 50%).
were used in the refinement. The final parameters were wR2¼0.045
24
Data for 59: mp 160–162 ꢁC (Et2O); [
a
]
ꢂ99.7 (c 1.3, CHCl3); nmax
and R1¼0.039 [I>2.0
s
(I)]. Crystallographic data (excluding struc-
D
(KBr) 3433 (O–H), 1727 (C]O); dH (400 MHz, C6D6) 0.81 (3H, s,
C(5)MeA),1.01–1.11 (1H, m, C(40)HA),1.22–1.34 (2H, m, C(50)H2),1.35–
1.41 (1H, m, C(60)HA),1.41 (3H, s, C(5)MeB),1.51–1.61 (1H, m, C(40)HB),
1.73–1.87 (2H, m, C(30)H2), 2.16–2.25 (1H, m, C(60)HB), 3.28 (3H, s,
OMe), 3.56 (1H, br s, OH), 4.08–4.17 (1H, m, C(20)H), 4.40 (1H, s,
C(4)H), 6.77–7.49 (5H, m, Ph); dC (100 MHz, C6D6) 22.2, 23.5, 23.7,
29.1, 31.4, 32.6, 51.4, 67.8, 73.2, 80.7, 91.6, 128.1, 128.2, 128.4, 140.1,
157.8; m/z (ESIþ) 661 ([2MþNa]þ,100%), 342 ([MþNa]þ, 53%); HRMS
ture factors) have been deposited with the Cambridge Crystallo-
graphic Data Centre as supplementary publication number CCDC
653140. Copies of the data can be obtained, free of charge, on ap-
plication to CCDC, 12 Union Road, Cambridge CB2 1EZ, UK [fax: þ44
(0) 1223 336033 or e-mail: deposit@ccdc.cam.ac.uk].
4.4.33. 2-Hydroxy-cyclohexanone 63
(ESIþ) found 342.1678, C18H25NNaOþ4 ([MþNa]þ) requires 342.1676.
O
20
Data for 60: [
a
]
þ24.1 (c 0.7, CHCl3), nmax (film) 3411 (O–H),
D
HO
1721 (C]O); dH (400 MHz, C6D6) 0.65 (3H, s, C(5)MeA), 0.79–0.92
(1H, m, C(40)HA), 1.06–1.18 (2H, m, C(50)H2), 1.29 (3H, s, C(5)MeB),
1.32–1.42 (1H, m, C(40)HB), 1.68–1.79 (4H, m, C(30)H2, C(60)H2), 3.09
(3H, s, OMe), 3.88–3.97 (1H, m, C(20)H), 4.09 (1H, br s, OH), 4.22 (1H,
s, C(4)H), 6.99–7.46 (5H, m, Ph); dC (100 MHz, C6D6) 22.3, 23.4, 24.0,
29.1, 31.7, 32.1, 50.9, 68.6, 74.7, 80.6, 91.2, 128.1, 128.2, 128.4, 139.5,
157.7; m/z (ESIþ) 378 ([Mþ59]þ, 100%); HRMS (ESIþ) found
320.1861, C18H26NO4þ ([MþH]þ) requires 320.1856.
Aq HCl (10%, 2 mL) was added to a solution of 59 (200 mg,
0.63 mmol) in THF (2 mL) at 0 ꢁC. The reaction mixture was allowed
to warm to rt over 12 h after which it was neutralised with satd aq
Na2CO3 (3 mL) and the aqueous phase was extracted with EtOAc
(3ꢃ10 mL). The combined organic extracts were then washed with
brine, dried over Na2SO4 and concentrated in vacuo. Purification via
Data for 61: found C, 67.65; H, 7.9; N, 4.4%. C18H25NO4 requires C,
flash column chromatography (eluent 30–40 ꢁC petrol/Et2O, 1:1)
24
67.7; H, 7.9; N, 4.4%. Mp 142–144 ꢁC (Et2O); [
a]
þ105.5 (c 1.0,
D
20
gave 63 as a colourless oil (39 mg, 55%); [
a
]
ꢂ1.5 (c 1.0, CHCl3)
D
CHCl3); nmax (KBr) 3391 (O–H), 1703 (C]O); dH (400 MHz, C6D6)
0.62 (3H, s, C(5)MeA), 1.15–1.23 (2H, m, C(40)HA, C(50)HA), 1.28 (3H, s,
C(5)MeB), 1.37–1.46 (1H, m, C(50)HB), 1.43–1.53 (1H, m, C(60)HA),
1.50–1.56 (1H, m, C(30)HA), 1.63–1.72 (2H, m, C(40)HB, C(60)HB,),
1.84–1.87 (1H, m, C(30)HB), 3.07 (3H, s, OMe), 4.16 (1H, d, J 3.0, OH),
4.33 (1H, s, C(4)H), 4.97 (1H, s, C(20)H), 6.98–7.31 (5H, m, Ph); dC
(100 MHz, C6D6) 19.3, 22.4, 24.4, 29.5, 29.6, 33.2, 49.7, 65.3, 67.0,
81.2, 92.6, 128.1, 128.3, 128.5, 140.5, 158.6; m/z (ESIþ) 378 ([Mþ59]þ,
100%); HRMS (ESIþ) found 342.1680, C18H25NNaOþ4 ([MþNa]þ)
requires 342.1676.
