involving transition-metal catalysis.5 Most known syn-
thetic strategies proceed with the nucleophilic substitution
of the corresponding 3,3-diarylpropylhalide.6
Superacid-catalyzed electrophilic aromatic substitution
has also been developed.7 In view of today’s criterion for
atom economy and green chemistry, the so-called hydro-
aminomethylation seems to hold great potential for in-
dustrial applications.
Scheme 1. Synthesis of Fenpiprane through
Hydroaminomethylation
Figure 2. Structures of the tested ligands.
The challenge of hydroaminomethylation is to combine
the highest chemo- and regioselectivity together to effi-
ciently obtain the expectedamines. In viewof 1, 1-diphenyl-
ethene, the regioselectivity is unworthy of mentioning due
to the steric hindrance, while the chemoselectivity and
the activity are the major problems. In order to achieve a
more convenient cascade approach to 3, 3-diphenylpro-
pylamines, the attempt was carried out in the hydroami-
nomethylation of 1, 1-diphenylethene with piperidine to
optimize the reaction parameters. Some representative
results were given in Table 1; to the best of our knowledge,
this is the first detailed discussion on the product dis-
tribution of the hydroaminomethylation of 1,1-diphenyl-
ethene. Similar to the earlier reports,5,10 the major byproduct
is 1,l-diarylethane from the direct hydrogenation of the olefin
double bond.
Different ligands (Figure 2) including monodentate, bi-
dentate, and multidentate phosphorus ligands were tested
with Rh(cod)2BF4 as metal precursor. As a reference, PPh3
was employed in this model reaction; only 36% conversion
and 23% of desired amine were achieved even with the
L/Rh ratio of up to 15 (Table 1, entry 1). The conversion was
improved up to 83% with Xantphos, while the undesired
byproducts (up to 66%) became predominant (Table 1, entry
2). Multiple chelating tetraphosphorus ligands were synthe-
sized by our group and have found wide application in
catalysis.14 Among them, the BTPP ligands were used
successfully in the highly linear-selective hydroformyla-
tion14d and hydroaminomethylation of styrene,14e while the
activity in this model reaction is not satisfactory (Table 1,
entry 3); this can be reconciled with the more electron-
withdrawing property of the pyrrole moiety and the steric
interactions between the more hindric tetraphosphorus
ligands and the bulky alkene. More promising results were
got when the Tetrabi ligands were applied, both the chemo-
selectivity and the activity of hydroaminomethylation to
Originally discovered by Reppe at BASF,8 the hydro-
aminomethylation consists of a cascade reaction of hydro-
formylation of an alkene to aldehyde and subsequent con-
densation with an amine to form enamine or imine followed
by hydrogenation. This one-pot cascade synthetic strategy is
very powerful as it can furnish amines directly from inexpen-
sive alkenes.1a,9 The synthesis of 3,3-diphenylpropylamine
using a hydroformylationÀreductive amination sequence
was first reported by Botteghi et al.;5,10 while the overall
yields range between 60 and 70% through a two-step ap-
proach, the yield for fenpiprane in a one-pot reaction was
only 20%. Eilbracht documented a more efficient one-pot
synthesis of 3,3-diphenylpropylamines via PBu3/[Rh(cod)-
C1]2 (1% Rh, L/Rh = 16) catalyzed hydroaminomethyla-
tion, and the yield of fenpiprane was improved to 72%.
Recently, Beller’s group developed several elegant methods
toward the synthesis of 3,3-diphenylpropylamines through
Rh-catalyzed hydroaminomethylation with Xantphos11 or
carbene3b,12 as ligands. Herein, we present a rhodium cata-
lytic system with Naphos13 as ligand (0.1% Rh, L/Rh = 4),
which allows for an efficient hydroaminomethylation of 1,1-
diphenylethene under relatively mild conditions (CO/H2 =
20/10 bar) to furnish 3,3-diphenylpropylamines (Scheme 1).
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