Influence of α-methyl substitution of proline-based organocatalysts on the asymmetric α-oxidation of aldehydes

Article abstract of DOI:10.1016/j.tet.2009.04.060

The direct asymmetric organocatalytic α-oxidation of aldehydes using trans-2-(p-methylphenylsulfonyl)-3-phenyloxaziridine is reported. This method affords the S isomer of α-hydroxy aldehydes, thereby complementing the selectivity for the R isomer observed using the two-step nitrosobenzene method. Use of α-methylproline and α-methylproline tetrazole significantly increases the enantioselectivity observed for the α-oxidation of aldehydes compared to analogous unsubstituted organocatalysts.

Full text of DOI:10.1016/j.tet.2009.04.060

Tetrahedron 65 (2009) 4801–4807
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Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Influence of
a
-methyl substitution of proline-based organocatalysts
on the asymmetric a-oxidation of aldehydes
*
Sok-Teng (Amy) Tong, Margaret A. Brimble, David Barker
Department of Chemistry, The University of Auckland, 23 Symonds Street, Auckland 1142, New Zealand
a r t i c l e i n f o
a b s t r a c t
Article history:
The direct asymmetric organocatalytic
3-phenyloxaziridine is reported. This method affords the S isomer of
a
-oxidation of aldehydes using trans-2-(p-methylphenylsulfonyl)-
-hydroxy aldehydes, thereby
complementing the selectivity for the R isomer observed using the two-step nitrosobenzene method. Use
of -methylproline and -methylproline tetrazole significantly increases the enantioselectivity observed
for the -oxidation of aldehydes compared to analogous unsubstituted organocatalysts.
Ó 2009 Elsevier Ltd. All rights reserved.
Received 29 January 2009
Received in revised form 30 March 2009
Accepted 17 April 2009
a
a
a
Available online 24 April 2009
a
1. Introduction
using several aliphatic aldehydes. Hayashi et al.,10 however, con-
ducted their reactions in acetonitrile with an even higher catalyst
loading (30 mol %) for a longer time (24 h) at low temperature
(ꢀ20 ꢁC) in an attempt to suppress side reactions (homo-dimer-
isation of nitrosobenzene and self-aldolisation of aldehydes).
Nevertheless, similarly moderate yields and excellent enantiose-
lectivities were obtained.
The direct enantioselective organocatalytic
a
-oxidation of car-
bonyl compounds provides a valuable synthetic tool to prepare
-hydroxy compounds, which are important building blocks in
organic synthesis.1,2 One-way to synthesise these is the
-hydroxy-
a
a
lation of enolates using chiral oxaziridines.3 There are several
asymmetric catalytic methods, includingSharplessdihydroxylationof
enol ethers,4 epoxidation of silyl enol ethers with chiral dioxiranes,5
epoxidation of enol ethers with chiral Mn–salen catalysts,6 and more
recently, Yamamoto’s BINAP–AgOTf catalytic system generating
With regards to ketone oxidation, Cordova et al.1 carried out the
reactions with 20 mol % of proline 1 and 10 equiv of ketone in
DMSO for 2–3 h, whilst Hayashi et al.2,11 performed their reactions
with 10 mol % of proline 1 with only 2 equiv of ketone in DMF for
4 h, with slow addition of nitrosobenzene to eliminate side re-
actions. In either case, excellent enantioselectivities were observed.
Meanwhile, Yamamoto et al.13 demonstrated the efficient
a
-aminoxy ketones from tin enolates and nitrosobenzene,7 which are
then converted to
-hydroxy ketones using CuSO4.8 In parallel to this
indirect -aminoxylation of enolates, several groups have also report-
ed a direct proline-catalysed variant of this -aminoxylation, inwhich
a
a
a
a
-aminoxylation of ketones and aldehydes using as little as 5 mol %
proline-tetrazole 2 in DMSO to afford good yields and excellent
enantioselectivities. They also showed that a higher yield of
preformation of the enolate is not required. The research groups of
Zhong,9 Hayashi10,11 and MacMillan12 have reported the direct
a
-
proline-catalysed
a
-aminoxylation of aldehydes whilst Hayashi2,11
aminoxylated cyclohexanone was obtained with proline-tetrazole
and Cordova1 have reported a similar reaction using ketones.
All these studies differ in the nature of the reaction conditions
used, such as the ratio of starting material to nitrosobenzene, cat-
alyst loading, solvent, reaction temperature and reaction time.
MacMillan et al.12 performed reactions in an aerobic atmosphere
with wet solvent (CHCl3). Use of as little as 2 mol % of proline
2 as compared to that with proline 1.
Although this
lysed by proline 1 and proline-tetrazole 2 provides excellent
enantioselectivities, the -aminoxylated carbonyl compounds are
only obtained over two steps, and in certain cases (mainly acyclic
ketones), the formation of -hydroxyamino carbonyl compounds is
a side reaction.1,2,11 Cordova et al.,14 however, have reported the
one-step direct asymmetric -oxidation of ketones using an oxa-
zidirine as oxidant catalysed by proline 1 and proline-related
a-aminoxylation of carbonyl compounds cata-
a
a
provided the
a-aminoxylated aldehydes with high reaction effi-
ciency and enantioselectivity, whilst a loading of 0.5 mol % did not
destroy the enantioselectivity. Zhong9 used DMSO as the solvent
and a higher catalyst loading (20 mol %) affording shorter reaction
times (10–20 min) with the same excellent enantioselectivities
a
organocatalysts to afford a-hydroxy ketones directly. Use of nitro-
sobenzene as the oxidant posed problems due to side reactions11,12
and the instability of the reagent.10 This oxaziridine methodology
provided an operationally simple method to prepare
a-hydroxy
ketones, albeit with low enantioselectivities and moderate yields
using a limited range of organocatalysts.
* Corresponding author. Tel.: þ64 9 373 7599x89703; fax: þ64 9 373 7422.
E-mail address: d.barker@auckland.ac.nz (D. Barker).
0040-4020/$ – see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2009.04.060

4802
S.-T.(Amy) Tong et al. / Tetrahedron 65 (2009) 4801–4807
R
O
S
O
R
CO2H
N
OMe
OMe
N
NH2
7
N
H
N
H
O
S
Ph
HN
N
N
1, R = H
2, R = H
91%
Ref. 16
O
3, R = Me
4, R = Me
8
Figure 1. Structures of proline-based organocatalysts 1–4.
O
S
O
mCPBA/KOH
O
N
92%
Ref. 17
Ph
Continuing our efforts to probe the effects of
the selectivity of proline-based organocatalysts, we have previously
reported our results on the use of -methylproline 3 and -methyl-
proline tetrazole 4.15 We demonstrated that the selectivity of aldol
reactions was improved when -methylproline tetrazole 4 was
used rather than the more well known proline-tetrazole 2 (Fig. 1).15
Therefore, we envisaged that -substituted organocatalysts 3 and 4,
may improve the enantioselectivity of aldehyde -oxidation re-
a-substitution on
6
a
a
Scheme 2. Synthesis of oxaziridine 6.
a
TLC after one hour and were isolated in reasonable yield after
24 h. Secondly, proline 1 and oxaziridine 6 were reacted together.
In this case oxaziridine 6 decomposed to give benzaldehyde, p-
toluenesulfonamide 7 and sulfonimine 8 as observed by TLC after
one hour, but no sulfonimine 8 was seen by TLC after 7 h and
none by 1H NMR of the crude product after 24 h suggesting
proline 1 catalyses the hydrolysis of sulfonimine 8.21 Finally ox-
idant 6 was stirred alone in DMSO establishing that oxaziridine 6
quickly (within 1 h) decomposed to sulfonimine 8 with some
benzaldehyde also present. This could result from the oxidation
of DMSO to the corresponding dimethyl sulfone with oxaziridine
6 being reduced to sulfonimine 8. Cordova et al.22 noted that
DMSO was oxidised to dimethyl sulfone in the organocatalytic a-
oxidation of cyclohexanone with molecular oxygen as the
oxidant.
Given that in DMSO oxaziridine 6 quickly decomposes to form
sulfonimine 8 but products 9–12 are not formed in the absence of
proline 1 we postulated that sulfonamide 12 is formed by either
a proline 1 catalysed Mannich reaction of cyclohexanone with
sulfonimine 8 or the Michael reaction of p-toluenesulfonamide 7
a
a
actions and the results of this study are reported herein.
2. Results and discussion
Cordova et al.14 reported that the oxidation of cyclohexanone to
(R)-2-hydroxycyclohexanone 5 using proline 1 or tetrazole 2 pro-
ceeded with 29% and 17% ee’s, respectively, using trans-2-(p-
methylphenylsulfonyl)-3-phenyloxaziridine 616 as the oxidant.
(Scheme 1) Whilst these authors did try (S)-a-methylproline 3 as
a catalyst, they found it resulted in no selectivity.
When we first attempted to repeat this asymmetric
a-oxidation
using proline 1 and oxaziridine 6 under the conditions reported by
Cordova et al.,14 we were surprised to find that the reaction formed
a complex mixture of products. More surprisingly, none of the de-
sired product 5 formed despite several attempts. Oxidant 6 was in
fact prepared in the attempted reaction (Scheme 2) from p-toluene-
sulfonimine 816,17 and its oxidant properties demonstrated by the
successful oxidation of triphenylphosphine to triphenylphosphine
oxide.16
with a,b-unsaturated ketone 10, which in turn requires proline 1 to
access the precursor aldol adduct 9.
To explore whether the proline-catalysed Mannich or Michael
reaction was more likely to have afforded sulfonamide 12, the
formation of sulfonamide 12 was monitored when 1 equiv of ke-
tone 1023 was reacted with 1 equiv of p-toluenesulfonamide 7 in
the presence of proline 1 and DMSO under ambient conditions.
After 3 days, TLC analysis showed only starting material, with no
sulfonamide 12 formed. When 1 equiv of sulfonimine 8 and 2 equiv
of cyclohexanone were stirred with proline 1 in DMSO at room
temperature for 17 h, a significant amount of sulfonamide 12 was
observed by TLC, together with small amounts of other unidentified
Satisfied that generation of the oxidant 6 was not responsible for
the lack of any
the many reaction products. Surprisingly, several of the products
were more commonly found in the aldol reaction, in particular
hydroxyketone 9, isolated in a 1.3:1 syn:anti ratio, its dehydration
product -unsaturated ketone 10, and diphenyloxapyrrolizidine
a-oxidation reaction, we decided to isolate some of
b
-
a,b
11 (Scheme 3).
Oxapyrrolizidine 11 is a known compound formed by the con-
densation of proline 1 and benzaldehyde18 whilst
b-hydroxyketone
9 is the aldol product formed between cyclohexanone and benz-
aldehyde. The only source of benzaldehyde is from the breakdown
of oxidant 6 during the reaction. Another interesting by-product
isolated was sulfonamide 12, isolated as a 4.4:1 (anti/syn) mixture
of diastereomers. The structure of sulfonamide 1219 was estab-
lished using X-ray crystallography.20
O
S
CO2H
O
N
H
O
N
+
(30 mol%)
Ph
O
DMSO, 24 h
To increase our understanding of oxidation reactions utilising
oxaziridine 6, a number of reactions were carried out where one
or more of the reagents were removed. Firstly, cyclohexanone
was reacted with oxaziridine 6 without proline 1 being added,
affording a mixture of benzaldehyde, p-toluenesulfonamide 7 and
sulfonimine 8. Benzaldehyde and sulfonimine 8 were observed by
6
O
OH
Ph
O
+
Ph
9 (26%)
1:1.3 anti:syn
10 (4%)
SO2
O
HN
O
O
S N
O
O
O
N
O
6
Ph
Ph
+
OH
catalyst (10-30 mol%)
Ph
Ph
DMSO
11 (2%)
12 (52%)
4.4:1 anti:syn
1; 44% yield, 29% ee
2; 69% yield, 17% ee
(R)-5
Scheme 3. Products formed during the proline 1 catalysed oxidation of cyclohexanone
with oxaziridine 6.
Scheme 1. Previously reported a
-oxidation of cyclohexanone.14

S.-T.(Amy) Tong et al. / Tetrahedron 65 (2009) 4801–4807
4803
compounds. Notably, sulfonimine 8 appeared to have been totally
consumed. As a result, we conclude that the proline-catalysed
Mannich reaction between cyclohexanone and sulfonimine 8 fur-
nishes sulfonamide 12 as a side product in the attempted proline-
derivative 14 thus allowing the enantiomeric excess to be de-
termined using chiral HPLC. Using this method, the efficiency and
stereoselectivity of the four catalysts 1–4 to effect the asymmetric
a-oxidation of cyclohexanone were examined (Table 1).
catalysed
a-oxidation of cyclohexanone in DMSO.
Our results indicated that the -methyl substituted catalysts
a
The fact that anti sulfonamide 12 was obtained as the major
isomer in the unexpected proline 1-catalysed Mannich reaction
were much less efficient than their parent catalysts. All oxaziridine
6 was consumed after 3 h when proline 1 and tetrazole 2 were used,
was not clearly understood.
from proline 1-catalysed Mannich reactions between aromatic
imines and ketones or aldehydes have the syn configuration.24
b
-Amino carbonyl compounds arising
providing 67% of the isolated diols. In contrast, when
a-methyl-
proline 3 and -methyl tetrazole 4 were used, a significant amount
a
A
of oxaziridine 6 still remained after 5 days, with the latter catalyst
being more effective. In terms of enantioselectivity, a 10% ee was
obtained with proline 1, whereas a 16% ee in favour of the opposite
enantiomer was observed with tetrazole 2. This result is surprising
given that the two catalysts usually lead to the same absolute
configuration of adducts in many organocatalytic reactions. Whilst
proline 1-catalysed Mannich reaction of 2-butanone and an E-p-
toluenesulfonimine in DMSO has also been reported to be syn
diastereoselective.25 It is thought that oxaziridine 6 has the E
configuration16,17 and sulfonimine 8, supposedly also with the E
configuration, should react with cyclohexanone to give syn sul-
fonamide 12 when catalysed by proline 1. The formation of more
anti-12 than syn-12 suggests that oxaziridine 6 decomposes in
DMSO to form more of the Z isomer of sulfonimine 8.
a
-methyl tetrazole 4 did not improve the enantioselectivity over
the unsubstituted catalysts, surprisingly -methylproline 3 gave
36% ee. This improved stereoselectivity of -methylproline 3 over
a
a
a-
The lack of information in the original report14 into the pro-
duction of these significant by-products 9–12 is somewhat
surprising especially in light of the fact that none of the desired 2-
hydroxycyclohexanone 5 was formed in our hands. Given that the
key problem appeared to be the rapid decomposition of oxidant 6
in DMSO, we decided to investigate other solvents.
methyl tetrazole 4 was in contrast to our previous comparison of
their relative performance in the catalytic aldol reaction.15
Our results are consistent with previous results22 on the
a
-oxi-
dation of cyclohexanone with molecular oxygen, in terms of the
effects of -substitution on the organocatalysis, where -methyl-
a
a
proline 3 decreased the yield but increased the enantioselectivity to
48% ee from the 18% ee obtained with proline 1. On the other hand,
To the best of our knowledge, there have been only several ex-
amples of stereoselective
a
-oxidation of carbonyl compounds using
acyclic a-methylvaline reduced both the yield and enantioselectivity.
oxaziridine 6. In all cases, the stereoselectivity was substrate-con-
trolled and THF was used as the solvent.26,27 Therefore, we envis-
Table 2
aged that proline-catalysed
proceed in THF. After confirming that oxaziridine 6 remained intact
after stirring the oxidant in THF overnight, we attempted the
a-oxidation of cyclohexanone should
Results of the organocatalysed a-oxidation of aldehydes with oxaziridine 6
O
O
S
O
catalyst
(30 mol%)
O
a
-
O
HO
N
+
oxidation of cyclohexanone with proline in THF. To our delight, all
oxaziridine 6 was reduced to sulfonimine 8 with the product 2-
hydroxyketone 5 visible by TLC after stirring overnight. Isolation of
the product by flash chromatography provided 2-hydroxyketone as
a yellow oil, whose 1H NMR data were consistent with literature
values.11 As the purified 2-hydroxyketone 5 appeared to oligo-
merise on standing, it was converted in-situ into 1,2-cyclohexane-
diol for determination of the stereoselectivity. Thus the trans diol 13
was isolated and converted to the bis-p-nitrobenzoyl ester
H
H
Ph
THF
R
O
R
6
15-18 (2 eq.)
COCl
O2N
or Ac2O
NaBH4
HO
R
O
OH
O
R
R
O
R
15a-18a
15b-18b
Timea
Yieldb
[
a
]
D
eed
c
Aldehyde
Catalyst
O
Table 1
1
2
3
4
1 h
1 h
2 h
2 h
35%
33%
23%
59%
0
1%
Results of the organocatalysed
a
-oxidation of cyclohexanone with oxaziridine 6
þ2.57
ꢀ6.64
þ11.75
5% (S)
12% (R)
28% (S)
H
O
O
S
O
O
Ph
catalyst
(30 mol%)
O
+
N
OH
15
Ph
O
THF
1
2
3
4
69 h
77 h
23 h
4 h
60%
56%
49%
58%
n.d.
3% (S)
6
5
ꢀ1.35
þ1.38
n.d.
15% (R)
25% (S)
20% (S)
H
O
O2N
OH
NO2
O
NaBH4
COCl
O2N
16
OH
O
O
1
2
22 h
19 h
19 h
55 h
4 h
67%
58%
64%
63%
63%
n.d.
5% (S)
5% (S)
48% (S)
39% (S)
37% (S)
O
ꢀ3.42
ꢀ14.53
ꢀ12.31
ꢀ11.79
13
H
3
14
3e
4
Bn
Catalyst
Timea
Yieldb
eec
17
1
2
3
4
3 h
3 h
5 days
5 days
67%
67%
7%
10%
16%d
36%
9%
1
2
3
4
21 h
28 h
22 h
4 h
66%
59%
67%
64%
n.d.
1% (S)
0% (S)
45% (S)
28% (S)
O
ꢀ3.95
ꢀ13.95
ꢀ7.94
H
25%
nBu
a
b
c
Duration of the
The isolated combined yields of the cis and trans diols.
The ee of the trans diester derivative determined by chiral HPLC. The absolute
a-oxidation before sodium borohydride was added.
18
a
Duration of the
a
-oxidation before sodium borohydride was added.
The isolated yields of diols 15a–18a.
The [ D of the diols 15a–18a.
b
c
configuration of the major enantiomer was determined by comparison of HPLC trace
with an enantiopure authentic sample.
a]
d
e
d
The ee of the diester derivatives 15b–18b as measured by chiral HPLC.
The reaction was carried out at 0 ꢁC.
The absolute configuration of the major enantiomer was 1R, 2R, the opposite to
the other three experiments.

