M. WIESNER, J. D. REVELL, H.

WENNEMERS* (UNIVERSITY OF BASEL, SWITZERLAND) C a te go r y

Tripeptides as Efficient Asymmetric Catalysts for 1,4-Addition Reactions of Aldehydes to Nitroolefins – A Rational Organo- and
Approach Biocatalysis
Angew. Chem. Int. Ed. 2008, 47, 1871-1874.

K e y w ord s

Tripeptides: Efficient Catalysts for 1,4-addition

reaction
1,4-Addition Reactions to Nitroolefins nitroolefins

peptides

enantioselectivity
H
N CONH2
N

month
O
CO2H

of the
O
NH·TFA 1
O O R2
(1–5 mol%) NO2
H + NO2 H
R2
R1 NMM (1–5 mol%)
R1
CHCl3–i-PrOH (9:1)
r.t. or –15 °C, 12–48 h

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R1 = Alk R2 = Ar, Alk 55–99% yield
dr = 4:1 to >99:1
er = 91:9 to >99:1

Selected examples:

S
O Ph O O Cy
NO2 NO2 NO2
H H H
Me Me Me

70% yield 94% yield 55% yield

dr > 99:1 dr = 30:1 dr = 4:1
er = 98:2 er = 98:2 er = 99:1

Significance: The authors designed tripeptide 1 Comment: Recently, organocatalytic asymmetric

as an efficient organocatalyst for the asymmetric
conjugate addition reactions between aldehydes
and nitroolefins. The authors have used N-methyl
morpholine (NMM) as an additive for this reaction.
After screening different solvents, a mixture of
CHCl3 and i-PrOH (9:1) has been found to be the
best solvent for this reaction. With 1–5 mol% of
catalyst 1, good to high diastereoselectivities (dr =
4:1 to >99:1) and excellent enantioselectivities
(er = 91:9 to >99:1) were obtained for different al-
dehydes and nitroolefins.
conjugate additions between aldehydes and nitro-
olefins have been reported by several groups (see
reviews below). This method as reported by the
present authors is attractive because of its low
catalyst loading (down to 1 mol%).
Reviews: S. B. Tsogoeva Eur. J. Org. Chem.
2007, 1701; S. Sulzer-Mossé, A. Alexakis Chem.
Commun. 2007, 3123.

SYNFACTS Contributors: Benjamin List, Subhas Chandra Pan

Synfacts 2008, 4, 0417-0417 Publishedonline:01.04.20 8 Published online: 19.03.2008
DOI: 10.1055/s-2008-1042835; Reg-No.: B01808SF © Georg Thieme Verlag Stuttgart · New York

2008 © THIEME STUTTGART • NEW YORK 417