20
{lit.31 for 90% ee [
a]
ꢂ13.3 (c 0.5, CHCl3); lit.32 for enantiomer, 96%
D
18
ee [
a
]
þ23.3 (c 0.6, CHCl3)}; dH (400 MHz, CDCl3) 1.45–1.76 (3H, m,
D
C(3)HA, C(4)HA, C(5)HA), 1.83–1.92 (1H, m, C(4)HB), 2.06–2.15 (1H,
m, C(5)HB), 2.32–2.37 (1H, m, C(6)HA), 2.41–2.49 (1H, m, C(3)HB),
2.52–2.61 (1H, m, C(6)HB), 3.63 (1H, br s, OH), 4.12 (1H, ddd, J 12.1,
6.6, 1.7, C(2)H).
4.4.34. (4S,10S,20S)-N(3)-(10-Methoxy-20-benzyloxy-cyclohex-10-
yl)-4-phenyl-5,5-dimethyl-oxazolidin-2-one 65
4.4.32.1. X-ray crystal structure determination for 59. Data were
Me
O
O
collected using an Enraf–Nonius
k-CCD diffractometer with
graphite monochromated Mo K radiation using standard pro-
a
O
N
cedures 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.42
OBn
Ph
NaH (60% dispersion in mineral oil, 26 mg, 0.64 mmol) and BnBr
(145 mg, 0.85 mmol) were sequentially added to a solution of 61
(135 mg, 0.42 mmol) in DMF (5 mL) at 0 ꢁC. The reaction mixture
was allowed to warm to rt and stirred for a further 6 h, after which
H2O was added and the aqueous phase was extracted with EtOAc
(2ꢃ10 mL). The combined organic extracts were washed with satd
aq Na2CO3 solution and brine, then dried over Na2SO4 and con-
centrated in vacuo. Purification via flash column chromatography
(silica, 30–40 ꢁC petrol/Et2O, 4:1) gave 65 as a white solid (165 mg,
X-ray crystal structure data for 59 [C18H25NO4]: M¼638.80, or-
thorhombic, space group P212121, a¼9.7982(2) Å, b¼13.8669(2) Å,
c¼25.6927(6) Å, V¼3490.88(12) Å3, Z¼8,
m
¼0.085 mmꢂ1, colourless
block, crystal dimensions¼0.1ꢃ0.1ꢃ0.1 mm3.
A total of 4385
unique reflections were measured for 5<q<27 and 3569 re-
flections were used in the refinement. The final parameters were
(I)]. Crystallographic data (ex-
wR2¼0.057 and R1¼0.051 [I>1.0
s
cluding structure factors) have been deposited with the Cambridge
Crystallographic Data Centre as supplementary publication num-
ber CCDC 661684. 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].
95%). Found C, 73.1; H, 7.6; N, 3.4%. C25H31NO4 requires C, 73.3; H,
23
7.6; N, 3.4%. Mp 134 ꢁC (Et2O); [
a
]
þ41.5 (c 0.9, CHCl3); nmax (KBr)
D
1733 (C]O); dH (400 MHz, C6D6) 0.63 (3H, s, C(5)MeA), 1.10–1.19
(1H, m, C(40)HA), 1.32–1.42 (1H, m, C(60)HA), 1.24 (3H, s, C(5)MeB),
1.63–1.78 (3H, m, C(40)HB, C(50)HA),1.79–1.92 (2H, m, C(30)H2), 2.57–
2.63 (1H, m, C(60)HB), 3.23 (3H, s, OMe), 4.26 (1H, s, C(4)H), 4.45 (1H,
d, J 10.7, OCHAHBPh), 4.53 (1H, d, J 10.7, OCHAHBPh), 4.80 (1H, br s,
C(20)H), 6.49–7.48 (10H, m, Ph); dC (100 MHz, CDCl3) 19.1, 22.7, 23.9,
26.5, 29.3, 34.1, 51.8, 68.1, 71.7, 80.1, 80.2, 90.4, 127.2, 127.7, 127.8,
128.0, 128.4, 139.3, 139.8, 155.5.
4.4.32.2. X-ray crystal structure determination for 61. Data were
collected using an Enraf–Nonius
graphite monochromated Mo K radiation using standard pro-
cedures at 190 K. The structure was solved by direct methods
k-CCD diffractometer with
a

C. Aciro et al. / Tetrahedron 64 (2008) 9320–9344
9341
4.4.35. (S)-2-Benzyloxycyclohexanone (S)-66
([Mþ59]þ, 45%); HRMS (FIþ) found 217.1107, C13H15NOþ2 ([M]þ)
requires 217.1097.