4804
S.-T.(Amy) Tong et al. / Tetrahedron 65 (2009) 4801–4807
These results, together with ours, suggest that the
a
-methyl group
of the anti-enamine, and the chirality at the asymmetric carbon of
the catalyst. The S acid (or tetrazole) favours the approach of the
oxidant to the re-face of the anti-enamine, either by forming a hy-
drogen bond with nitrosobenzene (A, Fig. 3), or by protonation of
has a detrimental effect on the efficiency of the reaction, probably
due to the increased steric hindrance around the secondary
amine that precluded the formation of the enamine species. On the
other hand, the increase in the enantioselectivity is specific to
the resultant
a-hydroxyl group in the oxidation with molecular
proline, which supports the postulation that the
a
-methyl group
oxygen (B, Fig. 3). The observed S configuration can only arise from
either nucleophilic si-facial attack of an anti-enamine on oxazir-
idine 6 (C, Fig. 3), or si-facial attack of a syn-enamine with potential
hydrogen bond formation (D, Fig. 3). At this preliminary stage, we
postulate that the latter case is more likely to lead to the (S)-isomer.
alters the conformation of the pyrrolidine ring such that the amine
and acid functionalities are in the optimal positions to effect ca-
talysis.15 The lower efficiency yet improved selectivity observed
using
a-methylproline 3 prompted us to extend our a-oxidation
procedure to aldehydes, which are more reactive than ketones.
Our results indicate that a-substituted proline catalysts give higher
Table 2 summarises the results of the
aldehydes.
a
-oxidation of various
stereoinduction, which will be unlikely if the former stereochem-
ical course C is followed. In this transition state, with no hydrogen
bonding, steric factors may be the major driving force, whereby
repulsion from the acid group may preclude the approach of oxa-
It is noteworthy that the formation of by-products was observed
in two of these reactions. In the -oxidation of phenylacetaldehyde
a
15 catalysed by proline 1, a significant quantity (w6%) of the sul-
fonamide 19 (Fig. 2), the reduced Mannich product between phe-
nylacetaldehyde 15 and sulfonimine 8, was isolated as a mixture of
ziridine 6 to the re-face. Based on this assumption, the a-methyl
group should lower this facial selectivity affording less (S)-isomer
than the non-methyl catalysts. We therefore propose that the fav-
oured transition state D involves a syn-enamine and a hydrogen
bond with oxaziridine 6.
diastereomers after NaBH4 reduction. On the other hand, in the a-
oxidation of hydrocinnamaldehyde 17 catalysed by all catalysts 1–4,
a significant amount of diol 20 (Fig. 2), the reduced self-aldolisation
adduct of hydrocinnamaldehyde 17, was isolated after NaBH4 re-
duction. Proline 1 was found to give diol 20 as a 1:1 mixture of
diastereomers.
The syn configuration could be more favoured over the anti,
given an earlier example of a similar phenomenon in the proline-
catalysed enantioselective a
-alkylation of aldehydes.28a A density
functional study on the alkylation reaction has shown that the syn
transition state benefits from a greater proximity of the leaving
group to the acid proton, and from a more planar iminium moiety.29
In fact, the planarity of the iminium transition state has also been
identified as one of the main contributors to the formation of the
major stereoisomer in the proline-catalysed intramolecular aldol
reaction between two keto groups.28b,c It is reasonable therefore to
assume that iminium planarity may also be critical in syn transition
state D, even though the catalysis of alkylation, intramolecular aldol
and oxidation reactions may be mechanistically different. To ra-
The production of sulfonamide 19 and diol 20 as by-products
illustrates the high reactivity of the aldehyde substrates, with
which the
efficiently. Our studies suggested that a small excess (2 equiv) of the
aldehyde was enough to provide a reasonable yield of the -hy-
a-methyl substituted catalysts can proceed reasonably
a
droxyl adduct, albeit with concomitant formation of the side
products noted above.
One remarkable finding is that
a-methyl tetrazole 4 exhibited
superior efficiency in all of the aldehyde
a-oxidations studied. With
isovaleraldehyde 16, hydrocinnamaldehyde 17 and hexanal 18,
complete consumption of the oxaziridine 6 within 4 h was ob-
served using 4 whilst the other three catalysts required 5–20 times
longer. Comparable yields of the isolated diols were obtained using
all four catalysts.
tionalise the increase in enantioselectivity when using
catalysts, we propose that replacement of the -hydrogen with
a methyl group, which gives rise to a tetrasubstituted asymmetric
a-methyl
a
To see whether a lower temperature would improve the enan-
O
anti enamine
O
tioselectivity further, the
a-oxidation of hydrocinnamaldehyde 17
re facial attack
N
Ph
H
PhNHO
-methylproline 3 was also carried out at 0 ꢁC. Dis-
N
O
R2
H
O
R1
catalysed by
a
R1
R2
appointingly, this led to a lower ee than that observed at room
temperature. This is in line with the findings of Cordova et al.14 who
R
A
reported that the a-oxidation of cyclohexanone with oxaziridine 6
in THF catalysed by (S)-1-(pyrrolidin-2-ylmethyl)pyrrolidine at 0 ꢁC
provided a lower ee than at room temperature.
O
anti enamine
O
N
re facial attack
O O
H
The stereochemistry observed in our studies represents an in-
OH
HOO
R1
R1
teresting outcome. All reported
catalysed by organocatalysts 1–3 using either nitrosobenzene1,2,9–12
or molecular oxygen22 gave (R)-
-hydroxy adducts as the major
a-oxidations of ketones or aldehydes
R2
R2
a
B
R
isomer, and the reported oxidations of ketones using oxaziridine 6
catalysed by proline 1 or tetrazole 2 (in DMSO) also favoured the
formation of the R isomer.14 In contrast, we found the S isomer to be
predominant in reactions catalysed by organocatalysts 1–4, with just
a few exceptions.
The R configuration reportedly arises from the nucleophilic re-
facial attack of anti-enamine on the electrophilic oxygen in the
oxidant. Such a transition state is favoured due to the lower energy
HO2C
N
anti enamine
si facial attack
Ph
O
H
R1
R2
N
O
SO2C6H4pMe
OH
C
R1
R2
O
O
S
syn enamine
N
si facial attack
Ph
HO
OH
Ph
pMeC6H4O2S
Ph
O
S
N
R1
H
O
HO
N
H
R2
Ph
O
Ph
20
19
Figure 2. Structures of by-products 19 and 20 formed in the
D
a
-oxidations of aldehydes.
