A direct intramolecular asymmetric catalytic aldol cyclodehydration of meso-3,4-disubstituted-1,6-dialdehydes

Article abstract of DOI:10.1016/j.tet.2004.10.034

The intramolecular asymmetric catalytic aldol cyclodehydration of 1,6-dialdehydes to the corresponding cyclopentene carbaldehydes was accomplished for the first time on the cases of meso-3,4-disubstituted hexanedials. It was found that the presence of a h

Full text of DOI:10.1016/j.tet.2004.10.034

Tetrahedron 61 (2005) 267–273
A direct intramolecular asymmetric catalytic aldol
cyclodehydration of meso-3,4-disubstituted-1,6-dialdehydes
Vanya B. Kurtevaa,b and Carlos A. M. Afonsoc,
*
aInstitute of Organic Chemistry, Bulgarian Academy of Sciences, Acad. G. Bonchev str., block 9, 1113 Sofia, Bulgaria
b
´ ˆ
REQUIMTE/CQFB, Departamento de Quımica, Faculdade de Ciencias e Tecnologia, Universidade Nova de Lisboa,
2829-516 Caparica, Portugal
c
´
´
CQFM, Departamento de Engenharia Quımica, Instituto Superior Tecnico, 1049-001 Lisboa, Portugal
Received 21 April 2004; revised 29 July 2004; accepted 1 October 2004
Available online 6 November 2004
Abstract—The intramolecular asymmetric catalytic aldol cyclodehydration of 1,6-dialdehydes to the corresponding cyclopentene
carbaldehydes was accomplished for the first time on the cases of meso-3,4-disubstituted hexanedials. It was found that the presence of a
hydroxyl group in the catalyst’s molecule seems to be crucial to reach stereocontrol. The chiral centre, bearing the carboxylate functionality,
in hydroxy amino acids controls the stereochemistry of the final product. In the case of amino alcohols, where carboxylate functionality does
not exist, the configuration of the carbon, connected with the hydroxyl group, seems to be the key one. Additionally, it was observed that
chiral phosphines and phosphites are effective catalysts for this cyclodehydration but without inducing stereocontrol.
q 2004 Elsevier Ltd. All rights reserved.
1. Introduction
biology, where it presents a critical biological transform-
ation in the context of metabolism. The enzymatic reactions,
catalysed by Type I aldolases, which accept hydrophobic
organic substrates, utilise an enamine mechanism.18 The
aldolase antibodies synthesis and application in aldol
reactions,19–24 as well as their chemical oversimplified
versions, have received considerable attention in recent
years. Proline-catalysed asymmetric intramolecular con-
densation of dicarbonyl compounds, well known as Hajos–
Parris–Eder–Sauer–Wiecher reaction, was discovered in the
1970s,25–29 and afterward widely exploited both in its
intermolecular30–37 and intramolecular38–46 variants. This
reaction involves an enamine intermediate, with the C–C
bond formation as the rate determining step and the
stereodifferentiation occurring in this step, before dehy-
dration. In the case of the Robinson annulating reaction it
was found45 that while proline, as well as a number of
similar chiral compounds, like hydroxy proline, azetidine
carboxylic acid etc., catalyse both steps of the transform-
ation, the chiral amines tested catalyse the annulation but
not the dehydration. It was suggested that chiral compounds
containing a secondary amine of pyrrolidine type and a
carboxylate functionality are the most efficient catalysts and
that the carboxylic acid functionality appears to be the key
to the dehydration step.
In recent years the synthesis of carbocyclic nucleoside
analogues has been the subject of great interest, due to their
wide range of biological activity profiles.1–4 In the sametime,
these compounds are chemically and enzymatically more
stable than the corresponding nucleosides, according to the
absence of a typical glucoside bond in their molecules.5 The
role of the methylene group in the carbocycle as a bioisostere
of oxygen is justified by the observed antiviral and antitumor
efficacies of some natural carbocyclic nucleosides, such as
Arystomicin6 and Neplanocin A,7 as well as synthetic ones,
as Carbovir8–10 and Abacavir.11–14 The latter shows great
anti-HIV activity and therefore, it is used clinically to treat
AIDS and AIDS-related complex.
