Cascade Reactions of Unprotected Ketoses with Ketones – A Stereoselective Access to C-Glycosides

Article abstract of DOI:10.1002/ejoc.201601058

A highly stereoselective de-Bruyn–Ekenstein rearrangement/aldol condensation/intramolecular oxa-Michael cascade reaction of unprotected ketoses with ketones was elaborated. By the utilization of this new and operationally simple methodology an access to β-C-glycosides is given. Extremely matched and mismatched cases were observed by using with natural or unnatural proline in these cascade reactions.

Full text of DOI:10.1002/ejoc.201601058

A Journal of
Accepted Article
Title: Cascade Reactions of Unprotected Ketoses with Ketones - a Stereoselective
Access to C-Glycosides
Authors: Rainer Mahrwald; Celin Richter; Michael Krumrey; Kristin Klaue
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To be cited as: Eur. J. Org. Chem. 10.1002/ejoc.201601058
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Cascade Reactions of Unprotected Ketoses with Ketones – a
Stereoselective Access to C-Glycosides
Celin Richter,[a] Michael Krumrey,[a] Kristin Klaue,[a] and Rainer Mahrwald*[a]
Abstract:
A
highly
stereoselective
de-Bruyn-Ekenstein
rearrangement / aldol condensation / intramolecular oxa-Michael
cascade reaction of unprotected ketoses with ketones was
elaborated. By the utilization of this new and operationally simple
methodology an access to β-C-glycosides is given. Extremely
matched and mismatched cases were observed by using with
natural or unnatural proline in these cascade reactions.
Introduction
Results and Discussion
Recently we described organocatalyzed reactions of hydroxy
ketones with 1,3-dicarbonyl compounds. During an amine-
In initial experiments we tested dihydroxyacetone and acetone
as substrates under reaction conditions described for the amine-
catalyzed Knoevenagel / ketalization / retro-aldol cascade
(catalytic amounts of DBU, water, r.t.).[1] No reactions were
observed under these conditions. After a careful optimization
equimolar amounts of proline were required to initiate the
reaction. The 1,4-diketone 3a was the only product we observed
under these conditions (35% yield). Further investigation
indicated an increase of yields by the application of 20 mol%
N,N,N’-trimethylethane-1,2-diamine (trimethylethylenediamine)
(45%, Scheme 2).
catalyzed Knoevenagel-addition
cascade high chemo- and stereoselectivities were detected. By
extending this transformation to reactions of ketohexoses with
/ ketalization / retro-aldol
acetylacetone,
the
corresponding
chain-elongated
3-
deoxyketoses were isolated as predominantly one stereoisomer.
Thus, this operationally simple cascade transformation gives an
access to optically pure branched ketoses.[1] Generated by the
retro-aldol reaction an acetyl fragment of the acetylacetone is
transferred to the primary hydroxyl group. To avoid the “loss” of
this acetyl fragment we explored the utility of unactivated methyl
ketones in this novel amine-mediated cascade reaction with
unprotected ketoses (Scheme 1).
Scheme 2. Amine-mediated cascade reaction of dihydroxyacetone with
acetone.[2]
The surprising and unexpected formation of the isolated
hydroxy-1,4-diketone 3 can be explained by a de-Bruyn-
[3]
Scheme 1. Proline-catalyzed reactions of L-sorbose (after acetylation of
reaction-products)
Ekenstein rearrangement
/ dehydration / aldol cascade. By
treatment of dihydroxyacetone with proline and DBU the
formation of glyceraldehyde 4 can be assumed via the enediol-
species A. Subsequent dehydration yields the enol B of 2-
oxopropanal 5 (pyruvic aldehyde, methylglyoxal).
[a]
Humboldt-University, Department of Chemistry, Brook-Taylor Str. 2,
12489 Berlin, Germany
E-Mail: rainer.mahrwald@rz.hu-berlin.de
https://www.chemie.hu-berlin.de/de/forschung/mahrwald
Supporting information for this article is given via a link at the end of
the document.
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European Journal of Organic Chemistry
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reaction however was observed, when used with proline. In
contrast to that the expected 1,4-diketone 3f was isolated with
36 % yields as a mixture of syn and anti diastereoisomers
(Scheme 5).
Scheme 3. Proposed reaction mechanism (enamine intermediates are not
indicated for the sake of simplicity)
Cross-aldol adducts 6 or 7 on the other hand were not detected.
To prove these considerations we reacted acetone with
methylglyoxal 5 under the same conditions. As expected
hydroxy-1,4-diketone 3a was isolated in identical yields under
the same conditions (Scheme 3).
Scheme 5. Amine-catalyzed cascade reaction of dihydroxyacetone with
cyclopentanone
Next, cyclohexanones 2g-k were tested as substrates in these
reactions. Higher yields were detected again, when used with
catalytic amounts of trimethylethylenediamine instead of proline
The enzymatic formation of methylglyoxal
5
from
[4]
dihydroxyacetone 1 is well-known
and is the subject of
intensive investigation as the “dark side of glycolysis”.[5]
Moreover, chemical transformations of dihydroxyacetone 1 to
methylglyoxal 5 were reported. However, the harsh conditions
reported for these chemical-induced tautomerizations are not
(Table 1). Interestingly,
a
reversal of the internal
diastereoselectivity is observed in BINAM-prolinamide-catalyzed
reactions of 4-methylcyclohexanone 2i (R1=H, R2=Me) with
methylglyoxal 5 (compare entry 6 with results reported in
reference 8a: main product by this cascade is 11b, whereas 11d
is described as the main product in reference 8a).
compatible with the physiological conditions of an
[6]
organocatalyzed transformation.
Indications for an amine- or
amino acid-catalyzed transformation of dihydroxyacetone to
pyruvic aldehyde were published.[7] Nonetheless, a preparative-
useful organocatalyzed protocol for this tautomerization have not
been reported so far.
Table 1. Amine-catalyzed cascade reaction of dihydroxyacetone with
cyclohexanones
To test the general applicability of these initial results, we
reacted
a
set of different methyl ketones 2a-2e with
dihydroxyacetone under the optimized reaction conditions. The
steric bulkiness of substituent R of methyl ketones dictates the
dimension of yields and the regioselectivity of the aldol step (e.g.
compare results of reaction with 2a and 2e, Scheme 4).
entry compound
yield[%]
syn-a
anti-b
syn-c
anti-d
1
2
3
4
5
6
7
8
9
10
9: R1=R2=H
33 66
54 46
30a
53b
10: R1=Me, R2=H
11: R1=H, R2=Me
12: R1=H, R2=Et
13: R1=H, R2=nPr
17
12
-
-
55 28 8a
22 66 27b
42 18 17a
14 27
12 70
10 19
17 56
12 20
10 51
14
46 25 20a
21
25b
2
34b
Scheme 4. Amine-mediated cascade reactions of dihydroxyacetone with
a
b
methyl ketones. Reaction conditions:
trimethylethylenediamine.
100% proline,
20 mol%
3
40 28 21a
34
6
38b
a
b
In further experiments we tested cyclic ketones as substrates in
these cascade reactions. Initially, we reacted cyclopentanone
with dihydroxyacetone under the optimized conditions. No
Reaction conditions:
equimolar amounts of proline;
20 mol%
trimethylethylenediamine. For the determination of configuration see reference
9.
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The yields of products could not be improved by longer reaction
times. It is assumed, that a competing Maillard-reaction and
Also, unprotected disaccharides containing the ketose-unit are
useful substrates in these cascade reactions, as this is shown by
the utilization of isomaltulose 25 (α-glucopyranosyl-D-fructose).
When used with isomaltulose 25 in reactions with acetone, the
expected gluco- and manno-configured C-glycosides 26 and 27
were isolated in a ratio of 1 /1 (Scheme 7).
consecutive
reactions
inactivate
proline
or
trimethylethylenediamine.
Since organocatalyzed, enantioselective direct aldol additions of
methylglyoxal 5 with cyclohexanones or acetone have been
reported,[8] we explored the deployment of substituted
hydroxyacetones - namely unprotected ketoses – as substrates
in these cascade reactions. We started these investigations with
amine-catalyzed reactions of acetone or cyclopentanone with L-
erythrulose 14. The expected 1,4-diketones 15 or 16 were
isolated under the same reaction conditions.
Scheme 6. Amine-catalyzed cascade reaction of L-erythrulose with acetone or
cyclopentanone. Reaction conditions: 40 mol% trimethylethylenediamine,
MeOH, rt, 48 h.
Based on the reaction mechanism this transformation is
associated with the loss of the optical activity of the starting
erythrulose 14. In order to get an access to chiral products by
this cascade transformation we reacted in a further series
several ketohexoses with acetone. The utilization of these
substrates required a further optimization of the reaction
conditions. No reactions were observed when used with proline
or trimetylethylenediamine as catalysts or in equimolar amounts.
Scheme 7. Amine-mediated cascade reaction of ketohexoses with acetone.
The acyclic structures of starting ketohexoses are depicted for reasons of
simplification. Reaction conditions: 100 mol% L-proline, 100 mol% DBU,
MeOH, 64oC, 24 h.
Instead, reactions were detected only when used by
a
combination of equimolar amounts of proline and DBU. The
reaction was carried out in MeOH at 64oC. The change of
reaction conditions resulted in a change of the cascade. Under
these conditions C-glycosides were detected as a result of a de-
In a further series we tested cyclopentanone as the enol-
component in these cascade reactions with several unprotected
ketohexoses. Once more high stereoselectivities were detected.
The ß-C-glycosides were the major products which were
obtained. Moreover, the additional stereogenic center at C2-
carbon atom of cyclopentanone was created with high degrees
of syn-stereoselectivity (Scheme 8). The purification and
analysis of the products of this series were carried out with their
acetylated derivatives.