Figure 3. Transition states leading to R or S configurations of a-hydroxy adducts.

S.-T.(Amy) Tong et al. / Tetrahedron 65 (2009) 4801–4807
4805
carbon, possibly changes the conformation of the amino acid de-
rived enamine intermediate.30 As such, the altered conformation of
4.3. Procedure for the a-oxidation of cyclohexanone
the
a
-methyl enamine intermediate in the anti configuration may
To a solution of oxaziridine 6 (1 equiv) in distilled THF was added,
under ambient atmosphere, the catalyst (1–4). The mixture was
stirred for 5 min, after which cyclohexanone (3 equiv) was added
and the mixture was stirred at room temperature for the reported
time. Excess NaBH4 was added to the mixture at 0 ꢁC and reaction
was stopped when TLC showed full consumption of 2-hydroxy-
cyclohexanone (Rf¼0.6, 3:1 EtOAc/hexane). Solvent was then re-
moved and silica gel and EtOAc were added to the residue. The
mixture was stirred for an hour, after which elution of the com-
pounds from the silica with EtOAc afforded the crude cis and trans
diol (cis diol: Rf¼0.3; trans diol: Rf¼0.2, 3:1 EtOAc/hexane). Column
chromatography with 2:1 EtOAc/hexane as the eluent as eluent
provided pure trans diol. To allow for chiral HPLC analysis, the trans
diol was then esterified: to a solution of the diol (1 equiv) in DCM
was added triethylamine (18 equiv), DMAP (catalytic amount) and
p-nitrobenzoyl chloride (5 equiv). The mixture was stirred at room
temperature overnight, after which it was quenched with pH 7
phosphate buffer. The organic phase was separated and the aqueous
phase was extracted with EtOAc (ꢂ3). The combined organics were
washed with brine, dried (MgSO4) and concentrated in vacuo. The
crude was purified by flash chromatography with 4:1 hexane/EtOAc
as the eluent to yield the bis-p-nitrobenzoate as a brown oil.17
proceed to an iminium that deviates from planarity,28 while the syn
iminium could still be relatively planar and hence the more fav-
oured transition state D.
3. Conclusion
This report provides the first example of a direct organo-
catalytic
phenylsulfonyl)-3-phenyloxaziridine 6 as the oxidant to afford the
-hydroxy adducts favouring the (S)-isomer. More significantly,
the positive effects of -methyl substitution in proline-based
organocatalysts are also demonstrated. -Methylproline 3 and
methyl tetrazole 4 dramatically increase the enantioselectivity of
the -oxidation compared to the unsubstituted catalysts and
a-oxidation of aldehydes using trans-2-(p-methyl-
a
a
a
a-
a
a-
methyl tetrazole 4 provides superior reaction efficiency over cat-
alysts 1–3.
4. Experimental
4.1. General
Reactions were monitored by TLC, using pre-coated silica gel TLC
plates obtained from Merck. Flash chromatography was carried out
on silica gel (Riedel–de Hae¨n, particle size 0.032–0.063 mm).
Hexane for flash chromatography was distilled before use. HPLC
analysis was performed on a Dionex Instrument (multi-wavelength
absorbance detector with a binary HPLC pump). The Chiralpak AD-
RH column was purchased from Daicel Chemical Industries Ltd.
Optical rotations were measured on a Perkin–Elmer 341 polari-
4.3.1. (1R,2R)-Cyclohexane-1,2-diyl bis(4-nitrobenzoate) (14)
Compound 14 was obtained as a yellow crystal.31 Rf¼0.7, 4:1
hexane/EtOAc. Mp¼107–110 ꢁC. 1H NMR (400 MHz, CDCl3):
d 1.42–
1.56 (m, 2H, 4Hax and 5Hax), 1.56–1.73 (m, 2H, 3Heq and 6Heq), 1.82–
1.95 (m, 2H, 4Heq and 5Heq), 2.20–2.33 (m, 2H, 3Hax and 6Hax),
5.23–5.33 (m, 2H, 1H and 2H), 8.11 (d, J¼8.9 Hz, 4H, CHCO2), 8.21 (d,
J¼9.0 Hz, 4H, CHCNO2). 13C NMR (100 MHz, CDCl3):
d 23.43 (C-4
meter (
l
¼589 nm, 0.1 dm cell). Melting point determinations were
and C-5), 60.18 (C-3 and C-6), 75.35 (C-1 and C-2),123.50 (CHCNO2),
130.63 (CHCO2), 135.19 (quat. CCO2), 150.54 (quat. CNO2), 164.01
performed on an ElectrothermalÒ melting point apparatus. 1H NMR
and 13C NMR spectra were recorded on Bruker Avance DRX
300 MHz or 400 MHz spectrometers at ambient temperatures.
(CO2). IR:
n
¼ 2941 (C–H), 1725 (ester C]O stretching), 1523
(asymmetric (N]O)2 stretching), 1321 (symmetric (N]O)2
stretching), 1262 (C(]O)–O stretching), 1117 (O–C–C stretching),
870 (C–N stretching) cmꢀ1. m/z (CIþ, NH3) 432 (0.44, MþNHþ4 ), 385
(0.13), 248 (0.14, C6H11OCOC6H5NOþ2 ), 150 (0.62, NO2C6H4COþ), 138
(0.62), 120 (1.00). HRMS: found MþNHþ4 , 432.14142; C20H22N3O8
requires 432.14069. The enantiomeric excess of 14 was measured at
254 nm on Chiralpak AD-RH HPLC column (75:25 MeCN/H2O,
0.4 mL/min), 15.70 min (1S,2S), 18.15 min (1R,2R).
Chemical shifts
d are expressed in parts per million and coupling
constants J are reported in hertz. TMS served as internal standard
(
d
¼0 ppm) for 1H NMR, and CDCl3 served as internal standard
(d
¼77.0 ppm) for 13C NMR. Infrared spectra were recorded on
a Perkin–Elmer spectrum one FT-IR spectrometer.
4.2. Procedure for the preparation of trans-2-(p-methyl-
phenylsulfonyl)-3-phenyloxaziridine (6)16,17
4.4. General procedure for the a-oxidation of aldehydes
To a round-bottomed flask equipped with a short-path dis-
tillation head was charged p-toluenesulfonamide 7 (10 mmol,
1.7 g) and benzaldehyde dimethylacetal (10 mmol, 1.5 g). The
mixture was heated at 180 ꢁC for 45 min, during which methanol
(w0.2 mL) was distilled from the mixture. The mixture was then
cooled at reduced pressure by which time the yellow liquid had
turned into a creamy white solid, which was re-dissolved in
warm DCM and hexane was added to precipitate the product.
