Enantioselective iridium-catalyzed allylic aminations of allylic carbonates with functionalized side chains. Asymmetric total synthesis of (S)-vigabatrin

Article abstract of DOI:10.1055/s-0028-1083158

Indium-catalyzed aminations of allylic carbonates containing a variety of O-functional groups have been explored. High degrees of regio- as well as enantioselectivity were achieved with diacylamides under salt-free conditions and with arylamines. The results allowed the antiepilepsy drug (5)-vigabatrin to be prepared via a very short route.

Full text of DOI:10.1055/s-0028-1083158

FEATURE ARTICLE
3331
Enantioselective Iridium-Catalyzed Allylic Aminations of Allylic Carbonates
with Functionalized Side Chains. Asymmetric Total Synthesis of
(S)-Vigabatrin
Enantioselective
h
r
lyzedA
l
i
lylic
A
s
minationstian Gnamm, Géraldine Franck, Nicole Miller, Timon Stork, Kerstin Brödner, Günter Helmchen*
Organisch-Chemisches Institut, Universität Heidelberg, Im Neuenheimer Feld 270, 69120 Heidelberg, Germany
Fax +49(6221)544205 ; E-mail: g.helmchen@oci.uni-heidelberg.de
Received 10 April 2008; revised 9 July 2008
Dedicated to Professor Andreas Pfaltz on the occasion of his 60th birthday.
Nu
Abstract: Iridium-catalyzed aminations of allylic carbonates con-
taining a variety of O-functional groups have been explored. High
degrees of regio- as well as enantioselectivity were achieved with
diacylamides under salt-free conditions and with arylamines. The
results allowed the antiepilepsy drug (S)-vigabatrin to be prepared
via a very short route.
HNu
[IrL*]
+
*
R
OCO2Me
R
Nu
R
R = CH2OH, CH2OSiMe2t-Bu, CH2OSiPh2t-Bu, CH2OCPh3
CH2CH2OCPh3, CH2CH2CO2Me
CH=CHCH2OCPh3
Key words: aminations, iridium, asymmetric catalysis, nucleo-
philes, regioselectivity
Scheme 1 Allylic substitution with substrates with a functional
group containing oxygen
tor-substituted cinnamyl carbonates is slightly reduced in
comparison to the parent cinnamyl carbonate.6a Similarly,
allylic substitutions of substrates with substituents
R = CH2OPG proceeded with a high degree of enantiose-
lectivity, however, with a variable (high8c or low5c) degree
of regioselectivity, depending on the nucleophile. We
have been particularly interested in functionalized sub-
strates, because they yield products, for example vinyl-
glycinol derivatives, that can be transformed into chiral
building blocks of interest for the synthesis of biologically
active compounds. In this area, Trost et al. have published
important work based on the palladium-catalyzed allylic
amination of vinyloxirane.10 In order to further develop
applications of the iridium-catalyzed allylic substitution,
we have extended our studies to aminations with the broad
range of substrates with O-functional groups that are list-
ed in Scheme 1.
The asymmetric allylic substitution reaction is a powerful
and widely employed tool in organic synthesis.1 For many
years palladium catalysts were mainly used. However, ex-
cepting a number of important examples,2 palladium cat-
alysts mainly give rise to the achiral linear substitution
product in reactions of monosubstituted allylic substrates.
In contrast, iridium catalysts induce preferential forma-
tion of the branched regioisomer. Over the last few years,
iridium complexes of phosphoramidites have been devel-
oped that induce high degrees of regio- as well as enan-
tioselectivity (Scheme 1).3 With the particularly effective
ligands L1–L3 (Figure 1),4 regioselectivities >95:5 in fa-
vor of the branched products and enantioselectivities
>97% ee can be achieved routinely with C-,5 N-,6–8 and O-
nucleophiles9 with substrates containing R = aryl, small
alkyl, and alkenyl groups.
The preparation of the allylic carbonates, which followed
standard procedures, is only described in the experimental
section. Some of the compounds have appeared repeated-
ly in the chemical literature, however, experimental de-
tails were lacking. For those cases spectroscopic data are
given.
Ar
S
O
O
L1 Ar = Ph
L2 Ar = 2-MeOC6H4
L3 Ar = 1-naphthyl
aS
P
N
S
Ar
Allylic substitutions with N-nucleophiles have mostly
been carried out with amines (aliphatic,6 aromatic7) as nu-
Figure 1 Phosphoramidites used as ligands
Often only allylic substrates with benchmark character are
investigated. Compounds containing functional groups
have been rarely used and have, indeed, revealed limita-
tions. For example, allylic carbonates with R = 2-
MeOC6H4 gave products with <90% ee in alkylations5e as
well as aminations.6a Regioselectivity with para-accep-
MeO
NH2
CH2NH2
BnNH2
4-MeOC6H4NH2
NO2
O
Boc
Boc
Boc
OC
CO
H
N
N
N
SO2NH2
H
R
H
HNBoc2
NaNBoc2
HN(CHO)Boc
o-NsNH2
HNPhth
SYNTHESIS 2008, No. 20, pp 3331–3350
Advanced online publication: 25.09.2008
x
x.
x
x
.
2
0
0
8
DOI: 10.1055/s-0028-1083158; Art ID: T05608SS
Figure 2 Nucleophiles and pronucleophiles used for allylic amina-
© Georg Thieme Verlag Stuttgart · New York
tions

3332
C. Gnamm et al.
FEATURE ARTICLE
Biographical Sketches
Christian Gnamm was is currently carrying out his is focused on iridium-cata-
born in Heidelberg in 1979. Ph.D. studies in the group of lyzed allylic substitution re-
He studied chemistry at the Prof. Helmchen and is fund- actions and their application
Ruprecht-Karls-Universität
ed by a Ph.D. grant from the in syntheses of piperidine
Heidelberg and received his ‘Studienstiftung des deut- alkaloids.
diploma degree in 2005. He schen Volkes’. His research
Géraldine Franck, who is Heidelberg and Bristol and um-catalyzed allylic substi-
currently carrying out her received her diploma degree tution reactions in syntheses
Ph.D. studies in the group of from the Ruprecht-Karls- of chiral building blocks and
Prof. Helmchen, was born in Universität Heidelberg in natural products.
Munich (Germany) in 1979. 2006. Her research interests
She studied chemistry in are the application of iridi-
Nicole Miller was born in precht-Karls-Universität
Auckland. Her current re-
Immenstadt im Allgäu (Ger- Heidelberg in 2007. After- search focuses on the syn-
many). She studied chemis- wards she became a post- thesis of neoglycopeptides
try in Ulm and received her doctoral research fellow in using a ‘click chemistry’ ap-
Ph.D. under the guidance of the group of Margaret A. proach.
Prof. Helmchen at the Ru- Brimble at the University of
Timon Stork was born in Heidelberg and received his ing his Ph.D. studies in the
Ludwigshafen/Oggersheim
diploma in 2007. His diplo- group of Professor Fürstner
(Germany) in 1981. He ma thesis was carried out in at the Max-Planck-Institut
studied chemistry at the the group of Prof. Helm- für Kohlenforschung in
Ruprecht-Karls-Universität
chen. He is currently pursu- Mülheim/Ruhr.
Kerstin Brödner was born Maximilians-Universität
She is working in the field
in Würzburg (Germany) in Würzburg between 1996 of asymmetric catalysis as
1978. She did her appren- and 1999. Then she moved well as natural product syn-
ticeship as laboratory tech- to Heidelberg to join the thesis.
nician at the Julius- group of Prof. Helmchen.
Günter Helmchen (b. ried out under the guidance his present position. His in-
1940) is a Full Professor at of Prof. V. Prelog at the terest in catalysis dates back
the Ruprecht-Karls-Univer- ETH Zürich in the area of to ca. 1990. His scientific
sität Heidelberg and director stereochemistry. He then work has found recognition
of the Institute of Organic carried out a Habilitations- by a variety of scientific
Chemistry. He pursued un- arbeit at the TU Stuttgart prizes and research awards,
dergraduate studies at the (1975–1980). In 1980 he international lectureships,
TH Hannover (Dipl.-Chem. was appointed Professor C3 and the invitation to join the
1965). His graduate work, at the Universität Würz- advisory boards of scientific
completed in 1971, was car- burg. In 1985 he moved to journals.
Synthesis 2008, No. 20, 3331–3350 © Thieme Stuttgart · New York

FEATURE ARTICLE
Enantioselective Iridium-Catalyzed Allylic Aminations
3333
–O2C
cleophiles, for example benzylamine and 4-methoxy-
aniline, leading to compounds with an N-protecting group,
which can be removed by dissolving metal reduction, cat-
alytic hydrogenation, or oxidation. Being interested in
natural products synthesis and ammonia equivalents, we
have extensively investigated reactions with N-sulfonyl-
amines and N,N-diacylamines as pronucleophiles (cf.
Figure 2, lower line).8 These compounds are sufficiently
acidic to allow the application of salt-free conditions,8a i.e.
the use of the conjugate acid of an anionic nucleophile
rather than a salt, which often displays low solubility in
tetrahydrofuran. These conditions are further advanta-
geous, because the catalyst is prepared by reaction of the
procatalyst [Ir(cod)Cl]2/L* with strong base in excess,
which can effect catalyst decomposition. The excess of
base is neutralized under salt-free conditions.
(S)-Vigabatrin
+NH3
Figure 3
As an application, a short enantioselective synthesis of
(S)-vigabatrin (Figure 3), a drug with anticonvulsant ac-
tivity, is presented.
First, aminations with the O-protected and O-unprotected
carbonates 1 and 2 were examined. The carbonates were
prepared according to standard procedures. Benzylamine
and 4-methoxyaniline were used as nucleophiles
(Scheme 2, Table 1). Amination of the carbonates 1a–c
with benzylamine gave unsatisfactory results (Table 1,
entries 1–9). While enantioselectivity was often accept-
able (84.5–98% ee), regioselectivity, with a value of
83:17 at best, was generally low.
1.3 equiv BnNH2 or
4-MeOC6H4NH2
NHR3
R1
NHR3
R1
OCO2R2
1 R2 = Me
R1
[Ir(cod)Cl]2 (2 mol%)
L* (4 mol%), TBD (8 mol%)
THF, r.t.
3 R3 = Bn
4 R3 = Bn
2 R2 = Et
5 R3 = 4-MeOC6H4
6 R3 = 4-MeOC6H4
1,3,4 a: R1 = CH2OSiMe2t-Bu
1,3,4 b: R1 = CH2OSiPh2t-Bu
1,3–6 c: R1 = CH2OCPh3
1–6 d: R1 = CH2OH
Scheme 2 Allylic aminations with benzylamine and 4-methoxyaniline as nucleophiles
Table 1 Iridium-Catalyzed Allylic Aminations with Benzylamine and 4-Methoxyaniline According to Scheme 2 and General Procedure 2
Entry
1d
2
Substrate
1a
Nucleophile
BnNH2
L*
L1
L2
L3
L1
L2
L3
L1
L2
L3
L1
L2
L3
L3
L1
L2
L3
Time (h)
Yielda (%)
Ratiob b/l
60:40
72:28
83:17
80:20
73:27
76:24
81:19e
67:33e
66:34e
81:19
88:12
94:6
eec (%)
84.5 (S)
96 (S)
97 (S)
98
20
2
65
78
87
57
68
80
70
51
61
81
70
90
68
73
67
69
1a
BnNH2
3d
4d
5
1a
BnNH2
2
1b
BnNH2
20
2
1b
BnNH2
97
6
1b
BnNH2
2
98
7
1c
BnNH2
1
96
8
1c
BnNH2
4.5
4
96
9
1c
BnNH2
98
10
11
12
13d
14
15
16
1c
4-MeOC6H4NH2
4-MeOC6H4NH2
4-MeOC6H4NH2
BnNH2
1
92.5
92.5
96
1c
1
1c
0.5
2.5
5
1d
98:2
88.5
87
2d
BnNH2
90:10
96:4
2d
BnNH2
5
85
2d
BnNH2
5
>99:1
93
Synthesis 2008, No. 20, 3331–3350 © Thieme Stuttgart · New York

3334
C. Gnamm et al.
FEATURE ARTICLE
Table 1 Iridium-Catalyzed Allylic Aminations with Benzylamine and 4-Methoxyaniline According to Scheme 2 and General Procedure 2
(continued)
Entry
17
Substrate
Nucleophile
L*
L1
L2
L3
Time (h)
Yielda (%)
Ratiob b/l
>99:1
eec (%)
75
1d
1d
1d
4-MeOC6H4NH2
4-MeOC6H4NH2
4-MeOC6H4NH2
5
4
1
72
74
96
18
>99:1
77
19
>99:1
84
a Isolated yield of combined regioisomers.
b Ratio of branched/linear isomers as determined by 1H NMR spectroscopy of the crude products or isolation of the regioisomers.
c Determined by HPLC on chiral columns. Assignment of absolute configuration is given for cases in which it was independently confirmed.
d This reaction was run with 20 mol% of tetrahydrothiophene (THT) as additive (cf. general procedure 2).
e The reaction of BnNH2 with the carbonate 1c gave the branched product 3c and the bis-allylated linear product BnN(CH2CH=CHCH2OCPh3)2
(4c¢); the monoallylated linear product 4c was not found.
In contrast, with 4-methoxyaniline as nucleophile a higher (Table 2, entry 2). Using L2 as ligand, regioselectivity of
level of regioselectivity, up to 94:6, high enantiomeric ex- b/l 89:11 and enantioselectivity of 97% ee were achieved
cess (up to 96% ee), and comparatively short reaction (Table 2, entry 3). Products derived from the pronucleo-
times were typical (Table 1, entries 10–12). Hartwig et al. phile HN(CHO)Boc are particularly versatile because the
have already established that unusually high levels of re- formyl and the Boc protecting group can be selectively re-
gio- as well as enantioselectivity are general characteris- moved under mild conditions.8a
tics of reactions with arylamines, particularly in
With NaNBoc2 as pronucleophile, reaction rates were
slightly higher than with HN(CHO)Boc, and yields as
conjunction with ligand L3.7
Substitutions at the unprotected substrates 1d and 2d pro- well as selectivities were excellent (Table 2, entries 5–7).
ceeded with high regioselectivity (Table 1, entries 13– With the optimal ligand L2, the allylated product 9 was
19). However, enantioselectivity was comparatively low obtained in 88% yield with a regioselectivity of 91:9 and
(75–93% ee). This may be caused by the free hydroxy excellent enantioselectivity of 98% ee (Table 2, entry 6).
group creating a microenvironment resembling a polar Almost identical results were obtained with HNBoc2 as
solvent. With ethanol as solvent, iridium-catalyzed allylic pronucleophile at a reaction temperature of 50 °C
substitutions generally display high regio- and compara- (Table 2, entries 8–10).
tively low enantioselectivity.
Products derived from the pronucleophiles phthalimide
The above mentioned N,N-diacylamines and N-sulfonyl- and o-nosylamide are useful as they can be deprotected
amines were next explored as pronucleophiles. The readi- under very mild conditions, with 1,2-diamines or thiophe-
ly available carbonate 1c was used for this study nol, respectively.11 Compared to the results with the Boc
(Scheme 3, Table 2).
With the pronucleophile HN(CHO)Boc,8a under salt-free
conditions, the amide 7 was formed in very good yield,
containing pronucleophiles, yields and regioselectivities
were slightly lower, while enantioselectivities were simi-
larly high (Table 2, entries 11–16).
also on a preparatively significant scale of 50 mmol of 1c After these encouraging results, reactions of the carbonate
with a reduced catalyst loading of 2 mol% of iridium 1d, with a free hydroxy group, were again examined
Nu
HNu or NaNu
[Ir(cod)Cl]2, L*
Ph3CO
Ph3CO
Ph3CO
OCO2Me
Nu
TBD, THF
1c
7
9
Nu = N(CHO)Boc
Nu = NBoc2
8
Nu = N(CHO)Boc
pronucleophiles:
HN(CHO)Boc, NaN(Boc)2,
HNBoc2, HNPhth, o-NsNH2
10 Nu = NBoc2
12 Nu = Phth
14 Nu = o-NsNH2
11 Nu = Phth
13 Nu = o-NsNH2
Scheme 3 Allylic aminations with N,N-diacylamines and N-sulfonylamines as pronucleophiles
R2
HNu or NaNu
R1O
R1O
HO
R2
OCO2Me
[Ir(cod)Cl]2, L*
TBD, THF, r.t.
1d
pronucleophiles:
HN(CHO)Boc,
NaNBoc2,
16 R1 = H, R2 = N(CHO)Boc
18 R1 = H, R2 = NBoc2
20 R1 = H, R2 = NPhth
15 R1 = H, R2 = NHBoc
17 R1 = Boc, R2 = NHBoc
19 R1 = H, R2 = NPhth
HNPhth
Scheme 4 Allylic aminations with O-unprotected substrates and N,N-diacylamines as pronucleophiles
Synthesis 2008, No. 20, 3331–3350 © Thieme Stuttgart · New York

FEATURE ARTICLE
Enantioselective Iridium-Catalyzed Allylic Aminations
3335
Table 2 Iridium-Catalyzed Allylic Aminations with N,N-Diacylamines and N-Sulfonylamines According to Scheme 3 and General
Procedure 2
Entry
1
Nucleophile
HN(CHO)Boc
HN(CHO)Boc
HN(CHO)Boc
HN(CHO)Boc
NaNBoc2
NaNBoc2
NaNBoc2
HNBoc2
Equiv
1.0
1.3
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.3
1.3
1.3
1.3
1.3
1.3
Ir (mol%) L*
Temp (°C) Time (h)
Yielda (%)
Ratiob b/l
88:12
85:15
89:11
81:19
74:26
91:9
eec (%)
4
2
4
4
4
4
4
4
4
4
4
4
4
4
4
4
L1
L1
L2
L3
L1
L2
L3
L1
L2
L3
L1
L2
L3
L1
L2
L3
r.t.
50
r.t.
r.t.
50
50
50
50
50
50
r.t.
r.t.
r.t.
50
50
50
24
26
2
98
97e
96e
97e
96e
97
98
97
95
98
98
96
98
93
92
97
95
2d
3
93
89
4
24
7
90
5
94
6
14
14
88
7
79
82:18
85:15
92:8
8
2.5
85
9
HNBoc2
3
1
85
10
11
12
13
14
15
16
HNBoc2
77
83:17
79:21
79:21
55:45
89:11
88:12
75:25
HNPhth
26
24
24
24
18
24
55 (100)
58
HNPhth
HNPhth
91
o-NsNH2
85
o-NsNH2
69
o-NsNH2
87
a Isolated yield of combined regioisomers; the corrected yield given in parentheses.
b Ratio of branched/linear isomers as determined by 1H NMR spectroscopy of the crude products or isolation of the regioisomers.
c Determined by HPLC on chiral columns.
d This reaction was run on a 50 mmol scale.
e The enantiomeric excess was determined after cleavage of the formyl protecting group.
Table 3 Iridium-Catalyzed Allylic Aminations of Carbonate 1d with N,N-Diacylamines and N-Sulfonylamines According to Scheme 4 and
General Procedure 2
Entry
Nucleophile
HN(CHO)Boc
HN(CHO)Boc
HN(CHO)Boc
NaNBoc2
Equiv
1.5
1.5
1.3
1.0
1.0
1.0
1.5
1.5
1.3
L*
L1
L2
L3
L1
L2
L3
L1
L2
L3
Time (h)
60
Product
15
Yielda (%)
42 (52)
73
Ratiob b/l
>95:5
>95:5
>95:5
>99:1
>99:1
>99:1
>99:1
>99:1
>99:1
eec (%)
81d (S)
93d (S)
95d (S)
80
1
2
3
4
5
6
7
8
9
48
15
24
15
65
24
17
18 (26)e
75e
NaNBoc2
3.5
3.5
48
17
89
NaNBoc2
17
68e
93
HNPhth
19
60 (85)
95
83 (S)
87 (S)
92 (S)
HNPhth
24
19
HNPhth
18
19
70
a Isolated yield of combined regioisomers; the corrected yield is given in parentheses.
b Ratio of branched/linear isomers as determined by 1H NMR spectroscopy of the crude products or isolation of the regioisomers.
c Determined by HPLC on chiral columns. Assignment of absolute configuration is given for cases in which it was independently confirmed.
d The amination product was benzylated before measuring the enantiomeric excess.
e Additionally, tert-butyl 2-oxo-4-vinyloxazolidinone-3-carboxylate12 was also isolated in 10–15% yield.
Synthesis 2008, No. 20, 3331–3350 © Thieme Stuttgart · New York