O
4.4.36.1. X-ray crystal structure determination for 72. Data were
BnO
collected using an Enraf–Nonius
k-CCD diffractometer with
graphite monochromated Mo K radiation using standard pro-
a
cedures 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.42
From 59. NaH (60% dispersion in mineral oil, 15 mg, 0.38 mmol)
and BnBr (63.9 mg, 0.38 mmol) were sequentially added to a solution
of 59 (100 mg, 0.31 mmol) in DMF (2 mL) at 0 ꢁC and the reaction
mixture was allowed to warm to rt. After stirring for a further 10 h,
H2O was added and the aqueous phase was extracted with EtOAc
(2ꢃ6 mL), the combined organic extracts were washed with satd aq
Na2CO3 (10 mL) and brine (10 mL), then dried and concentrated in
vacuo. Purification via flash column chromatography (eluent 30–
40 ꢁC petrol/EtOAc, 9:1) gave (S)-66 as a colourless oil (5.8 mg, 9%).
From 65. Aq HCl (10%, 2 mL) was added to a solution of 65
(100 mg, 0.24 mmol) in THF (2 mL) at 0 ꢁC. The reaction mixture
was allowed to warm to rt over 12 h, after which time satd aq
Na2CO3 (5 mL) was added and the aqueous phase was extracted
with EtOAc (3ꢃ5 mL). The combined organic extracts were washed
with brine (10 mL), dried and concentrated in vacuo. Purification
via flash column chromatography (eluent 30–40 ꢁC petrol/EtOAc,
9:1) gave (S)-66 as a colourless oil (44 mg, 69%).
X-ray crystal structure data for 72 [C13H15NO2]: M¼217.27, or-
thorhombic, space group P212121, a¼8.21470(10) Å, b¼11.4424(2) Å,
c¼12.7093(3) Å, V¼1194.62(4) Å3, Z¼4,
m
¼0.082 mmꢂ1, colourless
block, crystal dimensions¼0.2ꢃ0.2ꢃ0.2 mm3. A total of 1570
unique reflections were measured for 5<q<27 and 1173 reflections
were used in the refinement. The final parameters were wR2¼0.52
and R1¼0.047 [I>3.0
s
(I)]. Crystallographic data (excluding struc-
ture factors) have been deposited with the Cambridge Crystallo-
graphic Data Centre as supplementary publication number CCDC
653141. 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].
4.4.37. (4S,100R,E)-3-[10-(100-Hydroxy-100-phenyl-methyl)-20-phenyl-
ethenyl]-4-phenyl-5,5-dimethyl-oxazolidin-2-one 75
23
21
Data for (S)-66: [
a
]
ꢂ103.0 (c 0.8, CHCl3) {lit.34
[
a
]
D
ꢂ108.1 (c
D
1.2, CHCl3)}; nmax (film) 1725 (C]O); dH (400 MHz, CDCl3) 1.54–1.75
(2H, m, C(4)HA, C(5)HA), 1.81–1.88 (1H, m, C(3)HA), 1.90–1.99 (2H,
m, C(4)HB, C(5)HB), 2.17–2.22 (1H, m, C(3)HB), 2.23–2.31 (1H, m,
C(6)HA), 2.51–2.59 (1H, m, C(6)HB), 3.83–3.92 (1H, m, C(2)H), 4.49
(1H, d, J 12.0, OCHA) 4.79 (1H, d, J 12.0, OCHB), 7.28–7.40 (5H, m, Ph);
m/z (ESIþ) 205 ([MþH]þ, 100%); HRMS (ESIþ) found 205.1223,
HO
Ph
O
Ph
O
N
Ph
C
13H17Oþ2 ([MþH]þ) requires 205.1223.
tBuLi (1.7 M in pentane, 0.8 mL, 1.36 mmol) was added dropwise
via syringe to a solution of 14 (200 mg, 0.68 mmol) in THF (20 mL) at
ꢂ78 ꢁC and stirred for 45 min before the addition of PhCHO (144 mg,
1.36 mmol). The reaction mixture was stirred at ꢂ78 ꢁC for a further
2 h before being allowed to warm to rt over a further 12 h. The re-
action mixture was quenched with satd aq NH4Cl (5 mL) and diluted
with H2O (20 mL). The mixture was extracted with EtOAc (5ꢃ20 mL),
the combined organic extracts were dried and concentrated in vacuo
to give a 92.5:7.5 mixture of 75/76. Purification via flash column
4.4.36. (S)-N(3)-Ethenyl-4-phenyl-5,5-dimethyl-oxazolidin-
2-one 72
O
O
N
Ph
Preparation of (DPP)Pd(OCOCF3)2. A solution of Pd(OCOCF3)2
(100 mg, 0.30 mmol) in PhMe (2 mL) was added to a solution of
DPPy (100 mg, 0.30 mmol) in PhMe (2 mL) and stirred at rt for
12 h. The resultant slurry was filtered to give (DPP)Pd(OCOCF3)2
as a pale brown solid (180 mg, 90%) that was used without
purification.