Sulfonimine 8 was collected and washed with hexane to afford
a white shiny powdery solid (2.4 g, 91%), which was used di-
rectly in the next step without further purification. A mixture of
m-chloroperoxybenzoic acid (4.2 mmol, 0.95 g) and powdered
potassium hydroxide (13.5 mmol, 0.76 g) in DCM (10 mL) was
stirred vigorously at room temperature for 5 min. The mixture
To a solution of oxaziridine 6 (1 equiv) in distilled THF was
added, under ambient atmosphere, the catalyst (1–4). The mixture
was stirred for 5 min, after which the aldehyde (2 equiv) was added
and the mixture was stirred at room temperature for the reported
time. NaBH4 (2 equiv) was then added to the mixture at 0 ꢁC and
the mixture was stirred overnight. The mixture was poured onto
a mixture of 1 N HCl and EtOAc and stirred for 10 min. The organic
phase was separated, and the aqueous phase was further extracted
with EtOAc. The combined organics were dried (MgSO4) and
evaporated to afford a crude mixture, which was purified by flash
chromatography (2:1/1:1 hexane/EtOAc) to furnish the diol (Diols
15a–18a: Rf¼0.3, 1:1 EtOAc/hexane). To allow for chiral HPLC
analysis, the diol was then esterified: To a solution of the diol
(1 equiv) in DCM was added triethylamine (18 equiv), DMAP (cat-
alytic amount) and p-nitrobenzoyl chloride or acetic anhydride
(5 equiv). The mixture was stirred at room temperature overnight,
after which it was quenched with pH 7 phosphate buffer. The or-
ganic phase was separated and the aqueous phase was extracted
with EtOAc (ꢂ3). The combined organics were washed with brine,
dried (MgSO4) and concentrated in vacuo. The crude was purified
was further diluted with DCM (10 mL) and sulfonimine
8
(3.9 mmol, 1 g) was added. The white suspension was vigorously
stirred for another 5 min. The resultant white salt was filtered off
and the filtrate was concentrated in vacuo to furnish trans-2-(p-
methylphenylsulfonyl)-3-phenyloxaziridine 6 as a white solid
(0.98 g, 92%). The 1H NMR data of 6 was consistent with litera-
ture data.17

4806
S.-T.(Amy) Tong et al. / Tetrahedron 65 (2009) 4801–4807
by flash chromatography with a mixture of hexane/EtOAc to yield
the pure diester.
repeating the HPLC experiment on the same sample, while the
homogenous sample solution (made up by sonicating the solid bis-
p-nitrobenzoate in a mixture of hexane and isopropanol) was found
to show precipitation over time. These observations appeared to
suggest that the minor enantiomer crashed out at a higher rate than
the major enantiomer, giving the apparent increase in ee. This did
not happen with the diacetate derivative 17b and was thus
employed for the HPLC analysis. The enantiomeric excess of 17b
was measured at 210 nm on Chiralpak AD-RH HPLC column (25:75
MeCN/H2O, 0.3 mL/min), 77.43 min (R), 81.23 (S).
4.4.1. 1H NMR and optical rotation data for diols 15a–18a
Diols 15a–18a were obtained as pure compounds. Their 1H NMR
data were consistent with literature values: 15a–17a (Ref. 32) and
18a (Ref. 33).
The stereochemistry of diols 15a–18a were determined by
comparison of their optical rotation data with literature values. (S)-
23
20
15a: [
a
]
þ11.75 (c 1.11, CHCl3), 28% ee; lit. (R)-15a: [
a]
ꢀ62.7 (c
D
D
23
0.11, CHCl3), >99% ee.34 (S)-16a: [
lit. (S)-16a: [
a
]
þ1.38 (c 2.89, CHCl3), 25% ee;
D
23
a]
þ11.0 (c 0.6, CHCl3), >99% ee.32 (S)-17a: [
a
]
4.4.5. Hexane-1,2-diyl bis(4-nitrobenzoate) (18b)
D
D
24
ꢀ14.53 (c 2.00, EtOH), 48% ee; lit. (S)-17a: [
a]
ꢀ33.5 (c 0.93, EtOH),
Rf¼0.4, 6:1 hexane/EtOAc. Mp¼100–103 ꢁC. 1H NMR (400 MHz,
D
21
>98% ee.35 (S)-18a: [
a]
ꢀ13.95 (c 0.43, EtOH), 45% ee; lit. (S)-18a:
CDCl3):
d
0.91 (t, J¼6.8 Hz, 3H, CH3), 1.32–1.50 (m, 4H, CH3CH2CH2),
D
[
a]
D ꢀ22.0 (c 0.9, EtOH), >99% ee.32
1.73–1.92 (m, 2H, CH3CH2CH2CH2), 4.50 (dd, J¼12, 7.2 Hz, 1H,
CH2aO), 4.64 (dd, J¼12, 2.8 Hz, 1H, CH2bO), 5.49–5.58 (m, 1H, CH),
8.09–8.22 (m, 4H, CHCCO2), 8.22–8.31 (m, 4H, CHCNO2). 13C NMR
4.4.2. 1-Phenylethane-1,2-diyl bis(4-nitrobenzoate) (15b)
Rf¼0.3, 6:1 hexane/EtOAc. Mp¼110–113 ꢁC. 1H NMR (300 MHz,
(100 MHz, CDCl3):
d
13.82 (CH3), 22.39 (CH3CH2), 27.25
CDCl3):
d
4.74 (dd, J¼12.0, 3.6 Hz, 1H, 2Ha), 4.85 (dd, J¼12.0, 8.1 Hz,
(CH3CH2CH2), 30.45 (CH3CH2CH2CH2), 66.36 (CH2O), 73.20 (CH),
123.58 (CHCNO2), 130.71 (CHCCO2), 134.92, 135.24 (CCO2), 150.62
1H, 2Hb), 6.48 (dd, J¼8.1, 3.6 Hz, 1H, 1H), 7.35–7.49 (m, 3H, 30H, 40H
and 50H), 7.49–7.58 (m, 3H, 20H and 60H), 8.05–8.18 (m, 2H, 3%H and
7%H), 8.18–8.35 (m, 6H, 300H, 700H, 400H, 600H, 4%H and 6%H). 13C
(CNO2), 164.22, 164.30 (C]O–O). IR:
n
¼ 2957 (C–H), 1715 (ester
C]O stretching), 1523 (asymmetric (N]O)2 stretching), 1347
(symmetric (N]O)2 stretching), 1259 (C(]O)–O stretching), 1118
(O–C–C stretching of primary alcohol), 1100 (O–C–C stretching of
secondary alcohol), 870 (C–N stretching) cmꢀ1. m/z (FABþ) 417
(0.03, MþHþ), 400 (0.01), 250 (0.05, MꢀOCOC6H4NOþ2 ), 165 (0.04),
150 (0.20, NO2C6H4COþ), 120 (0.13, C6H4COOþ), 89 (0.24). HRMS:
found MHþ, 417.12985; C20H21N2O8 requires 417.12979. The enan-
tiomeric excess of 18b was measured at 254 nm on Chiralpak AD-
RH HPLC column (75:25 MeCN/H2O; 0.1% formic acid, 0.25
mL/min), 41.19 min (R), 45.49 min (S).