3336
C. Gnamm et al.
FEATURE ARTICLE
(Scheme 4, Table 3). Reactions with HN(CHO)Boc as R1 = Ph or n-Pr were not quite reached. Once more, L2
nucleophile gave directly the N-Boc-protected vinylglyci- was the preferable ligand.
nol derivative 15, i.e. the formyl group was removed un-
The substrate 1f, starting material for vigabatrin, was first
der the reaction conditions. Only traces of the linear
reacted with benzylamine (Table 4, entry 10). The result
product 16 could be detected (GC/MS). Accordingly, re-
was very similar to that obtained with the carbonate 1c,
gioselectivities were high (>95:5) (Table 3, entries 1–3).
i.e. the reaction proceeded with a very low degree of re-
The reaction rate and yield were optimal with ligand L2
gioselectivity. The branched substitution product 21f was
not isolated because of in situ further reaction to the lac-
tam (5S)-1-benzyl-5-vinylpyrrolidin-2-one (21f¢). Results
and enantioselectivity was best upon use of ligand L3
(95% ee) (Table 3, entry 3).
Similarly, the substitution reaction with the pronucleo- with 4-methoxyaniline as nucleophile also closely resem-
phile NaNBoc2 was accompanied by N,O-migration of ble those obtained with 1c. Improved results were ob-
one of the Boc groups to give the N,O-di-Boc-protected tained with NaNBoc2 as well as HNBoc2, i.e. under salt-
vinylglycinol derivative 17 as the main product (Table 3, free conditions, as pronucleophiles (Table 4, entries 14–
entries 4–6). In addition, the cyclization product tert-butyl 18). Remarkably, the latter reacted even at room tempera-
2-oxo-4-vinyloxazolidinone-3-carboxylate was isolated ture at about the same rate as the former. Conditions as de-
in 10–15% yield. Again, reaction products did not contain scribed in Table 4, entry 17 furnished an excellent result.
the linear amination product 18 according to GC and
Amination products derived from substrate 1g can be
HPLC. Reaction rates were significantly higher with the
transformed into aminosugars and other types of natural
ligands L2 and L3 than with ligand L1. The results again
products. The reactions with NaNBoc2 and with phthal-
imide gave the substitution products with very high yield
and >99% ee upon use of L2 as ligand. The regioselectiv-
ity was 90:10 at best, somewhat lower than anticipated.
show that the hydroxy group of the allylic side chain gives
rise to very high regioselectivity, however, it is detrimen-
tal for enantioselectivity.
Reactions with phthalimide as pronucleophile were not
accompanied by acyl migration (Table 3, entries 7–9). As
above, results with ligands L2 and L3 were superior to
those with L1. The vinylglycinol derivative 19 was ob-
The chiral amination products 19 and 15 were trans-
formed into (S)-2-aminobut-3-en-1-ol (vinylglycinol) and
its hydrochloride, respectively, using standard procedures
(Scheme 6). Enantiomerically enriched vinylglycinol is
tained in up to 95% yield with perfect regioselectivity
an important building block in organic synthesis.13
(>99:1) and tolerable enantioselectivity (87–92% ee).
Trost et al. have previously prepared this compound by a
NH3Cl
a
highly selective palladium-catalyzed allylic amination of
15
19
HO
HO
vinyloxirane.13
NH2
b
The above results clearly showed that O-protection is ad-
visable for iridium-catalyzed amination of allylic sub-
strates with hydroxy-containing substituents. With a view Scheme 6 Deprotection of amination products. Reagents and con-
ditions: (a) 5% HCl–EtOH, reflux, 2 h, quant. (b) (CH2NH2)2 (5
equiv), MeOH, reflux, 2 h, quant.
to applications in natural product chemistry, examples
with an O-functional group at Cb and Cg of the allylic side
chain were investigated (Scheme 5). N,N-Diacylamines
were mainly used as pronucleophiles. Benzylamine and (S)-Vigabatrin is currently used as antiepilepsy drug. It
4-methoxyaniline were additionally probed in the case of acts as an irreversible inhibitor of g-aminobutyric acid
carbonate 1f with R1 = CH2CH2CO2Me.
transaminase (GABA-T), an enzyme that degrades
GABA. Enantioselective synthesis of this compound has
been a probe for asymmetric syntheses of amines. Ex-
chiral pool syntheses as well as routes based on palladi-
um-catalyzed allylic substitution, asymmetric epoxida-
The reactions of substrate 1e with the three standard N,N-
diacylamines proceeded, under salt-free conditions, with
very good regio- as well as enantioselectivity (Table 4,
entries 1–9), although values typical for substrates with
Nu
HNu or NaNu (1.3 equiv)
R1
Nu
R1
R1
OCO2Me
[Ir(cod)Cl]2 (2 mol%)
L* (4 mol%), TBD (8 mol%)
THF, r.t.
1
21 Nu = NHBn
22 Nu = NHBn
23 Nu = NH(4-MeOC6H4)
25 Nu = N(CHO)Boc
27 Nu = NBoc2
nucleophiles/pronucleophiles:
BnNH2, 4-MeOC6H4NH2
HN(CHO)Boc, NaNBoc2,
HNBoc2, HNPhth
24 Nu = NH(4-MeOC6H4)
26 Nu = N(CHO)Boc
28 Nu = NBoc2
29 Nu = NPhth
30 Nu = NPhth
1, 25–30
e: R1 = CH2CH2OCPh3
1, 21–24, 27–28 f: R1 = CH2CH2CO2Me
1, 27–30
g: R1 = (E)-CH=CHCH2OCPh3
Scheme 5 Iridium-catalyzed allylic substitutions with substituents containing O-functionality in b- and g-positions of R1
Synthesis 2008, No. 20, 3331–3350 © Thieme Stuttgart · New York

FEATURE ARTICLE
Enantioselective Iridium-Catalyzed Allylic Aminations
3337
Table 4 Allylic Substitutions According to Scheme 5 and General Procedure 2
Entry
1
Substrate R1
CH2CH2OCPh3
Pronucleophile
HN(CHO)Boc
HN(CHO)Boc
HN(CHO)Boc
HNBoc2
L*
Time (h) Temp (°C) Yielda (%) Ratiob b/l eec (%)
1e
1e
1e
1e
1e
1e
1e
1e
1e
1f
1f
1f
1f
1f
1f
1f
1f
1f
1g
1g
1g
1g
L1
1
1
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
50
93
94
90
92
93
79
88
90
80
72d
72
70
86
73
72
70
85
69
99
99
90
82
93:7
91
92
89
95
97
98
91
93
88
93d
89
90
94
2
CH2CH2OCPh3
ent-L2
L3
94:6
3
CH2CH2OCPh3
1
89:11
95:5
4
CH2CH2OCPh3
L1
24
3
5
CH2CH2OCPh3
HNBoc2
L2
96:4
6
CH2CH2OCPh3
HNBoc2
L3
6
92:8
7
CH2CH2OCPh3
PhthNH
L1
72
1
88:12
93:7
8
CH2CH2OCPh3
PhthNH
ent-L2
L3
9
CH2CH2OCPh3
PhthNH
2
84:16
74:26
90:10
96:4
10
11
12
13
14
15
16
17
18
19
20f
21
22
CH2CH2CO2Me
CH2CH2CO2Me
CH2CH2CO2Me
CH2CH2CO2Me
CH2CH2CO2Me
CH2CH2CO2Me
CH2CH2CO2Me
CH2CH2CO2Me
CH2CH2CO2Me
(E)-CH=CHCH2OCPh3
(E)-CH=CHCH2OCPh3
(E)-CH=CHCH2OCPh3
(E)-CH=CHCH2OCPh3
BnNH2
ent-L2
L1
3
4-MeOC6H4NH2
4-MeOC6H4NH2
4-MeOC6H4NH2
NaNBoc2
2.5
L2
0.25
1
L3
93:7
L1
24
85:15
95:5
91 (R)e
95 (S)e
96 (R)e
98 (S)e
97 (R)e
NaNBoc2
ent-L2
L3
17
15
24
24
3
NaNBoc2
93:7
HNBoc2
ent-L2
L3
97:3
HNBoc2
95:5
NaNBoc2
L2
87:13
90:10
82:18
78:22
>99
NaNBoc2
L2
3
>99
>99
94
PhthNH
ent-L2
3
PhthNH
ent-L1
5
a Entries 1–9, 19–22: isolated yield of the combined regioisomers; entry 10–18: isolated yield of the branched regioisomer.
b Ratio of branched/linear isomers as determined by 1H NMR spectroscopy of the crude products.
c Determined by HPLC on chiral columns. Assignment of absolute configuration is given for cases in which it was independently confirmed.
d The reaction of BnNH2 with carbonate 1f did not yield the expected product 21f, but the lactam (5S)-1-benzyl-5-vinylpyrrolidin-2-one (21f¢),
which was formed by intramolecular nucleophilic substitution.
e Determined by HPLC after removal of one Boc-protecting group.
f These reactions were carried out with a reduced catalyst loading of 2% of Ir.
CH2(CO2Me)2
NaCl (s), H2O
150 °C, DMSO
MeO2C
OH
MeO2C
OH
O
Pd(PPh3)4, dppe, THF
–78 °C, 3 h
CO2Me
84%
78%
31
32
ClCO2Me, py
CH2Cl2, 0 °C, 1 h, then r.t.
98%
1. AcOH, HCl
12 h, 60 °C
–O2C
HNBoc2, [Ir(cod)Cl]2
MeO2C
MeO2C
OCO2Me
ent-L2, TBD, THF
2. Dowex W X 8
94%
+NH3
N
Boc
Boc
85%
(S)-Vigabatrin
(–)-(S)-27f
1f
Scheme 7 Synthesis of (S)-vigabatrin starting from vinyloxirane
Synthesis 2008, No. 20, 3331–3350 © Thieme Stuttgart · New York

3338
C. Gnamm et al.
FEATURE ARTICLE
tography under the conditions stated. In cases of very high regiose-
lectivity in favor of the branched product, the linear products were
prepared separately via Pd-catalyzed allylic substitution, noncata-
lyzed nucleophilic substitution at the corresponding allylic bro-
mide, or, in case of some unprotected substitution products, by
cleavage of the protecting group from the corresponding protected
substitution product. Yields were generally not optimized.
tion, and allylic rearrangement reactions have been
reported.13,14
Our synthesis (Scheme 7), like the synthesis of Trost et
al.,13 begins with the readily available vinyloxirane, which
was used as the substrate in a palladium-catalyzed allylic
alkylation with dimethyl malonate. Using a modified pro-
cedure of Echavarren et al.15 [2.5 mol% Pd2(dba)3/dppe,
r.t.], we obtained 31 in 74% yield with a 3:1 ratio of E- and
Z-isomers. This ratio was improved to 15:1 by running the
reaction at –78 °C with Pd(PPh3)4/dppe as catalyst.
Absolute configurations for new nonracemic chiral compounds
were assigned on the basis of a general rule concerning the steric
course of the Ir-catalyzed allylic substitution.3a This rule was found
to be correct for all cases that were verified.
Demethoxycarbonylation under Krapcho conditions16
gave the ester 32 in 84% yield. This was converted into
the carbonate 1f in 98% yield. The key allylic amination
of 1f furnished intermediate (–)-(S)-27f in excellent yield
and selectivity. Initially, NaNBoc2 was used as pronucleo-
phile (Table 4, entries 14–16). Better results, regioselec-
tivity of 97:3 and enantiomeric excess of 98% ee, were
obtained with HNBoc2 under salt-free conditions
(Table 4, entry 17). The amide (–)-(S)-27f was deprotect-
ed with acetic acid/hydrochloric acid to give (S)-vi-
gabatrin in 94% yield; the overall yield from vinyloxirane
via five steps was 51%.
Synthesis of Allylic Carbonates 1a–g, 2d; General Procedure 1
A soln of the alcohol (10 mmol) and pyridine (15 mmol) in anhyd
CH2Cl2 (20 mL) was cooled to 0 °C and methyl chloroformate (15
mmol) was added dropwise. In the case of but-2-ene-1,4-diol, only
11 mmol of methyl chloroformate or ethyl chloroformate were used
in order to minimize diacylation. The mixture was stirred at 0 °C for
1 h, allowed to warm up to r.t., and then stirred until complete con-
version (TLC). H2O (20 mL) was added, the phases were separated,
and the aqueous layer was extracted with CH2Cl2 (3 × 20 mL). The
combined organic phases were washed with sat. aq CuSO4 (20 mL)
and NH4Cl soln (2 × 30 mL), dried (Na2SO4), filtered, and concen-
trated in vacuo. The crude product was purified by flash chromatog-
raphy (silica gel, PE–EtOAc; detection: UV and KMnO4).
(2E)-4-(tert-Butyldimethylsiloxy)but-2-enyl Methyl Carbonate
(1a)
Following general procedure 1 using (2E)-4-(tert-butyldimethylsi-
loxy)but-2-en-1-ol17a gave 1a as a colorless oil; yield: 88%; TLC:
Rf = 0.34 [(2E)-4-(tert-butyldimethylsiloxy)but-2-en-1-ol], 0.60
(1a) (PE–EtOAc, 3:1, KMnO4).
1H NMR (300 MHz, CDCl3): d = 0.06 [s, 6 H, Si(CH3)2], 0.90 [s, 9
H, SiC(CH3)3], 3.78 (s, 3 H, OCH3), 4.17–4.19 (m, 2 H, CH2OSi),
4.62–4.64 (m, 2 H, CH2OC), 5.76–5.93 (m, 2 H, CH=CH).
13C NMR (75 MHz, CDCl3): d = –5.16 [q, Si(CH3)2], 18.52 [s,
SiC(CH3)3], 26.05 [q, SiC(CH3)3], 54.87 (q, OCH3), 62.86 (t,
CH2OSi), 68.02 (t, CH2OC), 122.96, 135.00 (2 d, CH=CH), 155.77
(s, C=O).
1H NMR spectra were recorded at r.t. on the following spectrome-
ters: Bruker DRX-200 (200 MHz), Bruker AC-300 (300 MHz), and
Bruker Avance 500 (500 MHz) with CHCl3 (dH = 7.26) as refer-
ence. 13C NMR spectra were recorded on the following spectrome-
ters: Bruker AC-300 (75 MHz) and Bruker Avance 500 MHz (125
MHz) with CHCl3 [dC = 77.16 (central line of the triplet)] as refer-
ence. The assignments of signals were confirmed by H,H-COSY,
H,C-COSY, and DEPT spectra. Optical rotations were measured
with a Perkin Elmer 341 Polarimeter in a 1-dm thermostated cuvette
using a Hg lamp. HRMS were recorded on a Jeol JMS-700 (EI+,
FAB+) or on a Bruker ApexQe FT-ICR (ESI+) mass spectrometer.
Elemental analyses were carried out at the Organisch-Chemisches
Institut, Universität Heidelberg.
HRMS (ESI): m/z [M + Na]+ calcd for C12H24NaO4Si: 283.1342;
Enantiomeric excess was determined by HPLC on a HP 1100 in-
strument. The following columns from Daicel were used: Chiralpak
AD-H (250 × 4.6 mm, 5 mm) with guard cartridge AD-H (10 × 4
mm, 5 mm), Chiralcel OD-H (250 × 4.6 mm, 5 mm), with guard car-
tridge OD-H (10 × 4 mm, 5 mm) and Chiralcel OJ-H (250 × 4.6 mm,
5 mm) with guard cartridge OJ-H (10 × 4 mm, 5 mm). Kugelrohr dis-
tillation was carried out with a Büchi B-580 instrument; boiling
points correspond to air bath temperatures. Flash column chroma-
tography was carried out with silica gel (0.032–0.062 mm) of Ma-
cherey, Nagel and Co. Petroleum ether = PE. Decomposition on
column is possible with allylamines. This can be minimized by the
addition of Et3N (ca. 1%) to the solvent, the use of a small column,
and fast elution.
found: 283.1336.
Anal. Calcd for C12H24O4Si: C, 55.35; H, 9.29. Found: C, 55.12; H,
9.34.
(2E)-4-(tert-Butyldiphenylsiloxy)but-2-enyl Methyl Carbonate
(1b)
Following general procedure 1 using (2E)-4-(tert-butyldiphenylsi-
loxy)but-2-en-1-ol17b gave 1b as a colorless oil; yield: 95%; TLC:
Rf = 0.33 [(2E)-4-(tert-butyldiphenylsiloxy)but-2-en-1-ol], 0.57
(1b) (PE–EtOAc, 3:1, KMnO4).
1H NMR (300 MHz, CDCl3): d = 1.07 [s, 9 H, SiC(CH3)3], 3.80 (s,
3 H, OCH3), 4.21–4.23 (m, 2 H, CH2OSi), 4.64–4.66 (m, 2 H,
CH2OC), 5.84–5.99 (m, 2 H, CH=CH), 7.36–7.47 (m, 6 H, Ph),
7.65–7.70 (m, 4 H, Ph).
13C NMR (75 MHz, CDCl3): d = 19.39 [s, SiC(CH3)3], 26.96 [q,
SiC(CH3)3], 54.88 (q, OCH3), 63.54 (t, CH2OSi), 68.06 (t, CH2OC),
122.97 (d, CH=), 127.84, 129.85 (2 d, Ph), 133.61 (s, Ph), 134.51
(d, CH=), 135.66 (d, Ph), 155.77 (s, C=O).
THF was dried over benzophenone ketyl and the H2O content was
determined by Karl Fischer titration. 1,5,7-Triazabicyclo[4.4.0]dec-
5-ene (TBD) was stored in a desiccator over KOH (alternative small
amounts were stored under argon in a Schlenk tube).
The following compounds were prepared as previously reported:
(2E)-4-(tert-butyldimethylsiloxy)but-2-en-1-ol from (2E)-4-(tert-
butyldimethylsiloxy)but-2-en-1-al17a by reduction with DIBAL-H,
(2E)-4-(tert-butyldiphenylsiloxy)but-2-en-1-ol,17b (2E)-4-(trityl-
oxy)but-2-en-1-ol,18 (2E)-but-2-ene-1,4-diol,19 1-(trityloxy)but-3-
yne,20 and (2Z)-4-(trityloxy)but-2-en-1-ol.21
HRMS (EI): m/z [M – t-C4H9]+ calcd for C18H19O4Si: 327.1021;
found: 327.1032.
Anal. Calcd for C22H28O4Si: C, 68.71; H, 7.34. Found: C, 68.70; H,
7.31.
Unless stated otherwise, linear amination products were obtained
from the Ir-catalyzed allylic substitution by flash column chroma-
Synthesis 2008, No. 20, 3331–3350 © Thieme Stuttgart · New York