Bruyn-Ekenstein rearrangement
/
aldol condensation
/
intramolecular oxa-Michael cascade (Scheme 7). These findings
are at variance with those obtained by the de-Bruyn-Ekenstein
rearrangement / dehydration / aldol cascade (compare Scheme
3 with Scheme 9). Support for these considerations is given by
NMR-experiments. By treatment of fructose with proline and
[9]
DBU, glucose and mannose can be detected.
High
stereoselectivities were observed in these experiments. The
formation of the corresponding β-configured C-glycosides was
observed only in this reaction. In reactions of fructose a 1:1 ratio
of gluco-C-glycoside 18 and manno-C-glycoside 19 was
observed as a result of an unselective de-Bruyn-Ekenstein
rearrangement. An increase of stereoselectivity is observed in
the tagatose-series. The galacto-23 and talo-C-glycoside 24
were isolated in a ratio of 2/1. When using L-sorbose a complete
stereoselectivity is observed. The gulo-C-glycoside 21 is the
only product which was observed in these reactions. The
corresponding ido-C-glycoside on the other hand was not
detected.
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European Journal of Organic Chemistry
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proline-catalyzed anomerization of protected C-glycosides was
published.[11] This process was carried out at 120oC and based
on the intramolecular retro-oxa-Michael addition. Thus, the high
stereoselectivity that was obtained by the formation of ß-C-
glycosides can be explained as a result of thermodynamically
controlled intramolecular oxa-Michael addition.
To verify the exceptionally high diastereoselectivity, the
corresponding unprotected aldohexoses, which deliver from the
de-Bruyn-Ekenstein rearrangement of D-fructose, glucose and
mannose were reacted with acetone under the same conditions
(proline, DBU, MeOH, 64oC). In these direct C-glycosylations the
corresponding manno-C-glycoside and gluco-C-glycoside were
detected with excellent diastereoselectivities (β/α: >95/5). These
results strongly contrast those which were obtained at room
temperature.[12] In these experiments unselective mixtures of
alternating configurations at the pseudo-anomeric carbon atom
were detected.[9]
Next, the configuration at the C2-carbon atom of the
carbohydrate does not influence the installation of configuration
of the pseudo-anomeric carbon atom. ß-C-glycosides were
detected as the only products in all reactions we carried out. In
cascade reactions of D-fructose the β-configured C-glycosides
18 of D-glucose (S-C2) and 19 of D-mannose (R-C2) were
obtained as the only products (Scheme 7).
And thirdly, notable and strong interactions between the
configuration of proline and the deployed ketohexoses were
detected. A matched case is noticed in reactions of D-fructose
with L-proline, whereas no reaction was observed with D-
fructose and D-proline. Moreover, a mismatched situation is
observed in reactions of D-proline and L-sorbose. On the other
hand the influence of configuration of proline is essentially
smaller in reactions with tagatose. Similar results were obtained
when used with D- or L-proline in reactions with tagatose
(Scheme 10).
Scheme 8. Amine-mediated cascade reaction of ketohexoses with
cyclopentanone. Reaction conditions: i = 100 mol% L-proline, 100 mol% DBU,
MeOH, 64oC, 24 h, ii = Ac2O, pyridine, rt.
A tentative working model for the mechanism of this cascade
reaction is depicted in Scheme 9. L-Gulose (C) is intermediately
formed by a de Bruyn-Ekenstein rearrangement of L-sorbose in
the presence of equimolar amounts of proline and DBU. A
further reaction with the enamine of acetone gives rise to the
iminium-species D. Finally, a subsequent intramolecular oxa-
Michael addition yields the gulo-C-glycoside 21.
Scheme 9. Proposed reaction mechanism
Several remarkable stereochemical observations have been
made in these investigations. The de-Bruyn
/ Ekenstein
rearrangement, the aldol condensation and the oxa-Michael
addition are equilibrium reactions. Secondary amine-catalyzed
retro-aldol-condensations were reported.[10] In addition, the
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European Journal of Organic Chemistry
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Scheme 11. Comparison of the reaction of L-sorbose and D-fructose with L-
proline
Conclusions
Scheme 10. Matched- and mismatched-cases in proline-mediated cascade
reaction of ketohexoses with acetone. D-talo-β-24 and D-talo-α-24 were
isolated and characterized with their corresponding tetraacetates.
These reported cascade reactions of unprotected ketoses with
proline are new, as they do not undergo the classical Amadori-
pathway.[13]
Amine-mediated
de-Bruyn-Ekenstein
rearrangements have not been reported so far, with the
exception of deployment of secondary or primary amines, to
obtain the corresponding α-amino ketones.[14] This combination
of the de-Bruyn-Ekenstein process with the C-C bond formation
of unprotected carbohydrates provides an elegant and highly
stereoselective access to β-C-glycosides. By the utilization of
these operationally simple cascade reactions an approach to C-
glycosides of rare carbohydrates is given, as was demonstrated
for the unnatural gulo-C-glycoside 21.
Based on these results and considerations the following model
for the stereochemical course of this cascade reaction was
developed (Scheme 11).
The configuration of the hydroxyl groups of the starting
ketohexoses dictates the installation of configuration at C2
carbon atom during the de-Bruyn-Ekenstein rearrangement. A
comparison of the configurative course of the subsequent
intramolecular oxa-Michael reaction is depicted in Scheme 10
for cascade reactions of sorbose and fructose with acetone.
The S-configured C5-hydroxyl group of L-sorbose dictates a
clear Re-side attack at the pseudoanomeric carbon atom (C1)
during the oxa-Michael process. This process proceeds with an
extremely high degree of stereoselectivity. As a consequence
the installation of the S-configured hydroxyl group at C2 is the
favoured one.
In contrast, a Si-side attack at C1 is observed during the oxa-
Michael process when used with D-fructose. To avoid steric
interactions with the C-glycosidic bond at C1 the hydroxyl group
at C2 is installed partially in the α- and β-configuration (18: R-
configuration at C2, 19: S-configuration at C2). This process is
guided by hydrogen bonds of the carboxylic group of proline with
the C2-hydroxyl group (see matched and mismatched case
when used with L- or D-proline, Scheme 10). For a complete
analysis of all conformations in the fructose-series see
Supporting Informations.
Experimental Section
General Information: 1H-NMR, 13C-NMR, DEPT and correlation
experiments H, H-COSY, HSQC, NOESY and JRES were
carried out at 600, 500 MHz and 125 MHz. The residual
1
protonated solvent was used as the internal standard: H-NMR:
7.26 ppm for CDCl3, 13C-NMR: 77.0 ppm for CDCl3, 1H-NMR:
3.31 ppm for MeOD, 13C-NMR: 49.0 ppm for MeOD and 1H-
NMR: 2.05 ppm for acetone-d6, 13C-NMR: 206.3 / 29.8 ppm for
acetone-d6, 1H-NMR: 4.79 ppm for D2O. Chemical shifts are
given in ppm, coupling constants in Hz. High resolution mass
spectroscopy was performed out on a LTQ-FT-ICR machine
(ESI-MS). Purification of products was accomplished by flash
chromatography (particle size 0.04 - 0.063 mm). Yields were
determined after column chromatography. The solvent mixtures
of CH2Cl2 (DCM) and methanol in ratio 80/20 → 95/5 and
hexane/acetone 8/2 → 1/1 were used as eluent. Development
was performed with cer(IV) sulfate / phosphormolybdic acid.
General Procedure for the Synthesis of 1,4-Diketones 3a-f,
8a-d and 9-13: Ketones 2a-2k (10.0 mmol), L-proline (230 mg,
2.0 mmol) were added to a suspension of dihydroxyacetone
(180 mg, 2.0 mmol) in isopropanol (9.0 mL). The resulting
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European Journal of Organic Chemistry
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+
mixture was stirred for 48 h at room temperature. Volatile
compounds were removed under reduced pressure and the
residue was directly purified by column chromatography. The
HRMS (ESI) calcd for C8H13O3 [M+H]+: 157.0859, found:
157.0856.
1
1,4-diketones 3a-f, 8a-d and 9-13 were isolated as colorless oils. 3-Hydroxy-4-ethylhexane-2,5-dione (8b): H NMR (500 MHz,
CDCl3) δ 4.37 (dd, J = 4.2, 3.4 Hz, 1H), 3.52 (d, J = 4.5 Hz, 1H),
3-Hydroxyhexane-2,5-dione (3a):[15] Yield: 91.0 mg; 35 %; 1H
NMR (500 MHz, CDCl3) δ 4.31 (ddd, J = 6.3, 5.0, 3.6 Hz, 1H),
2.87 – 2.84 (m, 1H), 2.27 (s, 6H), 1.83 (ddd, J = 14.2, 9.0, 7.4
Hz, 1H), 1.39 (ddd, J = 14.1, 7.5, 5.0 Hz, 1H), 0.92 (t, J = 7.5 Hz,
3.76 (d, J = 5.1 Hz, 1H), 2.94 (dd, J = 17.3, 3.8 Hz, 1H), 2.81 (dd, 3H).
J = 17.2, 6.5 Hz, 1H), 2.21 (s, 3H), 2.17 (s, 3H); 13C NMR (126
MHz, CDCl3) δ 209.4, 207.1, 73.7, 46.2, 30.8, 25.5; HRMS (ESI)
calcd for C6H11O3+ [M+H]+: 131.0703, found: 131.0703.
13C NMR (126 MHz, CDCl3) δ 210.5, 208.9, 77.3, 57.0, 29.8,
26.3, 19.4, 12.6. HRMS (ESI) calcd for C8H14O3Na+ [M+Na]+:
181.0835, found: 181.0839.
3-Hydroxyoctane-2,5-dione (3b):[16] Inseparable mixture 3b/8b:
93/7. Overall yield: 50.0 mg; 16 %.
Syn-3-hydroxy-4-phenylhexane-2,5-dione
(syn-8c):
Inseparable mixture syn/anti: 8/2. Overall Yield: 16.1 mg; 4 %.
