C O M M U N I C A T I O N S
Scheme 3. Synthesis of L-rhamnulofuranose 8 and
6-Deoxy-L-sorbose 9
lyzed by primary or secondary amines or aminoacids with regards
to the reaction mechanism.17 Further investigations are currently
conducted and will be published in a separate, forthcoming paper.
Acknowledgment. The authors gratefully acknowledge the
financial grants of the DFG and Bayer Schering Pharma AG. B.S.
gratefully acknowledges the financial grants of the Konrad-
Adenauer-Stiftung. P. Neubauer and B. Ziemer are gratefully
ackowledged for the X-ray structure analysis. W.-D. Fessner is
acknowledged for helpful discussion in the carbohydrate-structure
determination.
Supporting Information Available: NMR data of all synthesized
compounds and full characterization of novel compounds as well as
X-ray crystallographic data. This material is available free of charge
Scheme 4. Cinchonine-Catalyzed Aldol Addition of
Isopropylidene-(R)-glyceraldehyde 10 with DHA
References
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Scheme 2) were isolated.12 The hemiketals 3a-c and aldol adducts
4b and 4d were observed to have an extremely high degree of syn-
diastereoselectivity. Anti-configured hemiketals or aldol adducts
could not be detected under the reaction conditions described.
Hydrogen bonds are supposed to be responsible for this extremely
high syn-selectivity.13
Scheme 3 and 4 very instructively demonstrate the power of this
transformation. The DBU-catalyzed aldol addition of TBDMS-
protected (S)-lactaldehyde 5 with DHA provided an access to both
L-rhamnulofuranose 8 as well as 6-deoxy-L-sorbose 9. The products
were isolated with an extremely high degree of relative syn-
diastereoselectivity. Anti-configured products could not be detected.
In contrast to that, an internal diastereoselectivity derived from the
chiral lactaldehyde 5 could not be detected (1,2-asymmetric
induction). As a consequence of that, L-rhamnulofuranose 8 and
6-deoxy-L-sorbose 9 were isolated in a ratio of nearly 1:1 (overall
yields of 8 and 9 ) 51% yields) (Scheme 3).
(8) Shi, M.; Zhang, W. Tetrahedron 2005, 61, 11887-11894.
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Similar results with regards to stereoselectivities were obtained
in DBU-catalyzed aldol additions of isopropylidene-(R)-glyceral-
dehyde 10 and DHA. D-Fructose and D-sorbose were detected in a
ratio of 1:1. On the other hand, an extremely high stereoselective
aldol addition was observed when used with 30 mol % cinchonine
as the tertiary amine instead of DBU. This reaction furnished
D-fructose 11 with a high degree of syn-stereoselectivity. In addition
the internal anti-stereoselectivity derived from the starting chiral
isopropylidene-(R)-glyceraldehyde 10 was extremely high under
these reaction conditions (91:9).14 Thus, this amine-catalyzed aldol
addition represents a very easy and elegant approach to D-
fructopyranose 11 with high yields (71%) and with a high degree
of stereoselectivity. Since racemization of aldehydes 5 and 10 does
not occur under these reactions conditions, enantiomerically pure
aldol adducts can be obtained (>98% ee).15
In summary, we have uncovered a remarkable catalytic effect
of tertiary amines in aldol processes. This discovery resulted in
the development of an amine-catalyzed direct aldol addition. The
extremely high syn-stereoselectivity that we have observed in aldol
additions with unprotected dihydroxyacetone represents a valuable
addition to the anti-selectivities that have been described for proline-
catalyzed aldol reactions of protected dihydroxyacetone.16 In
addition, this reaction cannot be compared with aldol additions cata-
(10) Calter, M. A.; Orr, R. K. Tetrahedron Lett. 2003, 44, 5699-5701.
(11) (a) Markert, M.; Mahrwald, R. Synthesis 2004, 1429-1433. (b) Arnold,
A.; Markert, M.; Mahrwald, R. Synthesis 2006, 1099-1102.
(12) Even when hydroxyacetone was reacted with large excess of aldehydes
only small amounts of hemiketals of aldol adducts 2a-d were detected
(hemiketal of 2c, 12 %; exclusively syn-configured). The same result is
observed when isolated aldol adducts 2a-d were used under these reaction
conditions. Isolated anti-configured aldol adducts were partially equili-
brated to syn-configured aldol adducts during this process.
(13) See Supporting Information.
(14) For a nonselective enamine-catalyzed aldol addition of dihydroxacetone
and isopropylidene-D-glyceraldehyde see Co´rdova, A.; Notz, W.; Barbas,
C. F., III. Chem. Commun. 2002, 3024-3025.
(15) The enantiomeric excess was established by 1H NMR of the corresponding
Mosher esters of ketones 6, 7, and 5.6-isopropylidene-D-fructose (see
Supporting Information).
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F., III. J. Org. Chem. 2006, 71, 3822-3828. (b) Ibrahem, I.; Zou, W.;
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