FEATURE ARTICLE
Enantioselective Iridium-Catalyzed Allylic Aminations
3339
Methyl (2E)-4-(Trityloxy)but-2-enyl Carbonate (1c)
Following general procedure 1 using (2E)-4-(trityloxy)but-2-en-1-
ol18 gave 1c as a white powder; yield: 97%; mp 64–65 °C; TLC:
Rf = 0.17 [(2E)-4-(trityloxy)but-2-en-1-ol], 0.45 (1c) (PE–EtOAc,
4:1, KMnO4).
1H NMR (300 MHz, CDCl3): d = 3.66 (dd, J = 4.3 Hz, J = 1.3 Hz,
2 H, CH2OCO2), 3.80 (s, 3 H, OCH3), 4.67 (dd, J = 5.7 Hz, J = 0.9
Hz, 2 H, CH2OCPh3), 5.90 (dt, J = 15.6 Hz, J = 4.3 Hz, 1 H,
CHCH2OCO2), 6.01 (dtt, J = 15.5 Hz, J = 5.8 Hz, J = 1.3 Hz, 1 H,
CHCH2OCPh3), 7.21–7.34 (m, 9 H, Ph), 7.44–7.48 (m, 6 H, Ph).
13C NMR (75 MHz, CDCl3): d = 54.91 (q, OCH3), 63.78 (t,
CH2OCPh3), 68.15 (t, CH2OCO2), 87.03 (s, CPh3), 124.05 (d,
CH=), 127.16, 127.98, 128.71 (3 d, Ph), 132.51 (d, CH=), 144.13 (s,
Ph), 155.74 (s, CO2).
Anal. Calcd for C24H22O2: C, 84.18; H, 6.48. Found: C, 83.88; H,
6.55.
(2E)-5-(Trityloxy)pent-2-en-1-ol
A soln of 5-(trityloxy)pent-2-yn-1-ol (6.16 g, 18.0 mmol) in anhyd
THF (25 mL) was added dropwise, over a period of 15 min, to a
cooled (0 °C) suspension of LiAlH4 (0.85 g, 22.5 mmol) in anhyd
THF (25 mL). The mixture was heated at reflux for 2 h [TLC:
Rf = 0.16 [5-(trityloxy)pent-2-yn-1-ol], 0.11 [(2E)-5-(trityl-
oxy)pent-2-en-1-ol] (PE–EtOAc, 4:1, KMnO4)]. After cooling to
r.t., H2O (20 mL) was added dropwise. After stirring for 10 min, the
resulting suspension was extracted with Et2O (3 × 50 mL). The
combined organic layers were dried (Na2SO4), filtered, and concen-
trated in vacuo. The crude product was purified by flash chromatog-
raphy (silica gel, 200 g, PE–Et2O, 2:1) to yield (2E)-5-
(trityloxy)pent-2-en-1-ol (5.69 g, 92%) as a colorless powder; mp
61 °C.
HRMS (ESI): m/z [M + Na]+ calcd for C25H24NaO4: 411.1572;
found: 411.1567.
1H NMR (300 MHz, CDCl3): d = 1.31 (br s, OH), 2.35–2.41 (m, 2
H, CH2CH2O), 3.13 (t, J = 6.8 Hz, 2 H, CH2OCPh3), 4.08 (d, J = 3.6
Hz, 2 H, CH2OH), 5.63–5.76 (m, 2 H, CH=CH), 7.21–7.33 (m, 9 H,
Ph), 7.44–7.46 (m, 6 H, Ph).
13C NMR (75 MHz, CDCl3): d = 33.14 (t, CH2CH2O), 63.38 (t,
CH2OCPh3), 63.80 (t, CH2OH), 86.64 (s, CPh3), 127.04, 127.87,
128.81 (3 d, Ph), 129.75, 130.98 (2 d, CH=), 144.43 (s, Ph).
Anal. Calcd for C25H24O4: C, 77.30; H, 6.23. Found: C, 77.29; H,
6.19.
(2E)-4-Hydroxybut-2-enyl Methyl Carbonate (1d)
Following general procedure 1 using (2E)-but-2-ene-1,4-diol19 gave
1d as a colorless oil; yield: 46%; TLC: Rf = 0.02 [(2E)-but-2-ene-
1,4-diol], 0.21 (1d), 0.53 [(2E)-but-2-ene-1,4-diyl dimethyl biscar-
bonate] (PE–EtOAc, 3:1, KMnO4). In addition (2E)-but-2-ene-1,4-
diyl dimethyl biscarbonate22 (31%) was obtained as side product.
HRMS (ESI): m/z [M + K]+ calcd for C24H24KO2: 383.1408; found:
383.1408.
1H NMR (300 MHz, CDCl3): d = 1.75 (s, 1 H, OH), 3.78 (s, 3 H,
OCH3), 4.17 (dd, J = 4.8 Hz, J = 1.3 Hz, 2 H, CH2OH), 4.63 (dd,
J = 5.8 Hz, J = 1.0 Hz, 2 H, CH2OC), 5.83 (dtt, J = 15.5 Hz, J = 5.9
Hz, J = 1.4 Hz, 1 H, CHCH2OC), 5.96 (dtt, J = 15.5 Hz, J = 4.8 Hz,
J = 0.9 Hz, 1 H, CHCH2OH).
13C NMR (75 MHz, CDCl3): d = 54.96 (t, CH2OH), 62.67 (t,
CH2OC), 67.74 (q, OCH3), 124.35 (d, CHCH2OH), 134.50 (d,
CHCH2OC), 155.73 (s, CO2).
Anal. Calcd for C24H24O2: C, 83.69; H, 7.02. Found: C, 83.57; H,
7.16.
Methyl (2E)-5-(Trityloxy)pent-2-enyl Carbonate (1e)
Following general procedure 1 using (2E)-5-(trityloxy)pent-2-en-1-
ol gave 1e as a colorless oil; yield: 93%; TLC: Rf = 0.11 [(2E)-5-
(trityloxy)pent-2-en-1-ol], 0.40 (1e) (PE–EtOAc, 4:1, KMnO4)].
1H NMR (300 MHz, CDCl3): d = 2.39 (dt, J = 6.6 Hz, J = 6.6 Hz, 2
H, CH2CH2O), 3.15 (t, J = 6.7 Hz, 2 H, CH2OCPh3), 3.77 (s, 3 H,
OCH3), 4.59 (dd, J = 6.2 Hz, J = 0.8 Hz, 2 H, CH2OCO2), 5.66 (dtt,
J = 15.4 Hz, J = 6.5 Hz, J = 0.9 Hz, 1 H, CHCH2OCO2), 5.86 (dt,
J = 15.3 Hz, J = 6.9 Hz, 1 H, CHCH2CH2), 7.21–7.34 (m, 9 H, Ph),
7.44–7.47 (m, 6 H, Ph).
HRMS (EI): m/z [M]+ calcd for C6H10O4: 146.0579; found:
146.0587.
Anal. Calcd for C6H10O4: C, 49.31; H, 6.90. Found: C, 49.11; H,
6.83.
13C NMR (75 MHz, CDCl3): d = 33.17 (t, CH2CH2O), 54.82 (q,
OCH3), 62.97 (t, CH2OCPh3), 68.54 (t, CH2OCO2), 86.63 (s, CPh3),
125.27 (d, CHCH2OCO2), 127.04, 127.88, 128.79 (3 d, Ph), 133.88
(d, CHCH2CH2), 144.36 (s, Ph), 155.78 (s, CO2).
HRMS (ESI): m/z [M + Na]+ calcd for C26H26NaO4: 425.1723;
found: 425.1725.
Methyl (2E)-5-(Trityloxy)pent-2-enyl Carbonate (1e)
5-(Trityloxy)pent-2-yn-1-ol
A soln of 1.6 M n-BuLi in n-hexane (19.0 mL, 30.0 mmol) was add-
ed dropwise to a soln of 1-(trityloxy)but-3-yne20 (9.5 g, 30.0 mmol)
in THF (60 mL) at –40 °C. The mixture was stirred at this tempera-
ture for 15 min and transferred through a Teflon tube into a suspen-
sion of paraformaldehyde (2.7 g, 90.0 mmol) in THF (30 mL) at
–45 °C. The resultant mixture was allowed to warm up to r.t. and
stirred until complete conversion (1 h) [TLC: Rf = 0.49 [1-(trity-
loxy)but-3-yne], 0.16 [5-(trityloxy)pent-2-yn-1-ol] (PE–EtOAc,
4:1, KMnO4)]. Et2O (100 mL) was added. The organic phase was
separated and washed with brine (50 mL), dried (Na2SO4), and con-
centrated in vacuo. The crude product was subjected to flash chro-
matography (silica gel, 90 g, PE–EtOAc, 4:1) to yield 5-(trityl-
oxy)pent-2-yn-1-ol (6.8 g, 66%) as a colorless powder; mp 98–
99 °C.
1H NMR (300 MHz, CDCl3): d = 1.64 (br s, OH), 2.53 (tt, J = 7.1
Hz, J = 2.1 Hz, 2 H, CH2CH2O), 3.24 (t, J = 7.1 Hz, 2 H,
CH2OCPh3), 4.23 (s, 2 H, CH2OH), 7.22–7.35 (m, 9 H, Ph), 7.46–
7.49 (m, 6 H, Ph).
13C NMR (75 MHz, CDCl3): d = 20.41 (t, CH2CH2O), 51.45 (t,
CH2OH), 62.29 (t, CH2OCPh3), 79.49, 83.64 (2 s, C≡C), 86.82 (s,
CPh3), 127.15, 127.94, 128.77 (3 d, Ph), 144.11 (s, Ph).
Anal. Calcd for C26H26O4: C, 77.59; H, 6.51. Found: C, 77.68; H,
6.53.
Methyl (4E)-6-[(Methoxycarbonyl)oxy]hex-4-enoate (1f)
Following general procedure 1 using methyl (4E)-6-hydroxyhex-4-
enoate (32) gave 1f as a colorless oil; yield: 98%; TLC: Rf = 0.04
(32), 0.20 (1f) (PE–EtOAc, 4:1, KMnO4).
1H NMR (300 MHz, CDCl3): d = 2.33–2.43 (m, 4 H, CH2CH2), 3.65
(s, 3 H, CO2CH3), 3.76 (s, 3 H, OCO2CH3), 4.55 (d, J = 6.2 Hz, 2 H,
CH2OCO2), 5.61 (dt, J = 15.4 Hz, J = 6.3 Hz, 1 H, CHCH2OCO2),
5.75–5.85 (m, 1 H, CHCH2CH2).
13C NMR (75 MHz, CDCl3): d = 27.50 (t, CH2CH2CO2), 33.29 (t,
CH2CO2), 51.71 (q, CO2CH3), 54.83 (q, OCO2CH3), 68.29 (t,
CH2OCO2), 124.63 (d, CHCH2OCO2), 134.71 (d, CHCH2CH2),
155.69 (s, OCO2CH3), 173.28 (s, CO2CH3).
HRMS (FAB): m/z [M + H]+ calcd for C9H15O5: 203.0919; found:
203.0923.
HRMS (ESI): m/z [M + K]+ calcd for C24H22KO2: 381.1251; found:
381.1251.
Synthesis 2008, No. 20, 3331–3350 © Thieme Stuttgart · New York

3340
C. Gnamm et al.
FEATURE ARTICLE
(2E,4E)-6-(Trityloxy)hexa-2,4-dien-1-ol
Anal. Calcd for C9H14O5: C, 53.46; H, 6.98. Found: C, 53.69; H,
7.04.
Under argon, a soln of ethyl (2E,4E)-6-(trityloxy)hexa-2,4-dienoate
(16.8 g, 42.2 mmol) in anhyd Et2O (200 mL) was cooled to –78 °C.
1 M DIBAL-H in n-hexane (92.8 mL, 92.8 mmol) was added over
a period of 1 h through a dropping funnel. After 2 h, consumption
of the substrate was complete [TLC: Rf = 0.57 (educt), 0.21 (prod-
uct) (PE–EtOAc, 3:1, UV)]. The mixture was allowed to warm to
r.t. Sat. aq NH4Cl soln (40 mL) and sat. aq potassium sodium tar-
trate soln (50 mL) were added, and the mixture was stirred for 1 h
in order to dissolve the salts. Then, Et2O (100 mL) was added, the
phases were separated, and the aqueous phase was extracted with
Et2O (2 × 100 mL). The organic phases were combined and washed
with sat. aq NH4Cl soln (2 × 50 mL), dried (Na2SO4), and concen-
trated in vacuo. Flash column chromatography (silica gel, 300 g,
PE–EtOAc, 3:1) afforded (2E,4E)-6-(trityloxy)hexa-2,4-dien-1-ol
(14.96 g, >99%) as a colorless oil.
1H NMR (300 MHz, CDCl3): d = 1.38 (br s, 1 H, OH), 3.66 (d,
J = 5.1 Hz, 2 H, CH2OCPh3), 4.21 (d, J = 5.8 Hz, 2 H, CH2OH),
5.80 (dt, J = 14.8 Hz, J = 5.2 Hz, 1 H, CHCH2), 5.86 (dt, J = 14.7
Hz, J = 5.8 Hz, 1 H, CHCH2), 6.24–6.44 (m, 2 H, CHCHCH2),
7.21–7.34 (m, 9 H, Ph), 7.44–7.48 (m, 6 H, Ph).
13C NMR (75 MHz, CDCl3): d = 63.52 (t, CH2OH), 64.48 (t,
CH2OCPh3), 87.02 (s, CPh3), 127.13, 127.97, 128.76 (3 d, Ph),
130.20 (d, CHCH2), 130.92 (d, CHCHCH2), 131.27 (d, CHCH2),
131.80 (d, CHCHCH2), 144.27 (s, Ph).
Methyl (2E,4E)-6-(Trityloxy)hexa-2,4-dienyl Carbonate (1g)
(2E)-4-(Trityloxy)but-2-enal
In a flame-dried 500-mL 3-necked flask under argon, PCC (5.6 g,
26.0 mmol) and Celite (35.0 g) were suspended in anhyd CH2Cl2
(170 mL). A soln of (2Z)-4-(trityloxy)but-2-en-1-ol21 (5.6 g, 17.0
mmol) in anhyd CH2Cl2 (15 mL) was added and the brown mixture
was stirred at r.t. for 2 h until complete consumption of the alcohol
[TLC: Rf = 0.24 (educt), 0.40 (product) (PE–EtOAc, 3:1, UV)].
CH2Cl2 (170 mL) was added, the mixture was filtered through a pad
of Celite–Florisil (1:1, 100 g), which was washed with CH2Cl2 (4 ×
70 mL). The filtrate was concentrated in vacuo to give the crude
product as a green solid (5.0 g, 89%). This was subjected to flash
column chromatography (silica gel, 250 g, PE–EtOAc, 3:1) to yield
pure (2E)-4-(trityloxy)but-2-enal (4.8 g, 86%) as colorless needles;
mp 137–138 °C.
1H NMR (300 MHz, CDCl3): d = 3.95 (dd, J = 3.5 Hz, J = 1.9 Hz,
2 H, CH2), 6.64 (ddt, J = 15.7 Hz, J = 7.8 Hz, J = 1.9 Hz, 1 H,
CHCHO), 6.80 (dt, J = 15.7 Hz, J = 3.5 Hz, 1 H, CHCH2), 7.23–
7.35 (m, 9 H, Ph), 7.42–7.47 (m, 6 H, Ph), 9.58 (d, J = 7.8 Hz, 1 H,
CHO).
13C NMR (75 MHz, CDCl3): d = 63.27 (t, CH2), 87.35 (s, CPh3),
127.45 (d, Ph), 128.16, 128.62 (2 d, Ph), 131.26 (d, CHCHO),
143.63 (s, Ph), 153.89 (d, CHCH2), 193.67 (d, CHO).
HRMS (ESI): m/z [M + Na]+ calcd for C25H24NaO2: 379.1674;
found: 379.1669.
HRMS (FAB): m/z [M + Na]+ calcd for C23H20O2Na: 351.1361;
found: 351.1374.
Anal. Calcd for C25H24O2: C, 84.24; H, 6.79. Found: C, 83.95; H,
6.76.
Anal. Calcd for C23H20O2: C, 84.12; H, 6.14. Found: C, 83.83; H,
6.11.
Methyl (2E,4E)-6-(Trityloxy)hexa-2,4-dienyl Carbonate (1g)
Following general procedure 1 using (2E,4E)-6-(trityloxy)hexa-
2,4-dien-1-ol gave 1g as a white solid; yield: 83%; mp 82–84 °C;
TLC: Rf = 0.13 (educt), 0.50 (1g) (PE–EtOAc, 5:1, UV).
1H NMR (300 MHz, CDCl3): d = 3.67 (d, J = 5.0 Hz, 2 H,
CH2OCPh3), 3.80 (s, 3 H, CH3), 4.68 (d, J = 6.6 Hz, 2 H,
CH2OCO2), 5.75–5.89 (m, 2 H, CHCH2), 6.30–6.44 (m, 2 H,
CHCHCH2), 7.21–7.33 (m, 9 H, Ph), 7.43–7.47 (m, 6 H, Ph).
13C NMR (75 MHz, CDCl3): d = 54.94 (q, CH3), 64.29 (t,
CH2OCO2), 68.25 (t, CH2OCPh3), 87.03 (s, CPh3), 125.32 (d,
CHCH2), 127.16, 127.98, 128.74 (3 d, Ph), 129.49 (d, CHCHCH2),
132.49 (d, CHCH2), 134.80 (d, CHCHCH2), 144.21 (s, Ph), 155.80
(s, OCO2CH3).
Ethyl (2E,4E)-6-(Trityloxy)hexa-2,4-dienoate
In a flame-dried 250-mL 3-neck flask under argon, triethyl
phosphonoacetate (13.2 mL, 66.1 mmol) was added dropwise to a
suspension of NaH (1.45 g, 60.42 mmol) in anhyd THF (70 mL) at
r.t. The mixture was stirred for 30 min and then cooled to –78 °C.
(2E)-4-(Trityloxy)but-2-enal (16.70 g, 50.89 mmol) was added
dropwise and the mixture was allowed to warm to r.t. overnight and
complete consumption of the aldehyde was indicated [TLC:
Rf = 0.28 (educt), 0.41 (product) (PE–EtOAc, 9:1, KMnO4)]. The
mixture was cooled to –40 °C and Et2O (200 mL) and sat. NH4Cl
soln (200 mL) were added. The mixture was allowed to warm to r.t.,
the phases were separated, and the aqueous phase was extracted
with Et2O (2 × 90 mL). The combined organic phases were washed
with sat. aq NH4Cl soln (2 × 160 mL) and brine (100 mL), dried
(Na2SO4), and concentrated in vacuo to afford a colorless oil. This
was subjected to flash column chromatography (silica gel, 300 g,
PE–EtOAc, 20:1) to yield pure ethyl (2E,4E)-6-(trityloxy)hexa-2,4-
dienoate (16.90 g, 83%) as a white solid; mp 72–73 °C.
HRMS (FAB): m/z [M + Na]+ calcd for C27H26NaO4: 437.1729;
found: 437.1712.
Anal. Calcd for C27H26O4: C, 78.24; H, 6.32. Found: C, 78.17; H,
6.34.
1H NMR (300 MHz, CDCl3): d = 1.33 (t, J = 7.1 Hz, 3 H, CH3),
3.80 (d, J = 3.8 Hz, 2 H, CH2CH), 4.25 (q, J = 7.2 Hz, 2 H,
CH2CH3), 5.97 (d, J = 15.3 Hz, 1 H, CHCO2), 6.18 (dt, J = 15.3 Hz,
J = 4.7 Hz, 1 H, CHCH2), 6.57–6.66 (m, 1 H, CHCHCH2), 7.23–
7.39 (m, 10 H, CHCHCO2, Ph), 7.48–7.52 (m, 6 H, Ph).
13C NMR (75 MHz, CDCl3): d = 14.40 (q, CH3), 60.35 (t, CH2CH3),
64.03 (t, CH2CH), 87.15 (s, CPh3), 121.14 (d, CHCO2), 127.22 (d,
Ph), 127.93 (d, CHCHCH2), 128.00, 128.64 (2 d, Ph), 139.39 (d,
CHCH2), 143.96 (s, Ph), 144.21 (d, CHCHCO2), 167.12 (s, CO2).
Ethyl (2E)-4-Hydroxybut-2-enyl Carbonate (2d)
Following general procedure 1 using (2E)-but-2-ene-1,4-diol19 gave
2d as a colorless oil; yield: 48%; TLC: Rf = 0.54 (2d), 0.74 [(2E)-
but-2-ene-1,4-diyl diethyl biscarbonate] (PE–EtOAc, 3:2, KMnO4).
The reaction yielded (2E)-but-2-ene-1,4-diyl diethyl biscarbonate23
as colorless oil, in 25% yield as side product.
1H NMR (300 MHz, CDCl3): d = 1.30 (t, J = 7.0 Hz, 3 H, CH2CH3),
1.70 (br s, 1 H, OH), 4.14–4.19 (m, 2 H, CH2OH), 4.19 (q, J = 7.1
Hz, 2 H, CH2CH3), 4.62 (dd, J = 5.9 Hz, J = 1.1 Hz, 2 H, CH2OC),
5.83 (dtt, J = 15.6 Hz, J = 5.8 Hz, J = 1.3 Hz, 1 H, CHCH2OC), 5.96
(dtt, J = 15.6 Hz, J = 4.8 Hz, J = 1.1 Hz, 1 H, CHCH2OH).
HRMS (FAB): m/z [M + H]+ calcd for C27H27O3: 399.1960; found:
399.1957.
13C NMR (75 MHz, CDCl3): d = 14.37 (q, CH2CH3), 62.71 (t,
CH2CH3), 64.20 (t, CH2OH), 67.50 (t, CH2OC), 124.52, 134.40 (2
d, CH=CH), 155.12 (CO2).
Anal. Calcd for C27H26O3: C, 81.38; H, 6.58. Found: C, 81.66; H,
6.53.
Synthesis 2008, No. 20, 3331–3350 © Thieme Stuttgart · New York

