Tertiary Amine Promoted Asymmetric Aldol Reaction of Aldehydes
Table 3. Different aldehydes in the asymmetric aldol reaction.[a]
pounds, copies of 1H NMR and 13C NMR spectra, and HPLC and
GC analyses.
Acknowledgments
This project is operated within the Foundation for Polish Science
TEAM Programmes co-financed by the European Union European
Regional Development Fund. Financial support from the Polish
National Science Centre (MAESTRO Grant Nr. 2013/10/A/ST5/
00233) is gratefully acknowledged.
R
Product Yield [%][b] anti/syn ee anti [%][c]
1
2
3
4
5
6
7
8
9
10
Bn
6a
6b
6c
6d
6e
6f
81
68
77
57
72
69
40
45
59
55
63:37
73:27
62:38
62:38
75:25
66:34
66:34
75:25
77:23
80:20
81
65
70
66
60
67
65
4-MeOC6H4
4-F–C6H4
3,5-tBu2C6H3
4-NCC6H4
MOM
TBDMS
H
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6g
6h
6h
6h
17
[2] B. M. Trost, C. S. Brindle, Chem. Soc. Rev. 2010, 39, 1600–
H
H
45[d,e]
42[d,f]
1632.
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[a] Reaction conditions: 5a (1 mmol, catalyst 10 mol-%) for 5 d in
CHCl3 (2 mL). [b] Isolated yield. [c] Determined by chiral HPLC
of the derivatives. The absolute configuration of the major product
was proven to be (2R,3R) by comparison with authentic samples
prepared from d-glucose. For details see Supporting Information.
[d] Determined by chiral HPLC of the derivatives. The absolute
configuration of the major product was proven to be (2S,3S) by
comparison with authentic samples prepared from d-glucose. For
details see Supporting Information. [e] Reaction conditions: 3 d,
room temp. 20 mol-% of quinidine (2). [f] Reaction conditions: 3 d,
room temp. 20 mol-% of cinchonine (4).
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keto-esters see: b) A. Bogevig, N. Kumaragurubaran, K. A.
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contrast to the broadly discussed amino-acid-catalyzed neo-
genesis of carbohydrates,[12,20] such a possibility has never
been presented in the literature. Now, it is clear that alterna-
tive enolate-mediated syntheses of protected tetrose sugars
may also be accomplished by using chiral tertiary amine
organocatalysts.
Conclusions
In summary, we have presented the first direct enantiose-
lective catalytic self-aldol reaction of α-oxyaldehydes pro-
moted by tertiary amine organocatalysts. The desired aldol
products are obtained in good to high enantioselectivities
(up to 80% ee), opening new directions in metal-free enol-
ate-mediated aldol reactions. Significantly, naturally occur-
ring quinine generates tetroses (anti-aldol product) with the
natural d-configuration (predominantly d-erythrose), while
application of quinidine resulted in the formation of l-
sugars (l-erythrose) even for unprotected glycolaldehyde.
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Experimental Section
Representative Procedure for the Aldol Reaction: Benzyloxyacet-
aldehyde (1 mmol, 150 mg) was dissolved in CHCl3 (1 mL), then
quinine (32.4 mg, 10 mol-%) was added, and the resulting mixture
was stirred for 5 d at 4 °C. After this time, the reaction mixture was
poured directly on the silica gel. The aldol product was purified
by column chromatography (DCM/Et2O, 19:1) to give the desired
product (see Table 3).
Supporting Information (see footnote on the first page of this arti-
cle): Experimental procedures, characterization data for new com-
Eur. J. Org. Chem. 2015, 5075–5078
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