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Organic & Biomolecular Chemistry
Page 1 of 3
DOI: 10.1039/C8OB01831F
Journal Name
COMMUNICATION
Preparation of homoallylic amines via a three-component
coupling process†
Xiaoxu Ou,a Ricardo Labes,a Claudio Battilocchio,a,b* Steven V. Leya*
Received 00th January 20xx,
Accepted 00th January 20xx
DOI: 10.1039/x0xx00000x
A three-component synthesis of homoallylic amines is described. prepared via a Pd-catalysed procedure.6 Despite the lack of
The allylboronic species were generated in situ by homologation of stability and the limited scope of the boroxine component, the
vinyl boroxines with trimethylsilyldiazomethane, then followed by method has broad imine scope.
trapping of the allylboron intermediate with imines. Twenty-seven
Concerning the allylation of imines to afford homoallylic
compounds were successfully prepared in moderate to high yields. amines, although there are many reported studies to show
Imines bearing various functional groups were tolerated, including applicability of the various methods, there is however a need
aliphatic, aromatic and heteroaromatic substituents. Further for a complementary, more general method which would result
elaboration of some of the homoallylic amines to form azeditines is in a broader scope of the boronic precursors.
also reported.
Recently we have described a metal-free route to afford
homoallylic alcohols via in situ generation of allyl boronic
Homoallylic amines occur as a structural feature in various
species,
which
are
initially
formed
from
alkaloids and anti-cancer agents (Figure 1).1 As a result, there is
interest in developing efficient strategies for the formation of
these particular entities.
(trimethylsilyl)diazomethane (TMSCHN2) and a vinyl boronic
acid, and trapped with aldehydes.7 In addition to this, recent
DFT studies8 have shed light on the role that boroxines play in
the reactivity of this system.
Based on this previous work, we explored the use of
boroxines as reactive species to afford a broad class of
homoallylic amines, via homologation with TMSCHN2 followed
by combination with a variety of substituted imines.
Of special merit for their preparation is the addition of
allylboronic derivatives to imines.2-5 The first diastereoselective
allylboration of acyclic imines by allylic boroxines under
anhydrous conditions was reported in 2014.2 In this particular
case, the authors selected three boroxines, which were
In Table 1, N-methyl benzaldimine
boroxine were selected as model substrates for initial studies.
The reaction was performed under anhydrous conditions, to
avoid hydrolysis of the boroxine, and 1:1 ratio of
2 and chloro-methylvinyl
1
a
trimethylsilyldiazomethane vs boroxine was initially
investigated. When 1 equivalent of imine and boroxine were
reacted with trimethylsilyldiazomethane in CH2Cl2 at room
temperature for 24 hrs (Table 1, entry 1), we could isolate the
homoallylic amine 3 as a single diastereomer, but only in 13%
yield, alongside unreacted starting material and homoallylic
alcohol byproduct 4.
A series of further experiments highlighted that the yield
and reaction rate were affected by the stoichiometry of the
boroxine (Table 1, entry 3-5), whereby increasing the equivalent
of boroxine to 1.5 drove the reaction to completion. Employing
strictly anhydrous conditions, at 85°C, it was possible to obtain
the product in 94% yield, over 6h (Entry 11).
Figure 1 Natural products containing the homoallylic amine motif.
a. Innovative Technology Centre, Department of Chemistry, University of Cambridge,
Lensfield Road, CB2 1EW, Cambridge, UK. E-mail: svl1000@cam.ac.uk
b. Current address: Syngenta Crop Protection, Process Research,
Schaffhauserstrasse 101, CH-4332, Switzerland.
†
Electronic Supplementary Information (ESI) available: See DOI: 10.1039/x0xx0000
Additional data is available from the University of Cambridge Data Repository Web
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 1
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Battilocchio, Claudio