As precursors of the carbocyclic moieties of compounds like
nucleosides, carbohydrates and many other products of
biological importance, cyclopentanoids play a fundamental
role in synthetic organic chemistry. Among the broad range
of organic transformations for the five-membered ring
construction, the aldol condensation is an exceptionally
useful C–C bond-forming reaction.15–17 Its catalytic asym-
metric variant is a strategic one both in chemistry and in
Keywords: Cyclopentenecarbaldehydes; Aldol; Cyclodehydration; Asym-
metric catalysis; 1,6-Dialdehydes.
* Corresponding author. Tel.: C351 21 8417627; fax: C351 21 8417122;
e-mail: carlosafonso@ist.utl.pt
The asymmetric aldol reactions of diketones and ketoalde-
hydes are widely investigated, while the condensation of
0040–4020/$ - see front matter q 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2004.10.034

268
V. B. Kurteva, C. A. M. Afonso / Tetrahedron 61 (2005) 267–273
dialdehydes, well known in its non-chiral version reaction,
is much less studied. To the best of our knowledge, the only
paper on this subject reports the direct intramolecular
asymmetric catalytic aldol condensation of dialdehydes on
the case of proline-catalysed cyclisation of heptanedials.46
The corresponding hydroxy cyclohexanecarbaldehydes are
isolated with stereocontrol at the carbons, bearing the
hydroxyl and carbaldehyde functionalities, while no dehy-
dration products are detected, like in the most part of the
cases of six-membered ring formation. In contrast, the direct
catalytic intramolecular cross-aldol cyclisation of 1,6
dialdehydes, a widely exploited non-chiral transformation
in the synthesis of a broad range of biologically active
products,47–55 leads to dehydration products in general, the
corresponding cyclopentenecarbaldehydes. However, the
asymmetric variant, requiring an asymmetricity to be
induced at the b-carbon in respect to the aldehyde, is still
unknown.
version,56 gave an additional reason to concentrate our
attention on the asymmetric transformation of these
compounds.
As a first series several amino acids activities were checked
(Table 1), starting from (S)-proline as it has found to be a
highly efficient catalyst in many transformations, including
aldol cyclisation of heptanedials.46 It was observed that it is
also an effective catalyst in the formation of 3, but without
including stereocontrol (entry 1). By testing other amino
acids it was observed, that 2/3 transformation is catalysed
by simple acids, like (S)-(K)-aziridine carboxylic acid
(entry 2), (S)-(K)-azetidine carboxylic acid (entry 3) and N-
methyl-(S)-alanine (entry 8), leading to relatively high
chemical yields but without enantiomeric excess. On the
other hand, aromatic amino acids, such as (S)-(K)-2-
indoline carboxylic acid (entry 4) and (S)-(K)-tetrahydro-3-
isoquinoline carboxylic acid (entry 5), gave lower conver-
sion but better stereoselectivities. The chiral yield observed
with (R)-(K)-thiazolidin-4-carboxilic acid (36%, entry 7) in
comparison with (S)-proline could be an indication that the
sulphur atom in the catalyst molecule creates some
stereocontrol. However, as the variability of commercially
available sulphur containing chiral amino acids is very low,
no further detailed investigation of this class of compounds
were conducted.
As a part of our study on the cyclopentanoid synthesis, an
asymmetric version of the direct intramolecular catalytic
aldol cyclodehydration of meso-3,4-disubstituted-1,6-dia-
ldehydes, leading to the corresponding cyclopentene
carbaldehydes, is presented herein.
2. Results and discussion
The catalytic activities of different hydroxy prolines, which
have shown similar efficiency to that of proline in an
asymmetric Mannich reaction,36 were studied (Table 1). It
was observed that while both (2S,4R)-(C)-trans-4-hydro-
xyproline (entry 9) and (2R,4R)-(C)-cis-4-hydroxyproline
(entry 10) catalysed the construction of 3 slowly but with
significant stereocontrol, (2S,3S)-(K)-3-hydroxyproline
(entry 11) promoted better conversion but with lower
selectivity. When the diastereoisomers of 4-hydroxy
prolines were used, where the difference in the configuration
is only at C-2 centre, while that of the C-4 is the same, the
major products showed the opposite stereochemistry. This
could be an indication that the carbon, bearing the
carboxylate functionality, controls the selectivity in this
case, while that connected with the hydroxyl group has not
significant influence. The latter is in agreement with the
stereochemistry of the product of the reaction, catalysed by
3-hydroxy proline. In the cases of (S)-(K)-2,3,4,9-tetra-
hydro-1H-pyrido(3,4-b)indole-3-carboxilic acid (entry 6)
and (C)-yohimbinic acid (entry 12), very low solubility in
The meso-3,4-disubstituted-1,6-dialdehydes were readily
obtained by olefin oxidation of a series of differently meso-
4,5-disubstituted cyclohexenes, applying ozonolysis and
subsequent dimethyl sulphide (DMS) reductive work-up.