FEATURE ARTICLE
Enantioselective Iridium-Catalyzed Allylic Aminations
3341
HRMS (EI): m/z [M]+ calcd for C7H12O4: 160.0736; found:
HRMS (FAB): m/z [M + H]+ calcd for C17H30NOSi: 292.2097;
160.0756.
found: 292.2073.
Anal. Calcd for C7H12O4: C, 52.49; H, 7.55. Found: C, 52.31; H,
7.82.
Anal. Calcd for C17H29NOSi: C, 70.04; H, 10.03; N, 4.80. Found: C,
70.13; H, 10.05; N, 4.95.
Iridium-Catalyzed Allylic Amination; General Procedure 2
A Schlenk tube was dried under argon with a heat gun and charged
with a soln of [Ir(COD)Cl]2 (13.4 mg, 0.02 mmol) and L* (0.04
mmol) in anhyd THF (1.0 mL, content of H2O <30 mg/L, Karl–
Fischer titration). Anhyd TBD (11.1 mg, 0.08 mmol) was added and
the mixture stirred for 5 min (L2) or 1 h (L1, L3). Then the carbon-
ate (1 mmol), the nucleophile or pronucleophile (1.0–1.5 mmol) and
additives (Et3N or THT) were added. In case of low solubility of the
(pro)nucleophile, anhyd THF (up to 4 mL) was added, and the soln
was stirred for the time and at the temperature stated. Conversion
was monitored by TLC or GC. The solvent was removed under re-
duced pressure and the residue was analyzed with respect to the ra-
tio of branched and linear product by 1H NMR. Pure reaction
products were obtained by flash column chromatography.
(+)-(2S)-N-Benzyl-1-(tert-butyldiphenylsiloxy)but-3-en-2-
amine [(+)-(S)-3b] and (2E)-N-Benzyl-4-(tert-butyldiphenyl-
siloxy)but-2-en-1-amine (4b)
Following general procedure 2 using 1b (Table 1, entries 4–6) and
separation by flash column chromatography (silica gel, PE–Et2O,
15:1); TLC: Rf = 0.51 (1b), 0.48 (3b), 0.09 (4b) (PE–EtOAc, 5:1,
KMnO4). HPLC [Daicel Chiralcel OD-H, 250 × 4.6 mm, 5 mm, with
guard cartridge 10 × 4 mm, 5 mm, n-hexane–i-PrOH, 90:10,
flow = 0.5 mL min–1, r.t., 210 nm]: tR = 7.6 [(–)-(R)-3b], 8.7
[(+)-(S)-3b], 9.8 min (4b).
(+)-(2S)-N-Benzyl-1-(tert-butyldiphenylsiloxy)but-3-en-2-
amine [(+)-(S)-3b]
Colorless oil.
[a]D24 +20.7 (c 1.13, CHCl3, 98% ee).
(+)-(2S)-N-Benzyl-1-(tert-butyldimethylsiloxy)but-3-en-2-
amine24 [(+)-(S)-3a] and (2E)-N-Benzyl-4-(tert-butyldimethyl-
siloxy)but-2-en-1-amine (4a)
Following general procedure 2 using 1a (Table 1, entries 1–3) and
isolation by flash column chromatography (silica gel, PE–EtOAc,
2:1); TLC: Rf = 0.51 (1a), 0.48 (3a), 0.09 (4a) (PE–EtOAc, 5:1,
KMnO4). HPLC [Daicel Chiralcel OD-H, 250 × 4.6 mm, 5 mm, with
guard cartridge 10 × 4 mm, 5 mm, n-hexane–i-PrOH, 90:10,
flow = 0.5 mL min–1, r.t., 210 nm]: tR = 6.3 [(–)-(R)-3a], 7.4
[(+)-(S)-3a], 8.9 min (4a).
1H NMR (300 MHz, CDCl3): d = 1.06 [s, 9 H, SiC(CH3)3], 2.14 (br
s, 1 H, NH), 3.28 (ddd, J = 6.8 Hz, J = 6.7 Hz, J = 6.7 Hz, 1 H,
NCH), 3.65 (d, J = 6.2 Hz, 2 H, CH2O), 3.68 (d, J = 13.6 Hz, 1 H,
NCHaHb), 3.91 (d, J = 13.6 Hz, 1 H, NCHaHb), 5.17 (d, J = 9.7 Hz,
1 H, CH=CHEHZ), 5.19 (dd, J = 17.5 Hz, J = 1.4 Hz, 1 H,
CH=CHEHZ), 5.64 (ddd, J = 17.4 Hz, J = 10.1 Hz, J = 7.7 Hz, 1 H,
CH=CH2), 7.24–7.46 (m, 11 H, Ph), 7.62–7.68 (m, 4 H, Ph).
13C (75 MHz, CDCl3): d = 19.37 [s, SiC(CH3)3], 26.97 [q,
SiC(CH3)3], 51.10 (t, NCH2), 62.30 (d, NCH), 66.98 (t, CH2O),
118.00 (t, CH=CH2), 126.91, 127.82, 128.22, 128.54, 129.82 (5 d,
Ph), 133.46, 133.63 (2 s, Ph), 135.72 (d, Ph), 137.78 (d, CH=CH2),
140.77 (s, Ph).
(+)-(2S)-N-Benzyl-1-(tert-butyldimethylsiloxy)but-3-en-2-
amine24 [(+)-(S)-3a]
Colorless oil.
[a]D20 +19.0 [c 0.97, CHCl3, 97% ee (S)].24
HRMS (FAB): m/z [M + H]+ calcd for C27H34NOSi: 416.2410;
found: 416.2479.
1H NMR (500 MHz, CDCl3): d = 0.04, 0.05 [2 s, 6 H, Si(CH3)2],
0.89 [s, 9 H, SiC(CH3)3], 2.06 (br s, 1 H, NH), 3.20–3.24 (m, 1 H,
NCH), 3.52 (dd, J = 9.7 Hz, J = 8.4 Hz, 1 H, CHaHbO), 3.61 (dd,
J = 10.0 Hz, J = 4.0 Hz, 1 H, CHaHbO), 3.66 (d, J = 13.4 Hz, 1 H,
NCHaHb), 3.88 (d, J = 13.4 Hz, 1 H, NCHaHb), 5.20 (dd, J = 10.4
Hz, J = 1.7 Hz, 1 H, CH=CHEHZ), 5.25 (dd, J = 17.7 Hz, J = 1.7 Hz,
1 H, CH=CHEHZ), 5.66 (ddd, J = 17.6 Hz, J = 9.9 Hz, J = 7.9 Hz, 1
H, CH=CH2), 7.22–7.33 (m, 5 H, Ph).
13C NMR (125 MHz, CDCl3): d = –5.28, –5.20 [2 q, Si(CH3)2],
18.40 [s, SiC(CH3)3], 26.03 [q, SiC(CH3)3], 51.20 (t, NCH2), 62.61
(d, NCH), 66.33 (t, CH2O), 117.86 (t, CH=CH2), 126.86, 128.16,
128.50 (3 d, Ph), 138.05 (d, CH=CH2), 140.83 (s, Ph).
Anal. Calcd for C27H33NOSi: C, 78.02; H, 8.00; N, 3.37. Found: C,
78.03; H, 7.98; N, 3.49.
(2E)-N-Benzyl-4-(tert-butyldiphenylsiloxy)but-2-en-1-amine
(4b)
Colorless oil.
1H NMR (300 MHz, CDCl3): d = 1.07 [s, 9 H, SiC(CH3)3], 1.46 (br
s, 1 H, NH), 3.28 (dd, J = 5.8 Hz, J = 1.1 Hz, 2 H, NCH2CH), 3.79
(s, 2 H, NCH2Ph), 4.21–4.22 (m, 2 H, CH2O), 5.72 (dt, J = 15.4 Hz,
J = 4.5 Hz, 1 H, CHCH2O), 5.84 (dtt, J = 15.3 Hz, J = 5.9 Hz,
J = 1.3 Hz, 1 H, CHCH2N), 7.23–7.45 (m, 11 H, Ph), 7.68–7.71 (m,
4 H, Ph).
13C NMR (75 MHz, CDCl3): d = 19.38 [s, SiC(CH3)3], 26.99 [q,
SiC(CH3)3], 50.74 (t, NCH2CH), 64.26 (t, CH2O), 127.08, 127.79,
128.36, 128.54, 128.63, 129.76 (6 d, Ph, NCH2CH), 130.95 (d,
CHCH2O), 133.89 (s, Ph), 135.70 (d, Ph), 140.43 (s, Ph).
HRMS (FAB): m/z [M + H]+ calcd for C17H30NOSi: 292.2097;
found: 292.2072.
Anal. Calcd for C17H29NOSi: C, 70.04; H, 10.03; N, 4.80. Found: C,
69.88; H, 10.10; N, 4.98.
HRMS (FAB): m/z [M + H]+ calcd for C27H34NOSi: 416.2410;
found: 416.2396.
(2E)-N-Benzyl-4-(tert-butyldimethylsiloxy)but-2-en-1-amine
(4a)
Colorless oil.
Anal. Calcd for C27H33NOSi: C, 78.02; H, 8.00; N, 3.37. Found: C,
77.82; H, 8.18; N, 3.42.
1H NMR (300 MHz, CDCl3): d = 0.07 [s, 6 H, Si(CH3)2], 0.91 [s, 9
H, SiC(CH3)3], 1.50 (br s, 1 H, NH), 3.27 (d, J = 5.5 Hz, 2 H,
NCH2CH), 3.79 (s, 2 H, NCH2Ph), 4.16–4.18 (m, 2 H, CH2O), 5.71
(dt, J = 15.4 Hz, J = 4.2 Hz, 1 H, CHCH2O), 5.80 (dt, J = 15.7 Hz,
J = 5.5 Hz, 1 H, CHCH2N), 7.22–7.36 (m, 5 H, Ph).
13C NMR (75 MHz, CDCl3): d = –5.03 [q, Si(CH3)2], 18.58 [s,
SiC(CH3)3], 26.13 [q, SiC(CH3)3], 50.76 (t, NCH2CH), 53.50 (t,
NCH2Ph), 63.64 (t, CH2O), 127.07, 128.32, 128.54, 128.79 (4 d,
NCH2CH, Ph), 131.38 (d, CHCH2O), 140.48 (s, Ph).
(+)-(2S)-N-Benzyl-1-(trityloxy)but-3-en-2-amine [(+)-(S)-3c]
and (2E)-N-Benzyl-4-(trityloxy)-N-[(2E)-4-(trityloxy)but-2-
enyl]but-2-en-1-amine (4c¢)
Following general procedure 2 using 1c (Table 1, entries 7–9) and
separation by flash column chromatography (silica gel, PE–EtOAc,
20:1); TLC: Rf = 0.42 (1c), 0.45 (3c), 0.30 (4c¢) (PE–EtOAc, 2:1,
KMnO4). HPLC [Daicel Chiralpak AD-H, 250 × 4.6 mm, 5 mm,
with guard cartridge 10 × 4 mm, 5 mm, n-hexane–i-PrOH, 98:2,
Synthesis 2008, No. 20, 3331–3350 © Thieme Stuttgart · New York

3342
C. Gnamm et al.
FEATURE ARTICLE
flow = 0.5 mL min–1, r.t., 230 nm]: tR = 10.7 [(+)-(S)-3c], 12.9
[(–)-(R)-3c], 9.2 min [4c¢].
HRMS (FAB): m/z [M]+ calcd for C11H15NO: 177.1154; found:
177.1141.
Anal. Calcd for C11H15NO: C, 74.54; H, 8.53; N, 7.90. Found: C,
74.21; H, 8.59; N, 7.69.
(+)-(2S)-N-Benzyl-1-(trityloxy)but-3-en-2-amine [(+)-(S)-3c]
Colorless oil.
[a]D20 +15.4 (c 0.98, CHCl3, 97% ee).
(2E)-4-(Benzylamino)but-2-en-1-ol (4d)
Colorless oil.
1H NMR (300 MHz, CDCl3): d = 1.95 (br s, 1 H, NH), 3.12–3.23
(m, 2 H, CH2O), 3.25–3.32 (m, 1 H, CHN), 3.65 (d, J = 13.5 Hz, 1
H, NCHaHbPh), 3.85 (d, J = 13.5 Hz, 1 H, NCHaHbPh), 5.17 (dd,
J = 10.2 Hz, J = 1.6 Hz, 1 H, CH=CHEHZ), 5.19 (ddd, J = 17.2 Hz,
J = 1.6 Hz, J = 0.8 Hz, 1 H, CH=CHEHZ), 5.67 (ddd, J = 17.4 Hz,
J = 10.0 Hz, J = 7.5 Hz, 1 H, CH=CH2), 7.21–7.35 (m, 14 H, Ph),
7.41–7.45 (m, 6 H, Ph).
13C NMR (75 MHz, CDCl3): d = 51.14 (t, NCH2Ph), 60.89 (d,
CHN), 66.62 (t, CH2O), 86.76 (s, CPh3), 117.61 (t, CH=CH2),
126.94, 127.12, 127.92, 128.22, 128.52, 128.84 (6 d, Ph), 138.24 (d,
CH=CH2), 140.82, 144.17 (2 s, Ph).
1H NMR (300 MHz, CDCl3): d = 1.88–1.95 (m, 2 H, NH, OH),
3.26–3.28 (m, 2 H, NCH2CH), 3.79 (s, 2 H, NCH2Ph), 4.11–4.12
(m, 2 H, CH2O), 5.74–5.87 (m, 2 H, CH=CH), 7.22–7.35 (m, 5 H,
Ph).
13C NMR (75 MHz, CDCl3): d = 50.55 (t, NCH2), 53.46 (NCH2Ph),
63.20 (t, CH2O), 127.19, 128.35, 128.57, 129.97, 131.39 (5 d, Ph,
CH=CH), 140.03 (s, Ph).
HRMS (FAB): m/z [M]+ calcd for C11H15NO: 177.1154; found:
177.1104.
Anal. Calcd for C11H15NO: C, 74.54; H, 8.53; N, 7.90. Found: C,
74.80; H, 8.59; N, 7.87.
HRMS (FAB): m/z [M + H]+ calcd for C30H30NO: 420.2328; found:
420.2321.
Anal. Calcd for C30H29NO: C, 85.88; H, 6.97; N, 3.34. Found: C,
85.70; H, 6.97; N, 3.33.
(–)-(2S)-N-(4-Methoxyphenyl)-1-(trityloxy)but-3-en-2-amine
[(–)-(S)-5c] and (2E)-N-(4-Methoxyphenyl)-4-(trityloxy)but-2-
en-1-amine (6c)
(2E)-N-Benzyl-4-(trityloxy)-N-[(2E)-4-(trityloxy)but-2-
enyl]but-2-en-1-amine (4c¢)
Following general procedure 2 using 1c (Table 1, entries 10–12)
with separation by flash column chromatography (silica gel, PE–
EtOAc, 20:1); TLC: Rf = 0.42 (1c), 0.46 (5c), 0.34 (6c) (PE–EtOAc,
5:1, KMnO4). HPLC [Daicel Chiralpak AD-H, 250 × 4.6 mm, 5 mm,
with guard cartridge 10 × 4 mm, 5 mm, n-hexane–i-PrOH, 98:2,
flow = 0.5 mL min–1, r.t., 210 nm]: tR = 18.2 [(+)-(R)-5c], 22.6 min
[(–)-(S)-5c].
Colorless oil.
1H NMR (300 MHz, CDCl3): d = 3.15 (d, J = 5.9 Hz, 4 H, CH2),
3.62–3.65 (m, 6 H, CH2, CH2Ph), 5.77 (dt, J = 15.6 Hz, J = 4.9 Hz,
2 H, CH=), 5.90 (dt, J = 15.5 Hz, J = 6.2 Hz, 2 H, CH=), 7.21–7.39
(m, 23 H, Ph), 7.47–7.50 (m, 12 H, Ph).
13C NMR (75 MHz, CDCl3): d = 55.31 (t, CH2), 57.54 (t, CH2Ph),
64.51 (t, CH2), 86.82 (s, CPh3), 126.81, 126.91, 127.77, 128.16,
128.61, 128.85, 129.02 (7 d, =CH, Ph), 130.14 (d, CH=), 139.32,
144.22 (2 s, Ph).
HRMS (FAB): m/z [M + H]+ calcd for C53H50NO2: 732.3841;
found: 732.3815.
(–)-(2S)-N-(4-Methoxyphenyl)-1-(trityloxy)but-3-en-2-amine
[(–)-(S)-5c]
Colorless oil.
[a]D20 –15.8 (c 1.02, CHCl3, 96% ee).
1H NMR (300 MHz, CDCl3): d = 3.24 (dd, J = 9.2 Hz, J = 6.2 Hz,
1 H, CHaHbO), 3.32 (dd, J = 9.2 Hz, J = 4.7 Hz, 1 H, CHaHbO), 3.75
(s, 3 H, CH3), 3.88–3.94 (m, 1 H, NCH), 5.19 (ddd, J = 10.4 Hz,
J = 1.3 Hz, J = 1.3 Hz, 1 H, CH=CHEHZ), 5.29 (ddd, J = 17.2 Hz,
J = 1.4 Hz, J = 1.4 Hz, 1 H, CH=CHEHZ), 5.87 (ddd, J = 17.3 Hz,
J = 10.4 Hz, J = 5.9 Hz, 1 H, CH=CH2), 6.56–6.60 (m, 2 H, Ph),
6.74–6.78 (m, 2 H, Ph), 7.22–7.34 (m, 9 H, Ph), 7.43–7.47 (m, 6 H,
Ph).
13C NMR (75 MHz, CDCl3): d = 55.93 (q, CH3), 57.55 (d, NCH),
66.11 (t, CH2O), 86.83 (s, CPh3), 114.86, 115.39 (2 d, Ph), 116.63
(t, CH=CH2), 127.21, 127.99, 128.81 (3 d, Ph), 138.09 (d,
CH=CH2), 141.83 (s, Ar), 144.00 (s, Ph), 152.40 (s, Ar).
Anal. Calcd. for C53H49NO2: C, 86.97; H, 6.75; N, 1.91. Found: C,
86.78; H, 6.99; N, 1.82.
(+)-(2S)-2-(Benzylamino)but-3-en-1-ol [(+)-(S)-3d] and (2E)-4-
(Benzylamino)but-2-en-1-ol (4d)
Following general procedure 2 using 1d or 2d (Table 1, entries 13–
16) with separation by flash column chromatography (silica gel,
PE–EtOAc, 4:3 to 1:3); TLC: Rf = 0.47 (2d), 0.39 (3d), 0.10 (4d)
(EtOAc, KMnO4). HPLC [Daicel Chiralcel OD-H, 250 × 4.6 mm, 5
mm, with guard cartridge 10 × 4 mm, 5 mm, n-hexane–i-PrOH,
85:15, flow = 0.5 mL min–1, r.t., 210 nm]: tR = 11.0 [(–)-(R)-3d],
12.7 [(+)-(S)-3d], 15.8 min (4d).
HRMS (FAB): m/z [M]+ calcd for C30H29NO2: 435.2198; found:
435.2170.
(+)-(2S)-2-(Benzylamino)but-3-en-1-ol [(+)-(S)-3d]
Colorless solid; mp 57–58 °C.
[a]D20 +18.1 (c 0.98, CHCl3, 93% ee).
Anal. Calcd. for C30H29NO2: C, 82.73; H, 6.71; N, 3.22. Found: C,
82.96; H, 6.81; N, 3.05.
(2E)-N-(4-Methoxyphenyl)-4-(trityloxy)but-2-en-1-amine (6c)
Colorless oil.
1H NMR (300 MHz, CDCl3): d = 2.00 (br s, 2 H, NH, OH), 3.23
(ddd, J = 7.6 Hz, J = 7.6 Hz, J = 4.5 Hz, 1 H, NCH), 3.39 (dd,
J = 10.5 Hz, J = 7.9 Hz, 1 H, CHaHbO), 3.62 (dd, J = 10.5 Hz,
J = 4.5 Hz, 1 H, CHaHbO), 3.68 (d, J = 12.9 Hz, 1 H, NCHaHbPh),
3.89 (d, J = 13.0 Hz, 1 H, NCHaHbPh), 5.21–5.27 (m, 2 H,
CH=CH2), 5.62–5.76 (m, 1 H, CH=CH2), 7.22–7.34 (m, 5 H, Ph).
13C NMR (75 MHz, CDCl3): d = 51.06 (t, NCH2Ph), 62.17 (d,
NCH), 64.74 (t, CH2O), 117.95 (t, CH=CH2), 127.24, 128.36,
128.61 (3 d, Ph), 128.95 (s, Ph), 137.40 (d, CH=CH2), 140.20 (s,
Ph).
1H NMR (300 MHz, CDCl3): d = 3.28 (br s, 1 H, NH), 3.66 (dd,
J = 4.8 Hz, J = 1.3 Hz, 2 H, NCH2), 3.75–3.77 (m, 2 H, CH2O), 3.77
(s, 3 H, CH3), 5.83 (dt, J = 15.6 Hz, J = 4.9 Hz, 1 H, =CH), 5.97 (dt,
J = 15.5 Hz, J = 5.5 Hz, 1 H, =CH), 6.61–6.66 (m, 2 H, Ph), 6.78–
6.84 (m, 2 H, Ph), 7.23–7.35 (m, 9 H, Ph), 7.47–7.50 (m, 6 H, Ph).
13C NMR (75 MHz, CDCl3): d = 46.89 (t, CH2O), 55.91 (q, CH3),
64.41 (t, NCH2), 86.99 (s, CPh3), 114.56, 114.97 (2 d, Ar), 127.10,
127.94, 128.04, 128.73, 129.09 (5 d, Ph, CH=CH), 142.37 (s, Ar),
144.27 (s, Ph), 152.38 (s, Ar).
Synthesis 2008, No. 20, 3331–3350 © Thieme Stuttgart · New York