(DPP)Pd(OCOCF3)2 (100 mg, 0.15 mmol) was added to a solu-
tion of 13 (500 mg, 2.62 mmol) in butyl vinyl ether (3.4 mL,
26.2 mmol) and the reaction mixture was stirred at 76 ꢁC for 6 h
after which time an additional portion of (DPP)Pd(OCOCF3)2
(25 mg, 0.38 mmol) and butyl vinyl ether (3.4 mL, 26.2 mmol)
were added to the reaction mixture. Stirring was continued for
a further 6 h at 76 ꢁC before the mixture was allowed to cool to rt,
filtered and concentrated in vacuo. Purification via flash column
chromatography (eluent 30–40 ꢁC petrol/Et2O, 9:1) gave 72 as
chromatography (eluent 30–40 ꢁC petrol/Et2O, 5:1) gave 75 as
23
a white solid (162 mg, 60%, >98% de); mp 149 ꢁC (Et2O); [
a]
ꢂ222.9
D
(c 0.3, CHCl3); nmax (KBr) 3393 (O–H), 1710 (C]O); dH (400 MHz,
CDCl3), 0.83 (3H, s, C(5)MeA), 0.90 (3H, s, C(5)MeB), 4.79 (1H, s, C(4)H),
5.85 (1H, d, J 10.6, C(100)H), 6.04 (1H, d, J 10.6, OH), 6.22 (1H, s, C(20)H),
7.17–7.44 (15H, m, Ph); dC (125 MHz, CDCl3) 23.6, 27.7, 71.5, 73.0, 83.3,
124.6 125.5, 126.8, 127.1, 127.7, 128.2, 128.4, 128.9, 129.2, 134.9, 136.8,
138.4, 141.5, 157.3; m/z (ESIþ) 400 ([MþH]þ, 100%); HRMS (ESIþ)
found 400.1916, C26H26NOþ3 ([MþH]þ) requires 400.1907.
4.4.38. (4S,100R)-3-[(100-Hydroxy-100-phenyl-methyl)]ethenyl-
4-phenyl-5,5-dimethyl-oxazolidin-2-one 77
HO
Ph
O
a white solid (362 mg, 64%). Found C, 71.9; H, 7.0; N, 6.45%.
O
N
23
C
17H21NO2 requires C, 71.8; H, 7.0; N, 6.5%. Mp 135 ꢁC (Et2O); [
a]
D
þ85.0 (c 0.8, CHCl3); vmax (KBr) 1749; dH (400 MHz, CDCl3) 0.95
(3H, s, C(5)MeA), 1.60 (3H, s, C(5)MeB), 3.96 (1H, d, J 16.0, C(20)HA),
4.29 (1H, d, J 9.3, C(20)HB), 4.63 (1H, s, C(4)H), 6.90 (1H, dd, J 16.0,
9.3, C(10)H), 7.11–7.41 (5H, m, Ph); dC (100 MHz, CDCl3) 23.8, 29.3,
67.7, 82.2, 95.6, 128.6, 128.7, 128.9, 134.8, 154.8; m/z (ESIþ) 276
Ph
tBuLi (1.7 M in pentane, 0.5 mL, 0.83 mmol) was added drop-
wise via syringe to a solution of 72 (90 mg, 0.41 mmol) in THF
(5 mL) at ꢂ78 ꢁC and stirred for 45 min before the addition of
PhCHO (97 mg, 0.91 mmol). The reaction mixture was stirred at
ꢂ78 ꢁC for a further 2 h before being allowed to warm to rt over
a further 12 h. The reaction mixture was quenched with satd aq
y
DPP¼4,7-diphenyl-1,10-phenanthroline.

9342
C. Aciro et al. / Tetrahedron 64 (2008) 9320–9344
NH4Cl (1 mL) and diluted with H2O (10 mL). The mixture was
extracted with EtOAc (5ꢃ10 mL) and the combined organic ex-
tracts were dried and concentrated in vacuo to give a 67:33 mix-
ture of 77/78. Purification via flash column chromatography
(eluent PhMe/acetone, 100:1, and then increased to PhMe/acetone,
10:1) gave a 67:33 mixture of 77/78 as a colourless oil (80 mg,
60%).
4.4.40. (4S,100R,E)-N(3)-(10-(100-Benzyloxy-ethyl)-20-phenyl-
ethenyl)-4-phenyl-5,5-dimethyl-oxazolidin-2-one 82
BnO
O
Me
Ph
O
N
Selected peaks for 77: dH (400 MHz, CDCl3), 0.86 (3H, s,
C(5)MeA), 1.28 (3H, s, C(5)MeB), 4.52 (2H, d, J 2.2, C(30)H2), 4.83 (1H,
s, C(4)H), 4.99 (1H, d, J 7.8, OH), 5.63 (1H, d, J 7.8, C(10)H); dC
(100 MHz CDCl3) 23.6, 28.1, 71.6, 74.8, 82.6, 105.3, 135.4, 140.9,
144.8, 156.0.