Their asymmetric aldol cyclodehydration was conducted at
ambient temperature in a time scale of 18–20 h, using
different groups of compounds as catalysts (Scheme 1). In
our previous work56 several alkenes were tested in a non-
chiral transformation. Among them the cyclic amide 1
appeared to be a good model compound for the detailed
preliminary investigations, according to the observed high
stability of the 2,4-dinitrophenylhydrazone of the aldol
product (3, XZDNPH). Afterward the same catalysts were
applied in the cyclodehydration of the dialdehyde 5, where
the corresponding cyclopentenecarbaldehyde 6 presents a
direct precursor of a more functionalised cyclopentanoid
unit with its two hydroxyl groups in the molecule. The
difference in the behaviours of the dialdehydes 2 and 5 in
respect to the catalysts used, observed in the non-chiral
Scheme 1. Aldol cyclodehydration of dialdehydes 2 and 5: (i) O3, dry CH2Cl2, K78 8C, DMS; (ii) catalyst (0.2 equiv), rt, 18–20 h; (iii) 2,4-
dinitrophenylhydrazine, H2SO4, MeOH.

V. B. Kurteva, C. A. M. Afonso / Tetrahedron 61 (2005) 267–273
269
Table 1. Chiral amino acids and hydroxy amino acids, tested as catalysts in 2/3 and 5/6 conversions
Entry
Catalyst
Yield of 3 (6), % ee of 3 (6), %
Entry
Catalyst
Yield of 3 (6), % ee of 3 (6), %
1
73 (4)
0 (0)
7
58 (—)
85 (3)
36a (—)
16c (4d)
2
3
73 (—b)
0 (—)
8
9
88 (6)
0 (3d)
26 (—)
19 (—)
60 (6)
52a (—)
66c (—)
30a (2e)
4
5
57 (—)
42 (—)
58a (—)
26a (—)
10
11
6
18 (4)
6a (10e)
12
10 (—)
4c (—)
a Major isomer tRZ52 min.
b No reaction occurs.
c Major isomer tRZ60 min.
d Major isomer tRZ29 min.
e Major isomer tRZ22 min.
the reaction media was observed, which could be an
additional reason for the inefficiency of these compounds as
catalysts. As phenylalanine has found to be an effective
catalyst for the aldol condensation steps in the estrone57 and
(K)-ilimaquinone58 syntheses, the primary amino acids
(S)-valine and (S)-serine activities were ascertained, but
racemic products in low reaction yields were isolated in
both cases.
more effective than proline, creating some stereocontrol in
almost the same reaction extent, the indolyl derivatives
show the opposite behaviour. As hydroxy pyrrolidine
(Table 3, entry 5) catalysed the 2/3 conversion in the
same extent as 3-hydroxy proline (Table 1, entry 11) but
loosing the stereoselectivity (0 vs 30% ee), it could be
suggested that the carboxylate functionality plays a crucial
role in this case. Taking in consideration the stereo-
chemistry of the major products in ephedrine and pseudo-
ephedrine catalysed aldol condensation (Table 3), where
(1S,2R)-(C)-ephedrine (entry 9) and (1S,2S)-(C)-pseudoe-
phedrine (entry 10) originate mainly the product with a
positive value of [a]D, while (1R,2S)-(K)-ephedrine (entry
8) led to the negative one, it could be suggested that the
carbon, connected to the hydroxyl group, controls the
selectivity in this case, where a carboxylate functionality
does not exist. To ascertain this suggestion, as well as to
study as wide as possible range of catalysts, several open
chain secondary amino alcohols were prepared from
commercially available primary ones (Fig. 1).
