Chemistry of Pyruvate Enolates: Anti-Selective Direct Aldol Reactions of Pyruvate Ester with Sugar Aldehydes Promoted by a Dinuclear Zinc Catalyst

Article abstract of DOI:10.1002/adsc.201500169

A chiral dinuclear zinc complex can effectively catalyse the direct aldol reactions of pyruvic acid ester with various chiral sugar aldehydes, thus functionally mimicking the pyruvate-dependent type II aldolases. Application of sterically hindered aryl esters allows for the elusive aldol reaction of the pyruvate donor with controlled anti-selectivity en route to the short and efficient synthesis of 3-deoxy-2-ulosonic acids. Pyruvic acid ester is here used as a chemical equivalent of phosphoenol pyruvate (PEP) in imitation of the synthetic principle used in nature. The presented biomimetic methodologies use enol formation for the highly efficient and flexible formation of various C₆-C₉ ulosonic acids. Particularly, efficient and concise syntheses of 3-deoxy-D-erythro-hex-2-ulosonic acid (KDG, overall 50% yield), 3-deoxy-D-ribo-hept-2-ulosonic acid (DRH, overall 53% yield) and 3-deoxy-D-glycero-D-talo-non-2-ulosonic acid (4-epi-KDN, overall 78% yield) are described. This direct efficient application of pyruvic esters does not require additional demasking steps and thus surpassess previously methodologies utilising masked pyruvic synthons such 2-acetylthiazole and pyruvic aldehyde dimethyl acetal.

Full text of DOI:10.1002/adsc.201500169

FULL PAPERS
DOI: 10.1002/adsc.201500169
Chemistry of Pyruvate Enolates: anti-Selective Direct Aldol
Reactions of Pyruvate Ester with Sugar Aldehydes Promoted by
a Dinuclear Zinc Catalyst
a
a
a
a
Marta A. Molenda, Sebastian Ba s´ , Osama El-Sepelgy, Matylda Stefaniak,
a,b,
and Jacek Mlynarski *
Faculty of Chemistry, Jagiellonian University, Ingardena 3, 30-060 Krakow, Poland
a
Fax: (+48)-12-634 0515; phone: (+48)-12-663 2035; e-mail: jacek.mlynarski@gmail.com
Institute of Organic Chemistry, Polish Academy of Sciences, Kasprzaka 44/52, Warsaw, Poland
b
Received: February 17, 2015; Revised: April 22, 2015; Published online: June 10, 2015
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/adsc.201500169.
Abstract: A chiral dinuclear zinc complex can effec- cient and concise syntheses of 3-deoxy-d-erythro-
tively catalyse the direct aldol reactions of pyruvic hex-2-ulosonic acid (KDG, overall 50% yield), 3-
acid ester with various chiral sugar aldehydes, thus deoxy-d-ribo-hept-2-ulosonic acid (DRH, overall
functionally mimicking the pyruvate-dependent type 53% yield) and 3-deoxy-d-glycero-d-talo-non-2-ulo-
II aldolases. Application of sterically hindered aryl sonic acid (4-epi-KDN, overall 78% yield) are de-
esters allows for the elusive aldol reaction of the pyr- scribed. This direct efficient application of pyruvic
uvate donor with controlled anti-selectivity en route esters does not require additional demasking steps
to the short and efficient synthesis of 3-deoxy-2-ulo- and thus surpassess previously methodologies utilis-
sonic acids. Pyruvic acid ester is here used as a chemi- ing masked pyruvic synthons such 2-acetylthiazole
cal equivalent of phosphoenol pyruvate (PEP) in and pyruvic aldehyde dimethyl acetal.
imitation of the synthetic principle used in nature.