FEATURE ARTICLE
Enantioselective Iridium-Catalyzed Allylic Aminations
3343
HRMS (FAB): m/z [M]+ calcd for C30H29NO2: 435.2198; found:
435.2227.
flow = 0.5 mL min–1, r.t., 210 nm]: tR = 22.1 [(–)-(R)-7], 27.1 min
[(+)-(S)-7].
Anal. Calcd for C30H29NO2: C, 82.73; H, 6.71; N, 3.22. Found: C,
82.80; H, 6.82; N, 3.16.
tert-Butyl Formyl{(1S)-1-[(trityloxy)methyl]prop-2-enyl}car-
bamate [(+)-(S)-7]
Colorless oil.
[a]D20 +39.0 (c 1.08, CHCl3, 97% ee).
(+)-(2S)-2-[(4-Methoxyphenyl)amino]but-3-en-1-ol [(+)-(S)-5d]
Following general procedure 2 using 1d (Table 1, entries 17–19)
with purification by flash column chromatography (silica gel, PE–
EtOAc, 10:1) gave 5d as a yellow oil; TLC: Rf = 0.42 (1d), 0.46
(5d) (EtOAc, KMnO4). HPLC [Daicel Chiralcel OD-H, 250 × 4.6
mm, 5 mm, with guard cartridge 10 × 4 mm, 5 mm, n-hexane–
i-PrOH, 85:15, flow = 0.5 mL min–1, r.t., 210 nm]: tR = 18.3
[(+)-(S)-5d], 20.1 min [(–)-(R)-5d].
1H NMR (300 MHz, CDCl3): d = 1.42 [s, 9 H, C(CH3)3], 3.36 (dd,
J = 8.9 Hz, J = 5.9 Hz, 1 H, CHaHbO), 3.48 (dd, J = 9.0 Hz, J = 9.0
Hz, 1 H, CHaHb), 5.14 (ddd, J = 10.4 Hz, J = 1.2 Hz, J = 1.2 Hz, 1
H, CH=CHEHZ), 5.17 (ddd, J = 17.4 Hz, J = 1.3 Hz, J = 1.3 Hz, 1
H, CH=CHEHZ), 5.34 (ddd, J = 7.3 Hz, J = 7.2 Hz, J = 7.0 Hz, 1 H,
NCH), 5.91 (ddd, J = 17.3 Hz, J = 10.4 Hz, J = 6.7 Hz, 1 H,
CH=CH2), 7.20–7.33 (m, 9 H, Ph), 7.39–7.43 (m, 6 H, Ph), 9.29 (s,
1 H, CHO).
13C NMR (75 MHz, CDCl3): d = 28.07 [q, C(CH3)3], 54.17 (d,
NCH), 63.21 (t, CH2O), 84.15 [s, C(CH3)3], 86.65 (s, CPh3), 118.24
(t, CH=CH2), 127.14, 127.94, 128.75 (3 d, Ph), 133.84 (d,
CH=CH2), 143.94 (s, Ph), 152.55 (s, CO2), 163.41 (d, CHO).
[a]D20 +20.1 (c 1.02, CHCl3, 82.5% ee).
1H NMR (300 MHz, CDCl3): d = 2.72 (br s, 2 H, NH, OH), 3.59 (dd,
J = 10.8 Hz, J = 6.8 Hz, 1 H, CHaHbO), 3.74 (s, 3 H, CH3), 3.77 (dd,
J = 11.1 Hz, J = 4.4 Hz, 1 H, CHaHbO), 3.91–3.98 (m, 1 H, NCH),
5.23 (ddd, J = 10.4 Hz, J = 1.3 Hz, J = 1.3 Hz, 1 H, CH=CHEHZ),
5.29 (ddd, J = 17.2 Hz, J = 1.4 Hz, J = 1.4 Hz, 1 H, CH=CHEHZ),
5.79 (ddd, J = 17.4 Hz, J = 10.4 Hz, J = 5.7 Hz, 1 H, CH=CH2),
6.62–6.67 (m, 2 H, Ar), 6.73–6.80 (m, 2 H, Ar).
13C NMR (75 MHz, CDCl3): d = 55.87 (q, CH3), 59.02 (d, NCH),
65.06 (t, CH2O), 114.94 (d, Ar), 115.78 (d, Ar), 117.49 (t,
CH=CH2), 136.78 (d, CH=CH2), 141.35 (s, Ar), 152.76 (s, Ar).
HRMS (FAB): m/z [M + Na]+ calcd for C29H31NNaO4: 480.2151;
found: 480.2089.
Anal. Calcd for C29H31NO4: C, 76.12; H, 6.83; N, 3.06. Found: C,
76.19; H, 6.92; N, 3.07.
The enantiomeric excess of carbamate 7 was determined after
cleavage of the formyl protecting group. A soln of 7 (1.10 g, 2.40
mmol) in anhyd MeOH (20.0 mL) was treated with KOH (202 mg,
3.61 mmol) at r.t. for 7 h (complete conversion) [TLC: Rf = 0.19 (7),
0.15 (7¢) (PE–Et2O, 4:1)]. Acidic ion exchange resin (Amberlite IR-
120, Merck) was added in portions until pH 7 was reached. The
mixture was filtered, the filtrate concentrated in vacuo, and the res-
idue subjected to flash column chromatography (silica gel, PE–
Et2O, 9:1) to give tert-butyl {(1S)-1-[(trityloxy)methyl]prop-2-
enyl}carbamate (7¢) (1.03 g, quantitative yield) as a colorless solid;
mp 93–95 °C. HPLC [Daicel Chiralpak AD-H, 250 × 4.6 mm, 5 mm,
with guard cartridge 10 × 4 mm, 5 mm, n-hexane–i-PrOH, 99:1,
flow = 0.5 mL min–1, r.t., 210 nm] tR = 34.1 [(+)-(R)-7¢], 47.0 min
[(–)-(S)-7¢].
HRMS (FAB): m/z [M]+ calcd for C11H15NO2: 193.1103; found:
193.1118.
Anal. Calcd for C11H15NO2: C, 68.37; H, 7.82; N, 7.25. Found: C,
68.28; H, 7.84; N, 7.20.
(2E)-4-[(4-Methoxyphenyl)amino]but-2-en-1-ol (6d)
A
soln of (2E)-4-(tert-butyldiphenylsiloxy)-N-(4-methoxyphe-
nyl)but-2-en-1-amine25 (250 mg, 0.579 mmol) in anhyd MeOH (1
mL) was added dropwise to methanolic HCl prepared by dropping
AcCl (0.4 mL, 5.8 mmol, 10 equiv) into anhyd MeOH (8 mL). After
3 d [TLC: Rf = 0.17 (6d) (PE–EtOAc, 3:1, KMnO4)] the soln was
diluted with Et2O (20 mL) and washed with sat. aq NaHCO3 soln
(20 mL). The aqueous layer was separated and extracted with Et2O
(5 × 20 mL). The combined organic layers were dried (Na2SO4), fil-
tered, and concentrated in vacuo. Purification by flash column chro-
matography (silica gel, PE–EtOAc, 4:1) yielded 6d (81 mg, 72%)
as a colorless solid; mp 72–73 °C; HPLC [Daicel Chiralcel OD-H,
250 × 4.6 mm, 5 mm, with guard cartridge 10 × 4 mm, 5 mm, n-hex-
ane–i-PrOH, 85:15, flow = 0.5 mL min–1, r.t., 210 nm] tR = 37.0
min (6d).
tert-Butyl Formyl[(2E)-4-(trityloxy)but-2-enyl]carbamate (8)
Colorless solid; mp 89–91 °C.
1H NMR (300 MHz, CDCl3): d = 1.56 [s, 9 H, C(CH3)3], 3.58–3.59
(m, 2 H, CH2O), 4.21 (dd, J = 3.3 Hz, J = 1.2 Hz, 2 H, NCH2), 5.70–
5.84 (m, 2 H, CH=CH), 7.20–7.32 (m, 9 H, Ph), 7.41–7.45 (m, 6 H,
Ph), 9.20 (s, 1 H, CHO).
13C NMR (75 MHz, CDCl3): d = 28.20 [q, C(CH3)3], 41.95 (t,
CH2N), 64.09 (t, CH2O), 84.14 [s, C(CH3)3], 86.99 (s, CPh3), 125.15
(d, CH=), 127.13 127.95, 128.73 (3 d, Ph) 130.78 (d, CH=), 144.22
(s, Ph), 152.57 (s, CO2), 162.81 (d, CHO).
1H NMR (300 MHz, CDCl3): d = 2.55 (br s, 2 H, NH, OH), 3.71–
3.75 (m, 2 H, NCH2), 3.74 (s, 3 H, CH3), 4.12–4.14 (m, 2 H, CH2O),
5.77–5.92 (m, 2 H, CH=CH), 6.57–6.64 (m, 2 H, Ar), 6.75–6.81 (m,
2 H, Ar).
13C NMR (75 MHz, CDCl3): d = 46.55 (t, NCH2), 55.93 (q, CH3),
63.18 (t, CH2O), 114.57, 115.03 (2 d, Ar), 129.23 (d, NCH2CH),
131.16 (d, CHCH2O), 142.21, 152.45 (2 s, Ar).
HRMS (FAB): m/z [M]+ calcd for C29H31NO4: 457.2253; found:
457.2228.
Anal. Calcd for C29H31NO4: C, 76.12; H, 6.83; N, 3.06. Found: C,
76.11; H, 7.01; N, 3.18.
HRMS (FAB): m/z [M]+ calcd for C11H15NO2: 193.1103; found:
193.1111.
Anal. Calcd for C11H15NO2: C, 68.37; H, 7.82; N, 7.25. Found: C,
68.16; H, 7.76; N, 7.23.
(+)-Di-tert-butyl {(1S)-1-[(Trityloxy)methyl]prop-2-enyl}imi-
dodicarbonate [(+)-(S)-9] and Di-tert-butyl [(2E)-4-(Trityl-
oxy)but-2-enyl]imidodicarbonate (10)
tert-Butyl Formyl{(1S)-1-[(trityloxy)methyl]prop-2-enyl}car-
bamate [(+)-(S)-7] and tert-Butyl Formyl[(2E)-4-(trityloxy)but-
2-enyl]carbamate (8)
Following general procedure 2 using 1c (Table 2, entries 1–4) with
separation by flash column chromatography (silica gel, PE–Et2O,
10:1 to 5:1); TLC: Rf = 0.44 (1c), 0.50 (7), 0.44 (8) (PE–EtOAc, 3:1,
KMnO4). HPLC [Daicel Chiralpak AD-H, 250 × 4.6 mm, 5 mm,
with guard cartridge 10 × 4 mm, 5 mm, n-hexane–i-PrOH, 99.5:0.5,
Following general procedure 2 using 1c (Table 2, entries 5–10) with
separation by flash column chromatography (silica gel, PE–Et2O,
19:1 to 9:1); TLC: Rf = 0.24 (1c), 0.31 (9), 0.40 (10) (PE–EtOAc,
10:1, KMnO4). HPLC [Daicel Chiralcel OD-H, 250 × 4.6 mm, 5
mm, with guard cartridge 10 × 4 mm, 5 mm, n-hexane–i-PrOH,
99.5:0.5, flow = 0.5 mL min–1, r.t., 210 nm]: tR = 8.4 [(+)-(S)-9],
17.8 min [(–)-(R)-9].
Synthesis 2008, No. 20, 3331–3350 © Thieme Stuttgart · New York

