Evaluation Only. Created with Aspose.PDF. Copyright 2002-2021 Aspose Pty Ltd.
DOI: 10.1002/ejoc.201600612
Full Paper
One-Pot Reactions
One-Pot Synthesis of N-tert-Butylsulfinylimines and
Homoallylamine Derivatives from Epoxides
Alejandro Lahosa,[a,b,c] Francisco Foubelo,*[a,b,c] and Miguel Yus*[a,c]
Abstract: The reaction of epoxides with tert-butanesulfinamide tuted alkyl epoxides performed better than mono-alkyl-substi-
in the presence of a Lewis acid, such as erbium triflate or boron tuted compounds. After imine formation, a subsequent indium-
trifluoride–diethyl ether, in THF as solvent, under microwave or promoted allylation can be carried out in the same reaction
thermal activation, produces N-tert-butylsulfinylimines in rea- flask in a single synthetic operation leading to homoallylamine
sonable yields. Aromatic and gem-disubstituted and trisubsti- derivatives with generally high yields.
Introduction
electrophiles for a wide range of synthetic applications. The
ready availability of both enantiomers of tert-butanesulfinamide
on a large scale, the easy deprotection of the amine under mild
acidic conditions, and a practical procedure for recycling the
chiral auxiliary have undoubtedly contributed to the wide-
spread use of this approach.[6] The synthesis of these aldimines
in an enantioselective fashion was carried out for the first time
by García-Ruano, I. Fernández and coworkers from a tert-
The stereoselective addition of nucleophiles to imines is proba-
bly the most effective way of accessing molecules with a nitro-
gen atom bonded to a stereogenic centre.[1] Many of these chi-
ral aminated compounds are natural or synthetic molecules
that may show biological activity. Such molecules could also be
envisioned as key synthetic intermediates in the preparation of
more complex molecular architectures. Among the stereoselect-
ive methods for the synthesis of these compounds is catalytic
enantioselective addition.[2] This approach relies on the use of
either chiral Lewis acids,[3] which bind to the electrophile acti-
vating it towards nucleophilic attack, or chiral Lewis bases.[4]
Although the development of methods for catalytic enantio-
selective addition is a very attractive field, it has some limita-
tions. For instance, some of the reported catalytic methods use
a large excess of reagents to ensure the turnover of the catalyst.
Sometimes, when the catalytic activation does not significantly
increase the reaction rate, competitive noncatalytic addition re-
sults in a lower enantioselectivity. This is the reason why, in
the synthesis of complex organic molecules, including natural
products, stereoselective nucleophilic additions to imines are
more commonly carried out with stoichiometric amounts of chi-
ral reagents, namely chiral imines (substrate control), including
chiral auxiliaries.[5] Over the past decade chiral imines derived
from tert-butanesulfinamide have been extensively used as
butanesulfinate ester derived from diacetone
D-glucose; tert-
butanesulfinamide (1) was involved as a reaction intermediate,
but it was not isolated in this process.[7] Since the development
by Ellman's group of a protocol for the large-scale synthesis of
sulfinamide 1,[8] these imines could be prepared in a straightfor-
ward manner by direct condensation of tert-butanesulfinamide
(1) with carbonyl compounds 2 in the presence of a Lewis acid
and a water scavenger. Thus, Ellman and coworkers reported in
1997 the first synthesis of N-tert-butylsulfinyl aldimines 3 fol-
lowing this strategy.[9] The condensation of aldehydes and sulf-
inamide 1 took place in the presence of an excess of magne-
sium sulfate and a catalytic amount of pyridinium p-toluene-
sulfonate (PPTS), using dichloromethane as solvent at room
temperature.[10] Aldimines 3 were also prepared more efficiently
using copper sulfate in dichloromethane and titanium tetra-
ethoxide in THF as condensation reagents.[10] However, these
reaction conditions were not effective for the synthesis of ket-
imines 4, which were exclusively prepared under the influence
of titanium tetraethoxide in refluxing THF.[10,11] More recently,
new methods for the synthesis of N-tert-butylsulfinylimines 3
through the condensation of aldehydes 2 and tert-butane-
sulfinamide (1) under the influence of acids or bases have been
reported.[12] Interestingly, the condensation can be also carried
out using pyrrolidine as an organocatalyst in the absence of
acids or bases, with the process taking place through iminium
activation in the presence of molecular sieves (MS, 4 Å),[13] or
under microwave irradiation (MW).[14] In this last case, an envi-
ronmentally friendly synthesis of both aldimines 3 and more
challenging ketimines 4 was achieved under solvent-free condi-
tions in short reaction times (Scheme 1).
[a] Departamento de Química Orgánica, Facultad de Ciencias, Universidad de
Alicante,
Apdo. 99, 03080 Alicante, Spain
E-mail: foubelo@ua.es
[b] Instituto de Síntesis Orgánica, Universidad de Alicante, Apdo. 99,
03080 Alicante, Spain
[c] Centro de Innovación en Química Avanzada (ORFEO-CINQA), Universidad
de Alicante,
Apdo. 99, 03080 Alicante, Spain
Supporting information for this article is available on the WWW under
Eur. J. Org. Chem. 0000, 0–0
1
© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim