Palladium/BINAP(S)-catalyzed asymmetric allylic amination

Article abstract of DOI:10.1021/ol047624k

(Chemical Equation Presented) The enantioselective allylic amination of acyclic allylic carbonates catalyzed by a palladium/(S)-BINAP(S) system was investigated. Amination of several substrates proceeded with high ee. Crotyl carbonates show an unusually high regioselectivity for the branched isomer. The use of (S)-TolBINAP(S) and (S)-3,5-xylyl-BINAP(S) as ligands was found to increase the enantioselectivity of the aminations. A P,S binding mode of the BINAP(S) ligand was found in an X-ray crystallographic study.

Full text of DOI:10.1021/ol047624k

ORGANIC
LETTERS
2005
Vol. 7, No. 4
633-636
Palladium/BINAP(S)-Catalyzed
Asymmetric Allylic Amination
J. W. Faller* and Jeremy C. Wilt
Department of Chemistry, Yale UniVersity, New HaVen, Connecticut 06520
jack.faller@yale.edu
Received November 18, 2004
ABSTRACT
The enantioselective allylic amination of acyclic allylic carbonates catalyzed by a palladium/(S)-BINAP(S) system was investigated. Amination
of several substrates proceeded with high ee. Crotyl carbonates show an unusually high regioselectivity for the branched isomer. The use of
(S)-TolBINAP(S) and (S)-3,5-xylyl-BINAP(S) as ligands was found to increase the enantioselectivity of the aminations. A P,S binding mode of
the BINAP(S) ligand was found in an X-ray crystallographic study.
The transition-metal-catalyzed allylic substitution reaction
has developed into a powerful and versatile synthetic method
in recent years.1,2 In particular, the synthesis of secondary
and tertiary allylic amines via this method has become an
invaluable tool for synthetic chemists, as these types of
amines are otherwise difficult to prepare.3-14
Pd-catalyzed asymmetric synthesis of allylic esters16 utilizing
the readily prepared heterobidentate BINAP(S) ligand 1
(Scheme 1). We were pleased to find that this system was
Scheme 1
We have recently reported the highly selective Pd-
catalyzed kinetic resolution of allylic esters15 as well as a
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also effective for the allylic amination of various classes of
allylic substrates with several different classes of amine with
high enantioselectivity.
(13) Vonmatt, P.; Loiseleur, O.; Koch, G.; Pfaltz, A.; Lefeber, C.; Feucht,
T.; Helmchen, G. Tetrahedron: Asymmetry 1994, 5, 573-584.
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10.1021/ol047624k CCC: $30.25
© 2005 American Chemical Society
Published on Web 01/25/2005