3344
C. Gnamm et al.
FEATURE ARTICLE
(+)-Di-tert-butyl {(1S)-1-[(Trityloxy)methyl]prop-2-enyl}imi-
dodicarbonate [(+)-(S)-9]
HRMS (FAB): m/z [M + Na]+ calcd for C31H25NNaO3: 482.1732;
found: 482.1729.
Colorless rhombic plates; mp 143–146 °C.
[a]D20 +25.7 (c 0.97, CHCl3, 97% ee).
Anal. Calcd for C31H25NO3: C, 81.02; H, 5.48; N, 3.05. Found: C,
80.78; H, 5.44; N, 3.02.
1H NMR (500 MHz, CDCl3): d = 1.46 [s, 18 H, C(CH3)3], 3.22 (dd,
J = 8.9 Hz, J = 5.6 Hz, 1 H, CHaHbO), 3.56 (dd, J = 8.9 Hz, J = 8.8
Hz, 1 H, CHaHbO), 5.09–5.16 (m, 1 H, NCH), 5.11 (d, J = 10.1 Hz,
1 H, CH=CHEHZ), 5.16 (d, J = 17.4 Hz, 1 H, CH=CHEHZ), 5.87
(ddd, J = 17.2 Hz, J = 10.7 Hz, J = 6.3 Hz, 1 H, CH=CH2), 7.21–
7.24 (m, 3 H, Ph), 7.27–7.30 (m, 6 H, Ph), 7.44–7.46 (m, 6 H, Ph).
13C (125 MHz, CDCl3): d = 28.17 [q, C(CH3)3], 58.86 (d, NCH),
64.62 (t, CH2O), 82.33 [s, C(CH3)3], 86.59 (s, CPh3), 117.34 (t,
CH=CH2), 127.05, 127.84, 128.89 (3 d, Ph), 135.01 (d, CH=CH2),
144.18 (s, Ph), 153.00 (CO2).
2-[(2E)-4-(Trityloxy)but-2-enyl]-1H-isoindole-1,3(2H)-dione
(12)
White solid; mp 117–118 °C.
1H NMR (200 MHz, CDCl3): d = 3.59 (d, J = 3.3 Hz, 2 H, CH2O),
4.30 (d, J = 4.9 Hz, 2 H, CH2N), 5.77 (dt, J = 15.4 Hz, J = 4.0 Hz,
1 H, CHCH2O), 5.89 (dt, J = 15.6 Hz, J = 5.0 Hz, 1 H, CHCH2N),
7.14–7.30 (m, 9 H, Ph), 7.37–7.43 (m, 6 H, Ph), 7.65–7.74 (m, 2 H,
Ar), 7.80–7.89 (m, 2 H, Ar).
13C NMR (75 MHz, CDCl3): d = 39.36 (t, OCH2), 63.98 (t, NCH2),
87.01 (s, CPh3), 123.40 (d, Ar), 124.27 (d, NCH2CH), 127.08 (d,
Ph), 127.93, 128.71 (2 d, Ar), 131.10 (d, OCH2CH), 132.31 (s, Ar),
134.06 (d, Ar), 144.16 (s, Ph), 168.04 (s, C=O).
HRMS (FAB): m/z [M + H]+ calcd for C33H40NO5: 530.2907;
found: 530.2882.
Anal. Calcd for C33H39NO5: C, 74.83; H, 7.42; N, 2.64. Found: C,
74.83; H, 7.41; N, 2.68.
HRMS (FAB): m/z [M + Na]+ calcd for C31H25NNaO3: 482.1732;
found: 482.1747.
Di-tert-butyl [(2E)-4-(Trityloxy)but-2-enyl]imidodicarbonate
(10)
Anal. Calcd for C31H25NO3: C, 81.02; H, 5.48; N, 3.05. Found: C,
80.85; H, 5.49; N, 3.05.
Colorless oil.
(–)-2-Nitro-N-{(1S)-1-[(trityloxy)methyl]prop-2-enyl}benzene-
sulfonamide [(–)-(S)-13] and 2-Nitro-N-[(2E)-4-(trityloxy)but-
2-enyl]benzenesulfonamide (14)
Following general procedure 2 using 1c (Table 2, entries 14–16)
with separation by flash column chromatography (silica gel, PE–
EtOAc, 4:1); TLC: Rf = 0.49 (1c), 0.32 (13), 0.28 (14) (PE–EtOAc,
4:1, KMnO4). HPLC [Daicel Chiralpak AD-H, 250 × 4.6 mm, 5 mm,
with guard cartridge 10 × 4 mm, 5 mm, n-hexane–i-PrOH, 95:5,
flow = 0.5 mL min–1, r.t., 210 nm]: tR = 43.3 [(+)-(R)-13], 49.1 min
[(–)-(S)-13].
1H NMR (300 MHz, CDCl3): d = 1.53 [s, 18 H, C(CH3)3], 3.60 (d,
J = 4.7 Hz, 2 H, CH2O), 4.21 (d, J = 5.7 Hz, 2 H, CH2N), 5.76 (dt,
J = 15.7 Hz, J = 4.5 Hz, 1 H, CHCH2O), 5.87 (dt, J = 15.5 Hz,
J = 5.7 Hz, 1 H, CHCH2N), 7.27–7.33 (m, 9 H, Ph), 7.42–7.44 (m,
6 H, Ph).
13C NMR (75 MHz, CDCl3): d = 28.23 [q, C(CH3)3], 47.83 (t,
CH2O), 64.24 (t, CH2N), 82.40 [s, C(CH3)3], 86.93 (s, CPh3), 126.86
(d, CHCH2N), 127.10, 127.92, 128.73 (3 d, Ph), 129.68 (d,
CHCH2O), 144.28 (s, Ph), 152.39 (s, CO2).
HRMS (FAB): m/z [M + H]+ calcd for C33H40NO5: 530.2907;
found: 530.2953.
(–)-2-Nitro-N-{(1S)-1-[(trityloxy)methyl]prop-2-enyl}benzene-
sulfonamide [(–)-(S)-13]
White solid; mp 58–59 °C.
[a]D20 –5.85 (c 1.08, CHCl3, 95% ee).
Anal. Calcd for C33H39NO5: C, 74.83; H, 7.42; N, 2.64. Found: C,
74.54; H, 7.58; N, 2.44.
1H NMR (300 MHz, CDCl3): d = 3.17 (dd, J = 9.4 Hz, J = 4.1 Hz,
1 H, CHaHbO), 3.25 (dd, J = 9.4 Hz, J = 5.1 Hz, 1 H, CHaHbO), 4.07
(dddd, J = 5.8 Hz, J = 5.8 Hz, J = 5.8 Hz, J = 5.7 Hz, 1 H, NCH),
5.09 (d, J = 10.4 Hz, 1 H, CH=CHEHZ), 5.19 (d, J = 17.1 Hz, 1 H,
CH=CHEHZ), 5.80 (ddd, J = 17.1 Hz, J = 10.4 Hz, J = 6.6 Hz, 1 H,
CH=CH2), 5.97 (d, J = 7.5 Hz, 1 H, NH), 7.20–7.30 (m, 9 H, Ph),
7.33–7.42 (m, 6 H, Ph), 7.62–7.70 (m, 2 H, Ar), 7.80–7.85 (m, 1 H,
Ar), 8.01–8.06 (m, 1 H, Ar).
13C NMR (75 MHz, CDCl3): d = 57.50 (d, NCH), 65.81 (t, CH2O),
87.07 (s, CPh3), 117.63 (t, CH=CH2), 125.46 (d, Ar), 127.29,
127.97, 128.63 (3 d, Ph), 131.01, 132.80, 133.42 (3 d, Ar), 134.81
(s, Ar), 135.23 (d, CH=CH2), 143.37 (s, Ph), 147.82 (s, Ar).
(+)-2-{(1S)-1-[(Trityloxy)methyl]prop-2-enyl}-1H-isoindole-
1,3(2H)-dione [(+)-(S)-11] and 2-[(2E)-4-(Trityloxy)but-2-enyl]-
1H-isoindole-1,3(2H)-dione (12)
Following general procedure 2 using 1c (Table 2, entries 11–13)
with separation by flash column chromatography (silica gel, PE–
Et2O, 9:1); TLC: Rf = 0.42 (1c), 0.37 (11), 0.32 (12) (PE–EtOAc,
4:1, KMnO4). HPLC [Daicel Chiralpak AD-H, 250 × 4.6 mm, 5 mm,
with guard cartridge 10 × 4 mm, 5 mm, n-hexane–i-PrOH, 98.5:1.5,
flow = 0.5 mL min–1, r.t., 210 nm]: tR = 60.4 [(+)-(S)-11], 67.6 min
[(–)-(R)-11].
(+)-2-{(1S)-1-[(Trityloxy)methyl]prop-2-enyl}-1H-isoindole-
1,3(2H)-dione [(+)-(S)-11]
Colorless microcrystals; mp 98–99 °C.
HRMS (FAB): m/z [(32S)M]+ calcd for C29H26N2O532S: 514.1562;
found: 514.1553.
[a]D20 +30.5 (c 0.97, CHCl3, 96% ee).
Anal. Calcd for C29H26N2O5S: C, 67.69; H, 5.09; N, 5.44; S, 6.23.
Found: C, 67.59; H, 5.19; N, 5.18; S, 6.00.
1H NMR (300 MHz, CDCl3): d = 3.49 (dd, J = 9.4 Hz, J = 5.4 Hz,
1 H, CHaHbO), 3.73 (dd, J = 9.3 Hz, J = 9.3 Hz, 1 H, CHaHbO),
5.04–5.12 (m, 1 H, NCH), 5.21 (ddd, J = 10.4 Hz, J = 1.1 Hz,
J = 1.1 Hz, 1 H, CH=CHEHZ), 5.27 (ddd, J = 17.3 Hz, J = 1.2 Hz,
J = 1.2 Hz, 1 H, CH=CHEHZ), 6.16 (ddd, J = 17.4 Hz, J = 10.3 Hz,
J = 7.3 Hz, 1 H, CH=CH2), 7.17–7.27 (m, 9 H, Ph), 7.34–7.39 (m,
6 H, Ph), 7.68–7.74 (m, 2 H, Ar), 7.82–7.88 (m, 2 H, Ar).
13C NMR (75 MHz, CDCl3): d = 54.15 (d, NCH), 63.16 (t, CH2O),
86.76 (s, CPh3), 119.07 (t, CH=CH2), 123.29 (d, Ar), 127.10 (d, Ph),
127.88, 128.68 (2 d, Ph), 132.12 (s, Ar), 132.57 (d, CH=CH2),
133.99 (d, Ar), 143.82 (s, Ph), 168.02 (s, C=O).
2-Nitro-N-[(2E)-4-(trityloxy)but-2-enyl]benzenesulfonamide
(14)
White solid; mp 50–53 °C.
1H NMR (200 MHz, CDCl3): d = 3.51–3.52 (m, 2 H, CH2O), 3.77–
3.82 (m, 2 H, CH2N), 5.38 (t, J = 6.1 Hz, 1 H, NH), 5.61–5.81 (m,
2 H, CH=CH), 7.20–7.40 (m, 15 H, Ph), 7.59–7.72 (m, 2 H, Ar),
7.77–7.86 (m, 1 H, Ar), 8.09–8.18 (m, 1 H, Ar).
13C NMR (75 MHz, CDCl3): d = 45.73 (t, CH2N), 63.65 (t, CH2O),
87.00 (s, CPh3), 124.86 (d, =CH), 125.47 (d, Ar), 127.23, 127.98,
Synthesis 2008, No. 20, 3331–3350 © Thieme Stuttgart · New York

FEATURE ARTICLE
Enantioselective Iridium-Catalyzed Allylic Aminations
3345
128.66 (3 d, Ph), 131.26 (d, Ar), 131.47 (d, =CH), 132.90, 133.66
(2 d, Ar), 134.34 (s, Ar), 144.03 (s, Ph), 148.14 (s, Ar).
HRMS (FAB): m/z [(32S)M]+ calcd for C29H26N2O532S: 514.1562;
[a]D20 –31.1 (c 1.53, CHCl3, 93% ee).
1H NMR (300 MHz, CDCl3): d = 1.44, 1.47 [2 s, 18 H, C(CH3)3],
4.09 (dd, J = 11.0 Hz, J = 4.6 Hz, 1 H, CHaHbO), 4.15 (dd, J = 11.3
Hz, J = 5.5 Hz, 1 H, CHaHbO), 4.42 (br s, 1 H, NCH), 4.83 (br s, 1
H, NH), 5.20 (ddd, J = 10.5 Hz, J = 1.2 Hz, J = 1.2 Hz, 1 H,
CH=CHEHZ), 5.27 (ddd, J = 17.2 Hz, J = 1.6 Hz, J = 1.1 Hz, 1 H,
CH=CHEHZ), 5.80 (ddd, J = 17.2 Hz, J = 10.5 Hz, J = 5.3 Hz, 1 H,
CH=CH2).
13C NMR (75 MHz, CDCl3): d = 27.86, 28.49 [2 q, C(CH3)3], 52.07
(d, NCH), 68.25 (t, CH2O), 79.84, 82.61 [2 s, C(CH3)3], 116.80 (t,
=CH2), 134.94 (d, =CH), 153.58, 155.30 (2 s, CO2).
found: 514.1565.
Anal. Calcd for C29H26N2O5S: C, 67.69; H, 5.09; N, 5.44; S, 6.23.
Found: C, 67.74; H, 5.23; N, 5.16; S, 5.97.
tert-Butyl [(1S)-1-(Hydroxymethyl)prop-2-enyl]carbamate
[(S)-15]
Following general procedure 2 using 1d (Table 3, entries 1–3) with
purification by flash column chromatography (silica gel, PE–
EtOAc, 2:1 to 1:1 to 0:1). The 1H NMR data as well as the optical
rotation of this compound were in excellent agreement with report-
ed data.26 The 13C NMR data have not been reported and, therefore,
is given below.
13C NMR (75 MHz, CDCl3): d = 28.50 [q, C(CH3)3], 54.87 (d,
NCH), 65.40 (t, CH2O), 80.01 [s, C(CH3)3], 116.75 (t, =CH2),
135.57 (d, =CH), 156.13 (s, CO2).
HRMS (FAB): m/z [M + H]+ calcd for C14H26NO5: 288.1811;
found: 288.1763.
Anal. Calcd for C14H25NO5: C, 58.52; H, 8.77; N, 4.87. Found: C,
58.35; H, 8.68; N, 5.02.
Di-tert-Butyl [(2E)-4-Hydroxybut-2-enyl]imidodicarbonate
(18)
For determination of the enantiomeric purity of 15, a sample was
benzylated to give the known tert-butyl {(1S)-1-[(benzyloxy)meth-
yl]prop-2-enyl}carbamate (15¢).27 HPLC [Daicel Chiralcel OJ-H,
250 × 4.6 mm, 5 mm, with guard cartridge 10 × 4 mm, 5 mm, n-hex-
ane–i-PrOH, 99:1, flow = 0.5 mL min–1, r.t., 210 nm]: tR = 31.3
[(–)-(R)-15¢], 36.1 min [(+)-(S)-15¢].
Following general procedure 3 using (2E)-4-bromobut-2-en-1-ol
gave 18 as a colorless oil; TLC: Rf = 0.61 [(2E)-4-bromobut-2-en-
1-ol], 0.39 (18) (PE–EtOAc, 1:1, KMnO4).
1H NMR (300 MHz, CDCl3): d = 1.49 [s, 18 H, C(CH3)3], 1.54 (t,
J = 5.9 Hz, 1 H, OH), 4.13 (dd, J = 5.0 Hz, J = 5.0 Hz, 2 H, CH2O),
4.17 (d, J = 4.7 Hz, 2 H, CH2N), 5.72 (dt, J = 15.4 Hz, J = 4.6 Hz,
1 H, CHCH2N), 5.79 (dt, J = 15.4 Hz, J = 4.4 Hz, 1 H, CHCH2O).
13C NMR (75 MHz, CDCl3): d = 28.23 [q, C(CH3)3], 47.49 (t,
CH2N), 63.15 (t, CH2O), 82.54 [s, C(CH3)3], 127.20 (d, CHCH2N),
131.66 (d, CHCH2O), 152.52 (s, CO2).
Synthesis of Linear Allylic Amides from Allylic Bromides by
Nucleophilic Substitution; General Procedure 3
K2CO3 (2.0 mmol) and HN(CHO)Boc, NaNBoc2, or phthalimide
(1.0 mmol) were added to a soln of (2E)-4-bromobut-2-en-1-ol (1.0
mmol) in anhyd DMF (10 mL) and the mixture was stirred at r.t. un-
til complete conversion was reached. H2O (10 mL) was added, and
the mixture was extracted with EtOAc (2 × 20 mL). The combined
organic layers were washed with H2O, dried (anhyd Na2SO4), and
concentrated in vacuo. Pure products were obtained by flash col-
umn chromatography (silica gel, PE–EtOAc, detection: UV and
KMnO4).
HRMS (FAB): m/z [M + H]+ calcd for C14H26NO5: 288.1811;
found: 288.1833.
Anal. Calcd for C14H25NO5: C, 58.52; H, 8.77; N, 4.87. Found: C,
58.29; H, 8.75; N, 4.94.
(–)-2-[(1S)-1-(Hydroxymethyl)prop-2-enyl]-1H-isoindole-
1,3(2H)-dione [(–)-(S)-19]
Following general procedure 2 using 1d (Table 3, entries 7–9). The
spectroscopic data was in full agreement with that reported.13 HPLC
[Daicel Chiralcel OJ-H, 250 × 4.6 mm, 5 mm, with guard cartridge
10 × 4 mm, 5 mm, n-hexane–i-PrOH, 90:10, flow = 0.5 mL min–1,
r.t., 210 nm]: tR = 39.2 [(–)-(S)-19], 42.1 min [(+)-(R)-19].
tert-Butyl Formyl[(2E)-4-hydroxybut-2-enyl]carbamate (16)
Following general procedure 3 using (2E)-4-bromobut-2-en-1-ol
gave 16 as a colorless oil; TLC: Rf = 0.61 [(2E)-4-bromobut-2-en-
1-ol], 0.32 (16) (PE–EtOAc, 1:1, KMnO4).
1H NMR (300 MHz, CDCl3): d = 1.48 (t, J = 5.8 Hz, 1 H, OH), 1.54
[s, 9 H, C(CH3)3], 4.12 (dd, J = 4.9 Hz, J = 4.9 Hz, 2 H, CH2O), 4.19
(dd, J = 5.8 Hz, J = 1.1 Hz, 2 H, CH2N), 5.66 (dtt, J = 15.5 Hz,
J = 5.7 Hz, J = 1.3 Hz, 1 H, CHCH2N), 5.80 (dtt, J = 15.5 Hz,
J = 5.1 Hz, J = 1.0 Hz, 1 H, CHCH2O), 9.17 (s, 1 H, CHO).
13C NMR (75 MHz, CDCl3): d = 28.19 [q, C(CH3)3], 41.70 (t,
CH2N), 62.93 (t, CH2O), 84.32 [s, C(CH3)3], 125.40 (d, CHCH2N),
132.65 (d, CHCH2O), 152.34 (s, CO2), 162.81 (d, CHO).
HRMS (EI): m/z [M]+ calcd for C10H17NO4: 215.1158; found:
215.1147.
2-[(2E)-4-Hydroxybut-2-enyl]-1H-isoindole-1,3(2H)-dione (20)
Following general procedure 3 using (2E)-4-bromobut-2-en-1-ol
(Table 3, entries 7–9) except for purification after extractive work-
up. Prior to chromatography, the crude product was extracted with
PE–CH2Cl2 (1:2, 3 ×) in order to remove phthalimide. The resulting
soln was concentrated in vacuo and the residue subjected to flash
column chromatography; TLC: Rf = 0.61 [(2E)-4-bromobut-2-en-1-
ol], 0.40 (20) (PE–EtOAc, 1:1, KMnO4). The spectroscopic data for
this compound was in full agreement with that reported.21,28
Anal. Calcd for C10H17NO4: C, 55.80; H, 7.96; N, 6.51. Found: C,
55.85; H, 8.04; N, 6.45.
(+)-(5S)-1-Benzyl-5-vinylpyrrolidin-2-one [(+)-(S)-21f¢] and
Methyl (4E)-6-(Benzylamino)hex-4-enoate (22f)
Following general procedure 2 using 1f (Table 4, entry 10) and ent-
L2 as ligand; separation was by flash column chromatography (sil-
ica gel, PE–EtOAc, 1:1 to 1:2); TLC: Rf = 0.47 (1f), 0.14 (21f¢),
0.02 (22f) (PE–EtOAc, 1:1, KMnO4). HPLC [Daicel Chiralpak AD-
H, 250 × 4.6 mm, 5 mm, with guard cartridge 10 × 4 mm, 5 mm, n-
hexane–i-PrOH, 97:3, flow = 0.5 mL min–1, r.t., 210 nm]: tR = 42.3
[(+)-(S)-21f¢], 44.2 min [(–)-(R)-21f¢].
(–)-(2S)-2-[(tert-Butoxycarbonyl)amino]but-3-enyl tert-Butyl
Carbonate [(–)-(S)-17]
Following general procedure 2 using 1d with NaNBoc2 (Table 3,
entries 4–6) with purification by flash column chromatography (sil-
ica gel, PE–EtOAc, 9:1 to EtOAc) to give 17 as a colorless oil; TLC:
Rf = 0.29 (1d), 0.63 (17), 0.28 (tert-butyl 2-oxo-4-vinyloxazolidi-
none-3-carboxylate) (PE–EtOAc, 1:1, KMnO4). GC [Chrompack
permethyl-b-cyclodextrin, 25 m × 0.25 mm, temperature 130 °C,
injector temperature 200 °C]: tR = 60.7 [(+)-(R)-17], 62.7 min
[(–)-(S)-17].
(+)-(5S)-1-Benzyl-5-vinylpyrrolidin-2-one [(+)-(S)-21f¢]
Pale brown oil.
[a]D20 +164 [c 0.85, MeOH, 93% ee (S)].
Synthesis 2008, No. 20, 3331–3350 © Thieme Stuttgart · New York