The presented biomimetic methodologies use enol
formation for the highly efficient and flexible forma- Keywords: aldol reaction; asymmetric synthesis; pyr-
tion of various C –C ulosonic acids. Particularly, effi- uvate esters; ulosonic acids; zinc catalysts
6
9
Introduction
nised as a suitable substrate in catalytic aldol reac-
tions truly mimicking enzymatic transformations. In
[6]
Asymmetric aldol reactions of biologically relevant general, our knowledge on catalytic asymmetric aldol
substrates are of exceptional importance due to their reactions of puruvate acid and its derivatives remains
usefulness in the synthesis of natural products and restricted to a few examples despite the break-
drugs in a way closely related to enzyme-promoted throughs in many other fields of direct aldol reac-
[
1]
[7]
biotransformations. Among known variants of asym- tions. The first example of the direct use of a 1,2-di-
[
2]
[8]
metric CÀC bond forming reactions, the pyruvate- carbonyl prenucleophile was limited to the asym-
[9]
dependent aldol reaction is particularly important for metric homo-aldol reaction of ethyl pyruvate. To
many life processes where pyruvic acid is used as achieve this goal, Jørgensen and co-workers, devel-
[
3]
a key C donor unit. Phosphoenol pyruvate (PEP), oped a chiral copper-bisoxazoline catalyst providing
3
being the reactive form of pyruvic acid, is implicated diethyl 2-hydroxy-2-methyl-4-oxoglutarate in high
as the intermediate in the biosynthesis of 3-deoxy-2- yield and 96% ee isolated as the more stable isote-
ketoaldonic acids (ulosonic acids) and sialic acids by tronic acid. The authors postulated that the Cu-based
[
4]
way of the addition of PEP to aldoses. Only en- chiral Lewis acid promotes both the formation of enol
zymes – aldolases, which catalyse this reaction in pyruvate and controls the stereochemistry of the reac-
[
9]
nature, have recently been used to mimic the reaction tion. Interestingly, a similar homoaldol reaction of
[
5]
between PEP and various aldehydes.
ethyl pyruvate leading to enantiomerically enriched
Surprisingly, the enol form of pyruvic acid widely isotetronic acid was observed by Dondoni under
used as a nucleophile by nature has not been recog- chiral pyrrolidine control, thus suggesting enamine-
2098
ꢀ 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2015, 357, 2098 – 2104

FULL PAPERS
Chemistry of Pyruvate Enolates: anti-Selective Direct Aldol Reactions
based organocatalytic activation of the 1,2-dicarbonyl Results and Discussion
[10,11]
substrate.
On the other hand, the organocatalytic
cross-aldol reaction of pyruvate ester has been limited Previously we showed that pyruvic derivatives such as
to only one example of the highly active chloral hy- dimethyl acetals or thiazole rings can be used as
drate. The proline-tetrazole catalyst presumably acti- chemical equivalents of pyruvic esters in the metal
vates the ethyl pyruvate by formation of the corre- enolate-based catalytic reaction with chiral aldehydes
[
13]
sponding enamine enhancing its reactivity to give the en route to ulosonic acid precursors. Unfortunately,
[
12]
desired b-aldol in 55% yield and 86% ee.
the elusive direct activation of pyruvate ethyl or
In spite of the presented efforts, the scope of the methyl esters by using broad range of metal-based
[
6]
known pyruvate-dependent aldol methodologies is catalysts was unsuccessful. Therefore, general meth-
narrow and strictly limited to highly active non-enolis- ods for the generation of a metal enolate of pyruvic
able aldehydes or self-condensation of pyruvate ester were explored to find the optimal conditions
esters. Consequently there is a need for efficient cata- whereby a stereoselective aldol reaction between an
lysts for asymmetric cross-aldol reactions of pyruvate enolate and a chiral glyceraldehyde could be per-
esters and aliphatic aldehydes, this being the realm of formed.