As a second series, the trifluoroacetates of various
secondary amines were studied, due to their high effective-
ness as catalysts in the non-chiral version. Starting with
some chiral analogues of dibenzylamine (Table 2, entries
1–3), a strong dependence of the conversion on the steric
hindrance in the catalyst molecule was observed, but
without inducing stereocontrol. As all amines tested showed
similar patterns, it could be summarised that these
compounds, which have shown activity in Robinson
annulation45 but not in Manich condensation,36 are not
efficient catalysts for the asymmetric transformation,
described herein.
The racemic products were formed with all catalysts of
this series, where the hydroxyl group is connected with a
non-chiral centre. The latter supports the suggestion that
the configuration of the carbon, bearing the hydroxyl
group, is crucial for induction of stereocontrol in substrates
studied.
Based on the observed better selectivities using hydroxy
prolines in respect to proline, the trifluoroacetates of some
amino alcohols activities were tested (Table 3). Variable
conversion was observed without substantial selectivity, but
some comments could be done. Comparing the efficiencies
of some cyclic amino alcohols (Table 3, entries 1–3) with
those of the corresponding carboxylic acids (Table 1, entries
1, 4 and 5), it could be summarised that while prolinol is
Applying a part of the catalysts tested in 2/3 conversion to
the construction of 6 from 5, it was observed that the

270
V. B. Kurteva, C. A. M. Afonso / Tetrahedron 61 (2005) 267–273
Table 2. Chiral aminesa, tested as catalysts in 2/3 and 5/6 conversions
Entry
1
Catalyst
Yield of 3 (6), % ee of 3 (6), %
Entry
5
Catalyst
Yield of 3 (6), % ee of 3 (6), %
b
—
—
78 (6)
4c (6d)
2
3
59
97
0
0
6
10 (—)
4e (—)
7
73 (10)
6c (0)
4
(8)
(14d)
a As trifluoroacetates.
b No reaction occurs.
c Major isomer tRZ52 min.
d Major isomer tRZ22 min.
e Major isomer tRZ60 min.
transformation in this case is rather slow in general and
without inducing significant stereocontrol. The only excep-
tion is in the case of 2-(diphenylhydroxymethyl)pyrrolidine
(Table 3, entry 4), where 70% ee was observed but in very
low conversion. An attempt to increase the reaction yield by
prolonging the reaction time resulted in a significant
decrease in the selectivity. The fact that no reaction
occurred with several amino acids and ammonium trifluor-
oacetates is in accordance with the observed in our previous
work56 that dibenzylammonium trifluoroacetate does not
catalyse the aldol condensation of 5. As it was found that
dibenzylamine itself is an efficient catalyst, the basic
components of some of the catalysts used were checked.
Thus, 2-methylpiperazine (Table 2, entry 6), which salt was
inactive, created the product in almost the highest chemical
yield, observed in this case, but with very low selectivity
(34 and 8% ee). On the other hand, the ephedrines did not
catalyse the reaction at all. The (S)-(K)-2-(diphenyl-
hydroxymethyl)pyrrolidine, which salt gave the best chiral
excess, generated the product in better extent but with
reduced stereocontrol (6 and 70% ee vs 18 and 36% ee). The
latter could be an indication that the faster reaction in this
case leads to a loose of selectivity and/or that the acidic
component of the catalyst controls it, but as such behaviour
was observed only with this catalyst, no substantial
conclusions could be done in general. Surprisingly, it was
observed that the catalyst (S)-(K)-2-(pyrrolidinomethyl)-
pyrrolidine, apart of giving some desired transformation
(21 and 2% ee), originated 7,7a-dihydro-4-hydroxy-2,2-
dimethylbenzo[d][1,3]dioxol-5(6H)-one as a main product.
The same compound was found to be a side product in the
non-chiral variant of this reaction performed in wet
dichloromethane and the main one if hydroxycyclohexene
was used as a starting material.56
Additionally, in a search of better catalysts, some chiral
phosphites and phosphines were studied in both 2/3 and
5/6 cyclodehydration (Table 4). It was found that the
transformation occurs in moderate to excellent yield, but
without stereocontrol. The only exception was (2S,4S)-(K)-
4-(diphenylphosphino)-2-(diphenylphosphinomethyl)pyrro-
lidine (entry 6), which gave moderate selectivity (24% ee).