3346
C. Gnamm et al.
FEATURE ARTICLE
1H NMR (300 MHz, CDCl3): d = 1.69–1.81 (m, 1 H, NCHCHaHb),
2.10–2.23 (m, 1 H, NCHCHaHb), 2.32–2.55 (m, 2 H, CH2CO),
3.83–3.90 (m, 1 H, NCH), 3.84 (d, J = 14.8 Hz, 1 H, PhCHaHb),
4.98 (d, J = 14.6 Hz, 1 H, PhCHaHb), 5.13 (dd, J = 17.2 Hz,
J = 0.7 Hz, 1 H, CH=CHEHZ), 5.21 (dd, J = 10.1 Hz, J = 1.2 Hz, 1
H, CH=CHEHZ), 5.64 (ddd, J = 17.0 Hz, J = 10.0 Hz, J = 8.4 Hz, 1
H, CH=CH2), 7.20–7.33 (m, 5 H, Ph).
13C NMR (75 MHz, CDCl3): d = 25.40 (t, NCHCH2), 30.10 (t,
CH2CO), 44.27 (t, PhCH2), 60.49 (d, NCH), 118.31 (t, CH=CH2),
127.49, 128.44, 128.65 (3 d, Ph), 136.86 (s, Ph), 137.59 (d,
CH=CH2), 174.98 (s, CO).
Methyl (4E)-6-[(4-Methoxyphenyl)amino]hex-4-enoate (24f)
Colorless oil.
1H NMR (300 MHz, CDCl3): d = 2.36–2.43 (m, 4 H, CH2CH2), 3.43
(br s, 1 H, NH), 3.65–3.69 (m, 2 H, NCH2), 3.67 (s, 3 H, CO2CH3),
3.75 (s, 3 H, OCH3), 5.57–5.76 (m, 2 H, CH=CH), 6.55–6.61 (m, 2
H, Ar), 6.74–6.80 (m, 2 H, Ar).
13C NMR (75 MHz, CDCl3): d = 27.68, 33.81 (2 t, CH2CH2), 46.97
(t, NCH2), 51.70 (q, CO2CH3), 55.92 (q, OCH3), 114.47, 114.97 (2
d, Ar), 128.71, 130.75 (2 d, CH=CH), 142.46, 152.32 (2 s, Ar),
173.56 (s, CO2).
HRMS (EI): m/z [M]+ calcd for C14H19NO3: 249.1365; found:
249.1375.
HRMS (EI): m/z [M]+ calcd for C13H15NO: 201.1154; found:
201.1167.
(–)-tert-Butyl Formyl{(1S)-1-[2-(trityloxy)ethyl]prop-2-
enyl}carbamate [(–)-(S)-25e] and tert-Butyl Formyl[(2E)-5-(tri-
tyloxy)pent-2-enyl]carbamate (26e)
Following general procedure 2 using 1e (Table 4, entry 2) and ent-
L2 as ligand; separation was by flash column chromatography (sil-
ica gel, PE–Et2O 10:1); TLC: Rf = 0.40 (1e), 0.47 (25e), 0.44 (26e)
(PE–EtOAc, 4:1, KMnO4). HPLC [Daicel Chiralpak AD-H, 250 ×
4.6 mm, 5 mm, with guard cartridge 10 × 4 mm, 5 mm, n-hexane–
i-PrOH, 95:5, flow = 0.5 mL min–1, r.t., 220 nm]: tR = 11.6 [(–)-(S)-
25e], 13.2 min [(+)-(R)-25e].
Methyl (4E)-6-(Benzylamino)hex-4-enoate (22f)
Pale brown oil.
1H NMR (300 MHz, CDCl3): d = 1.44 (br s, 1 H, NH), 2.35–2.42
(m, 4 H, CH2CH2), 3.20–3.22 (m, 2 H, NCH2), 3.67 (s, 3 H, OCH3),
3.76 (s, 2 H, PhCH2), 5.59–5.61 (m, 2 H, CH=CH), 7.22–7.29 (m, 5
H, Ph).
13C NMR (75 MHz, CDCl3): d = 27.75 (t, CH2CH2CO2), 33.91 (t,
CH2CO2), 51.04 (t, NCH2CH), 51.68 (q, CH3), 53.40 (t, PhCH2),
127.05, 128.31, 128.52, 129.73, 130.49 (5 d, Ph, CH=), 140.44 (s,
Ph), 173.64 (s, CO2).
(–)-tert-Butyl Formyl{(1S)-1-[2-(trityloxy)ethyl]prop-2-
enyl}carbamate [(–)-(S)-25e]
Colorless solid; mp 89–90 °C.
HRMS (EI): m/z [M]+ calcd for C14H19NO2: 233.1416; found:
233.1411.
[a]D20 –12.6 [c 1.20, CHCl3, 92% ee (S)].
Anal. Calcd for C14H19NO2: C, 72.07; H, 8.21; N, 6.00. Found: C,
71.78; H, 8.06; N, 5.94.
1H NMR (300 MHz, CDCl3): d = 1.47 [s, 9 H, C(CH3)3], 2.06–2.28
(m, 2 H, NCHCH2), 2.98–3.11 (m, 2 H, CH2O), 5.06 (dd, J = 10.1
Hz, J = 1.0 Hz, 1 H, CH=CHEHZ), 5.11 (dd, J = 17.0 Hz, J = 1.2 Hz,
1 H, CH=CHEHZ), 5.17 (ddd, J = 7.1 Hz, J = 7.1 Hz, J = 7.1 Hz, 1
H, CHN), 5.97 (ddd, J = 17.2 Hz, J = 10.2 Hz, J = 6.9 Hz, 1 H,
CH=CH2), 7.19–7.31 (m, 9 H, Ph), 7.41–7.44 (m, 6 H, Ph), 9.10 (s,
1 H, CHO).
13C NMR (75 MHz, CDCl3): d = 28.16 [q, C(CH3)3], 32.50 (t,
NCHCH2), 52.12 (d, NCH), 60.53 (t, CH2O), 84.03 [s, C(CH3)3],
86.75 (s, CPh3), 117.15 (t, CH=CH2), 127.04, 127.85, 128.82 (3 d,
Ph), 136.46 (d, CH=CH2), 144.26 (s, Ph), 152.48 (s, CO2), 163.30
(d, CHO).
(+)-Methyl (4S)-4-[(4-Methoxyphenyl)amino]hex-5-enoate
[(+)-(S)-23f] and Methyl (4E)-6-[(4-Methoxyphenyl)amino]hex-
4-enoate (24f)
Following general procedure 2 using 1f (Table 4, entries 11–13)
with separation by flash column chromatography (silica gel, PE–
EtOAc, 10:1); TLC: Rf = 0.34 (1f), 0.29 (23f), 0.19 (24f) (PE–Et2O,
1:1, KMnO4). HPLC [Daicel Chiralcel OD-H, 250 × 4.6 mm, 5 mm,
with guard cartridge 10 × 4 mm, 5 mm, n-hexane–i-PrOH, 9:1,
flow = 0.5 mL min–1, r.t., 254 nm]: tR = 22.8 [(–)-(R)-23f], 38.8 min
[(+)-(S)-23f].
(+)-Methyl (4S-)4-[(4-Methoxyphenyl)amino]hex-5-enoate
[(+)-(S)-23f]
Colorless oil.
[a]D20 +9.6 [c 0.96, MeOH, 90% ee (S)].
HRMS (ESI): m/z [M + Na]+ calcd for C30H33NNaO4: 494.2302;
found: 494.2303.
Anal. Calcd for C30H33NO4: C, 76.41; H, 7.05; N, 2.97. Found: C,
76.67; H, 7.14; N, 2.89.
1H NMR (300 MHz, CDCl3): d = 1.90 (dt, J = 7.1 Hz, J = 7.1 Hz, 2
H, CH2CH2CO2), 2.46 (t, J = 7.3 Hz, 2 H, CH2CO2), 3.42 (br s, 1 H,
NH), 3.67 (s, 3 H, CO2CH3), 3.73 (s, 3 H, OCH3), 3.79 (ddd,J = 6.7
Hz, J = 6.7 Hz, J = 6.6 Hz, 1 H, NCH), 5.14 (ddd, J = 10.3 Hz,
J = 1.2 Hz, J = 1.2 Hz, 1 H, CH=CHEHZ), 5.20 (ddd, J = 17.2 Hz,
J = 1.3 Hz, J = 1.3 Hz, 1 H, CH=CHEHZ), 5.72 (ddd, J = 17.1 Hz,
J = 10.4 Hz, J = 6.4 Hz, 1 H, CH=CH2), 6.54–6.59 (m, 2 H, Ar),
6.73–6.78 (m, 2 H, Ar).
13C NMR (75 MHz, CDCl3): d = 30.51 (t, CH2CO2), 30.78 (t,
CH2CH2CO2), 51.74 (q, CO2CH3), 55.88 (q, OCH3), 56.57 (d,
NCH), 114.92, 114.98 (2 d, Ar), 115.93 (t, CH=CH2), 139.68 (d,
CH=CH2), 141.57, 152.22 (2 s, Ar), 174.13 (s, CO2).
tert-Butyl Formyl[(2E)-5-(trityloxy)pent-2-enyl]carbamate
(26e)
Colorless oil.
1H NMR (300 MHz, CDCl3): d = 1.43 [s, 9 H, C(CH3)3], 2.27 (dt,
J = 6.7 Hz, J = 6.7 Hz, 2 H, CH2CH2O), 3.02 (t, J = 6.8 Hz, 2 H,
CH2O), 4.07 (d, J = 6.0 Hz, 2 H, NCH2), 5.41 (dt, J = 15.4 Hz,
J = 6.2 Hz, 1 H, CHCH2N), 5.62 (dt, J = 15.1 Hz, J = 7.2 Hz, 1 H,
CH=CHCH2O), 7.16–7.26 (m, 9 H, Ph), 7.35–7.38 (m, 6 H, Ph),
9.11 (s, 1 H, CHO).
13C NMR (75 MHz, CDCl3): d = 28.16 [q, C(CH3)3], 33.15 (t,
CH2CH2O), 42.20 (t, CH2N), 63.19 (t, CH2O), 83.98 [s, C(CH3)3],
86.58 (s, CPh3), 125.85 (d, CH=), 127.01 127.87, 128.79 (3 d, Ph),
131.28 (d, CH=), 144.38 (s, Ph), 152.49 (s, CO2), 162.79 (d, CHO).
HRMS (EI): m/z [M]+ calcd for C14H19NO3: 249.1365; found:
249.1378.
Anal. Calcd. for C14H19NO3: C, 67.45; H, 7.68; N, 5.62. Found: C,
67.42; H, 7.68; N, 5.66.
HRMS (ESI): m/z [M + K]+ calcd for C30H33KNO4: 510.2041;
found: 510.2048.
Anal. Calcd for C30H33NO4: C, 76.41; H, 7.05; N, 2.97. Found: C,
76.63; H, 6.99; N, 2.86.
Synthesis 2008, No. 20, 3331–3350 © Thieme Stuttgart · New York

FEATURE ARTICLE
Enantioselective Iridium-Catalyzed Allylic Aminations
3347
(+)-Di-tert-butyl {(1R)-[2-(Trityloxy)ethyl]prop-2-enyl}imido-
dicarbonate [(+)-(R)-27e] and Di-tert-butyl [(2E)-5-(Trityl-
oxy)pent-2-enyl]imidodicarbonate (28e)
Following general procedure 2 using 1e (Table 4, entries 4–6) with
separation by flash column chromatography (silica gel, PE–Et2O,
15:1); TLC: Rf = 0.38 (1e), 0.47 (27e), 0.44 (28e) (PE–EtOAc, 4:1,
KMnO4). HPLC [Daicel Chiralpak AD-H, 250 × 4.6 mm, 5 mm,
with guard cartridge 10 × 4 mm, 5 mm, n-hexane–i-PrOH, 96:4,
flow = 0.5 mL min–1, r.t., 210 nm] tR = 8.1 [(–)-(S)-27e], 8.8 min
[(+)-(R)-27e].
1H NMR (300 MHz, CDCl3): d = 1.48 [s, 18 H, C(CH3)3], 2.01–2.26
(m, 2 H, CH2CH2CO2), 2.33 (t, J = 7.8 Hz, 2 H, CH2CO2), 3.66 (s,
3 H, OCH3), 4.63–4.70 (m, 1 H, NCH), 5.13 (ddd, J = 10.7 Hz.
J = 1.3 Hz, J = 1.3 Hz, 1 H, CH=CHEHZ), 5.18 (ddd, 17.5 Hz,
J = 1.4 Hz, J = 1.4 Hz, 1 H, CH=CHEHZ), 5.97 (ddd, J = 17.2 Hz,
J = 10.5 Hz, J = 6.7 Hz, 1 H, CH=CH2).
13C NMR (75 MHz, CDCl3): d = 27.81 (t, CH2CH2CO2), 28.15 [q,
C(CH3)3], 31.08 (t, CH2CO2), 51.73 (q, OCH3), 58.47 (d, NCH),
82.52 [s, C(CH3)3], 117.03 (t, CH=CH2), 137.16 (d, CH=CH2),
153.02 (s, NCO2), 173.53 (s, CO2CH3).
HRMS (FAB): m/z [M + Na]+ calcd for C17H29NNaO6: 366.1893;
found: 366.1869.
(+)-Di-tert-butyl {(1R)-[2-(Trityloxy)ethyl]prop-2-enyl}imido-
dicarbonate [(+)-(R)-27e]
Colorless powder; mp 85–86 °C.
[a]D20 +3.2 [c 1.42, CHCl3, 98% ee (R)].
Anal. Calcd for C17H29NO6: C, 59.46; H, 8.51; N, 4.08. Found: C,
59.49; H, 8.47; N, 4.24.
1H NMR (300 MHz, CDCl3): d = 1.47 [s, 18 H, C(CH3)3], 2.08
(dddd, J = 13.8 Hz, J = 6.8 Hz, J = 6.8 Hz J = 6.7 Hz, 1 H, NCH-
CHaHb), 2.22 (dddd, J = 13.7 Hz, J = 7.1 Hz, J = 7.0 Hz J = 6.9 Hz,
1 H, NCHCHaHb), 3.04–3.18 (m, 2 H, CH2O), 4.94 (ddd, J = 7.2
Hz, J = 7.2 Hz, J = 7.1 Hz, 1 H, NCH), 5.08 (ddd, J = 10.3 Hz,
J = 1.2 Hz, J = 1.2 Hz, 1 H, CH=CHEHZ), 5.14 (ddd, J = 17.3 Hz,
J = 1.4 Hz, J = 1.4 Hz, 1 H, CH=CHEHZ), 5.98 (ddd, J = 17.2 Hz,
J = 10.4 Hz, J = 6.7 Hz, 1 H, CH=CH2), 7.21–7.34 (m, 9 H, Ph),
7.44–7.48 (m, 6 H, Ph).
13C NMR (75 MHz, CDCl3): d = 28.16 [q, C(CH3)3], 33.35 (t,
NCHCH2), 56.50 (d, NCH), 60.67 (t, CH2O), 82.21 [s, C(CH3)3],
86.67 (s, CPh3), 116.46 (t, CH=CH2), 126.97, 127.84, 128.83 (3 d,
Ph), 137.52 (d, CH=CH2), 144.43 (s, Ph), 152.97 (CO2).
The enantiomeric excess of this compound was determined after the
removal of one Boc group as follows. A soln of carbamate 27f (46.2
mg, 0.13 mmol) in CH2Cl2 (1 mL) was treated with TFA (18 mg,
0.16 mmol) at 0 °C. The resulting soln was stirred at r.t. for 6 h until
complete conversion (TLC). The solvent was evaporated in vacuo,
and the crude product was subjected to flash chromatography (silica
gel, PE–EtOAc, 4:1) to yield methyl (4S)-4-[(tert-butoxycarbon-
yl)amino]hex-5-enoate (27f¢) (30.7 mg, 97%) as a colorless pow-
der; mp 53–54 °C. HPLC [Daicel Chiralpak AD-H, 250 × 4.6 mm,
5 mm, with guard cartridge 10 × 4 mm, 5 mm, n-hexane–i-PrOH,
95:5, flow = 0.5 mL min–1, r.t., 210 nm]: tR = 21.6 [(–)-(S)-27f¢],
23.1 min [(+)-(R)-27f¢].
Methyl (4E)-6-[Bis(tert-butoxycarbonyl)amino]hex-4-enoate
(28f)
HRMS (ESI): m/z [M + K]+ calcd for C34H41KNO5: 582.2616;
found: 582.2624.
Colorless oil.
Anal. Calcd for C34H41NO5: C, 75.11; H, 7.60; N, 2.58. Found: C,
74.89; H, 7.54; N, 2.52.
1H NMR (300 MHz, CDCl3): d = 1.48 [s, 18 H, C(CH3)3], 2.30–2.40
(m, 4 H, CH2CH2), 3.65 (s, 3 H, OCH3), 4.08 (d, J = 5.3 Hz, 2 H,
NCH2), 5.44–5.65 (m, 2 H, CH=CH).
Di-tert-butyl [(2E)-5-(Trityloxy)pent-2-enyl]imidodicarbonate
(28e)
Colorless oil.
13C NMR (75 MHz, CDCl3): d = 27.59 (t, CH2CH2CO2), 28.19 [q,
C(CH3)3], 33.77 (t, CH2CO2), 47.88 (t, NCH2), 51.67 (q, OCH3),
82.33 [s, C(CH3)3], 126.69 (d, NCH2CH), 131.36 (d, CH2CH2CH),
152.44 (s, NCO2), 173.47 (s, CO2CH3).
HRMS (FAB): m/z [M + H]+ calcd for C17H30NO6: 344.2073;
found: 344.2072.
1H NMR (300 MHz, CDCl3): d = 1.45 [s, 18 H, C(CH3)3], 2.35 (dt,
J = 6.8 Hz, J = 6.7 Hz, 2 H, CH2CH2O), 3.08 (t, J = 6.9 Hz, 2 H,
CH2O), 4.09 (d, J = 5.7 Hz, 2 H, CH2N), 5.51 (dt, J = 15.6 Hz,
J = 5.7 Hz, 1 H, CHCH2N), 5.63 (dt, J = 15.4 Hz, J = 6.5 Hz, 1 H,
CHCH2CH2O), 7.19–7.31 (m, 9 H, Ph), 7.40–7.44 (m, 6 H, Ph).
13C NMR (75 MHz, CDCl3): d = 28.21 [q, C(CH3)3], 33.19 (t,
CH2CH2O), 48.04 (t, CH2O), 63.47 (t, CH2N), 82.25 [s, C(CH3)3],
86.60 (s, CPh3), 126.99 (d, Ph), 127.34 (d, CH=), 127.86, 128.79 (2
d, Ph), 130.15 (d, CH=), 144.41 (s, Ph), 152.47 (s, CO2).
Anal. Calcd for C17H29NO6: C, 59.46; H, 8.51; N, 4.08. Found: C,
59.55; H, 8.56; N, 4.07.
(+)-Di-tert-butyl [(1S,2E)-4-(Trityloxy)-1-vinylbut-2-enyl]imi-
dodicarbonate [(+)-(S)-27g] and Di-tert-butyl [(2E,4E)-6-(Tri-
tyloxy)hexa-2,4-dienyl]imidodicarbonate (28g)
Following general procedure 2 using 1g (Table 4, entries 19, 20)
with separation by flash column chromatography (silica gel, n-pen-
tane–i-PrOH, 20:1); TLC: Rf = 0.35 (1g), 0.44 (27g), 0.39 (28g)
(PE–EtOAc, 5:1, KMnO4). HPLC [Daicel Chiralcel OD-H, 250 ×
4.6 mm, 5 mm, with guard cartridge 10 × 4 mm, 5 mm, n-hexane–
i-PrOH, 99.1:0.1, flow = 0.5 mL min–1, r.t., 220 nm]: tR = 29.8
[(–)-(R)-27g], 32.0 min [(+)-(S)-27g].
HRMS (ESI): m/z [M + K]+ calcd for C34H41KNO5: 582.2616;
found: 582.2618.
Anal. Calcd for C34H41NO5: C, 75.11; H, 7.60; N, 2.58. Found: C,
74.94; H, 7.39; N, 2.35.
(–)-Methyl (4S)-4-[Bis(tert-butoxycarbonyl)amino]hex-5-
enoate [(–)-(S)-27f] and Methyl (4E)-6-[Bis(tert-butoxycarbon-
yl)amino]hex-4-enoate (28f)
Following general procedure 2 using 1f (Table 4, entry 17) and ent-
L2 as ligand; separation was by flash column chromatography (sil-
ica gel, PE–EtOAc, 15:1); TLC: Rf = 0.16 (1f), 0.29 (27f), 0.21
(28f) (PE–EtOAc, 4:1, KMnO4).
(+)-Di-tert-butyl [(1S,2E)-4-(Trityloxy)-1-vinylbut-2-enyl]imi-
dodicarbonate [(+)-(S)-27g]
Colorless oil.
[a]D20 +1.27 [c 0.99, CHCl3, >99% ee (S)].
1H NMR (300 MHz, CDCl3): d = 1.51 (s, 18 H, CH3), 3.63 (d,
J = 4.7 Hz, 2 H, CH2OCPh3), 5.19 (dt, J = 10.3 Hz, J = 1.4 Hz, 1 H,
CH=CHEHZ), 5.22 (dt, J = 17.3 Hz, J = 1.4 Hz, 1 H, CH=CHEHZ),
5.29–5.33 (m, 1 H, CHN), 5.75 (ddt, J = 15.7 Hz, J = 4.8 Hz, J = 1.2
Hz, 1 H, CHCH2O), 6.02–6.14 (m, 2 H, CH=CH2, CHCHCH2),
7.20–7.33 (m, 9 H, Ph), 7.44–7.48 (m, 6 H, Ph).
(–)-Methyl (4S)-4-[Bis(tert-butoxycarbonyl)amino]hex-5-
enoate [(–)-(S)-27f]
Colorless oil.
[a]D20 –5.70 [c 1.28, MeOH, 98% ee (S)].
Synthesis 2008, No. 20, 3331–3350 © Thieme Stuttgart · New York