1H NMR (500 MHz, CDCl3) δ 7.35 – 7.31 (m, 3H), 7.24 – 7.22 (m,
2H), 4.78 (dd, J = 4.3, 3.4 Hz, 1H), 4.11 (d, J = 4.2 Hz, 1H), 3.39
(d, J = 3.5 Hz, 1H), 2.13 (s, 3H), 2.01 (s, 3H). 13C NMR (126
MHz, CDCl3) δ 209.4, 208.2, 133.4, 129.9, 129.1, 128.4, 77.6,
61.1, 29.5, 26.9. HRMS (ESI) calcd for C12H14O3Na+ [M+Na]+:
229.0835, found: 229.0837.
1H NMR (500 MHz, CDCl3) δ 4.33 (td, J = 5.9, 3.9 Hz, 1H), 3.72
(d, J = 5.4 Hz, 1H), 2.94 (dd, J = 17.2, 3.8 Hz, 1H), 2.82 (dd, J =
17.1, 6.3 Hz, 1H), 2.45 (t, J = 7.3 Hz, 2H), 2.26 (s, 3H), 1.61
(sext, J = 7.4 Hz, 2H), 0.91 (t, J = 7.4 Hz, 3H). 13C NMR (126
MHz, CDCl3) δ 209.7, 209.5, 74.0, 45.7, 45.4, 25.5, 17.1, 13.7.
4-Hydroxy-1-phenylhexane-2,5-dione (3c):[17] Yield: 46.2 mg;
12 %. 1H NMR (500 MHz, CDCl3) δ 7.34 (t, J = 1.6 Hz, 1H), 7.32
(t, J = 1.8 Hz, 1H), 7.28 (dt, J = 4.7, 1.9 Hz, 1H), 7.20 – 7.18 (m,
1H), 7.18 – 7.17 (m, 1H), 4.32 (dt, J = 5.9, 4.2 Hz, 1H), 3.75 (s,
2H), 3.70 (d, J = 5.4 Hz, 1H), 2.98 (dd, J = 17.3, 3.9 Hz, 1H),
2.85 (dd, J = 17.3, 6.4 Hz, 1H), 2.20 (s, 3H). 13C NMR (126 MHz,
CDCl3) δ 209.2, 206.9, 133.3, 129.6, 129.0, 127.4, 73.8, 50.9,
44.7, 25.5. HRMS (ESI) calcd for C12H14O3Na+ [M+H]+: 229.0835,
found: 229.0837.
Anti-3-hydroxy-4-phenylhexane-2,5-dione (anti-8c): 1H NMR
(500 MHz, CDCl3) δ 7.34 – 7.29 (m, 3H), 7.28 – 7.24 (m, 1H),
7.18 – 7.15 (m, 1H), 4.28 (dd, J = 8.0, 5.2 Hz, 1H), 4.13 (d, J =
5.2 Hz, 1H), 3.82 (d, J = 8.2 Hz, 1H), 2.04 (s, 3H), 2.04 (s, 3H).
13C NMR (126 MHz, CDCl3) δ 210.26, 209.22, 134.89, 129.39,
129.26, 128.38, 79.52, 61.34, 30.01, 27.08.
3-Hydroxy-4-n-pentylhexane-2,5-dione (8d): 1H NMR (500
MHz, CDCl3) δ 4.35 (dd, J = 4.3, 3.3 Hz, 1H), 3.54 (d, J = 4.5 Hz,
1H), 2.92 – 2.88 (m, 1H), 2.26 (s, 6H), 1.82 – 1.73 (m, 1H), 1.59
3-Hydroxyundecane-2,5-dione
(3d):[18]
For
L-proline:
Inseparable mixture 3d/8d: 62/38. Overall yield: 81.3 mg; 21 %.
1H NMR (500 MHz, CDCl3) δ 4.33 (ddd, J = 6.2, 5.5, 4.0 Hz, 1H),
– 1.52 (m, 1H), 1.33 – 1.27 (m, 6H), 0.86 (t, J = 6.8 Hz, 3H). 13
C
NMR (126 MHz, CDCl3) δ 210.6, 208.9, 76.9, 55.5, 32.0, 29.7,
3.72 (d, J = 5.4 Hz, 1H), 2.94 (dd, J = 17.2, 3.8 Hz, 1H), 2.82 (dd, 27.7, 26.3, 26.9, 22.5, 14.1. HRMS (ESI) calcd for C11H20O3Na+
J = 17.2, 6.3 Hz, 1H), 2.45 (t, J = 7.5 Hz, 2H), 2.25 (s, 3H), 1.59
– 1.52 (m, 2H), 1.30 – 1.22 (m, 6H), 0.86 (t, J = 7.4 Hz, 3H). 13
[M+Na]+: 223.1305, found: 223.1305.
C
NMR (126 MHz, CDCl3) δ 209.8, 209.5, 74.0, 45.4, 43.9, 31.7,
Syn-2-(1-hydroxy-2-oxopropyl)cyclohexan-1-one
(syn-9a):
28.9, 25.5, 23.5, 22.6, 14.1.
Inseparable mixture syn/anti: 33/66. Overall yield: 100.0 mg;
30 %.
3-Hydroxy-7-methyloctane-2,5-dione (3e): Yield: 49.6 mg;
15 %. H NMR (500 MHz, CDCl3) δ 4.32 (dd, J = 6.3, 3.8 Hz,
1H NMR (500 MHz, CDCl3) δ 4.62 (dd, J = 4.2, 2.4 Hz, 1H), 3.33
(d, J = 4.7 Hz, 1H), 2.81 – 2.76 (m, 1H), 2.47 – 2.42 (m, 1H),
2.39 – 2.26 (m, 1H), 2.19 (s, 3H), 1.77 – 1.70 (m, 3H), 1.69 –
1.57 (m, 3H). 13C NMR (126 MHz, CDCl3) δ 211.2, 210.5, 75.5,
1
1H), 2.92 (dd, J = 17.3, 3.8 Hz, 1H), 2.81 (dd, J = 17.3, 6.3 Hz,
1H), 2.33 (m, 2H), 2.26 (s, 3H) 2.13 (h, J = 6.9 Hz, 1H), 0.91 (d,
J = 6.7 Hz, 6H). 13C NMR (126 MHz, CDCl3) δ 209.5, 209.4, 74.0, 53.1, 42.1, 26.8, 26.5, 26.5, 24.5. HRMS (ESI) calcd for
52.7, 45.8, 25.5, 24.6, 22.6. HRMS (ESI) calcd for C9H16O3Na+
[M+Na]+: 195.0992, found: 195.0991.
C9H14O3Na+ [M+Na]+: 193.0835, found: 193.0833.
Anti-2-(1-hydroxy-2-oxopropyl)cyclohexan-1-one (anti-9a):[8a]
1H NMR (500 MHz, CDCl3) δ 3.81 (dd, J = 7.5, 2.9 Hz, 1H), 3.57
(d, J = 7.7 Hz, 1H), 3.02 (dddd, J = 12.8, 5.9, 3.0, 1.1 Hz, 1H),
2.39 – 2.26 (m, 2H), 2.24 (s, 3H), 2.12 – 2.00 (m, 3H), 1.96 –
1.80 (m, 3H). 13C NMR (126 MHz, CDCl3) δ 212.2, 210.1, 77.9,
53.8, 42.0, 30.3, 26.9, 25.8, 24.8.
Syn-2-(1-hydroxy-2-oxopropyl)cyclopentan-1-one (syn-3f):[8a]
Inseparable mixture syn/anti: 65/35. Overall yield: 112.4 mg;
36 %.
1H NMR (500 MHz, CDCl3) δ 4.72 (dd, J = 4.7, 2.3 Hz, 1H), 3.49
(d, J = 4.7 Hz, 1H), 2.55 – 2.49 (m, 1H), 2.22 (s, 3H), 2.20 – 2.05
(m, 4H), 1.85 – 1.77 (m, 2H). 13C NMR (126 MHz, CDCl3) δ
217.8, 208.7, 75.7, 50.7, 38.4, 25.2, 21.8, 20.8.
Syn-2-(1-hydroxy-2-oxopropyl)-5-methylcyclohexan-1-one
(syn-10a): Inseparable mixture: syn-a/syn-c/anti-d: 12/22/66.
Overall yield: 99.1 mg ; 27 %. 1H NMR (500 MHz, CDCl3) δ 4.61
(br. s, 1H), 3.33 (br. s, 1H), 2.80 – 2.76 (m, 1H), 2.35 (dd, J =
14.1, 5.4 Hz, 1H), 2.35 – 2.31 (m, 1H), 2.26 – 2.22 (m, 1H), 2.22
(s, 3H), 1.99 – 1.91 (m, 2H), 1.68 – 1.58 (m, 2H), 0.95 (d, J = 7.1
Hz, 3H).
Anti-2-(1-hydroxy-2-oxopropyl)cyclopentan-1-one (anti-3f):
1H NMR (500 MHz, CDCl3) δ 4.12 (t, J = 3.4 Hz, 1H), 3.85 (d, J =
3.5 Hz, 1H), 2.79 – 2.73 (m, 1H), 2.37 – 2.30 (m, 4H), 2.27 (s,
3H), 1.85 – 1.77 (m, 2H). 13C NMR (126 MHz, CDCl3) δ 218.6,
208.0, 76.4, 51.5, 38.8, 26.4, 25.4, 21.2.
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European Journal of Organic Chemistry
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FULL PAPER
13C NMR (126 MHz, CDCl3) δ 212.1, 210.4, 76.2, 52.4, 48.7,
NMR (126 MHz, CDCl3) δ 212.2, 210.0, 76.6, 48.8, 38.5, 33.9,
31.5, 30.2, 26.6, 21.9, 19.3.
29.8, 29.8, 26.3, 25.6, 12.2.