NMR (75.5 MHz, CDCl3): d
67.07 (C-2), 74.82 (C-1), 123.61 (C-400 and
C-600 or C-4% and C-6%), 123.65 (C-400 and C-600 or C-4% and C-6%),
126.68 (C-20 and C-60), 129.01 (C-30 and C-50), 129.27 (C-40), 130.73
(C-3% and C-7%), 130.81 (C-300 and C-700), 134.81 and 134.98 (C-200
and C-2%), 135.36 (C-10), 150.69 and 150.75 (C-500 and C-5%), 163.75
(C-100), 164.23 (C-1%). IR:
n
¼ 1721 (ester C]O stretching), 1520
(asymmetric (N]O)2 stretching), 1347 (symmetric (N]O)2
stretching), 1257 (C(]O)–O stretching), 1117 (O–C–C stretching of
primary alcohol), 1101 (O–C–C stretching of secondary alcohol), 874
(C–N stretching) cmꢀ1. m/z (CIþ, NH3) 454 (0.21, MþNHþ4 ), 270
(0.25, MꢀOCOC6H4NO2þ), 240 (0.17), 150 (0.78, NO2C6H4COþ), 138
(1.00), 120 (0.91, C6H5CHCH2Oþ). HRMS: found MþNH4þ, 454.12575;
C22H20N3O8 requires 454.12504. The enantiomeric excess of 15b
was measured at 254 nm on Chiralpak AD-RH HPLC column (65:35
MeCN/H2O, 0.4 mL/min), 36.45 min (S), 42.27 (R).
4.4.6. N-(3-hydroxy-1,2-diphenylpropyl)-4-methylbenzene-
sulfonamide (19)
Compound 19 was obtained as a colourless crystal.37 Rf¼0.2, 3:1
hexane/EtOAc. Mp¼152–155 ꢁC. 1H NMR (300 MHz, CDCl3):
d 2.28
(s, 3H, CH3), 3.00–3.12 (m, 1H, CHCH2OH), 3.64 (dd, J¼5.6, 11.3 Hz,
1H, CHaOH), 3.91 (dd, J¼8.3, 11.3 Hz, 1H, CHbOH), 4.76 (dd, J¼6.2,
8.3 Hz,1H, CHNH), 5.39 (d, J¼8.4 Hz,1H, NH), 6.79 (dd, J¼1.4, 7.4 Hz,
2H, Ar0–H), 6.90 (dd, J¼1.7, 7.4 Hz, 2H, Ar–H), 7.00 (d, J¼8.1 Hz, 2H,
CHCCH3), 7.03–7.10 (m, 3H, Ar0-H), 7.13–7.24 (m, 3H, Ar-H), 7.39 (d,
4.4.3. 3-Methylbutane-1,2-diyl bis(4-nitrobenzoate) (16b)
Rf¼0.5, 5:1 hexane/EtOAc. 1H NMR (300 MHz, CDCl3):
d 1.107 (d,
J¼6.9 Hz, 3H, CH3), 1.108 (d, J¼6.6 Hz, 3H, CH3), 2.10–2.39 (m, 1H,
3H), 4.55 (dd, J¼7.7, 12 Hz, 1H, 1Ha), 4.69 (dd, J¼3, 12 Hz, 1Hb), 5.35–
5.46 (m, 1H, 2H), 8.05–8.15 (m, 2H, 30H and 70H), 8.15–8.35 (m, 6H,
40H, 60H, 300H, 700H, 400H and 600H). 13C NMR (75.5 MHz, CDCl3):
J¼4.5 Hz, 2H, CHCSO2). 13C NMR (75.5 MHz, CDCl3):
d 21.32 (CH3),
53.91 (CHCH2OH), 58.40 (CHNH), 62.93 (CH2OH), 126.38 (CHAr0),
126.94 (CHCSO2), 127.03 (CHAr0), 127.17 (CHAr), 127.54 (CHAr0),
128.49 (CHAr), 128.58 (CHCCH3), 128.96 (CHAr), 136.88 (CCH3 or
Cquat.–Ar0), 136.91 (CCH3 or Cquat.–Ar0), 138.68 (Cquat.–Ar), 142.95
d
17.98 (CH3), 18.65 (CH3), 29.66 (C-3), 65.21 (C-1), 77.29 (C-2),
123.59 (C-40 and C-60 or C-400 and C-600), 123.63 (C-40 and C-60 or 0C0 -
400 and C-600),130.71 (C-30, C-70, C-300 and C-700),134.94 (C-20 or C-2 ),
135.26 (C-20 or C-200), 150.68 (C-50 or C-500), 164.27 (C-10 or C-100),
(Cquat.–SO2). IR:
n
¼ 3668 (O–H stretching), 3322 (sulfonamide N–
H stretching), 1494, 1455 (aromatic C–C stretching), 1317 (sulfon-
amide S]O stretching), 1148, 759, 698, 669 (aromatic C–H bend-
ing). m/z (FABþ) 382 (0.04, MþHþ), 260 (0.12, MꢀC6H5CHCH2OHþ),
181 (0.08), 172 (0.09), 149 (0.13), 120 (0.13), 91 (0.24, C6H4CH3).
HRMS: found MHþ, 382.14847; C22H24NO3S requires 382.14769.