3348
C. Gnamm et al.
FEATURE ARTICLE
13C NMR (75 MHz, CDCl3): d = 28.21 (q, CH3), 60.23 (d, CHN),
64.18 (t, CH2O), 82.56 (s, CCH3), 86.96 (s, CPh3), 116.71 (t, =CH2),
127.10, 127.92, 128.75 (3 d, Ph), 129.26 (d, CHCHCH2), 130.14 (d,
CHCH2), 137.28 (d, CH=CH2), 144.29 (s, Ph), 152.54 (s, CO2).
HRMS (FAB): m/z [M + Na]+ calcd for C35H41NNaO5: 578.2882;
found: 578.2907.
1H NMR (300 MHz, CDCl3): d = 2.32 (dt, J = 6.5 Hz, J = 6.5 Hz, 2
H, CH2CH2O), 3.07 (t, J = 6.7 Hz, 2 H, CH2O), 4.24 (dd, J = 6.0 Hz,
J = 0.8 Hz, 2 H, CH2N), 5.58 (dt, J = 15.3 Hz, J = 6.1 Hz, 1 H,
CHCH2N), 5.77 (dt, J = 15.1 Hz, J = 6.9 Hz, 1 H, CHCH2CH2O),
7.17–7.30 (m, 9 H, Ph), 7.36–7.41 (m, 6 H, Ph), 7.67–7.72 (m, 2 H,
Ar), 7.81–7.84 (m, 2 H, Ar).
13C NMR (75 MHz, CDCl3): d = 33.10 (t, CH2CH2O), 39.60 (t,
OCH2), 62.96 (t, NCH2), 86.53 (s, CPh3), 123.37 (d, Ar), 125.27 (d,
NCH2CH), 126.97, 127.85, 128.79 (3 d, Ph), 131.70 (d,
CH2CH2CH), 132.34 (s, Ar), 134.00 (d, Ar), 144.37 (s, Ph), 168.08
(s, C=O).
Anal. Calcd for C35H41NO5: C, 75.65; H, 7.44; N, 2.52. Found: C,
75.65; H, 7.49; N, 2.51.
Di-tert-butyl [(2E,4E)-6-(Trityloxy)hexa-2,4-dienyl]imidodicar-
bonate (28g)
Colorless plates.
HRMS (ESI): m/z [M + K]+ calcd for C32H27KNO3: 512.1622;
found: 512.1627.
1H NMR (300 MHz, CDCl3): d = 1.51 (s, 18 H, CH3), 3.65 (d,
J = 5.0 Hz, 2 H, CH2OCPh3), 4.21 (d, J = 6.2 Hz, 2 H, CH2N), 5.66–
5.79 (m, 2 H, CHCH2), 6.15–6.39 (m, 2 H, CHCHCH2), 7.20–7.33
(m, 9 H, Ph), 7.43–7.47 (m, 6 H, Ph).
Anal. Calcd for C32H27NO3: C, 81.16; H, 5.75; N, 2.96. Found: C,
81.19; H, 5.92; N, 2.82.
(+)-2-[(1R,2E)-4-(Trityloxy)-1-vinylbut-2-enyl]-1H-isoindole-
1,3(2H)-dione [(+)-(R)-29g] and 2-[(2E,4E)-6-(Trityloxy)hexa-
2,4-dienyl]-1H-isoindole-1,3(2H)-dione (30g)
Following general procedure 2 using 1g (Table 4, entries 21, 22)
and ent-L1 and ent-L2 as ligands; separation was by flash column
chromatography (silica gel, PE–EtOAc, 9:1); TLC: Rf = 0.35 (1g),
0.27 (29g), 0.21 (30g) (PE–EtOAc, 5:1, KMnO4). HPLC [Daicel
Chiralcel OD-H, 250 × 4.6 mm, 5 mm, with guard cartridge 10 × 4
mm, 5 mm, n-hexane–i-PrOH, 98:2, flow = 0.5 mL min–1, r.t., 220
nm]: tR = 21.2 [(+)-(R)-29g], 23.5 min [(–)-(S)-29g].
13C NMR (75 MHz, CDCl3): d = 28.25 (q, CH3), 47.95 (t, CH2N),
64.49 (t, CH2OCPh3), 82.47 [s, C(CH3)3], 87.00 (s, CPh3), 127.11,
127.95 (2 d, Ph), 128.40 (d, CHCH2N), 128.77 (d, Ph), 130.27 (d,
CHCH2O), 130.42 (d, CHCHCH2O), 132.33 (d, CHCHCH2N),
144.28 (s, Ph), 152.52 (s, NCO2).
HRMS (FAB): m/z [M + Na]+ calcd for C35H41NNaO5: 578.2882;
found: 578.2928.
Anal. Calcd for C35H41NO5: C, 75.65; H, 7.44; N, 2.52. Found: C,
75.58; H, 7.51; N, 2.50.
(+)-2-[(1R,2E)-4-(Trityloxy)-1-vinylbut-2-enyl]-1H-isoindole-
1,3(2H)-dione [(+)-(R)-29g]
Colorless solid; mp 47–49 °C.
[a]D20 +0.73 [c 1.01, CHCl3, >99% ee (R)].
1H NMR (300 MHz, CDCl3): d = 3.64 (d, J = 5.1 Hz, 2 H, OCH2),
5.23–5.33 (m, 2 H, =CH2), 5.34–5.39 (m, 1 H, CHN), 5.85 (ddt,
J = 15.5 Hz, J = 5.1 Hz, J = 1.0 Hz, 1 H, CHCH2O), 6.15–6.28 (m,
2 H, CHCHCH2, CH=CH2), 7.18–7.30 (m, 9 H, Ph), 7.41–7.45 (m,
6 H, Ph), 7.68–7.74 (m, 2 H, Ar), 7.81–7.87 (m, 2 H, Ar).
13C NMR (75 MHz, CDCl3): d = 55.03 (d, NCH), 64.28 (t,
CH2OCPh3), 87.10 (s, CPh3), 117.91 (t, =CH2), 123.40 (d, Ar),
127.11 (d, Ph), 127.37 (d, CHCHCH2), 127.95, 128.75 (2 d, Ph),
131.23 (d, CHCH2), 132.17 (s, Ar), 134.10 (d, Ar), 134.93 (d,
CH=CH2), 144.17 (s, Ph), 167.69 (s, C=O).
(+)-2-{(1S)-1-[2-(Trityloxy)ethyl]prop-2-enyl}-1H-isoindole-
1,3(2H)-dione [(+)-(S)-29e] and 2-[(2E)-5-(Trityloxy)pent-2-
enyl]-1H-isoindole-1,3(2H)-dione (30e)
Following general procedure 2 using 1e (Table 4, entry 8) and ent-
L2 as ligand; separation was by flash column chromatography (sil-
ica gel, PE–Et2O, 10:1); TLC: Rf = 0.36 (1e), 0.31 (29e), 0.26 (30e)
(PE–EtOAc, 4:1, KMnO4). HPLC [Daicel Chiralpak AD-H, 250 ×
4.6 mm, 5 mm, with guard cartridge 10 × 4 mm, 5 mm, n-hexane–
i-PrOH, 95:5, flow = 0.5 mL min–1, r.t., 220 nm]: tR = 19.9 [(+)-(S)-
29e], 28.5 min [(–)-(R)-29e].
(+)-2-{(1S)-1-[2-(Trityloxy)ethyl]prop-2-enyl}-1H-isoindole-
1,3(2H)-dione [(+)-(S)-29e]
Colorless foam; mp 42–43 °C.
[a]D20 +36.3 [c 1.40, CHCl3, 93% ee (S)].
1H NMR (300 MHz, CDCl3): d = 2.19–2.30 (m, 1 H, NCHCHaHb),
2.47–2.58 (m, 1 H, NCHCHaHb), 3.06–3.19 (m, 2 H, CH2O), 5.12
(ddd, J = 7.8 Hz, J = 7.6 Hz, J = 7.1 Hz, 1 H, NCH), 5.16 (dd,
J = 10.2 Hz, J = 0.9 Hz, 1 H, CH=CHEHZ), 5.23 (dd, J = 17.1 Hz,
J = 1.1 Hz, 1 H, CH=CHEHZ), 6.16 (dddd, J = 17.2 Hz, J = 10.2 Hz,
J = 7.2 Hz, J = 0.9 Hz, 1 H, CH=CH2), 7.15–7.30 (m, 9 H, Ph),
7.39–7.42 (m, 6 H, Ph), 7.70–7.75 (m, 2 H, Ar), 7.79–7.83 (m, 2 H,
Ar).
HRMS (FAB): m/z [M + Na]+ calcd for C33H27NO3Na: 508.1888;
found: 508.1921.
Anal. Calcd for C33H27NO3: C, 81.63; H, 5.60; N, 2.88. Found: C,
81.36; H, 5.60; N, 2.94.
2-[(2E,4E)-6-(Trityloxy)hexa-2,4-dienyl]-1H-isoindole-1,3(2H)-
dione (30g)
Colorless, rectangular plates; mp 179–181 °C.
13C NMR (75 MHz, CDCl3): d = 32.15 (t, NCHCH2), 51.44 (d,
NCH), 60.32 (t, CH2O), 86.68 (s, CPh3), 117.29 (t, CH=CH2),
123.21 (d, Ar), 126.89, 127.77, 128.71 (3 d, Ph), 132.11 (s, Ar),
133.85 (d, CH=CH2), 135.68 (d, Ar), 144.06 (s, Ph), 168.10 (s,
C=O).
1H NMR (300 MHz, CDCl3): d = 3.59 (d, J = 5.1 Hz, 2 H,
CH2OCPh3), 4.31 (d, J = 6.2 Hz, 2 H, CH2N), 5.68–5.82 (m, 2 H,
CHCH2), 6.23–6.37 (m, 2 H, CHCHCH2), 7.16–7.29 (m, 9 H, Ph),
7.38–7.42 (m, 6 H, Ph), 7.66–7.72 (m, 2 H, Ar), 7.80–7.86 (m, 2 H,
Ar).
HRMS (ESI): m/z [M + K]+ calcd for C32H27KNO3: 512.1623;
found: 512.1623.
13C NMR (75 MHz, CDCl3): d = 39.43 (t, CH2N), 64.29 (t,
CH2OCPh3), 86.95 (s, CPh3), 123.44 (d, Ar), 125.90 (d, CHCH2N),
127.10, 127.95, 128.73 (3 d, Ph), 129.61 (d, CHCHCH2O), 131.55
(d, CHCH2O), 132.33 (s, Ar), 133.61 (d, CHCHCH2N.), 134.09 (d,
Ar), 144.23 (s, Ph), 168.07 (s, C=O).
Anal. Calcd for C32H27NO3: C, 81.16; H, 5.75; N, 2.96. Found: C,
81.09; H, 5.91; N, 2.82.
2-[(2E)-5-(Trityloxy)pent-2-enyl]-1H-isoindole-1,3(2H)-dione
(30e)
HRMS (FAB): m/z [M + Na]+ calcd for C33H27NO3Na: 508.1888;
found: 508.1932.
Colorless solid; mp 108–109 °C.
Anal. Calcd for C33H27NO3: C, 81.63; H, 5.60; N, 2.88. Found: C,
81.38; H, 5.64; N, 2.94.
Synthesis 2008, No. 20, 3331–3350 © Thieme Stuttgart · New York

FEATURE ARTICLE
Enantioselective Iridium-Catalyzed Allylic Aminations
3349
Dimethyl [(2E)-4-Hydroxybut-2-enyl]malonate (31)
References
2-Vinyloxirane (1.77 g, 25.4 mmol) was added dropwise to a soln
of dimethyl malonate (2.23 g, 16.9 mmol), Pd(PPh3)4 (97 mg, 84
mmol), and dppe (33 mg, 84 mmol) in anhyd THF (30 mL) under an
argon atmosphere at –78 °C. The mixture was stirred for 3 h until
complete consumption of the substrate [TLC: Rf = 0.42 (dimethyl
malonate), 0.15 (31) (PE–Et2O, 1:1, KMnO4)]. The mixture was al-
lowed to warm to r.t. and the solvent was removed in vacuo. The re-
sidual oil (E/Z ratio of 15:1, determined by 1H NMR) was purified
by flash chromatography (silica gel, 150 g, PE–EtOAc, 1:1) to yield
pure 31 (2.67 g, 78%) as a colorless oil. The spectroscopic data for
31 was in full agreement with that reported.15
(1) (a) Trost, B. M.; Lee, C. In Catalytic Asymmetric Synthesis,
2nd ed.; Ojima, I., Ed.; Wiley-VCH: New York, 2000, 593.
(b) Pfaltz, A.; Lautens, M. In Comprehensive Asymmetric
Catalysis I-III; Jacobsen, E. N.; Pfaltz, A.; Yamamoto, H.,
Eds.; Springer: Berlin, 1999, 833.
(2) (a) Dai, L.-X.; Tu, T.; You, S.-L.; Deng, W.-P.; Hou, X.-L.
Acc. Chem. Res. 2003, 36, 659. (b) Trost, B. M.; Jiang, C.
Org. Lett. 2003, 5, 1563; and literature cited. (c) Johns,
A. M.; Liu, Z.; Hartwig, J. F. Angew. Chem. Int. Ed. 2007,
46, 7259.
(3) Reviews: (a) Helmchen, G.; Dahnz, A.; Dübon, P.;
Schelwies, M.; Weihofen, R. Chem. Commun. 2007, 675.
(b) Takeuchi, R.; Kezuka, S. Synthesis 2006, 3349.
(c) Miyabe, H.; Takemoto, Y. Synlett 2005, 1641.
(4) (a) Feringa, B. L. Acc. Chem. Res. 2000, 33, 346.
(b) Tissot-Croset, K.; Polet, D.; Gille, S.; Hawner, C.;
Alexakis, A. Synthesis 2004, 2586.
(5) (a) Bartels, B.; Helmchen, G. Chem. Commun. 1999, 741.
(b) Bartels, B.; Garcia-Yebra, C.; Helmchen, G. Eur. J. Org.
Chem. 2003, 1097. (c) Lipowsky, G.; Miller, N.; Helmchen,
G. Angew. Chem. Int. Ed. 2004, 43, 4595; Angew. Chem.
2004, 116, 4695. (d) Streiff, S.; Welter, C.; Schelwies, M.;
Lipowsky, G.; Miller, N.; Helmchen, G. Chem. Commun.
2005, 2957. (e) Polet, D.; Alexakis, A.; Tissot-Croset, K.;
Corminboeuf, C.; Ditrich, K. Chem.–Eur. J. 2006, 12, 3596;
and literature cited. (f) Kanayama, T.; Yoshida, K.; Miyabe,
H.; Takemoto, Y. Angew. Chem. Int. Ed. 2003, 42, 2054;
Angew. Chem. 2003, 115, 2100.
Methyl (4E)-6-Hydroxyhex-4-enoate (32)
A flame-dried Schlenk tube under argon was charged with NaCl
(1.75 g, 30.0 mmol), 31 (3.03 g, 15.0 mmol), H2O (1.62 g, 90.0
mmol), a small amount (<0.1 mg) of 2,6-di-tert-butyl-4-methylphe-
nol as radical inhibitor, and DMSO (10 mL). The mixture was
stirred at 150 °C for 15 h until complete conversion of the starting
material [TLC and GC/MS monitoring: Rf = 0.20 (32), 0.15 (31)
(PE–Et2O, 1:2, KMnO4)]. Then H2O (75 mL) was added and the
aqueous phase was extracted with Et2O (4 × 150 mL). The com-
bined organic phases were washed with H2O (1 × 60 mL) and brine
(1 × 60 mL), dried (Na2SO4), filtered, and concentrated in vacuo.
The residue was subjected by flash chromatography [silica gel, 120
g, PE–Et2O, 1:2, Rf = 0.2 (32) (KMnO4)] to give 32 (1.82 g, 84%)
as a colorless oil.
1H NMR (300 MHz, CDCl3): d = 1.88 (br s, 1 H, OH), 2.32–2.42
(m, 4 H, CH2CH2), 3.65 (s, 3 H, OCH3), 4.05 (br s, 2 H, CH2OH),
5.59–5.72 (m, 2 H, CH=CH).
(6) (a) Ohmura, T.; Hartwig, J. F. J. Am. Chem. Soc. 2002, 124,
15164. (b) Kiener, C. A.; Shu, C.; Incarvito, C.; Hartwig,
J. F. J. Am. Chem. Soc. 2003, 125, 14272. (c) Lipowsky,
G.; Helmchen, G. Chem. Commun. 2004, 116. (d) Welter,
C.; Koch, O.; Lipowsky, G.; Helmchen, G. Chem. Commun.
2004, 896. (e) Welter, C.; Dahnz, A.; Brunner, B.; Streiff,
S.; Dübon, P.; Helmchen, G. Org. Lett. 2005, 7, 1239.
(f) Leitner, A.; Shu, C.; Hartwig, J. F. Org. Lett. 2005, 7,
1093. (g) Polet, D.; Alexakis, A. Org. Lett. 2005, 7, 1621.
(h) Welter, C.; Moreno, R. M.; Streiff, S.; Helmchen, G.
Org. Biomol. Chem. 2005, 3, 3266. (i) See ref. 3c.
(7) (a) Shu, C.; Leitner, A.; Hartwig, J. F. Angew. Chem. Int. Ed.
2004, 43, 4797; Angew. Chem. 2004, 116, 4901.
13C NMR (75 MHz, CDCl3): d = 27.48 (t, CH2CH2CH), 33.64 (t,
CH2CO2), 51.68 (q, CH3), 63.43 (t, CH2OH), 130.39, 130.49 (2 d,
CH=), 173.59 (s, CO2).
HRMS (EI): m/z [M]+ calcd for C7H12O3: 144.0786; found:
144.0816.
Anal. Calcd for C7H12O3: C, 58.32; H, 8.39. Found: C, 58.05; H,
8.44.
(4S)-4-Ammoniohex-5-enoate [(S)-Vigabatrin]
A mixture of (–)-(S)-27f (300 mg, 0.87 mmol), glacial AcOH (2.6
mL) and concd aq HCl (37%, 3.2 mL) was stirred at 60 °C for 12 h.
The solvent was removed in vacuo, and the residue was dissolved
in H2O (1 mL). This soln was passed through a column of Dowex
50WX8 ion exchange resin (4 g, 200–400 mesh, H+ form). The col-
umn was eluted with H2O until the eluant was neutral. Further elu-
tion with 0.2 M aq NH4OH, and removal of the latter in vacuo,
afforded (S)-vigabatrin (106 mg, 94%) as a colorless solid; mp 169–
171 °C. The spectroscopic data for this compound was in full agree-
ment with that reported.14
(b) Leitner, A.; Shekhar, S.; Pouy, M. J.; Hartwig, J. F.
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[a]D20 +12.0 [c 2.32, H2O, 98% ee (S)].
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Acknowledgment
This work was supported by the Deutsche Forschungsgemeinschaft
(SFB 623), the Fonds der Chemischen Industrie and the Studienstif-
tung des Deutschen Volkes. We thank Michel Neumann and Arina
Rybina for experimental assistance and Prof. Dr. Klaus Ditrich
(BASF AG) for enantiomerically pure 1-arylethylamines.
(11) We found deprotection of phthalimide derivatives with
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Synthesis 2008, No. 20, 3331–3350 © Thieme Stuttgart · New York