In an attempt to determine the absolute configuration of the
aldol product 3, which is explicit if a chiral centre with
known configuration exists in the molecule as a norm,
several derivatisations and transformations were performed.
Chiral hydrazones (using SAMP and RAMP), chiral
enamines and subsequent reduction to the corresponding
amines, hydrogenation of the aldehyde followed by chiral
ether or ester formation etc. were done, but a crystal of pure
enantiomer was not isolated. When providing the cyclode-
hydration, starting from an analogue of 1, having (S)-
phenylethylamino group instead of benzylamino in the
substituent part, the dinitrophenylhydrazone of the corre-
sponding cyclopentene carbaldehyde was isolated in the
same extent and stereochemistry as 3. After several
recrystallisations from ethylacetate, where racemic crystals
were always formed, the enriched to the major isomer
mother liquors were submitted to a PTLC using multiple
developments of the plates, as both isomers have the same
Rf-values. A pure isomer was isolated, but the crystals,
created in several different solvent systems, were always
rather small and thus, X-ray data were not obtained.

V. B. Kurteva, C. A. M. Afonso / Tetrahedron 61 (2005) 267–273
Table 3. Chiral amino alcoholsa, tested as catalysts in 2/3 and 5/6 conversions
271
Entry
Catalyst
Yield of 3 (6), % ee of 3 (6), %
Entry
Catalyst
Yield of 3 (6), % ee of 3 (6), %
1
81
12b
8
64 (11)
73 (10)
73 (25)
(14)
18c (20d)
44b (0)
16b (6e)
(6d)
2
3
4
45
27b
9
70
22b
10
11
71 (6)
12b (70e)
5
63 (12)
0 (10d)
12
27 (15)
0 (2d)
6
7
37 (—f)
96 (16)
8c (—)
13
14
44 (3)
24c (32d)
1b (8e)
(9)
(10d)
a As trifluoroacetates.
b Major isomer tRZ52 min.
c Major isomer tRZ60 min.
d Major isomer tRZ29 min.
e Major isomer tRZ22 min.
f
No reaction occurs.
3. Conclusions
feasible and that to reach stereocontrol, the presence of a
hydroxyl group in the catalyst’s molecule seems to be
crucial. The chiral centre in hydroxy amino acids, bearing
the carboxylate functionality, controls the stereochemistry
of the final product. In the case of amino alcohols, where
carboxylate functionality does not exist, the configuration of
the carbon, connected with the hydroxyl group, seems to be
the key one. Additionally, it was found that chiral
phosphines and phosphites are effective catalysts for this
cyclodehydration but without inducing stereocontrol.
A first direct intramolecular asymmetric catalytic aldol
cyclodehydration of 1,6-dialdehydes to the corresponding
cyclopentene carbaldehydes was accomplished. Variable
conversion was observed with dialdehyde 2, having amide
substituents, while in the case of acetonide protected diol 5,
the transformation was rather slow in general and without
inducing substantial selectivity. Among the broad range of
the catalysts tested, it appears that for the substrates studied
some hydroxy amino acids, like hydroxy prolines, as well as
amino alcohols, like ephedrines and pseudoephedrines, are
the most efficient chiral ones for insertion of asymmetricity
at the b-carbon in respect to the aldehyde. The results
obtained clearly demonstrate that the chiral version is
4. Experimental
All reagents and the most part of the catalysts were
purchased from Aldrich and Fluka and were used without
any further purification. The chiral phosphites were
prepared in the laboratory.59 The amino alcohols, shown
in Figure 1, were synthesised from (S)-(C)-alaninol, (S)-
(K)-phenylalaninol, (S)-(C)-leucinol and (S)-(C)-valinol
by azomethyne formation with benzaldehyde, acetaldehyde
Figure 1. A series of chiral secondary amines.