Ph
Following General Procedure 3, 14 (200 mg, 0.68 mmol), tBuLi
(1.7 M in pentane, 0.8 mL, 1.36 mmol), MeCHO (84 L, 1.50 mmol)
and BnBr (0.16 mL,1.36 mmol) in THF (20 mL) gave an 83:17 mixture
m
Selected peaks for 78: dH (400 MHz, CDCl3), 0.85 (3H, s,
C(5)MeA), 1.32 (3H, s, C(5)MeB), 4.83 (1H, s, C(4)H), 4.60 (1H, d, J 7.0,
OH), 4.66 (1H, s, C(30)HA), 4.73 (1H, s, C(30)HB), 5.72 (1H, d, J 7.0,
C(10)H); dC (100 MHz, CDCl3) 23.8, 28.2, 70.9, 74.3, 82.4, 105.3,135.0,
140.6, 144.6, 155.8.
of 82/83. Purification via flash column chromatography (eluent 30–
40 ꢁC petrol/Et2O, 4:1) gave 82 as a colourless oil (148 mg, 51%, >98%
21
de); [a]
þ48.8 (c 0.8, CHCl3); nmax (film) 1749; dH (400 MHz, CDCl3)
D
0.96 (3H, s, C(5)MeA), 1.19 (3H, d, J 5.0, C(40)H3), 1.58 (3H, s, C(5)MeB),
4.26 (1H, d, J 11.5, OCHA), 4.51 (1H, q, J 7.0, C(30)H), 4.60 (1H, d, J 11.5,
OCHB), 5.13 (1H, s, C(4)H), 7.01–7.45 (16H, m, C(10)H, Ph); dC
(100 MHz, CDCl3) 21.9, 24.2, 28.8, 69.7, 70.9, 71.3, 81.0, 125.4, 126.5,
127.4, 127.6, 128.2, 128.4, 128.6, 128.7, 128.9, 132.1, 134.9, 135.7, 136.3,
137.8, 156.6; m/z (ESIþ) 877 ([2MþNa]þ, 100%), 450 (87); HRMS
(ESIþ) found 450.2044, C28H29NNaOþ3 ([MþNa]þ) requires 450.2040.
4.4.39. (4S,100R,E)- and (4S,100S,E)-N(3)-[10-(100-Hydroxy-ethyl)-
20-phenyl-ethenyl]-4-phenyl-5,5-dimethyl-oxazolidin-2-one
(4S,100R,E)-79 and (4S,100S,E)-80, and (S)-N(3)-(10-phenyl-
20-hydroxy-20-methyl-propyl)-4-benzoyl-5-methyl-oxazolid-4-en-
2-one 81
4.4.41. (4S,100R,E)- and (4S,100S,E)-N(3)-[10-(100-Benzyloxy-100phenyl-
methyl)-20-phenyl-ethenyl]-4-phenyl-5,5-dimethyl-oxazolidin-
2-one (4S,100R,E)-84 and (4S,100S,E)-85
HO
N
HO
Me
Ph
Me
Ph
Me
Ph
O
N
O
O
HO
SiO2
+
O
O
N
BnO
O
BnO
O
Ph
Ph
Ph
81
Ph
79
Ph
80
+
Ph
Ph
O
N
O
N
tBuLi (1.7 M in pentane, 0.8 mL, 1.36 mmol) was added drop-
wise via syringe to a solution of 14 (200 mg, 0.68 mmol) in THF
(20 mL) at ꢂ78 ꢁC and stirred for 45 min before the addition of
Ph
84
Ph
85
t
MeCHO (60
m
L, 1.36 mmol). The reaction mixture was stirred at
Following General Procedure 3, 14 (200 mg, 0.68 mmol), BuLi
(1.7 M, 0.8 mL, 1.36 mmol), PhCHO (0.16 mL, 1.50 mmol) and BnBr
(0.16 mL, 1.36 mmol) in THF (20 mL) gave a 92:8 mixture of 84/85.
Purification via flash column chromatography (eluent 30–40 ꢁC
petrol/Et2O, 4:1) gave 84 as a white solid (first to elute, 279 mg, 83%,
>98% de) and a 17:83 mixture of 84/85 as a colourless oil (second to
ꢂ78 ꢁC for a further 2 h before being allowed to warm to rt over
a further 12 h. The reaction mixture was quenched with satd aq
NH4Cl (5 mL) and diluted with H2O (20 mL). The mixture was
extracted with EtOAc (5ꢃ20 mL), the combined organic extracts
were dried and concentrated in vacuo to give an 83:17 mixture of
79/80. Filtration through silica (eluent 30–40 ꢁC petrol/Et2O, 5:1)
gave an 83:17 mixture of 79/80 as colourless oil (156 mg, 57%);
nmax (film) 3416 (O–H), 1736 (C]O); m/z (ESIþ) 360 ([MþNa]þ,
100%); HRMS (ESIþ) found 338.1753, C21H24NOþ3 ([MþH]þ) re-
quires 338.1751.
Data for 79: dH (400 MHz, CDCl3) 1.27 (3H, s, C(5)MeA), 1.42 (3H,
d, J 6.3, C(200)H3), 1.55 (3H, s, C(5)MeB), 4.41 (1H, s, C(4)H), 5.58–5.63
(1H, m, C(100)H), 5.80 (1H, s, C(20)H), 7.09–7.52 (10H, m, Ph); dC
(100 MHz, CDCl3) 19.6, 28.2, 29.1, 67.8, 71.8, 75.6, 101.6, 126.7, 126.7,
127.9, 128.0, 128.3, 128.8, 129.5, 136.4, 141.5, 158.4.
elute, 24 mg, 7%).
