FULL PAPER
DOI: 10.1002/ejoc.200601081
Diastereoselective Cyclisation of N-Alkenylideneamines into 3,4-Dihydro-2H-
pyrrol-1-ium Halides
Daniela Schley
[a]
and Jürgen Liebscher*
[a]
Dedicated to Prof. Dr. Manfred Christl on the occasion of his 65th birthday
Keywords: Diastereoselective cyclisation / Pyrrolin-1-ium salts / Pyrrolidines / Heterocycles / Synthetic methods
A number of new chiral 2-(α-bromoalkyl)pyrrolinium salts
and 2-(α-selenoalkyl)pyrrolidines were synthesized by the
halocyclisation and selenocyclisation, respectively, of N-(alk-
enylidene)alkylamines and subsequent reduction. These cy-
clisations were implemented in a diastereomeric fashion for
the first time. Substrate control (starting imines possessing
chirality in the N-alkyl or the N-alkenyl substituent) and re-
Introduction
The asymmetric functionalisation of olefins is an impor-
tant goal in synthetic organic chemistry. Thus, highly
stereoselective epoxidations, dihydroxylations and hydro-
borations were developed. The addition of electrophiles to
C=C bonds can also be combined with an intramolecular
nucleophilic attack by ring formation, when alkenes with
additional nucleophilic sites (O, S or N) are used as sub-
strates. This electrophile-induced cyclisation is a versatile
strategy for the construction of heterocycles. The halolac-
tonisation, where unsaturated carboxylic acids are cyclised
by a reaction with halogens to form lactones, is a well-
known example of this type of reaction. Other common
starting materials are unsaturated carboxylic acid deriva-
tives, imines (Scheme 1), alcohols and amines. Halogens, N-
halogenated succinimides, mercury(II) acetate, tert-butyl
hydroperoxide
[1]
(Sharpless conditions) and organose-
lenenyl halides
[2–5]
commonly serve as electrophiles.
[6]
The general mechanism of the electrophile-induced
cyclisation of unsaturated imines is shown in Scheme 1.
Chemo-, regio- and diastereoselectivity are important as-
pects of such ring formations. Thus, the reaction of the elec-
trophile can give just an addition to the double bond (e.g.
to adduct 5) rather than undergoing a cyclisation to prod-
ucts 6 or 7. On the other hand, in accordance with the Bal-
dwin rules
[7]
the cyclisation can follow either the exo-trig or
[a] Institut für Chemie, Humboldt-Universität Berlin,
Brook-Taylor-Straße 2, 12489 Berlin, Germany
E-mail: liebscher@chemie.hu-berlin.de
Supporting information for this article is available on the
WWW under http://www.eurjoc.org or from the author.
Eur. J. Org. Chem. 2007, 2945–2957 © 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim 2945
agent control (chiral organoselenenyl bromides) were
applied. Asymmetric induction by stereocentres of the alken-
ylidene or double asymmetric induction by chiral selenenyl
bromides on unsaturated imines with a chiral N-alkyl group
resulted in diatereoselectivities up to 84:16.
(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
Germany, 2007)
Scheme 1. General mechanism of the electrophile-induced cyclis-
ation of unsaturated imines.
the endo-trig mode, leading to ring 3 or 4, respectively. Fi-
nally, cis-trans isomers can be formed when nucleophiles are
added to the primary cyclisation products affording cyclic
amine 6 or 7. A number of studies were devoted to the
influence of different electrophiles and reaction conditions
on the mode of the cyclisation of alcohols,
[2–4,6]
thio-