Syn-2-(1-hydroxy-2-oxopropyl)-5-methylcyclohexan-1-one
Anti-2-(1-hydroxy-2-oxopropyl)-4-ethylcyclohexan-1-one
(syn-10c): 1H NMR (500 MHz, CDCl3) δ 4.65 (br. s, 1H), 3.24 (br. (anti-12b): 1H NMR (500 MHz, CDCl3) δ 3.84 (dd, J = 7.7, 2.9 Hz,
s, 1H), 2.77 – 2.72 (m, 1H), 2.45 (ddd, J = 13.8, 3.8, 2.4 Hz, 1H),
2.22 (s, 3H), 2.06 (dd, J = 5.7, 3.1 Hz, 2H), 1.95 – 1.79 (m, 2H),
1.80 – 1.70 (m, 1H), 1.47 – 1.34 (m, 1H), 1.01 (d, J = 6.3 Hz,
3H).
1H), 3.55 (d, J = 7.8 Hz, 1H), 3.09 (dddd, J = 13.3, 5.7, 2.9, 1.0
Hz, 1H), 2.40 – 2.34 (m, 1H), 2.27 (s, 3H), 2.15 – 2.04 (m, 2H),
1.80 – 1.69 (m, 2H), 1.59 (m, 2H), 1.36 (q, J = 7.5 Hz, 2H), 0.95
(t, J = 7.5 Hz, 3H). 13C NMR (126 MHz, CDCl3) δ 212.7, 210.0,
78.0, 53.0, 41.3, 38.3, 36.0, 32.6, 28.8, 25.9, 11.9. HRMS (ESI)
calcd for C11H18O3Na+ [M+Na]+: 221.1148, found: 221.1146
13C NMR (126 MHz, CDCl3) δ 211.0, 210.7, 75.5, 52.4, 50.4,
34.8, 33.4, 26.7, 25.5, 22.5.
Anti-2-(1-hydroxy-2-oxopropyl)-5-methylcyclohexan-1-one
Syn-2-(1-hydroxy-2-oxopropyl)-4-ethylcyclohexan-1-one
(anti-10d): 1H NMR (500 MHz, CDCl3) δ 3.85 (br. s, 1H), 3.54 (br. (syn-12c): 1H NMR (500 MHz, CDCl3) δ 4.67 (dd, J = 4.8, 2.3 Hz,
s, 1H), 2.99 (dddd, J = 13.1, 5.9, 3.0, 1.2 Hz, 1H), 2.36 (ddd, J =
13.8, 3.9, 2.2 Hz, 1H), 2.26 (s, 3H), 2.03 – 1.97 (m, 1H), 1.95 –
1.79 (m, 4H), 1.47 – 1.34 (m, 1H), 1.02 (d, J = 6.5 Hz, 3H). 13C
NMR (126 MHz, CDCl3) δ 212.1, 210.4, 77.9, 53.1, 50.3, 34.9,
33.7, 29.3, 26.0, 22.5. HRMS (ESI) calcd for C10H17O3+ [M+H]+:
185.1172, found: 185.1173.
1H), 3.24 (d, J = 4.8 Hz, 1H), 2.86 – 2.82 (m, 1H), 2.51 – 2.42
(m, 1H), 2.23 (s, 3H), 2.14 – 2.04 (m, 2H), 1.95 – 1.87 (m, 2H),
1.80 – 1.69 (m, 2H), 1.47 (q, J = 7.4 Hz, 2H), 0.94 (t, J = 7.4 Hz,
3H).
13C NMR (126 MHz, CDCl3) δ 211.6, 210.6, 75.6, 52.3, 41.3,
37.9, 32.4, 32.2, 28.9, 26.6, 11.8.
Syn-2-(1-hydroxy-2-oxopropyl)-4-methylcyclohexan-1-one
Anti-2-(1-hydroxy-2-oxopropyl)-4-ethylcyclohexan-1-one
(anti-12d): H NMR (300 MHz, CDCl3) δ 3.89 – 3.84 (m, 1H),
1
(syn-11a):
Inseparable
mixture
syn-a/anti-b/syn-c/anti-d:
1
12/70/14/2. Overall yield: 122.7 mg; 34 %. H NMR (500 MHz,
CDCl3) δ 4.62 (br. s, 1H), 3.39 (br. s, 1H), 2.92 – 2.85 (m, 1H),
2.53 – 2.43 (m, 1H), 2.21 (s, 3H), 2.06 – 1.88 (m, 3H), 1.72 –
1.33 (m, 3H), 1.09 (d, J = 7.0 Hz, 3H). 13C NMR (126 MHz,
CDCl3) δ 212.1, 210.0, 76.7, 48.9, 41.4, 38.5, 32.4, 32.3, 26.3,
19.1.
3.15 – 3.07 (m, 1H), 2.53 – 2.35 (m, 2H), 2.28 (s, 3H), 2.15 –
2.02 (m, 2H), 1.97 – 1.82 (m, 2H), 1.74 – 1.65 (m, 2H), 1.58 –
1.46 (m, 2H), 0.98 (t, J = 5.9 Hz, 3H). 13C NMR (75 MHz, CDCl3)
δ 212.9, 209.8, 78.6, 49.4, 38.2, 33.8, 33.8, 29.8, 28.8, 25.2,
12.3.
Syn-2-(1-hydroxy-2-oxopropyl)-4-propylcyclohexan-1-one
Anti-2-(1-hydroxy-2-oxopropyl)-4-methylcyclohexan-1-one
(anti-11b): [8a] 1H NMR (500 MHz, CDCl3) δ 3.82 (br. s, 1H), 3.55
(br. s, 1H), 3.10 (ddd, J = 13.6, 5.4, 3.0 Hz, 1H), 2.35 (dd, J =
8.4, 3.6 Hz, 1H), 2.25 (s, 3H), 1.99 (m, 3H), 1.64 (m, 1H), 1.36 –
1.33 (m, 2H), 1.02 (d, J = 6.2 Hz, 3H). 13C NMR (126 MHz,
CDCl3) δ 212.5, 210.1, 77.9, 53.1, 41.4, 38.4, 35.0, 31.8, 25.9,
21.5. HRMS (ESI) calcd for C10H17O3+ [M+H]+: 185.1172, found:
185.1175.
(syn-13a):
Inseparable
mixture
syn-a/anti-b/syn-c/anti-d:
1
10/51/34/6. Overall yield: 157.5 mg; 38 %. H NMR (500 MHz,
CDCl3) δ 4.64 (dd, J = 4.7, 2.6 Hz, 1H), 3.35 (d, J = 4.8 Hz, 1H),
2.89 – 2.85 (m, 1H), 2.45 – 2.44 (m, 1H), 2.41 – 2.38 (m, 1H),
2.21 (s, 3H), 1.94 – 1.86 (m, 1H), 1.87 – 1.73 (m, 2H), 1.74 –
1.68 (m, 2H), 1.55 – 1.45 (m, 2H), 1.40 – 1.34 (m, 2H), 0.96 –
0.92 (m, 3H). 13C NMR (126 MHz, CDCl3) δ 212.1, 210.0, 76.5,
48.9, 38.5, 35.0, 31.7, 30.2, 30.1, 26.3, 20.8, 14.3.
Syn-2-(1-hydroxy-2-oxopropyl)-4-methylcyclohexan-1-one
Anti-2-(1-hydroxy-2-oxopropyl)-4-propylcyclohexan-1-one
(syn-11c): 1H NMR (500 MHz, CDCl3) δ 4.65 (br. s, 1H), 3.27 (br. (anti-13b): 1H NMR (500 MHz, CDCl3) δ 3.84 (dd, J = 7.7, 2.9 Hz,
s, 1H), 2.85 (dddd, J = 13.0, 5.8, 2.3, 1.0 Hz, 1H), 2.53 – 2.43 (m, 1H), 3.55 (d, J = 7.8 Hz, 1H), 3.09 (ddd, J = 13.3, 5.7, 2.9 Hz,
1H), 2.21 (s, 3H), 2.06 – 1.88 (m, 3H), 1.72 – 1.33 (m, 3H), 0.98
(d, J = 6.4 Hz, 3H). 13C NMR (126 MHz, CDCl3) δ 211.4, 210.7,
75.6, 52.3, 34.9, 34.5, 31.5, 27.0, 26.7, 21.6.
1H), 2.38 – 2.35 (m, 1H), 2.26 (s, 3H), 2.12 – 2.02 (m, 2H), 1.87
– 1.73 (m, 2H), 1.63 – 1.54 (m, 2H), 1.40 – 1.23 (m, 4H), 0.91 (t,
J = 7.1 Hz, 3H). 13C NMR (126 MHz, CDCl3) δ 212.6, 210.1, 77.9,
53.1, 41.3, 38.2, 36.3, 36.3, 33.0, 25.9, 20.4, 14.3. HRMS (ESI)
calcd for C12H20O3Na+ [M+Na]+: 235.1305, found: 235.1305.
Anti-2-(1-hydroxy-2-oxopropyl)-4-methylcyclohexan-1-one
(anti-11d): 1H NMR (300 MHz, CDCl3) δ 3.86 (d, J = 3.0 Hz, 1H),
3.22 - 3.12 (m, 1H), 2.51 – 2.35 (m, 1H), 2.28 (s, 3H), 2.04 –
1.91 (m, 2H), 1.72 – 1.60 (m, 3H), 1.47 – 1.36 (m, 2H), 1.17 (d, J
= 7.0 Hz, 3H). 13C NMR (126 MHz, CDCl3) δ 212.7, 209.8, 78.6,
49.3, 36.2, 32.3, 29.8, 29.4, 24.0, 18.6.