23
Data for 84: mp 45 ꢁC (Et2O); [
a
]
þ24.3 (c 1.6, CHCl3); nmax
D
(KBr) 1748; dH (400 MHz, CDCl3) 0.83 (3H, s, C(5)MeA), 1.47 (3H, s,
C(5)MeB), 4.32 (1H, s, C(4)H), 4.52 (1H, d, J 11.6, OCHA), 4.94 (1H, d, J
11.6, OCHB), 5.65 (1H, s, C(30)H), 7.03–7.51 (21H, m, C(10)H, Ph); dC
(100 MHz, CDCl3) 24.1, 28.8, 69.1, 71.2, 74.5, 81.3, 125.4, 125.6, 127.4,
127.7, 127.8, 127.9, 128.0, 128.1, 128.2, 128.3, 128.4, 128.5, 132.7,
134.6, 136.3, 137.6, 139.1, 156.9; m/z (ESIþ) 548 ([Mþ59]þ, 100%);
HRMS (FIþ) found 489.2319, C33H31NOþ3 ([M]þ) requires 489.2298.
Data for 85: dH (400 MHz, CDCl3) 0.75 (3H, s, C(5)MeA), 0.81 (3H,
s, C(5)MeB), 3.61 (1H, d, J 12.4, OCHA), 3.81 (1H, d, J 12.4, OCHB), 4.86
(1H, s, C(4)H), 5.67 (1H, s, C(30)H), 7.01–7.68 (21H, m, C(10)H, Ph); dC
(100 MHz, CDCl3) 24.0, 27.9, 69.3, 69.9, 74.4, 81.2, 125.5, 126.1, 127.4,
127.6, 127.7, 127.9, 128.1, 128.4, 128.5, 128.6, 131.8, 134.5, 137.3, 137.4,
139.3, 157.0.
Data for 80: dH (400 MHz, CDCl3) 0.99 (3H, s, C(5)MeA), 1.19 (3H,
d, J 6.3, C(200)H3), 1.26 (3H, s, C(5)MeB), 4.41 (1H, s, C(4)H), 5.77–5.82
(1H, m, C(100)H), 5.90 (1H, s, C(20)H), 7.09–7.52 (10H, m, Ph); dC
(100 MHz, CDCl3) 18.8, 27.9, 29.0, 67.8, 71.1, 75.9, 101.6, 127.6, 128.0,
128.1, 128.2, 128.8, 129.2, 136.0, 137.9, 157.2.
Attempted further purification via flash column chromatogra-
phy (eluent 30–40 ꢁC petrol/Et2O, 5:1) gave 81 as a colourless oil
4.4.41.1. X-ray crystal structure determination for 84. Data were
23
(156 mg, quant); [
a]
ꢂ149.8 (c 1.3, CHCl3); nmax (film) 3381 (O–
collected using an Enraf–Nonius
k-CCD diffractometer with
D
H), 1734 (C]O); dH (400 MHz, CDCl3), 0.87 (3H, s, C(20)MeA), 0.99
(3H, s, C(20)MeB), 2.13 (3H, s, C(5)Me), 3.41 (1H, d, J 16.9,
CHAHBPh), 3.78 (1H, d, J 16.9, CHAHBPh), 4.20 (1H, s, C(10)H), 5.91
(1H, br s, OH), 7.18–7.41 (10H, m, Ph); dC (100 MHz, CDCl3) 10.1,
27.9, 28.3, 28.9, 68.0, 71.1, 121.2, 127.6, 128.0, 128.1, 128.3, 128.8,
129.2, 134.9, 136.0, 138.0, 157.2; m/z (ESIþ) 360 ([MþNa]þ, 100%);
HRMS (ESIþ) found 338.1758, C21H24NOþ3 ([MþH]þ) requires
338.1751.
graphite monochromated Mo K radiation using standard pro-
a
cedures 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.42
X-ray crystal structure data for 84 [C33H31NO3]: M¼489.61, tri-
gonal, space group P31, a¼9.6347(2) Å, b¼9.6347(2) Å,
c¼24.8494(5) Å, V¼1997.67(7) Å3, Z¼3,
m
¼0.077 mmꢂ1, colourless

C. Aciro et al. / Tetrahedron 64 (2008) 9320–9344
9343
block, crystal dimensions¼0.2ꢃ0.2ꢃ0.2 mm. A total of 2941 unique
reflections were measured for 5< <27 and 2184 reflections were
used in the refinement. The final parameters were wR2¼0.036 and
(I)]. Crystallographic data (excluding structure
factors) have been deposited with the Cambridge Crystallographic
Data Centre as supplementary publication number CCDC 653142.
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].