enzymes and thus remaining a challenging endeavour
As a starting point, a variety pyruvic esters was
of great interest. Solving this problem would also con- screened in the reaction with optically pure (R)-glyc-
stitute an excellent and biomimetic attempt to achieve eraldehyde acetonide (1) to assess both reaction effi-
the formation of 3-deoxy-2-ulosonic acids and sialic ciency and stereoselectivity in the addition of lithium
acids, which are essential sugar units for many biolog- enolates controlled by a chiral aldehyde. Attempts to
[
4]
ical processes and transformations. In this paper we perform an aldol reaction by metallation of esters 3–5
report that chiral zinc complexes can act as a pyru- with a solution of lithium tert-butoxide at À788C in
vate-dependent aldolase, i.e., a type II aldolase, to THF and then introducing aldehyde (1) revealed that
catalyse the direct asymmetric aldol reaction of pyru- only the application of 2,6-di-tert-butyl-4-methoxy-
vate esters with chiral aldehyde electrophiles. It is im- phenyl pyruvate (5) resulted in formation of the de-
portant to mention that the direct catalytic aldol reac- sired aldols, albeit in low yields (Table 1). Only aryl
tion of pyruvic esters with chiral aldehydes has not ester 5 was identified as a workable aldol donor due
been reported so far.
to steric hindrance preventing self-condensation of
[
14]
the corresponding enolate. Under optimised condi-
tions, anti-6 and syn-configured aldols have been iso-
lated in 28% overall yield (Table 1, entry 3). From the
[a]
Table 1. Aldol reactions of lithium enolates of pyruvic esters with sugar aldehydes.
[b]
Entry
Aldehyde
Pyruvate ester
Base
Yield [%]
anti/syn
1
2
3
4
3
4
5
5
t-BuOLi
t-BuOLi
t-BuOLi
t-BuOLi, ZnCl2
0
0
28
5
–
–
1.5/1
3/1
[
[
c]
c]
5
6
5
5
t-BuOLi
t-BuOLi, ZnCl2
30
8
1/1
4/1
[
a]
Reaction conditions: aldehyde (0.2 mmol), pyruvate ester (0.2 mmol), t-BuOLi (0.22 mmol, 110 mol%) in THF at À788C
for 2 h and then 1 h at room temperature.
[
b]
c]
1
Determined by H NMR spectroscopy.
[
Reactions were performed with ZnCl (0.22 mmol, 110 mol%).
2
Adv. Synth. Catal. 2015, 357, 2098 – 2104
ꢀ 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
2099

Marta A. Molenda et al.
FULL PAPERS
[a]
Table 2. Direct aldol reaction of the pyruvic ester with protected (R)-glyceraldehyde.
[b]
Entry
Catalyst
Yield [%]
anti/syn
1
2
(R)-8 (5 mol%)
(S)-8 (5 mol%)
62
62
8/1
3/1
[
a]
b]
Reactions were performed with 1 (0.1 mmol), 5 (0.1 mmol), catalyst 8 (5 mol%) in THF at room temperature for 12 h.
Determined by H NMR spectroscopy.
[
1
chiral aldols, the corresponding anti-aldol 6 was ob- butyl-4-methoxyphenyl ester to avoid self-condensa-
tained as a major isomer, albeit with poor diastereose- tion of the ketone was decisive (Table 2).
lectivity (1.5:1). This result was consistent with a reac-
Finally, after careful tuning of solvent and tempera-
tion via a non-chelation-controlled transition state ture, the reaction of ester 5 with (R)-glyceraldehyde
matching the Felkin–Anh model for an asymmetric acetonide 1 promoted by only 5 mol% of (R)-ProPhe-
[
15]
addition to chiral aldehydes, however the observed nol catalyst 8 resulted in a clean and efficient forma-
diastereoselectivity was simply disappointing. tion of the desired cross-aldol products with a very
Similar anti-selectivity was previously reported for good level of diastereoselectivity, favouring anti
the addition of various ketone enolates to a-alkoxy isomer 6 (Table 2, entry 1). Application of the (S)-
[16]
[17]
aldehydes
including glyceraldehyde acetonide,
configured catalysts resulted in the loss of stereoselec-
while stereoselective additions of the lithium enolate tivity, apparently as a result of the formation of a mis-
of pyruvic acid esters have not been previously docu- matched pair between chiral catalyst and optically
mented, surprisingly. It is likely that the lithium ion pure aldehyde (Table 2, entry 2).