Syn-2-(1-hydroxy-2-oxopropyl)-4-propylcyclohexan-1-one
(syn-13c): 1H NMR (500 MHz, CDCl3) δ 4.66 (dd, J = 4.8, 2.3 Hz,
1H), 3.24 (d, J = 4.8 Hz, 1H), 2.84 (dddd, J = 13.1, 5.7, 2.3, 0.9
Hz, 1H), 2.45 (dd, J = 4.5, 2.6 Hz, 1H), 2.40 (dd, J = 5.5, 2.8 Hz,
1H), 2.23 (s, 3H), 1.94 – 1.87 (m, 1H), 1.87 – 1.73 (m, 2H), 1.73
– 1.66 (m, 2H), 1.54 – 1.45 (m, 2H), 1.40 – 1.27 (m, 2H), 0.89 (t,
J = 7.1 Hz, 3H). 13C NMR (126 MHz, CDCl3) δ 211.55, 210.57,
75.55, 52.29, 41.33, 38.34, 35.96, 32.77, 32.56, 26.59, 20.36,
14.34.
Syn-2-(1-hydroxy-2-oxopropyl)-4-ethylcyclohexan-1-one
(syn-12a):
Inseparable
mixture
syn-a/anti-b/syn-c/anti-d:
1
17/56/21/3. Overall yield: 97.5 mg; 25 %. H NMR (500 MHz,
CDCl3) δ 4.64 (dd, J = 4.7, 2.6 Hz, 1H), 3.35 (d, J = 4.8 Hz, 1H),
2.89 – 2.85 (m, 1H), 2.51 – 2.42 (m, 1H), 2.21 (s, 3H), 2.14 –
2.04 (m, 2H), 1.95 – 1.87 (m, 1H), 1.86 – 1.79 (m, 1H), 1.80 –
1.69 (m, 2H), 1.56 – 1.47 (m, 2H), 0.91 (t, J = 7.5 Hz, 3H). 13C
Anti-2-(1-hydroxy-2-oxopropyl)-4-propylcyclohexan-1-one
(anti-13d): 1H NMR (300 MHz, CDCl3) δ 3.86 (d, J = 2.8 Hz, 1H),
3.18 – 3.09 (m, 1H), 2.47 – 2.35 (m, 2H), 2.28 (s, 3H), 2.13 –
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European Journal of Organic Chemistry
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FULL PAPER
2.00 (m, 2H), 1.93 – 1.76 (m, 2H), 1.57 – 1.45 (m, 2H), 1.42 –
1.22 (m, 4H), 0.95 (t, J = 7.1 Hz, 3H). 13C NMR (75 MHz, CDCl3)
δ 213.0, 209.9, 78.5, 49.5, 38.4, 34.6, 34.1, 31.9, 30.2, 26.6,
20.9, 14.3.
3.99 (t, J = 3.5 Hz, 1H), 3.87 (ddd, J = 6.8, 5.6, 1.2 Hz, 1H), 3.84
(dd, J = 3.8, 1.0 Hz, 1H), 3.66 (d, J = 2.4 Hz, 1H), 3.65 (d, J =
1.0 Hz, 1H), 3.63 (dd, J = 10.1, 3.3 Hz, 1H), 2.98 (dd, J = 16.6,
3.2 Hz, 1H), 2.69 (dd, J = 16.5, 9.4 Hz, 1H), 2.27 (s, 3H). 13C
NMR (126 MHz, D2O) δ 213.7, 75.0, 71.7, 70.0, 69.6, 67.7, 61.1,
25
General Procedure for the Reactions of Ketoses with
Acetone or Cyclopentanone: Ketones (10.0 mmol), L-proline
(230 mg, 2.0 mmol) and DBU (304 mg, 2.0 mmol) were added to
a suspension of ketoses (2.0 mmol) in methanol (20.0 mL). The
46.0, 29.8. [α]D = +12 (c = 1, methanol). HRMS (ESI) calcd for
C9H16O6Na+ [M+Na]+: 243.0839, found: 243.0839
1-C-(β-D-Galactopyranosyl)-propan-2-one (23):[21] Yield: 74.0
mg; 17 %. 1H NMR (500 MHz, D2O): δ 3.93 (dd, J = 3.5, 0.5 Hz,
1H), 3.73 (td, J = 9.4, 3.1 Hz, 1H), 3.69 - 3.61 (m, 3H), 3.62 (dd,
J = 9.6, 3.4 Hz, 1H), 3.44 (dd, J = 9.6, 9.6 Hz, 1H) 3.00 (dd, J =
16.7, 3.0 Hz, 1H), 2.74 (dd, J = 16.6, 9.2 Hz, 1H), 2.25 (s, 3H).
13C NMR (126 MHz, D2O) δ 213.7, 78.9, 76.0, 74.1, 70.8, 69.4,
61.5, 46.1, 30.1. [α]D25 = +2 (c = 1, methanol). HRMS (ESI) calcd
resulting mixture was stirred for 24
h at 64°C. Volatile
compounds were removed under reduced pressure and the
residue was directly purified by column chromatography. The
compounds were isolated as colorless oils.
4,7-Dihydroxyheptane-2,5-dione (15): Yield: 45.8 mg; 15%. 1H
NMR (500 MHz, CDCl3) δ 4.34 (dd, J = 5.6, 4.0 Hz, 1H), 3.92 (td, for C9H16O6Na+ [M+Na]+: 243.0839, found: 243.0835.
J = 5.6, 3.5 Hz, 2H), 3.78 (s, 1H), 3.03 (dd, J = 17.6, 3.8 Hz, 1H),
2.91 (dd, J = 17.6, 6.1 Hz, 1H), 2.84 (t, J = 5.5 Hz, 2H), 2.47 (s,
1H), 2.21 (s, 3H). 13C NMR (126 MHz, CDCl3) δ 212.1, 207.8,
73.9, 57.9, 46.2, 40.4, 30.9. HRMS (ESI) calcd for C7H12O4Na+
[M+H]+: 183.0628, found: 183.0634.
1-C-(2,3,4,6-Tetra-O-acetyl-β-D-talopyranosyl)-propan-2-one
(β-24): Yield: 55.1 mg; 8 %. 1H NMR (500 MHz, acetone) δ 5.28
(dt, J = 3.8, 1.0 Hz, 1H), 5.23 (t, J = 3.8 Hz, 1H), 5.21 – 5.19 (dt,
J = 3.8, 1.0 Hz, 1H), 4.29 (ddd, J = 7.8, 5.1, 1.4 Hz, 1H), 4.13 –
4.05 (m, 3H), 2.78 (dd, J = 17.0, 7.8 Hz, 1H), 2.57 (dd, J = 17.0,
5.1 Hz, 1H), 2.12 (s, 3H), 2.12 (s, 3H), 2.09 (s, 3H), 1.97 (s, 3H),
Syn-2-(1,4-dihydroxy-2-oxobutyl)cyclopentan-1-one (syn-16):
Inseparable mixture of syn/anti: 6/4. Overall yield: 36.5 mg; 10 %. 1.89 (s, 3H). 13C NMR (126 MHz, acetone) δ 205.1, 170.9, 170.8,
1H NMR (500 MHz, CDCl3) δ 4.72 (d, J = 2.4 Hz, 1H), 3.99 –
3.93 (m, 2H), 2.74 (ddd, J = 13.4, 6.7, 4.2 Hz, 2H), 2.59 – 2.53
(m, 1H), 2.42 – 2.22 (m, 2H), 2.20 – 2.03 (m, 2H), 1.89 – 1.72
(m, 2H).
170.6, 169.7, 75.5, 74.1, 69.4, 68.6, 66.5, 62.8, 44.9, 30.2, 20.7,
25
20.7, 20.6, 20.5. [α]D = -8 (c = 1, acetone). HRMS (ESI) calcd
for C17H24O10Na+ [M+Na]+: 411.1262, found: 411.1263.
13C NMR (126 MHz, CDCl3) δ 218.3, 211.6, 75.6, 57.7, 51.0,
40.4, 38.4, 22.1, 20.7. HRMS (ESI) calcd for C9H14O4Na+
[M+Na]+: 209.0784, found: 209.0790.
1-C-(2,3,4,6-Tetra-O-acetyl-α-D-talopyranosyl)-propan-2-one
(α-24): Yield: 14.8 mg; 2 %. 1H NMR (500 MHz, acetone) δ 5.34
(ddd, J = 7.3, 5.2, 4.0 Hz, 1H), 5.22 (dd, J = 3.8, 1.1 Hz, 1H),
5.04 (dd, J = 3.6, 1.1 Hz, 1H), 4.45 (ddd, J = 6.8, 6.4, 3.8 Hz,
1H), 4.31 (dd, J = 11.9, 4.0 Hz, 1H), 4.13 (dd, J = 11.9, 7.3 Hz,
1H), 3.98 (dd, J = 5.2, 3.6 Hz, 1H), 2.87 (dd, J = 17.3, 6.7 Hz,
1H), 2.75 (dd, J = 17.3, 6.2 Hz, 1H), 2.13 (s, 3H), 2.09 (s, 3H),
2.08 (s, 3H), 2.05 (s, 3H), 1.98 (s, 3H). 13C NMR (126 MHz,
acetone) δ 205.4, 170.8, 170.5, 170.2, 170.1, 82.5, 79.0, 77.9,
Anti-2-(1,4-dihydroxy-2-oxobutyl)cyclopentan-1-one
(anti-
1
16): H NMR (500 MHz, CDCl3) δ 4.16 (d, J = 3.4 Hz, 1H), 3.94
– 3.86 (m, 2H), 2.89 (ddd, J = 17.1, 6.7, 4.1 Hz, 1H), 2.84 – 2.78
(m, 1H), 2.70 (ddd, J = 17.1, 6.8, 4.1 Hz, 1H), 2.42 – 2.22 (m,
2H), 2.20 – 2.03 (m, 2H), 1.89 – 1.72 (m, 2H). 13C NMR (126
MHz, CDCl3) δ 219.6, 210.8, 76.6, 58.0, 51.6, 40.5, 38.8, 26.3,
21.2.