In addition, we wish to report the unambiguous identifica-
tion of a κ2-P,S binding mode of BINAP(S) on Pd based on
an X-ray crystallographic study.
Our investigation into the Pd/(S)-BINAP(S)-catalyzed
allylic amination was initiated using the ethyl carbonate of
1,3-diphenylallyl alcohol 2. The results are summarized in
Table 1. Primary amines benzylamine and allylamine (entries
when using chiral racemic substrates in the Pd-catalyzed
allylic substitution reaction.
Phthalimide derivative 3e (a precursor to primary amines)
was produced in high ee, but unfortunately the reaction with
sodium p-toluenesulfonamide did not proceed even after
prolonged reaction times.
Having established that this system allowed reaction with
a range of amines, the reaction scope with respect to different
allylic substrates (Table 2) was examined. We were pleased
Table 1. Allylic Amination of 2 with Various Aminesa
Table 2. Allylic Amination of Various Substrates with
Benzylaminea
conversionb
(%)
eec
(%)
abs
configd
entry amine T (°C)
t (h)
1
2
a
b
c
c
d
d
e
f
-25
-25
-25
-25
-25
-25
rt
24
24
0.5
16
0.5
16
21
48
99
99
99
99
99
99
99
0
95 (-)-(R)
94 (-)
3
55 (-)-(R)
89 (-)-(R)
75 (-)-(R)
90 (-)-(R)
97 (-)-(R)
N/A N/A
4e
5
6e
7
%
ee
abs
8
rt
entry substrate T (°C) t (h) conversionb b/cb,c (%) configf
a For general experimental procedure, see the Supporting Information.
b Determined by 1H NMR spectroscopy of the quenched crude reaction
mixture. c Determined by 1H NMR chiral shift experiments using (-)-MTPA
as shift reagent. d Assigned by comparison of sign of optical rotation with
published values. e Performed at 5× dilution.
1
2
3
4
5
6
4a
5a
6a
7a
8a
9a
-25
-25
-25
-25
-25
rt
22
22
22
18
22
22
99
99
99
99
99
99
N/A 87d (-)-(S)
93:7 44d (+)-(S)
6:94 45d (+)-(S)
0:100 N/A N/A
91:9 N/A N/A
N/A 13e (-)-(S)
a For general experimental procedure, see the Supporting Information.
b Determined by1H NMR spectroscopy of the quenched crude reaction
mixture. c Note that 5b ) 6c which are the branched products. d Determined
by 1H NMR chiral shift experiments using (-)-MTPA as shift reagent.
e Determined by HPLC. f Assigned by comparison of sign of optical rotation
with published values.
1 and 2) reacted smoothly under our optimized conditions
to produce allylic amines 3a and 3b with excellent enanti-
oselectivity. Under the same conditions, the use of the
secondary amines morpholine and piperidine (entries 3 and
5) led to diminished enantioselectivities.
Interestingly, upon dilution of the overall reaction con-
centration by a factor of 5 (entries 4 and 6), products 3c and
3d were obtained in comparable enantiomeric excesses as
their primary amine counterparts.
to find that sterically less demanding substrate 4a was
aminated in 87% ee; this represents a significant improve-
ment over the previous best result (73%) for this substrate.3
Unsymmetrically substituted substrates 5a, 6a, and 7a
allowed us to examine the regioselectivity of this catalytic
system along with its enantioselectivity. In accordance with
our previous studies, regioisomeric substrates 5a and 6a were
preferentially substituted in the more-substituted position to
yield branched products with moderate ee. Even the doubly
substituted terminus of the 3-methylbut-2-en-1-yl ester 8a
was aminated with 91% regioselectivity. This obserVed
regioselectiVity is the reVerse of that found for most Pd
systems,2 which give predominantly linear substitution
products. This is in contrast to metals such as Ir,7,10,11,21 Rh,6,22
Mo,23 and Ru,24 which favor the branched substitution
These results can be rationalized in terms of a memory
effect,3,17-20 i.e., an incomplete scrambling of stereochemical
information of the initially formed Pd-π-allyl intermediate.
Presumably, nucleophilic attack on the Pd-π-allyl intermedi-
ate is a second-order process, whereas the Pd-π-allyl
diastereomeric equilibration is a first-order process. There-
fore, by diluting the reaction mixture, nucleophilic attack
should be slowed with respect to Pd-π-allyl diastereomeric
equilibration. This allows for the establishment of the
Curtin-Hammett conditions necessary to produce high ee’s
(17) Lloyd-Jones, G. C.; Stephen, S. C. Chem. Eur. J. 1998, 4, 2539-
2549.
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Chem. Eur. J. 2002, 8, 4443-4453.
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Vyskocil, S.; Kocovsky, P. Chem. Eur. J. 2000, 6, 4348-4357.
(20) Faller, J. W.; Sarantopoulos, N. Organometallics 2004, 23, 2179-
2185.
(21) Takeuchi, R.; Ue, N.; Tanabe, K.; Yamashita, K.; Shiga, N. J. Am.
Chem. Soc. 2001, 123, 9525-9534.
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634
Org. Lett., Vol. 7, No. 4, 2005