coordinates to both carbonyl groups in pyruvate acid
The anti-configured aldol 6 obtained from (R)-glyc-
ester instead of the formyl oxygen in the aldehyde. eraldehyde acetonide and pyruvic acid ester possess
Reactions promoted by LDA were unsuccessful. Ap- the configuration of natural 3-deoxy-d-erythro-hex-2-
plication of the above reaction sequence to the aldol ulosonic acid (2-keto-3-deoxy-d-glucosonic acid,
[
20]
reaction of d-arabinose 2 and pyruvic ester 5 resulted KDG). Thus, the elaborated efficient C +C strat-
3
3
in the unselective formation of anti- and syn-aldols egy seems to be closely related to the biosynthesis of
Table 1, entry 5) suggesting that a stereoselective ad- natural sugar by using ester 5 as a chemical equivalent
(
dition of lithium enolates to chiral aldehydes could of PEP (phosphoenol pyruvate). The observed high
not be directly predicted by using the Felkin–Anh anti-stereoselectivity encouraged us to study the fur-
model. Surprisingly worse results in terms of yield ther transformation of the protected aldol into a natu-
were obtained when an attempt was made to prepare ral sugar in hemiketal form, which will be described
the corresponding zinc enolate, but the observed in the next part of the manuscript.
higher diastereoselectivity was noteworthy in both
cases and encouraged a search for Zn-based catalysts ious protected aldehydes derived from d-erythrose (9,
Table 1, entries 4 and 6). 10), d-arabinose (2), and d-hexoses (11-13) (Table 3).
Consequently, we turned our attention to metal- To our delight, the previously observed principle of
This methodology was successfully applied with var-
(
promoted processes by using catalysts capable of si- anti-selectivity was maintained also for the reaction of
multaneous activation of the donor and acceptor alde- protected d-erythrose (9). The corresponding anti-
hyde in a chiral environment thus possibly improving aldol 14 was formed as the major product by using
the expected stereoselectivity. These catalysts can be optimal 20 mol% of (R)-configured catalyst
8
compared mechanistically to the type II aldolases, (Table 3, entry 2). The observed diastereoselectivity
[
18]
which employ zinc ion to form an active enolate.
(7:1) could be improved by using a lower amount of
[
19]
After many trials, we found Zn-(R)-ProPhenol 8 to the catalyst albeit at the expense of overall yield (en-
be the catalyst of choice for the enolisation of pyruvic tries 3 and 4). Interestingly, application of (S)-config-
acid ester 5. Again, employing the bulky 2,6-di-tert- ured catalyst 8 resulted also in the selective formation
2100
asc.wiley-vch.de
ꢀ 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2015, 357, 2098 – 2104

FULL PAPERS
Chemistry of Pyruvate Enolates: anti-Selective Direct Aldol Reactions
Table 3. Direct aldol reaction of the pyruvic ester with protected d-erythrose, d-arabinose,
and d-hexoses.
[
[
a]
b]
Reaction conditions: aldehyde (0.1 mmol),
5 (0.2 mmol), aldehyde concentration
À1
0
.1 mmolmL . Performed in dry THF, at À25 88 C for 4 days.
1
Determined by H NMR spectroscopy.
of the anti-aldol with inferior yield (Table 3, entry 1).
Further analysis of the kind of protection groups
This suggests that both features: chirality of zinc eno- used in the aldehyde revealed that substrate confor-
late (from catalyst) and Felkin–Anh principles (chiral mation plays an additional role in controlling stereo-
aldehyde) play pivotal roles in controlling the sense selectivity. Thus, application of more sterically rigid
of asymmetric induction.
2,3-O-isopropylidene derivative of the same d-eryth-
Adv. Synth. Catal. 2015, 357, 2098 – 2104
ꢀ 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
2101

Marta A. Molenda et al.