25
77.1, 70.8, 63.4, 42.7, 20.9, 20.7, 20.7, 20.6. [α]D = +7 (c = 0.7,
acetone). HRMS (ESI) calcd for C17H24O10Na+ [M+Na]+:
411.1262, found: 411.1261.
1-C-(β-D-Glucopyranosyl)-propan-2-one (18):[19] Inseparable
1
mixture of 18/19: 40/60. Overall yield: 116.7 mg; 27 %. H NMR
1-C-(β-D-Isomaltosyl)-propan-2-one (26): Inseparable mixture
of 26/27: 1/1. Overall Yield: 146.8 mg; 20 %. 1H NMR (500 MHz,
D2O) δ 4.90 (d, J = 3.6 Hz, 1H), 3.89 (dd, J = 11.2, 4.8 Hz, 1H),
3.86 – 3.78 (m, 3H), 3.76 – 3.57 (m, 9H), 3.55 – 3.49 (m, 2H),
3.49 – 3.44 (m, 2H), 3.44 – 3.36 (m, 2H), 3.25 – 3.18 (m, 1H),
(500 MHz, D2O): δ 3.85 (dd, J = 12.3, 2.0 Hz, 1H), 3.80 (ddd, J =
9.5, 9.2, 3.1 Hz, 1H), 3.68 (dd, J = 12.3, 5.0 Hz, 1H), 3.49 (dd, J
= 9.3, 8.9 Hz 1H), 3.45-3.34 (m, 2H), 3.23 (dd, J = 9.5, 9.3 Hz,
1H), 3.04 (dd, J = 16.7, 3.1, 1H), 2.73 (dd, J = 16.7, 9.2 Hz, 1H),
2.27 (s, 3H). 13C NMR (126 MHz, D2O): δ 215.7, 82.1, 79.7, 77.8, 3.03 (dd, J = 16.9, 2.9 Hz, 1H), 2.69 (dd, J = 16.9, 9.6 Hz, 1H),
75.6, 72.3, 63.2, 48.2, 32.4. HRMS (ESI) calcd for C9H16O6Na+
[M+Na]+: 243.0839, found: 243.0840.
2.26 (s, 3H). 13C NMR (126 MHz, D2O) δ 212.8, 97.8, 78.1, 77.4,
75.5, 73.2, 73.0, 71.7, 71.4, 69.5, 69.4, 65.7, 60.4, 45.5, 29.8.
HRMS (ESI) calcd for C15H26O11Na+ [M+Na]+: 405.1367, found:
405.1366.
1-C-(β-D-Mannopyranosyl)-propan-2-one (19):[20] 1H NMR
(500 MHz, D2O): δ 4.03 (ddd, J = 8.4, 4.5, 0.6 Hz, 1H), 3.86 (dd,
J = 12.2, 2.3 Hz, 1H), 3.86-3.84 (m, 1H), 3.68 (dd, J = 12.2, 6.1
Hz, 1H), 3.67 (dd, J = 9.7, 3.8 Hz, 1H), 3.56 (dd, J = 9.7, 9.6 Hz,
1H), 3.36 (ddd, J = 9.6, 6.1, 2.3 Hz, 1H), 2.94 (dd, J = 17.2, 8.4
Hz, 1H), 2,80 (dd, J = 17.2, 4.5 Hz, 1H), 2.27 (s, 3H). 13C NMR
1-C-(β-D-Epiisomaltosyl)-propan-2-one (27): 1H NMR (500
MHz, D2O) δ 4.90 (d, J = 3.6 Hz, 1H), 4.06 (ddd, J = 8.9, 4.0, 0.9
Hz, 1H), 3.93 (dd, J = 11.1, 4.6 Hz, 1H), 3.83 – 3.78 (m, 2H),
3.72 – 3.53 (m, 9H), 3.55 – 3.49 (m, 2H), 3.47 – 3.42 (m, 2H),
(126 MHz, D2O): δ 213.3, 80.5, 74.6, 74.4, 71.3, 67.6, 61.7, 45.1, 3.41 – 3.38 (m, 2H), 3.25 – 3.18 (m, 1H), 2.93 (dd, J = 17.4, 8.8
30.4.
Hz, 1H), 2.78 (dd, J = 17.5, 4.1 Hz, 1H), 2.24 (s, 3H). 13C NMR
(126 MHz, D2O) δ 212.5, 97.8, 78.2, 74.3, 74.1, 73.1, 71.7, 71.4,
70.7, 69.5, 66.6, 65.8, 60.5, 44.4, 29.7.
1-C-(β-L-Gulopyranosyl)-propan-2-one (21): Yield: 92.9 mg;
22 %. H NMR (500 MHz, D2O) δ 4.07 (td, J = 9.7, 3.1 Hz, 1H),
1
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European Journal of Organic Chemistry
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Syn-1-C-(2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyl)-
CDCl3) δ 217.7, 170.7, 170.0, 169.9, 169.4, 78.0, 77.2, 76.3,
76.3, 72.6, 62.3, 49.1, 38.3, 25.6, 21.1, 21.0, 21.0, 20.9, 20.8.
HRMS (ESI) calcd for C19H26O10Na+ [M+Na]+: 437.1418, found:
437.1419.
1
cyclopentan-2-one (syn-β-28): Yield: 94.5 mg; 12 %. H NMR
(500 MHz, CDCl3) δ 5.16 (t, J = 9.4 Hz, 1H), 5.01 – 4.96 (t, J =
9.8 Hz, 1H), 4.95 (dd, J = 10.2, 9.4 Hz, 1H), 4.18 (dd, J = 12.3,
5.0 Hz, 1H), 3.97 (dd, J = 12.3, 2.3 Hz, 1H), 3.92 (dd, J = 10.2,
1.6 Hz, 1H), 3.61 (ddd, J = 10.1, 5.0, 2.3 Hz, 1H), 2.34 – 2.25 (m, Anti-1-C-(2,3,4,6-tetra-O-acetyl-β-L-gulopyranosyl)-
1H), 2.16 – 2.08 (m, 2H), 2.08 – 2.02 (m, 2H), 2.01 (s, 3H), 2.00
(s, 3H), 1.99 (s, 3H), 1.97 (s, 3H), 1.99 – 1.94 (m, 1H), 1.75 –
1.64 (m, 1H). 13C NMR (126 MHz, CDCl3) δ 218.4, 170.7, 170.3,
169.8, 169.7, 75.7, 75.6, 74.4, 69.9, 68.6, 62.0, 48.9, 39.0, 22.5,
cyclopentan-2-one (anti-β-31): 1H NMR (500 MHz, CDCl3) δ
5.31 (dd, J = 9.0, 3.4 Hz, 1H), 5.10 (dt, J = 7.2, 4.5 Hz, 1H), 4.88
(dd, J = 3.7, 1.4 Hz, 1H), 4.31 – 4.27 (m, 1H), 4.20 (dd, J = 11.8,
4.2 Hz, 1H), 4.03 (dd, J = 10.0, 2.1 Hz, 1H), 3.95 (dd, J = 11.8,
7.2 Hz, 1H), 2.34 (t, J = 10.1 Hz, 1H), 2.12 – 2.07 (m, 2H), 2.07
(s, 3H), 2.05 (s, 3H), 2.05 – 2.02 (m, 2H), 2.02 (s, 3H), 2.01 –
1.98 (m, 1H), 1.87 (s, 3H), 1.77 – 1.66 (m, 1H). 13C NMR (126
MHz, CDCl3) δ 216.9, 170.7, 169.8, 169.6, 169.3, 73.7, 69.7,
68.5, 66.7, 66.5, 62.8, 48.8, 39.4, 25.7, 21.3, 21.0, 20.9, 20.9,
20.8.
25
20.8, 20.8, 20.7, 20.7, 20.7. [α]D = -42 (c = 1.0, acetone).
HRMS (ESI) calcd for C19H26O10Na+ [M+Na]+: 437.1418, found:
437.1424.
Anti-1-C-(2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyl)-
cyclopentan-2-one (anti-β-28): Inseparable mixture of anti-β-
28/syn-β-29: 2/8. Overall yield: 57.2 mg; 7 %. 1H NMR (500 MHz,
CDCl3) δ 5.39 (dd, J = 9.9, 9.3 Hz, 1H), 5.12 (t, J = 9.4 Hz, 1H),
5.02 (t, J = 9.7 Hz, 1H), 4.14 (dd, J = 12.3, 2.5 Hz, 1H), 4.08 (dd,
J = 12.3, 4.9 Hz, 1H), 3.81 (dd, J = 10.0, 2.3 Hz, 1H), 3.64 –
3.62 (m, 1H), 2.42 – 2.32 (m, 1H), 2.23 – 2.17 (m, 1H), 2.09 –
2.04 (m, 2H), 2.04 (s, 3H), 2.00 (s, 3H), 2.01 – 1.96 (m, 2H),
1.97 (s, 3H), 1.94 (s, 3H), 1.92 – 1.85 (m, 1H). 13C NMR (126
MHz, CDCl3) δ 216.1, 170.7, 170.5, 169.5, 169.5, 76.9, 76.0,
74.8, 69.3, 68.5, 62.2, 49.0, 39.2, 25.7, 23.9, 21.0, 20.7, 20.7,
20.6.