0.81 (3H, s, C(5)MeA), 1.46 (3H, s, C(5)MeB), 4.31 (1H, s, C(4)H), 4.55
(1H, d, J 11.7, OCHA), 4.95 (1H, d, J 11.7, OCHB), 5.61 (1H, s, C(30)H),
7.01–7.53 (20H, m, C(10)H, Ar, Ph); dC (100 MHz, CDCl3) 24.0, 28.7,
69.1, 71.2, 73.7, 81.3, 122.2, 122.6, 124.0, 124.1, 125.3, 127.9, 128.1,
128.4, 128.5, 128.6, 128.8, 130.6 (quartet), 132.2, 134.4, 134.7, 135.8,
137.1, 140.3, 156.7; m/z (ESIþ) 616 ([Mþ59]þ, 100%); HRMS (FIþ)
found 580.2076, C34H30F3NNaOþ3 ([MþNa]þ) requires 580.2070.
q
R1¼0.036 [I>3.0
s
4.4.43.1. X-ray crystal structure determination for 88. Data were
collected using an Enraf–Nonius
k-CCD diffractometer with
4.4.42. (4S,100R,E)- and (4S,100S,E)-N(3)-[10-(100-Benzyloxy-100-p-
methoxyphenyl-methyl)-20-phenyl-ethenyl]-4-phenyl-5,5-
dimethyl-oxazolidin-2-one (4S,100R,E)-86 and (4S,100S,E)-87
graphite monochromated Mo K radiation using standard pro-
a
cedures 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 po-
sitions. The structure was refined using CRYSTALS.42
OMe
+
OMe
X-ray crystal structure data for 88 [C34H30F3NO3]: M¼557.61,
BnO
O
BnO
O
monoclinic,
space
group
P1211,
b
a¼11.59210(10) Å,
b¼
12.77350(10) Å, c¼19.7303(2) Å,
¼98.0963(4)ꢁ, V¼2892.38(4) Å3,
Ph
Ph
¼0.094 mmꢂ1, colourless plate, crystal dimensions¼0.1ꢃ
O
N
O
N
Z¼4,
m
0.1ꢃ0.2 mm3. A total of 6850 unique reflections were measured for
Ph
Ph
5<q<27 and 5452 reflections were used in the refinement. The final
86
87
parameters were wR2¼0.176 and R1¼0.118 [I>0.5
s(I)]. Crystallo-
t
graphic data (excluding structure factors) have been deposited with
the Cambridge Crystallographic Data Centre as supplementary
publication number CCDC 653143. 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].
Following General Procedure 3, 14 (200 mg, 0.68 mmol), BuLi
(1.7 M in pentane, 0.8 mL, 1.36 mmol), p-anisaldehyde (0.16 mL,
1.50 mmol) and BnBr (0.16 mL, 1.36 mmol) in THF (20 mL) gave
a 78:22 mixture of 86/87. Purification via flash column chroma-
tography (eluent 30–40 ꢁC petrol/Et2O, 9:1) gave 86 as a colourless
oil (first to elute, 353 mg, 72%, >98% de) and 87 as a colourless oil
(second to elute, 25 mg, 7%, >98% de).
23
4.4.44. (4S,20R)-N(3)-(20-Benzyloxy-20-phenyl-acetyl)-4-phenyl-
5,5-dimethyl-oxazolidin-2-one 94
Data for 86: [
a
]
D
þ178.9 (c 0.8, CHCl3); nmax (film) 1748 (C]O);
dH (400 MHz, CDCl3) 0.80 (3H, s, C(5)MeA), 1.43 (3H, s, C(5)MeB),
3.77 (3H, s, OMe), 4.37 (1H, s, C(4)H), 4.47 (1H, d, J 11.6, OCHA), 4.87
(1H, d, J 11.6, OCHB), 5.54 (1H, s, C(30)H), 6.61 (2H, d, J 8.7, Ar), 7.09
(2H, d, J 8.7, Ar), 7.10–7.44 (16H, m, C(10)H, Ph); dC (100 MHz, CDCl3)
24.1, 28.7, 55.3, 69.1, 71.2, 74.3, 81.2, 113.5, 126.7, 127.6, 127.7, 127.9,
128.1, 128.2, 128.3, 128.4, 128.6, 130.9, 132.7, 136.5, 137.6, 156.8,
158.7; m/z (ESIþ) 578 ([Mþ59]þ, 100%); HRMS (FIþ) found 519.2426,
BnO
O
Ph
O
O
N
Ph
C
34H33NOþ4 ([M]þ) requires 519.2404.
23
NaIO4 (120 mg, 0.56 mmol) was added to a vigorously stirred
solution of 84 (100 mg, 0.20 mmol) in CCl4 (2 mL), MeCN (2 mL)
and H2O (3 mL). RuCl3 (2.2 mg, 0.01 mmol) was added and the
solution stirred at rt for 12 h after which time H2O (15 mL) was
added and the mixture extracted with EtOAc (3ꢃ10 mL). The
combined organic extracts were dried and concentrated in vacuo.
Data for 87: [
a
]
ꢂ191.1 (c 0.9, CHCl3); nmax (film) 1748 (C]O);
D
dH (400 MHz, CDCl3) 0.82 (3H, s, C(5)MeA), 0.85 (3H, s, C(5)MeB),
3.60 (1H, d, J 12.3, OCHA), 3.80 (1H, d, J 12.3, OCHB), 3.84 (3H, s,
OMe), 4.91 (1H, s, C(4)H), 5.59 (1H, s, C(30)H), 6.71 (2H, d, J 6.9, Ar),
7.06–7.44 (18H, m, C(10)H, Ar, Ph); dC (100 MHz, CDCl3) 24.0, 28.1,
55.4, 69.3, 69.9, 74.3, 81.2, 113.9, 127.3, 127.5, 128.7, 128.9, 128.1,
128.2, 128.4, 128.6, 128.7, 134.6, 131.2, 131.6, 135.2, 137.3, 137.4,
156.8, 159.2; m/z (ESIþ) 578 ([Mþ59]þ, 100%); HRMS (FIþ) found
542.2295, C34H33NNaO4þ ([MþNa]þ) requires 542.2302.