272
V. B. Kurteva, C. A. M. Afonso / Tetrahedron 61 (2005) 267–273
Table 4. Chiral phosphites and phosphines, tested as catalysts in 2/3 and 5/6 conversions
Entry
1
Catalyst
Yield of 3 (6), % ee of 3 (6), %
Entry
4
Catalyst
Yield of 3 (6), % ee of 3 (6), %
83 (17)
2a (0)
48 (—b)
0 (—)
2
97 (13)
0 (4c)
5
50
4a
3
64 (25)
0 (4c)
6
93
24d
a Major isomer tRZ60 min.
b No reaction occurs.
c Major isomer tRZ29 min.
d Major isomer tRZ52 min.
and acetone and subsequent LiAlH4 reduction, following
standard procedures. The dichloromethane was dried over
P2O5. The ozonolysis were performed on a Fischer Ozon
Generator 500 M using dry (in-steam molecular sieve-silica
gel blue tube) oxygen. The HPLC analyses were carried out
using Merck and Hitachi components L-600A, L-4250,
T-6300, D-600 on a Chiralpak AD column, Diacel Chemical
Industries, Ltd (0.46 and 25 cm). The optical rotations were
recorded on a AA-100 Polarimeter, Optical Activity, Ltd
(Na-lamp, lZ589 nm, 0.5 dm cell, cZ1 in CHCl3).
C79.38 (entry 7), K38.78 (entry 8), C119.58 (entry 9),
K169.08 (entry 10), C61.78 (entry 11), K11.98 (entry 12);
Table 3, [a]DZK48.48 (entry 8), C97.28 (entry 9), C39.28
(entry 10), K56.18 (entry 13).
Acknowledgements
ˆ
We thank Fundac¸a˜o para a Ciencia e Tecnologia and
FEDER (Ref. SFRH/BPD/5531/2001) for the financial
support. We also thank Dr. Eurico Cabrita for supplying
us with samples of the chiral phosphites.
All experimental details and physical and spectroscopic data
for the starting materials, intermediately formed dialde-
hydes and final products are given in our previous report.56
General procedure for 1/3 and 4/6 transformation.
Through a solution of an alkene (1 mmol) in dry
dichloromethane (5 ml) a steam of ozone in oxygen was
bubbled at K78 8C until the solution turned blue. The
system was purged with argon until the colour disappeared
and dimethylsulphide (4 mmol, 0.3 ml) was then added. The
solution was kept at rt for 2 h and a catalyst (0.2 mmol,
20%), was added. After 18–20 h at rt the solvent was
removed in vacuo and the product was purified by
chromatography directly in the case of 6 and after
derivatisation as DNPH for 3.
References and notes
1. Borthwick, A.; Biggadike, K. Tetrahedron 1992, 48, 571–623.
2. Agrofoglio, L.; Suhas, E.; Farese, A.; Condom, R.; Challand,
S.; Earl, R.; Guedj, R. Tetrahedron 1994, 50, 10611–10670.
3. Crimmins, M. T. Tetrahedron 1998, 54, 9229–9272.
4. Ferrero, M.; Gotor, V. Chem. Rev. 2000, 100, 4319–4348.
5. Jones, M. Chem. Br. 1988, 24, 1122–1126.
6. Kusaka, T.; Yamamoto, H.; Shibata, M.; Muroi, M.; Kishi, T.;
Mizuno, K. J. Antibiot. 1968, 21, 255–263.
7. Yaginuma, S.; Muto, N.; Tsujino, M.; Sudate, Y.; Hayashi, M.;
Otani, M. J. Antibiot. 1981, 34, 359–366.
The selectivities were determined by chiral-phase HPLC
analysis at 25 8C using the following conditions: (a) for the
DNPH derivative of 3: mobile phase 50% i-PrOH and 50%
hexane, flow rate 0.6 ml/min, wave length 372 nm, retention
times tRZ52 min and tRZ60 min; (b) for the product 6:
mobile phase 1% i-PrOH and 99% hexane, flow rate 1.5 ml/
min, wave length 240 nm, retention times tRZ22 min and
tRZ29 min.
8. Vince, R.; Hua, M. J. Med. Chem. 1990, 33, 17–21.
9. Jones, M.; Myers, P.; Robertson, C.; Storer, R.; Williamson, C.
J. Chem. Soc., Perkin Trans. 1 1991, 2479–2484.
10. Trost, B.; Madsen, R.; Guile, S.; Brown, B. J. Am. Chem. Soc.
2000, 122, 5947–5956.
