.
Angewandte
Communications
DOI: 10.1002/anie.201107703
Stereoselective Synthesis
Highly Stereoselective Metal-Free Oxyaminations Using Chiral
Hypervalent Iodine Reagents**
Umar Farid and Thomas Wirth*
Hypervalent iodine reagents are frequently used and have
found wide applications in synthesis.[1,2] They are used in
a wide range of transformations as environmentally friendly,
mild and highly selective oxidants because they avoid the
issues of toxicity or the complicated ligands of many
transition-metal-based systems. They can also be employed
as electrophilic reagents for the functionalization of alkenes
in halolactonizations[3] and dioxytosylations,[4] for the oxida-
tive dearomatization of phenols,[5] and the a-functionalization
of ketones.[6,7] In this context, the use of chiral hypervalent
iodine reagents for asymmetric transformations has emerged
as an interesting area of research in recent years.[8] Only
recently the catalytic use of iodine compounds in synthesis has
been developed.[9] We reported the first catalytic use of
enantiomerically pure iodoarenes in asymmetric reactions,[10]
which opened the possibility to employ a wide range of such
compounds with various structural features as catalysts.[11]
The 1,2-difunctionalization of alkenes is a very important
transformation as is illustrated by the occurrence of the 1,2-
amino alcohol moiety in a huge range of bioactive com-
pounds, natural products, and chiral reagents for stereoselec-
tive synthesis. Transition-metal-catalyzed oxidative amination
reactions are established methods for the synthesis of new
carbon–nitrogen and carbon–oxygen bonds through the
functionalization of alkenes.[12] The osmium-based catalytic
aminohydroxylation is an early efficient route developed by
Sharpless et al.,[13] but other metal catalysts, such as palladium
and platinum, have also been used for intramolecular
aminations.[14] The use of bifunctional nucleophiles together
with hypervalent iodine reagents in additions to alkenes can
lead to versatile building blocks as shown in the amino-
hydroxylations of alkenes.[15]
activation of the double bond with the hypervalent iodine
reagent, the first nucleophile reacts to give intermediate 2.
The hypervalent iodine moiety is then attached to an sp3-
hybridized carbon atom and is therefore an excellent leaving
group, several orders of magnitude more reactive than
triflates or tosylates.[16] The subsequent substitution reaction
directly yields bicyclic compounds 3. It has already been
shown that, depending on the reaction conditions, such
cyclizations can lead either to isoureas 3a or to the formation
of diamination products 3b (Scheme 1).[15c,17]
Scheme 1. Cyclization of urea bisnucleophiles with alkenes using
hypervalent iodine reagents (Ar-IL2) for the synthesis of isoureas 3a
(path a) or of cyclic ureas 3b (path b).
Initial cyclizations of substrate 4 were performed by
modifying literature procedures.[15c] [Bis(trifluoroacetoxy)io-
do]benzene led to the reaction products 5a and 5b in low
yields in a very slow reaction (Table 1, entry 1). Also the
addition of catalytic amounts of diphenyl diselenide, a catalyst
which was successful in a series of other cyclization–elimi-
nation sequences,[18] did not provide a substantial improve-
ment as reaction time is still long (entry 2). The addition of
tert-butyldimethylsilyl triflate (TBDMSOTf, Table 1,
entries 3 and 4) or trimethylsilyl triflate (TMSOTf) to
(diacetoxyiodo)benzene generates in situ, as evidenced by
NMR spectroscopic investigations (see the Supporting Infor-
Herein we describe the first efficient stereoselective
oxyaminations using chiral hypervalent iodine compounds.
For these reactions we have investigated sulfonyl-substituted
homoallylic urea derivatives of type 1 (Scheme 1). After the
Table 1: Different hypervalent iodine reagents for the cyclization of 4.
[*] U. Farid, Prof. Dr. T. Wirth
School of Chemistry, Cardiff University
Park Place, Main Building, Cardiff CF10 3AT (UK)
E-mail: wirth@cf.ac.uk
Entry
Reagents
Solvent,
Yield [%]
[**] We thank Dr. Benson Kariuki (Cardiff University) for the X-ray
analysis of 8, Grꢀgory Bonnamain (University of Nantes, France)
and Pierre-Henri Belin, (ESCOM, France) for assistance in the
synthesis of some starting materials, and the EPSRC National Mass
Spectrometry Service Centre, Swansea, for mass spectrometric
data. We thank The Charles Wallace Pakistan Trust (U.F.) and Cardiff
University for financial support.
Conditions
5a
5b
1
2
PhI(OCOCF3)2
PhI(OCOCF3)2,
5 mol% (PhSe)2
PhI(OAc)2,
TBDMSOTf
PhI(OCOCF3)2,
TBDMSOTf
CH2Cl2, RT, 120 h
CH2Cl2, RT, 72 h
26
62
28
6
3
4
CH2Cl2, À78 to
RT, 8 h
48
50
20
22
CH2Cl2, À78 to
Supporting information for this article is available on the WWW
RT, 3 h
3462
ꢀ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2012, 51, 3462 –3465