Syn-1-C-(2,3,4,6-tetra-O-acetyl-α-L-gulopyranosyl)-
cyclopentan-2-one (syn-α-31): Yield: 5.0 mg; 1 %. 1H NMR
(500 MHz, CDCl3) δ 5.02 (t, J = 2.7 Hz, 1H), 4.96 (ddd, J = 2.7,
1.6, 1.1 Hz, 1H), 4.81 – 4.79 (m, 3H), 4.19 – 4.13 (m, 1H), 4.09
– 4.04 (m, 1H), 2.36 – 2.24 (m, 1H), 2.15 (s, 3H), 2.17 – 2.12 (m,
2H), 2.11 (s, 3H), 2.10 (s, 3H), 2.12 – 2.07 (m, 2H), 2.07 – 2.01
(m, 1H), 2.03 (s, 3H), 1.79 – 1.69 (m, 1H). 13C NMR (126 MHz,
CDCl3) δ 218.3, 170.7, 169.7, 169.7, 168.4, 73.6, 73.0, 68.0,
66.4, 65.4, 62.3, 50.3, 38.4, 25.2, 21.1, 21.1, 21.0, 20.9, 20.9.
25
[α]D
= +11 (c = 0.5, acetone). HRMS (ESI) calcd for
Syn-1-C-(2,3,4,6-tetra-O-acetyl-β-D-mannopyranosyl)-
cyclopentan-2-one (syn-β-29): 1H NMR (500 MHz, CDCl3) δ
5.51 (dd, J = 3.4, 1.0 Hz, 1H), 5.17 (t, J = 10.0 Hz, 1H), 5.05 (dd,
J = 10.1, 3.4 Hz, 1H), 4.21 (dd, J = 12.2, 5.8 Hz, 1H), 4.02 (dd, J
= 12.2, 2.5 Hz, 1H), 3.98 (dd, J = 3.8, 1.0 Hz, 1H), 3.60 (ddd, J =
9.9, 5.8, 2.5 Hz, 1H), 2.33 – 2.23 (m, 1H), 2.14 (s, 3H), 2.19 –
2.10 (m, 2H), 2.09 – 2.02 (m, 2H), 2.03 (s, 3H), 2.01 (s, 3H),
2.02 – 1.97 (m, 1H), 1.95 (s, 3H), 1.73 – 1.64 (m, 1H). 13C NMR
(126 MHz, CDCl3) δ 217.5, 170.7, 170.3, 170.1, 169.9, 76.4,
75.1, 72.4, 70.4, 66.2, 62.8, 50.4, 38.0, 24.8, 21.1, 20.9, 20.8,
20.8, 20.7. HRMS (ESI) calcd for C19H26O10Na+ [M+Na]+:
437.1418, found: 437.1422.
C19H26O10Na+ [M+Na]+: 437.1418, found: 437.1418.
Syn-1-C-(2,3,4,6-tetra-O-acetyl-β-L-gulopyranosyl)-
cyclopentan-2-one (syn-ß-31): 1H NMR (500 MHz, CDCl3) δ
5.33 (t, J = 3.5 Hz, 1H), 4.97 (dd, J = 10.6, 3.2 Hz, 1H), 4.94 (dd,
J = 3.8, 1.1 Hz, 1H), 4.29 (dd, J = 10.6, 2.1 Hz, 1H), 4.09 (dd, J
= 5.4, 1.4 Hz, 1H), 4.09 – 4.05 (m, 1H), 3.97 (dd, J = 10.3, 5.1
Hz, 1H), 2.34 – 2.26 (m, 1H), 2.21 – 2.16 (m, 1H), 2.14 (s, 3H),
2.14 (s, 3H), 2.13 – 2.08 (m, 2H), 2.08 – 2.04 (m, 1H), 2.04 –
1.99 (m, 1H), 2.01 (s, 3H), 1.98 (s, 3H), 1.78 – 1.67 (m, 1H). 13
C
NMR (126 MHz, CDCl3) δ 219.4, 170.6, 169.8, 169.7, 169.4,
72.2, 72.0, 68.4, 66.7, 66.7, 61.7, 48.8, 39.3, 22.4, 21.0, 20.9,
20.8, 20.8, 20.8. HRMS (ESI) calcd for C19H26O10Na+ [M+Na]+:
437.1418, found: 437.1420.
Syn-1-C-(2,3,4,6-tetra-O-acetyl-β-L-idopyranosyl)-
cyclopentan-2-one (syn-α-30): Inseparable mixture of syn-α-
30/syn-β-31: 1/9. Overall yield: 62.0 mg; 8 %. 1H NMR (500 MHz, Syn-1-C-(2,3,4,6-tetra-O-acetyl-β-D-galactopyranosyl)-
1
CDCl3) δ 5.45 – 5.39 (m, 1H), 5.08 (dd, J = 9.9, 6.6 Hz, 1H),
4.95 – 4.91 (m, 2H), 4.62 (dd, J = 12.7, 8.2 Hz, 1H), 4.21 (dd, J
= 10.2, 1.8 Hz, 1H), 4.08 – 4.05 (m, 1H), 2.31 – 2.26 (m, 1H),
2.19 – 2.15 (m, 2H), 2.14 (s, 3H), 2.14 (s, 3H), 2.13 – 2.09 (m,
2H), 2.03 (s, 3H), 2.02 (s, 3H), 2.03 – 1.97 (m, 1H), 1.80 – 1.76
(m, 1H). 13C NMR (126 MHz, CDCl3) δ 217.9, 170.7, 169.9,
169.9, 169.8, 71.0, 70.6, 70.4, 69.8, 69.7, 60.3, 48.9, 39.0, 22.4,
21.0, 20.8, 20.8, 20.8, 20.7.
cyclopentan-2-one (syn-β-32): Yield: 89.5 mg; 11 %. H NMR
(500 MHz, CDCl3) δ 5.40 (dd, J = 3.4, 1.1 Hz, 1H), 5.16 (t, J =
10.0 Hz, 1H), 5.03 (dd, J = 10.0, 3.4 Hz, 1H), 4.07 (dd, J = 11.2,
6.7 Hz, 1H), 3.97 (dd, J = 11.2, 6.7 Hz, 1H), 3.93 (dd, J = 10.0,
1.3 Hz, 1H), 3.86 (td, J = 6.7, 1.1 Hz, 1H), 2.34 – 2.26 (m, 1H),
2.15 – 2.13 (m, 2H), 2.14 (s, 3H) 2.12 – 2.02 (m, 2H), 2.04 (s,
3H), 2.00 (s, 3H), 1.97 (s, 3H), 1.79 – 1.69 (m, 2H). 13C NMR
(126 MHz, CDCl3) δ 218.8, 170.6, 170.4, 170.2, 170.1, 76.3,
74.1, 72.4, 67.7, 67.4, 61.3, 49.0, 39.3, 22.7, 20.9, 20.8, 20.8,
25
Syn-1-C-(2,3,4,6-tetra-O-acetyl-β-L-idopyranosyl)-
20.8, 20.8. [α]D = -42 (c = 1, acetone). HRMS (ESI) calcd for
cyclopentan-2-one (syn-β-30): Inseparable mixture of syn-β-
C19H26O10Na+ [M+Na]+: 437.1418, found: 437.1423.
1
30/anti-β-31: 45/55. Overall yield: 47.9 mg; 6 %. H NMR (500
MHz, CDCl3) δ 5.41 (dd, J = 5.3, 3.5 Hz, 1H), 5.28 (dd, J = 6.2,
3.4 Hz, 1H), 4.53 (t, J = 5.1 Hz, 1H), 4.30 (dd, J = 5.7, 5.1 Hz,
1H), 4.06 – 4.03 (m, 1H), 4.05 – 4.02 (m, 1H), 3.99 (dd, J = 9.1,
5.5 Hz, 1H), 2.27 – 2.20 (m, 1H), 2.10 – 2.03 (m, 2H), 2.09 (s,
3H), 2.02 (s, 3H), 1.99 (s, 3H), 2.01 – 1.95 (m, 2H), 1.96 (s, 3H),
1.90 – 1.80 (m, 1H), 1.77 – 1.66 (m, 1H). 13C NMR (126 MHz,
Syn-1-C-(2,3,4,6-tetra-O-acetyl-β-D-talopyranosyl)-
cyclopentan-2-one (syn-β-33): Inseparable mixture syn-β-
33/syn-α-33/anti-α-33: 6/2/2. Overall yield: 45.6 mg; 6 %. 1H
NMR (500 MHz, CDCl3) δ 5.35 (dd, J = 4.1, 1.4 Hz, 1H), 5.32
(ddd, J = 7.1, 5.5, 3.9 Hz, 1H), 5.04 (dd, J = 3.6, 1.3 Hz, 1H),
4.35 (dd, J = 12.0, 3.9 Hz, 1H), 4.30 (dd, J = 4.7, 4.3 Hz, 1H),
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European Journal of Organic Chemistry
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FULL PAPER
4.09 (dd, J = 11.9, 7.2 Hz, 1H), 3.90 (dd, J = 5.6, 3.6 Hz, 1H),
2.14 – 2.11 (m, 2H), 2.11 (s, 3H), 2.09 (s, 3H), 2.10 – 2.05 (m,
2H), 2.07 (s, 3H), 2.03 (s, 3H), 2.04 – 2.00 (m, 2H), 1.83 – 1.76
(m, 1H). 13C NMR (126 MHz, CDCl3) δ 217.6, 170.6, 170.1,
169.6, 169.5, 81.3, 79.0, 77.9, 77.4, 70.0, 62.8, 48.4, 38.0, 25.6,
21.0, 20.9, 20.9, 20.7, 20.7. HRMS (ESI) calcd for C19H26O10Na+
[M+Na]+: 437.1418, found: 437.1422.
73.1, 71.4, 71.0, 70.6, 69.6, 68.4, 67.3, 67.1, 62.8, 50.3, 38.4,
26.4, 21.3, 20.9, 20.8, 20.7, 20.6, 20.6. HRMS (ESI) calcd for
C31H42O18Na+ [M+Na]+: 725.2263, found: 725.2263.
Supporting Information (see footnote on the first page of this
article): Conformation analysis, proof of configuration and copies
of 1H NMR and 13C NMR spectra are available in the Supporting
Information.
Syn-1-C-(2,3,4,6-tetra-O-acetyl-α-D-talopyranosyl)-
cyclopentan-2-one (syn-α-33): 1H NMR (500 MHz, CDCl3) δ
5.33 (ddd, J = 6.7, 3.5, 1.1 Hz, 1H), 5.18 (ddd, J = 7.3, 4.8, 3.0
Hz, 1H), 5.09 (t, J = 3.5 Hz, 1H), 4.98 – 4.94 (m, 1H), 4.35 (dd, J
= 6.7, 2.6 Hz, 1H), 4.18 (dd, J = 11.7, 4.8 Hz, 1H), 3.99 – 3.94
(m, 1H), 2.31 – 2.25 (m, 1H), 2.13 – 2.06 (m, 1H), 2.07 (s, 3H),
2.07 (s, 3H), 2.02 (s, 3H), 2.02 (s, 3H), 2.03 – 1.97 (m, 2H), 1.97
– 1.90 (m, 1H), 1.81 – 1.70 (m, 2H). 13C NMR (126 MHz, CDCl3)
δ 218.1, 170.3, 170.1, 170.0, 169.9, 81.3, 80.1, 78.6, 72.0, 70.0,
62.4, 49.9, 38.8, 22.7, 20.9, 20.8, 20.8, 20.7, 20.7.
Acknowledgements
The authors thank Deutsche Forschungsgemeinschaft for
financial support.
Keywords: amine-catalysis; cascade reaction; C-glycosides;
mechanism
[1]
[2]
[3]
C. Richter, B. Voigt, R. Mahrwald, RSC Advances 2015, 5, 45571-
45574.
Anti-1-C-(2,3,4,6-tetra-O-acetyl-β-D-talopyranosyl)-
cyclopentan-2-one (anti-α-33): 1H NMR (500 MHz, CDCl3) δ
5.25 – 5.23 (m, 1H), 5.14 (dd, J = 6.0, 3.2 Hz, 1H), 5.10 - 5.06
(m, 1H), 4.33 (dd, J = 6.1, 3.9 Hz, 1H), 4.27 – 4.24 (m, 1H), 4.10
– 4.06 (m, 1H), 4.06 – 4.03 (m, 1H), 2.40 – 2.33 (m, 1H), 2.13 –
2.06 (m, 1H), 2.03 (s, 3H), 2.03 – 1.97 (m, 2H), 1.99 (s, 3H),
1.98 (s, 3H), 1.98 (s, 3H), 1.97 – 1.90 (m, 1H), 1.81 – 1.70 (m,
2H). 13C NMR (126 MHz, CDCl3) δ 217.6, 170.7, 170.7, 170.2,
170.0, 81.2, 79.2, 78.7, 71.6, 70.2, 62.7, 50.6, 38.8, 23.8, 21.0,
20.9, 20.9, 20.8, 20.7.
Dihydroxyacetone exists in solid state as a dimeric structure. For
reasons of simplification the monomeric structure is depicted.
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I. Allaman, M. Belanger, P. J. Magistretti, Neurosci. 2015, 9, 1-12.
a) J. Dijkmans, M. Dusselier, D. Gabriels, K. Houthoofd, P. C. M. M.
Magusin, S. Huang, Y. Pontikes, M. Trekels, A. Vantomme, L. Giebeler,
S. Oswald, B. F. Sels, ACS Catalysis 2015, 5, 928-940; b) tin
phosphate / 140oC: X. Wang, F. Liang, C. Huang, Y. Li, B. Chen, Cat.
Science & Techn. 2015, 5, 4410-4421; c) Hydrothermal decomposition
at 210oC: X. Liang, A. Rahubadda, B. S. Haynes, A. Montoya, Ind. &
Eng. Chem. Res. 2015, 54, 8437-8447; d) Zeolithes / 100oC: P. Y.
Dapsens, B. T. Kusema, C. Mondelli, J. Perez-Ramirez, J. Mol. Cat. A:
Chem., 2014, 388-389, 141-147; e) Lewis-acid / 100oC: Y. Koito, K.
Nakajima, R. Hasegawa, H. Kobayashi, M. Kitano, M. Hara, Catalysis
Today, 2014, 226, 198-203; f) Lewis-acid /140oC: C. B. Rasrendra, B.
A. Fachri, I. Makertihartha, B. N. Gusti, S. Adisasmito, H. J. Heeres,
ChemSusChem 2011, 4, 768-777; g) H2SO4 / 140oC: M. J. Antal, Jr., W.
Syn-1-C-(2,3,4,6,8,9,10,12-octa-O-acetyl-β-D-isomatosyl)-
cyclopentan-2-one (syn-34): impure with 5 % syn-35, yield:
87.1 mg; 7 %. 1H NMR (500 MHz, acetone) δ 5.39 (dd, J = 10.2,
9.5 Hz, 1H), 5.27 (t, J = 9.4 Hz, 1H), 5.07 (d, J = 3.6 Hz, 1H),
5.03 (d, J = 9.7 Hz, 1H), 4.99 (d, J = 9.5 Hz, 1H), 4.93 (dd, J =
9.8 Hz, 1H), 4.84 (dd, J = 10.2, 3.7 Hz, 1H), 4.19 (dd, J = 12.2,
5.4 Hz, 1H), 4.08 (dd, J = 12.2, 2.4 Hz, 1H), 4.03 (dd, J = 10.3,
2.0 Hz, 1H), 3.99 (ddd, J = 10.2, 5.4, 2.4 Hz, 1H), 3.83 (ddd, J =
9.9, 5.5, 2.6 Hz, 1H), 3.73 (dd, J = 11.5, 5.4 Hz, 1H), 3.61 (dd, J
= 11.4, 2.6 Hz, 1H), 2.30 – 2.23 (m, 1H), 2.24 – 2.15 (m, 2H),
2.08 (s, 3H), 2.03 (s, 3H), 2.04 – 2.00 (m, 2H), 2.01 (s, 3H), 2.01
(s, 3H), 2.00 (s, 3H), 1.95 (s, 3H), 1.94 (s, 3H), 1.82 – 1.70 (m,
2H). 13C NMR (126 MHz, acetone) δ 217.4, 170.8, 170.7, 170.4,
170.2, 170.1, 170.1, 170.1, 96.2, 76.9, 76.2, 75.1, 71.4, 70.7,
70.6, 70.0, 69.5, 68.3, 66.6, 62.7, 49.2, 39.2, 24.5, 23.2, 21.2,
20.8, 20.7, 20.6, 20.6. HRMS (ESI) calcd for C31H42O18Na+
[M+Na]+: 725.2263, found: 725.2265.
[5]
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S. L. Mok, G. N. Richards, Carb. Res. 1990, 199, 111-115; h) H2SO4
/
100oC: B. Görlich, Chem. Ber. 1956, 89, 2145-2154; i) for a very first
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Syn-1-C-(2,3,4,6,8,9,10,12-Octa-O-acetyl-β-D-epiisomatosyl)-
cyclopentan-2-one (syn-35): impure with 5 % syn-34, yield:
80.5 mg; 6 %. H NMR (500 MHz, acetone) δ 5.61 (dd, J = 3.4,
1
a) for organocatalyzed aldol additions of methylglyoxal with ketones
see F. J. N. Moles, G. Guillena, C. Najera, Synlett 2015, 26, 656-660;
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Hayashi, Y. Yasui, M. Kojima, T. Kawamura, H. Ishikawa, Chem.
Comm., 2012, 48, 4570-4572; c) for organocatalyzed aldol reactions of
acetone with methylglyoxal see D. G. Alberg, T. B. Poulsen, S.
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Sc(III)-catalyzed aldol addition of α-keto aldehydes to 2-oxindoles see K.
Shen, X. Liu, K. Zheng, W. Li, X. Hu, L. Lin, X. Feng, Chem.-Eur. J.
2010, 16, 3736-3741.
1.1 Hz, 1H), 5.44 (dd, J = 10.2, 9.4 Hz, 1H), 5.17 (dd, J = 10.1,
3.4 Hz, 1H), 5.11 (d, J = 9.9 Hz, 1H), 5.08 (d, J = 3.5 Hz, 1H),
5.01 (dd, J = 10.1, 9.4 Hz, 1H), 4.84 (dd, J = 10.3, 3.6 Hz, 1H),
4.17 – 4.15 (m, 2H), 4.11 (dd, J = 11.0, 3.1 Hz, 1H), 4.10 (dd, J
= 5.5, 1.2 Hz, 1H), 3.86 – 3.81 (m, 1H), 3.73 (dd, J = 10.8, 7.0
Hz, 1H), 3.59 (dd, J = 10.8, 2.6 Hz, 1H), 2.39 – 2.33 (m, 1H),
2.27 – 2.18 (m, 2H), 2.12 (s, 3H), 2.14 – 2.08 (m, 2H), 2.06 (s,
3H), 2.05 (s, 3H), 2.03 (s, 3H), 2.01 (s, 3H), 1.96 (s, 3H), 1.91 (s,
3H), 1.85 – 1.73 (m, 2H). 13C NMR (126 MHz, acetone) δ 217.0,
170.7, 170.6, 170.6, 170.4, 170.3, 170.2, 170.1, 95.7, 77.4, 75.9,
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Cascade reactions, carbohydrates
Amine-mediated cascade reactions of
unprotected ketoses were elaborated.
Extremely matched or mismatched
cases were detected by deployment of
D- or L-proline in these
Celin Richter, Michael Krumrey, Kristin
Klaue, Rainer Mahrwald*
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Title
transformations.
*cascade reactions, carbohydrates
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Cascade reactions, carbohydrates
Celin Richter, Michael Krumrey, Kristin
Klaue, Rainer Mahrwald*
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Title
Text for Table of Contents
Amine-mediated cascade reactions of unprotected ketoses were elaborated.
Extremely matched or mismatched cases were detected by deployment of D- or L-
proline in these transformations.
*cascade reactions, carbohydrates
This article is protected by copyright. All rights reserved