FULL PAPERS
Scheme 1. Stereochemical rationalisation.
rose sugar 10 led to lower selectivity when compared
As was mentioned above, all obtained aldols could
to the more flexible 2-O-Bn isomer 9 (Table 3, entry 2 serve as intermediates in the synthesis of cyclic 3-
vs. entry 6). deoxy-2-keto acids (ulosonic acids) via deprotection
Surprisingly, the reaction of d-arabinose diaceto- and hemiketalisation. In recent years, a number of
nide 2 was far less selective when compared to the chemical and enzymatic methodologies have been re-
[21]
above mentioned examples by using either (R)- or ported for the synthesis of sialic and ulosonic acids
S)-ProPhenol (Table 3, entries 7 and 8). Such an un- but our attempt seems to be so far the simplest and
(
selective formation of both aldols was similar to the closely related to the enzymatic pathway. In contrast
reaction operating under Felkin–Anh control to previously presented flexible synthesis of ulosonic
(
Table 1). However, protected d-mannose 11 with the acids utilising masked pyruvate synthons (i.e., 2-ace-
same configuration at C-2 exhibits a much higher tylthiazole, pyruvic aldehyde dimethyl acetal) this at-
anti-selectivity when promoted by (R)-catalyst tempt uses only a stoichiometric amount of promoter
(
Table 3, entry 10). This time, switching to rigid and does not require tedious demasking of the thia-
[
22]
isomer 12 improved yield and selectivity regardless of zole ring. To end-up the synthesis of ulosonic acid
the catalyst antipode used (entries 11 and 12). Ob- by using the thus elaborated efficient attempt, we car-
tained as a sole isomer, anti-aldol 17 with the d-glyc- ried out the necessary deprotections as depicted at
ero-d-talo-configuration is a valuable C-4 epimer of Scheme 2.
natural
3-deoxy-d-glycero-d-galacto-non-2-ulosonic
Obviously the most valuable achievement is the
acid (KDN). In regards to the d-glucose, the use of direct stereoselective synthesis of protected 3-deoxy-
a 2,3-O-isopropylidene derivative 13 along with the d-erythro-hex-2-ulosonic acid KDG (6). anti-Config-
(
R)-ProPhenol led to the best results in terms of yield ured linear aldol 6 possesses the configuration of nat-
and anti-selectivity (Table 3, entry 14). ural KDG and can be easily transformed into this bio-
Based on a previously described observation and molecule. To end-up this C +C protocol, anti-aldol 6
3
3
the only slight influence of the chirality of the catalyst was easily deprotected when treated with an acidic
on the reaction stereoselectivity, we propose that the ion-exchange resin (DOWEX) in methanol to give
stereochemical outcome of these reactions can be ra- the mixture of cyclic forms of the KDG ester 19
tionalized by a dinuclear model in which zinc-ProPhe- (Scheme 2). For the reason of clarity the stereochem-
1
nol catalyst is complexing the enol from pyruvic ester istry of this molecule was established by H NMR
(
5). The thus formed zinc-enolate attacks the chiral analysis of the cyclic furanose and pyranose forms of
[20]
aldehyde according to Felkin–Anh principles the ester. Hydrolysis of the used aryl ester could be
Scheme 1) resulting in anti-aldol 6. Coordination of achieved by treatment of 19 with potassium tert-but-
(
the aldehyde to the zinc atom is more speculative al- oxide in THF at À308C, according to the Enders pro-
[
23]
though it cannot be excluded. Combining chiral cata- cedure. It is noteworthy that KDG ester was ach-
lyst and chiral aldehydes with more than one stereo- ieved by using this concise two-step protocol in 50%
genic centre resulted in the formation of aldols in overall yield, starting from protected glyceraldehyde
a less predictable way when compared to the classical (1).
addition of non-chiral enolates to chiral aldehydes,
anti-Aldol 14 prepared from d-erythrose could be
however. Nevertheless, such a scenario explains the transformed into unnatural 3-deoxy-d-ribo-hept-2-
[
24]
predominant formation of anti-aldols in spite of the ulosonic acid ester (20, DRH, 4-epi-DAH) with re-
configuration of stereogenic centre in the a-position markable 53% overall yield (Scheme 2).
to the carbonyl group in the chiral aldehyde.