11. Crimmins, M.; King, B. J. Org. Chem. 1996, 61, 4192–4193.
12. Daluge, S.; Good, S.; Faletto, M.; Miller, W.; Wayne, H.; St.
Clair, M.; Boone, L.; Tisdale, M.; Parry, N.; Reardon, J.;
Dornsife, R.; Averett, D.; Krenitsky, T. Antimicrob. Agents
Chemother. 1997, 41, 1082–1093.
Optical rotations of selected samples of the DNPH of 3:
Table 1, [a]DZC137.08 (entry 4), C59.08 (entry 5),

V. B. Kurteva, C. A. M. Afonso / Tetrahedron 61 (2005) 267–273
273
13. Faletto, M.; Miller, W.; Garvey, E.; St. Clair, M.; Daluge, S.;
Good, S. Antimicrob. Agents Chemother. 1997, 41,
1099–1107.
39. Woodward, R.; Logusch, E.; Nambiar, K.; Sakan, K.; Ward,
D.; Au-Yeung, B.-W.; Balaran, P.; Browne, L.; Card, P.; Chen,
ˆ
C.; Chenevert, R.; Fliri, A.; Frobel, K.; Gais, H.-J.; Garratt, D.;
14. Foster, R.; Faulds, D. Drugs 1998, 729–736.
15. Heathcock, C. H. In Morrison, J. D., Ed.; Asymmetric
Synthesis; Academic: New York, 1984; Vol. 3, Chapter 2,
pp 111–212.
Hayakawa, K.; Heggie, W.; Hesson, D.; Hoppe, D.; Hoppe, I.;
Hyatt, J.; Ikeda, D.; Jacobi, P.; Kim, K.; Kobuke, Y.; Kojima,
K.; Krowicki, K.; Lee, V.; Leutert, T.; Malchenko, S.;
Martens, J.; Matthews, R.; Ong, B.; Press, J.; Rajan Babu,
T.; Rousseau, G.; Sauter, H.; Suzuki, M.; Tatsuta, K.; Tolbert,
L.; Truesdale, E.; Uchida, I.; Ueda, Y.; Uyehara, T.; Vasella,
A.; Vladuchick, W.; Wade, P.; Williams, R.; Wong, H. J. Am.
Chem. Soc. 1981, 103, 3210–3213.
16. Kim, B. M.; Williams, S. F.; Masamune, S. In Trost, B. M.,
Fleming, I., Eds.; Comprehensive Organic Synthesis;
Pergamon: Oxford, 1991; Vol. 2, Chapter 1.7, pp 239–275.
17. Danheiser, R. In Lindberg, T., Ed.; Strategies and Tactics in
Organic Synthesis; Academic: London, 1984; Vol. 1,
pp 21–70.
40. Agami, C.; Platzer, N.; Puchot, C.; Sevestre, H. Tetrahedron
1987, 43, 1091–1098.
18. Wong, C.-H.; Whitesides, G. Enzymes in Synthetic Organic
Chemistry; Pergamon: Oxford, 1994.
41. Agami, C. Bull. Soc. Chim. Fr. 1988, 499–507.
42. Reymond, J. J. Mol. Catal. B 1998, 5, 331–337.
43. Nelson, S. Tetrahedron: Asymmetry 1998, 9, 357–389.
44. Carreira, E. In Jacobsen, E., Pfaltz, A., Yamamoto, H., Eds.;
Comprehensive Asymmetric Catalysis; Springer: Heidelberg,
1999; Vol. 3, Chapter 29.1.
19. Wagner, J.; Lerner, R.; Barbas, C., III Science 1995, 270,
1797–1800.
20. Reymond, J.-L.; Chen, Y. J. Org. Chem. 1995, 60, 6970–6979.
21. List, B.; Lerner, R.; Barbas, C. F., III Org. Lett. 1999, 1, 59–61.
22. List, B.; Lerner, R.; Barbas, C., III Org. Lett. 1999, 1,
1623–1626.
45. Bui, T.; Barbas, C. F., III Tetrahedron Lett. 2000, 41,
6951–6954.