products. The cinnamyl substrate 7a, however, was substi-
tuted exclusively in the less substituted position, giving rise
to achiral 7b under the conditions examined.
The cyclohexenylamine 9b, however, was produced with
low enantioselectivity for reactions carried out at ambient
temperature. Low enantioselectivity for cyclic substrates is
frequently encountered, but high enantioselectivity can
occasionally be observed.4,25
In an attempt to increase the ee of the branched product
5b/6c, allylpalladium complexes 10 and 11 derived from the
monosulfides of (S)-TolBINAP26 and (S)-3,5-xylyl-BINAP,
respectively, were prepared and tested in the amination of
6a with benzylamine (Table 3). Using 10 and 11 as catalysts,
Figure 1. ORTEP diagram of (S)-BINAP(S)PdCl2 (12): Pd1-
Cl1 ) 2.342(2); Pd1-Cl2 ) 2.314(2); P2-S1-Pd1 ) 105.5(1).
Table 3. Ligand Effects on Amination of 6a with Benzylamine
respect to the inverse regioselectivities that we observe
relative to most Pd-catalyzed allylic substitutions. The greater
trans influence of P versus S is also evident in the elongation
of the bonds to atoms trans to P relative those trans to S.
entry
catalyst
b/c
ee
abs config
1
2
3
1
10
11
6:94
5:95
5:95
45
58
65
(+)-(S)
(+)-(S)
(+)-(S)
6c was produced with similar regioselectivity, but with
significantly enhanced enantioselectivity with respect to using
the catalyst derived from 1. The methyl substituents appar-
ently enhance the chiral environment presented by the parent
(S)-BINAP(S) ligand.27
To elucidate further the factors controlling the regio- and
enantioselectivity observed in these reactions, X-ray crystal-
lographic studies were performed on complexes 12 and 13
(Figures 1 and 2). Interestingly, the P2-S-Pd angle in both
complexes is ∼105° as compared to a recently reported28
analogous structure to 13 using (S)-BINAP(O) as a ligand
in which the P-O-Pd angle is 130°. This can be attributed
to the preference for sulfur to use pure p-orbitals relative to
the greater hybridization observed with oxygen. The effect
of this large difference in bond angles is to orient the
naphthyl group attached to the phosphine sulfide underneath
the allylic portion of the complex to a much greater extent
than in the BINAP(O) complex. This modification of ligand
backbone orientation resulting from the use of a sulfur donor
rather than oxygen may have important consequences with
Figure 2. ORTEP diagram of [(η3-allyl)Pd(S-BINAP(S)]BF4
(13): Pd1-C1 ) 2.205(6); Pd1-C3 ) 2.225(7); P2-S1-Pd1 )
104.6(1).
The crystal structures show that there is a Pd-S bond in
the isolated allyl complex; however, it is possible that under
the catalytic reaction conditions the sulfur could be displaced
by ethyl carbonate and the BINAP(S) functions as a
hemilabile monodentate ligand.28 This could account for
some of the memory effects observed.
In conclusion, the allylic amination of a structurally diverse
set of allylic substrates was achieved with high regio- and
enantioselectivity. This easily prepared system provides one
of the few cases where >90% regioselectivity for the
branched isomer is observed for crotyl substrates in pal-
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1485.
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Org. Lett., Vol. 7, No. 4, 2005
635

ladium-catalyzed reactions.2,12,30 Modification of the parent
bisphosphine monosulfide 1 led to an increase in enantiose-
lectivity for the amination of the crotyl substrate while
retaining high regiocontrol.
Supporting Information Available: Synthetic procedures
and characterization data for complexes 10-13, preparation
of (S)-3,5-xylyl-BINAP(S), general procedure for allylic
aminations, as well as X-ray data. This material is available
free of charge via the Internet at http://pubs.acs.org.
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1990, 31, 1743-1746.
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