Purification via flash column chromatography (eluent 30–40 ꢁC
23
petrol/Et2O, 3:1) gave 94 as a colourless oil (76 mg, 92%); [
a
]
D
ꢂ4.9
(c 1.3, CHCl3); nmax (film) 1775 (C]O), 1716 (C]O); dH (400 MHz,
CDCl3) 0.88 (3H, s, C(5)MeA), 1.60 (3H, s, C(5)MeB), 4.58 (2H, d, J 3.2,
OCH2), 5.14 (1H, s, C(4)H), 6.37 (1H, s, C(20)H), 6.57–7.62 (15H, m,
Ph); dC (100 MHz, CDCl3) 23.9, 29.1, 66.9, 71.4, 79.0, 82.9, 127.8,
128.2, 128.4, 128.5, 129.0, 130.2, 135.0, 135.1, 137.4, 152.5, 170.4; m/z
(CIþ) 433 ([MþNH4]þ, 100%); HRMS (CIþ) found 433.2123,
4.4.43. (4S,100R,E)-N(3)-[10-(100-Benzyloxy-100-m-trifluoromethyl-
phenyl-methyl)-200-phenyl-ethenyl]-4-phenyl-5,5-dimethyl-
oxazolidin-2-one 88
C
26H29N2Oþ4 ([MþNH4]þ) requires 433.2122.
BnO
4.4.45. Methyl (R)-2-benzyloxy-2-phenylacetate 95
O
CF3
Ph
O
N
BnO
MeO
Ph
O
Ph
t
Following General Procedure 3, 14 (200 mg, 0.68 mmol), BuLi
(1.7 M in pentane, 0.8 mL, 1.36 mmol), m-trifluoromethyl-
benzaldehyde (0.16 mL, 1.50 mmol) and BnBr (0.16 mL, 1.36 mmol)
in THF (10 mL) gave a 94:6 mixture of 88/89. Purification via flash
column chromatography (eluent 30–40 ꢁC petrol/Et2O, 9:1) gave 88
as a colourless solid (236 mg, 62%, >98% de); mp 96 ꢁC; [
A solution of 94 (70 mg, 0.17 mmol) in MeOH (1 mL) was added
to a 0.1 M solution of MeOMgBr [3.1 mL, 0.34 mmol; prepared by
addition of MeMgBr (0.1 mL, 0.84 mmol) to MeOH (3 mL)] at 0 ꢁC.
After stirring for 20 min, satd aq NH4Cl (2 mL) was added and the
mixture was extracted with Et2O (3ꢃ5 mL). The combined organic
extracts were dried and concentrated in vacuo. Purification via
23
a]
D
þ133.5 (c 0.6, CHCl3); nmax (KBr) 1749 (C]O); dH (400 MHz, CDCl3)

9344
C. Aciro et al. / Tetrahedron 64 (2008) 9320–9344
flash column chromatography (eluent 30–40 ꢁC petrol/Et2O, 1:1)
12. SuperQuat 13 was prepared from (S)-phenylglycine according to the procedure
of Bull, S. D.; Davies, S. G.; Jones, S.; Polywka, M. E. C.; Prasad, R. S.; Sanganee,
H. J. Synlett 1998, 519.
13. Zezza, C. A.; Smith, M. B. Synth. Commun. 1987, 17, 729.
14. Jiang, L.; Job, G. E.; Klapars, A.; Buchwald, S. L. Org. Lett. 2003, 5, 3667.
15. DMDO was prepared and titrated according to the procedures outlined by
Adam et al.; see: (a) Adam, W.; Bialas, J.; Hadjiarapoglou, L. Chem. Ber. 1991, 124,
2377; (b) Adam, W.; Chan, Y.-Y.; Cremer, D.; Gauss, J.; Scheutzow, D.; Schindler,
M. J. Org. Chem. 1987, 52, 2800.
23
gave 95 as a colourless oil (34 mg, 79%); [
a
]
ꢂ84.9 (c 1.15, CHCl3)
D
20
{lit.40 for >99% ee [
a
]
D
ꢂ95.9 (c 1.1, CHCl3)}; dH (500 MHz, CDCl3)
3.78 (3H, s, OMe), 4.66 (2H, ABq, OCH2), 5.01 (1H, s, C(2)H), 7.31–
7.67 (10H, m, Ph).
References and notes
16. Epoxide 19 proved susceptible to hydrolysis upon standing.
17. Crystallographic data (excluding structure factors) have been deposited with
the Cambridge Crystallographic Data Centre as supplementary publication
number CCDC 213199, see Ref. 10.
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observed as the major product.
19. Compound 31 was prepared from SuperQuat 13 according to the procedure of
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´
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