Non-selective synthesis of aldol 7 from d-arabinose
seems to be only one example of an inconvenient
2
102
asc.wiley-vch.de
ꢀ 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2015, 357, 2098 – 2104

FULL PAPERS
Chemistry of Pyruvate Enolates: anti-Selective Direct Aldol Reactions
Scheme 2. Synthesis of various ulosonic acid esters.
methodology en route to natural 3-deoxy-d-manno- synthesis of ulosonic acids. Thus, a new synthetic
oct-2-ulosonic acid (KDO). Nevertheless, major pro- route from protected acyclic optically pure aldehydes
tected anti-aldol 7 was liberated to form the natural to cyclic ulosonic acid esters having six, seven, eight,
octulosonic acid ester 21 (KDO) with lower, 42% and nine carbon atoms has been opened up. Based on
overall yield. Apparently, in this particular case the this principle, we have provided practical protocols
parallel organocatalytic protocol seems to be more for the stereoselective synthesis of several six-, seven-,
promising when compared to the discussed metal-pro- eight-, and nine-carbon 3-deoxy-2-ulosonic acids in-
[
6]
moted aldol reaction.
cluding the relevant 3-deoxy-d-erythro-hex-2-ulosonic
In contrast, a highly stereoselective C +C strategy acid (KDG, overall 50% yield), 3-deoxy-d-ribo-hept-
6
3
leading to a nine-carbon chain from mannose (12) de- 2-ulosonic acid (DRH, overall 53% yield) and 3-
livered anti-aldol 17, exclusively. This, in turn, was deoxy-d-glycero-d-talo-non-2-ulosonic acid (4-epi-
transformed into the ester of the rare higher sugar: 3- KDN, overall 78% yield) in their pyranose/furanose
deoxy-d-glycero-d-talo-non-2-ulosonic acid (22, 4-epi- forms. This direct efficient application of pyruvic
KDN) by removal of the isopropylidene and O- esters does not require additional demasking steps
benzyl residues (Scheme 2). Isomeric 3-deoxy-d-glyc- and thus surpasses previously methodologies utilising
ero-d-gulo-non-2-ulosonic acid (5-epi-KDN) 23 was masked pyruvic synthons.
easily reached after cyclisation of anti-aldol 18, pre-
pared from glucose. Final examination of the NMR
spectra of ulosonic acids in their pyranose/furanose
Experimental Section
cyclic forms provided the ultimate confirmation of the
[
20]
structures of all anti-aldol precursors.
Representative Procedure for Direct Aldol Reaction
of the Pyruvic Ester 5 with Protected Sugar
Aldehydes
Conclusions
Commercial Trost ProPhenol ligand (12.8 mg, 0.02 mmol)
was dissolved in dry THF (0.5 mL) at room temperature
under an argon atmosphere and treated with a solution of
diethylzinc (1M in hexane, 0.04 mL, 0.04 mmol). The reac-
tion mixture was stirred for 30 min to give 0.02 mmol of the
catalyst 8. The thus prepared catalyst was added to a solution
of aldehyde (0.1 mmol) and aryl pyruvate 5 in 0.5 mL of
In conclusion, we have shown that Zn-based ProPhe-
nol complexes (Trostꢁs catalysts) can initiate stable
enol formation from hindered pyruvate esters which
can be further trapped by electrophilic aldehydes.
This is the first example of an efficient catalytic anti-
selective direct aldol reaction of pyruvate esters with THF at À258C under an argon atmosphere. The reaction
sugar aldehydes closely resembling the biomimetic mixture was stirred for 4 days at À258C, then quenched by
Adv. Synth. Catal. 2015, 357, 2098 – 2104
ꢀ 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
2103

Marta A. Molenda et al.