23. Machajewski, T.; Wong, C.-H. Angew. Chem., Int. Ed. 2000,
39, 1352–1374.
46. Pidathala, C.; Hoang, L.; Vignola, N.; List, B. Angew. Chem.,
Int. Ed. 2003, 42, 2785–2788.
24. Heine, A.; DeSantis, G.; Luz, J.; Mitchell, M.; Wong, C.-H.;
Wilson, I. Science 2001, 294, 369–374.
47. Woodward, R. B.; Sondheimer, F.; Taub, D.; Heusler, K. W.;
McLamore, W. J. Am. Chem. Soc. 1952, 74, 4223–4251.
48. Barkley, L.; Farrar, M.; Knowles, W.; Raffelson, H.;
Thompson, Q. J. Am. Chem. Soc. 1954, 76, 5014–5017.
49. Truesdale, L.; Swanson, D.; Sun, R. Tetrahedron Lett. 1985,
26, 5009–5012.
25. Hajos, Z.; Parris, D. German Patent DE 2102623, July 29,
1971.
26. Hajos, Z.; Parris, D. J. Org. Chem. 1973, 38, 3239–3243.
27. Hajos, Z.; Parris, D. J. Org. Chem. 1974, 39, 1615–1621.
28. Eder, U.; Sauer, G.; Wiecher; R. German Patent DE 2014757,
Oct 7, 1971.
50. Hetmanski, M.; Purcell, N.; Stoodley, R.; Palfreyman, M.
J. Chem. Soc., Perkin Trans. 1 1984, 2089–2096.
51. Corey, E.; Danheiser, R.; Chandrasekaran, S.; Siret, P.; Keck,
G.; Gras, J.-L. J. Am. Chem. Soc. 1978, 100, 8031–8034.
52. Tamura, N.; Natsugari, H.; Kawano, Y.; Matsushita, Y.;
Yoshioka, K.; Ochiai, M. Chem. Pharm. Bull. 1987, 35,
996–1015.
29. Eder, U.; Sauer, G.; Wiecher, R. Angew. Chem., Int. Ed. Engl.
1971, 10, 496–497.
30. List, B.; Lerner, R.; Barbas, C., III J. Am. Chem. Soc. 2000,
122, 2395–2396.
¨
31. Groger, H.; Wilken, J. Angew. Chem., Int. Ed. 2001, 40,
529–532.
53. Bryce, M.; Gardiner, J. J. Chem. Soc., Chem. Commun. 1989,
1162–1164.
32. List, B. Tetrahedron 2002, 58, 5573–5590.
33. Alcaide, B.; Almendros, P. Eur. J. Org. Chem. 2002,
1595–1601.
54. Hodgson, D.; Parsons, P.; Stones, P. Tetrahedron 1991, 47,
4133–4142.
34. Northrup, A.; McMillan, D. J. Am. Chem. Soc. 2002, 124,
6798–6799.
55. Singh, R.; Cooper, R. Tetrahedron 1994, 50, 12049–12064.
56. Kurteva, V.; Afonso, C. 14th International Symposium on
Homogeneous Catalysis, July 5–9, 2004, Munich, Germany,
P108, Book of Abstracts, p 126; submitted for publication as a
full paper.
35. Melchiorre, P.; Jørgensen, K. J. Org. Chem. 2003, 68,
4151–4157.
36. Notz, W.; Tanaka, F.; Watanabe, Sh.; Chowdari, N.; Turner, J.;
Thayumanavan, R.; Barbas, C., III J. Org. Chem. 2003, 68,
9624–9634.
57. Danishefsky, S.; Cain, P. J. Am. Chem. Soc. 1976, 16,
4975–4982.
37. Alcaide, B.; Almendros, P. Angew. Chem., Int. Ed. 2003, 42,
858–860.
58. Bruner, S.; Radeke, H.; Tallarico, J.; Snapper, M. J. Org.
Chem. 1995, 60, 1114–1115.
38. Brown, K.; Damm, L.; Dunitz, J.; Eschenmoser, A.; Hobi, R.;
Kratky, Chr. Helv. Chim. Acta 1978, 61, 3108–3135.
59. Cabrita, E.; Afonso, C.; Santos, A. Chem. Eur. J. 2001, 7,
1455–1467 and unpublished results.