164.37 (C-10 or C-100). IR:
n
¼ 2968 (C–H), 1717 (ester C]O
stretching), 1521 (asymmetric (N]O)2 stretching), 1343 (symmet-
ric (N]O)2 stretching), 1258 (C(]O)–O stretching), 1115 (O–C–C
stretching of primary alcohol), 1097 (O–C–C stretching of secondary
alcohol), 871 (C–N stretching) cmꢀ1. m/z (FABþ) 403 (0.05, MþHþ),
236 (0.07, MꢀCO2C6H4NO2þ), 165 (0.06), 150 (0.19, COC6H4NOþ2 ), 120
(0.14), 89 (0.28). HRMS: found MHþ, 403.11430; C19H19N2O8 re-
quires 403.11414. The enantiomeric excess of 16b was measured at
210 nm on Chiralpak AD-RH HPLC column (55:45 MeCN/H2O,
0.4 mL/min), 64.13 min (R), 69.73 (S).
4.4.7. 2-Benzyl-5-phenylpentane-1,3-diol (20)
Rf¼0.3, 2:1 hexane/EtOAc. 1H NMR (300 MHz, CDCl3):
d 1.69–
2.03 (m, 3H, 2H and 4H), 2.48–2.92 (m, 4H, 5H and 6H), 3.27 (bs, 2H,
OHs), 3.50–3.60 (m, 1H, 1Ha of diastereomer A), 3.60–3.68 (m, 2H,
1Ha and 1Hb of diastereomer B), 3.68–3.78 (m, 2H, 3H of di-
astereomer B), 3.80–3.97 (m, 1H, 1Hb of diastereomer A and 3H of
diastereomer A), 7.0–7.4 (m, 10H, Ar–Hs), as a 1:1 mixture of di-
4.4.4. 3-Phenylpropane-1,2-diyl diacetate (17b)
The 1H NMR data of diacetate 17b were consistent with litera-
ture data.36 The diacetate of 3-phenylpropane-1,2-diol was used for
the determination of ee via HPLC instead of the bis-p-nitrobenzoate
derivative, i.e., 3-phenylpropane-1,2-diyl bis(4-nitrobenzoate) be-
cause the latter was found to give inconsistent ee over successive
runs of the HPLC experiment. Increasing ee was obtained on
astereomers A and B. 13C NMR (75.5 MHz, CDCl3):
d 31.60 and 32.20
(C-5), 32.52 and 35.04 (C-6), 35.27 and 37.49 (C-4), 45.97 and 46.39
(C-2), 62.74 and 63.96 (C-1), 73.82 and 74.26 (C-3), 125.79 and
125.82, 125.92 and 125.99, 128.32 and 128.34, 128.37 and 128.39,
128.89 and 129.02 (Ar–Cs), 140.13 and 140.29 (Ar C-quat.), 141.88
and 141.90 (Ar C-quat.). IR:
n
¼ 3241 (br d, O-H stretch), 2941,1602,

S.-T.(Amy) Tong et al. / Tetrahedron 65 (2009) 4801–4807
4807
17. Garcı´a Ruano, J. L.; Alema´n, J.; Fajardo, C.; Parra, A. Org. Lett. 2005, 7, 5493–5496.
18. Forte, M.; Orsini, F.; Pelizzoni, F. Gazz. Chim. Ital. 1985, 115, 569–571.
1492 (aromatic C–C stretch), 1453 and 1331 (O-H bending), 1060,
1029 (alcohol C–O stretch), 742 (aromatic C–H bending), 694. m/z
(EIþ) 252 (0.07, MþꢀH2O), 234 (0.16, Mþꢀ2H2O), 143 (0.21,
Mþꢀ2H2OꢀC6H5CH2), 117 (0.31,MþꢀH2OꢀC6H5(CH2)2CHOH), 104
(0.14, C6H5CH2CHþ), 91 (1.00, C6H5CH2þ), 77 (0.90, C6Hþ5 ). HRMS:
found MꢀH2O, 252.15129; C18H20O requires 252.15142.
19. Fujisawa, H.; Takahashi, E.; Mukaiyama, T. Chem.dEur. J. 2006, 12, 5082–5093.
20. Whilst the X-ray crystal structure allowed confirmation of the structure of
sulfonamide 12 the resolution is insufficient for addition to the Cambridge
structural database. Data for compound 12: 1H NMR (400 MHz, CDCl3):
d 1.50–
2.01 (m, 6H, c-Hex), 2.15–2.40 (m, 5H, c-Hex and CH3), 2.70–2.82 and 2.82–2.92
(m, 1H, COCH), 4.34–4.40 (dd, J¼8.4, 4.8 Hz, 1H, CHPh) and 4.40–4.48 (dd, J¼9.
6, 5.6 Hz, 1H, CHPh), 5.90–5.96 (d, J¼9.3 Hz, 1H, NH) and 5.96–6.06 (d, J¼8.4 Hz,
1H, NH), 6.95–7.10 (m, 7H, Ar–H), 7.38–7.50 (m, 2H, Ar–H) as a mixture of
Acknowledgements
diastereoisomers.13C NMR (100 MHz, CDCl3):
d 21.36, 24.51, 26.77 and 27.94, 30.
63 and 32.38, 42.32 and 42.59, 55.51 and 56.78, 58.81 and 59.29, 126.99, 127.05,
128.03, 129.08, 127.98, 128.19 (quat. Ar–C), 137.59, 139.07, 142.74, (quat. Ar–C),
221.71 and 212.63, as a mixture of diastereoisomers. m/z (FAB) 358 (0.13, MþH),
260 (0.29), 187(0.25), 91 (0.27). HRMS: found MHþ, 358.14718; C20H24NO3S
requires 358.14769.
We wish to thank the New Zealand Government for the NZ In-
ternational Doctoral Research Scholarship (STT) and the University
of Auckland for financial assistance.
21. While Davis et al.16 stated that sulfonimine was resistant to hydrolysis, our
results suggested that in the presence of proline, sulfonimine 8 underwent
hydrolysis readily.
Supplementary data
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procedures: Peijnenburg, W. J. G. M.; Buck, H. M. Tetrahedron 1988, 44,
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Optical rotation data for diols 15a–18a along with HPLC traces
for diesters 15b–18b can be found as Supplementary data. Sup-
plementary data associated with this article can be found in the
online version, at doi:10.1016/j.tet.2009.04.060.
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