FULL PAPERS
saturated ammonium chloride, extracted with ethyl acetate,
dried with sodium sulphate and evaporated. The crude prod-
uct was purified on silica gel by column chromatography
using hexane-ethyl acetate (4:1 or 9:1) as eluent to afford
the desired anti-aldols. Isomeric syn-aldols have been isolat-
ed only in the case of more yielding and less selective reac-
tions.
non-asymmetric variants, see c) D. Lee, S. G. Newman,
M. S. Taylor, Org. Lett. 2009, 11, 5486; d) Y. Sun, H.
Chen, Z. Li, Q. Wang, F. Tao, Synthesis 2008, 589.
[12] H. Torii, M. Nakadai, K. Ishihara, S. Saito, H. Yama-
moto, Angew. Chem. 2004, 116, 2017; Angew. Chem.
Int. Ed. 2004, 43, 1983.
[13] a) O. El-Sepelgy, D. Schwarzer, P. Oskwarek, J. Mlynar-
ski, Eur. J. Org. Chem. 2012, 2724; for similar reactions
of pyruvic derivatives promoted by organocatalysts,
see: b) D. Enders, T. Gasperi, Chem. Commun. 2007,
88; c) S. Luo, H. Xu, L. Chen, J.-P. Cheng, Org. Lett.
Acknowledgements
2
008, 10, 1775.
Financial support from the Polish National Science Centre
[14] 2,6-di-tert-Butyl-4-methoxyphenyl ester was used by
Enders for the synthesis of hindered SAMP-hydrazone:
a) D. Enders, H. Dyker, G. Raabe, Angew. Chem. 1992,
(
MAESTRO Grant Nr. 2013/10A/ST5/00233) is gratefully ac-
knowledged.
1
04, 649; Angew. Chem. Int. Ed. Engl. 1992, 31, 618;
b) D. Enders, H. Dyker, G. Raabe, Angew. Chem. 1993,
105, 420; Angew. Chem. Int. Ed. Engl. 1993, 32, 421;
see also: c) O. J.-C. Nicaise, D. M. Mans, A. D. Morrow,
E. Villa Hefti, E. M. Palkovacs, R. K. Singh, M. A. Zu-
kowska, M. D. Morin, Tetrahedron 2003, 59, 6433.
[15] A. Mengel, O. Reiser, Chem. Rev. 1999, 99, 1191.
[16] C. H. Heathcock, S. D. Young, J. P. Hagen, M. C. Pir-
rung, C. T. White, D. VanDerveer, J. Org. Chem. 1980,
45, 3846.
References
[1] a) D. Enders, A. A. Narine, J. Org. Chem. 2008, 73,
7858; b) M. Markert, R. Mahrwald, Chem. Eur. J. 2008,
14, 48; c) J. Mlynarski, B. Gut, Chem. Soc. Rev. 2012,
41, 587.
[
[
2] R. Mahrwald, (Ed.), Modern Aldol Reactions, Wiley-
VCH, Weinheim, 2004.
3] a) M. F. Utter, D. B. Keech, J. Biol. Chem. 1963, 238,
[17] J. Jurczak, S. Pikul, T. Bauer, Tetrahedron 1986, 42, 447.
[18] M. Shibasaki, S. Matsunaga, Chem. Soc. Rev. 2006, 35,
269.
rd
2
603; b) D. Voet, J. G. Voet, Biochemistry, 3 edn.,
John Wiley & Sons, New York, 2004.
[
4] a) F. M. Unger, Adv. Carbohydr. Chem. Biochem. 1980,
[19] a) B. M. Trost, H. Ito, J. Am. Chem. Soc. 2000, 122,
12003; for other papers relevant to the use of Zn-
ProPhenol catalyst, see: b) B. M. Trost, E. R. Silcoff, H.
Ito, Org. Lett. 2001, 3, 2497; c) B. M. Trost, A. Fettes,
B. T. Shireman, J. Am. Chem. Soc. 2004, 126, 2660;
d) B. M. Trost, S. Shin, J. A. Sclafani, J. Am. Chem. Soc.
2005, 127, 8602; e) B. M. Trost, H. Ito, E. R. Silcoff, J.
Am. Chem. Soc. 2001, 123, 3367; f) B. M. Trost, D. J.
Michaelis, M. I. Truica, Org. Lett. 2013, 15, 451;
g) B. M. Trost, D. Amans, W. M. Seganish, C. K. Chung,
J. Am. Chem. Soc. 2009, 131, 17087; h) B. M. Trost, F.
Miege, J. Am. Chem. Soc. 2014, 136, 3016.
3
8, 323; b) R. Schauer, Adv. Carbohydr. Chem. Bio-
chem. 1982, 40, 132; c) B. Lindberg, Adv. Carbohydr.
Chem. Biochem. 1990, 48, 279; d) A. Banaszek, J. Mly-
narski, Stud. Nat. Prod. Chem. 2005, 30, 419.
[
5] a) M. Brovetto, D. Gamenara, P. Saenz MØndez, G. A.
Seoane, Chem. Rev. 2011, 111, 4346; b) S. M. Dean,
W. A. Greenberg, C.-H. Wong, Adv. Synth. Catal. 2007,
3
49, 1308.
[
6] For our preliminary report mostly focused on applica-
tion of chiral tertiary amines, see: O. El-Sepelgy, J.
Mlynarski, Adv. Synth. Catal. 2013, 355, 281.
[
[
[
7] B. M. Trost, C. S. Brindle, Chem. Soc. Rev. 2010, 39,
[20] The stereochemistry of all compounds was established
1
1600.
by H NMR analysis of the cyclic products derived
8] W. Raimondi, D. Bonne, J. Rodriguez, Chem.
Commun. 2012, 48, 448, 6763.
9] a) K. Juhl, N. Gathergood, K. A. Jørgensen, Chem.
Commun. 2000, 2211; b) N. Gathergood, K. Juhl, T. B.
Poulsen, K. Thordrup, K. A. Jørgensen, Org. Biomol.
Chem. 2004, 2, 1077.
from all aldols after appropriate deprotection of hy-
droxy groups. For detailed information, see the Sup-
porting Information. This includes also information on
the anomeric equilibria of pyranose and furanose
forms.
[21] I. Hemeon, A. J. Benet, Synthesis 2007, 1899.
[22] a) A. Dondoni, A. Marra, P. Merino, J. Am. Chem. Soc.
1994, 116, 3324; b) A. Dondoni, P. Merino, J. Org.
Chem. 1991, 56, 5294; for reviews, see: c) A. Dondoni,
Org. Biomol. Chem. 2010, 8, 3366.
[
[
10] P. Dambruoso, A. Massi, A. Dondoni, Org. Lett. 2005,
, 4657.
7
11] For the organocatalytic asymmetric synthesis of isote-
tronic acid derivatives, see a) J.-M. Vincent, C. Margot-
tin, M. Berlande, D. Cavagnat, T. Buffeteau, Y. Land-
ais, Chem. Commun. 2007, 4782; b) B. Zhang, Z. Jiang,
X. Zhou, S. Lu, J. Li, Y. Liu, C. Li, Angew. Chem. 2012,
[23] D. Enders, H. Sun, F. R. Leusink, Tetrahedron 1999, 55,
6129.
[24] K.-G. Liu, S.-G. Hu, Y. Wu, Z.-J. Yao, Y.-L. Wu, J.
Chem. Soc. Perkin Trans. 1 2002, 1890.
1
24, 13336; Angew. Chem. Int. Ed. 2012, 51, 13159; for
2104
asc.wiley-vch.de
ꢀ 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2015, 357, 2098 – 2104