Intramolecular hydroamination of unactivated alkenes with secondary alkylamines catalyzed by iridium phosphino-phenolate complexes

Article abstract of DOI:10.1139/V09-181

The phosphino-phenolate complex (k²-{2-i-Pr₂PC ₆H₄}O)Ir(COD) (COD = η⁴-1,5-cyclooctadiene; 1) is shown to be an effective precatalyst for the intramolecular hydroamination of unactivated alkenes with

Full text of DOI:10.1139/V09-181

700
Intramolecular hydroamination of unactivated
alkenes with secondary alkylamines catalyzed by
iridium phosphino–phenolate complexes
Kevin D. Hesp, Robert McDonald, and Mark Stradiotto
Abstract: The phosphino–phenolate complex (k2-{2-i-Pr2PC6H4}O)Ir(COD) (COD = h4-1,5-cyclooctadiene; 1) is shown to
be an effective precatalyst for the intramolecular hydroamination of unactivated alkenes with pendant secondary alkyl-
amines, providing either pyrrolidine or piperidine heterocycles in high isolated yields. While monitoring the progress of a
1
selected test reaction of this type, a significant induction period (~3 h) was observed; variable-temperature H and 31P
NMR studies (25–100 8C) under catalytically relevant conditions revealed no new metal-containing species. In an effort to
develop an enantiopure variant of 1, a synthetic route to the chiral (k2-P,O)Ir(COD) complex (7), which features a 1-aryl-
2,5-dialkylphospholane structure derived from (2S,5S)-2,5-hexanediol cyclic sulfate, was developed. The structure of 7 was
confirmed by use of single-crystal X-ray diffraction techniques. While 7 failed to provide enantioselectivity in the intramo-
lecular hydroamination of unactivated alkenes with pendant secondary alkylamines, the activity of 7 was found to be com-
parable to that of 1.
Key words: catalysis, hydroamination, iridium, ligand design.
2
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Resume : On montre que le complexe phosphino–phenolate, (k -{2-iPr2PC6H4}O)Ir(COD) (1), est un precatalyseur effi-
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´
ˆ
´
cace pour l’hydroamination intramoleculaire d’alcenes non actives portant des chaınes laterales avec des alkylamines se-
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´
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condaires qui conduit a la formation d’heterocycles pyrrolidine ou piperidine avec des rendements eleves en produits
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isoles. En observant le progres d’une reaction de ce type choisie comme representative, on a observe une periode d’in-
1
31
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duction significative (environ 3 heures); des etudes de RMN du H et du P a temperature variable (25 a 100 8C), dans
´
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des conditions catalytiquement appropriees ont revele qu’il n’y a pas de nouvelles especes contenant un metal. Dans un ef-
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fort pour developper une variete enantiomeriquement pure du compose 1, on a mis au point une voie de synthese du com-
2
`
plexe chiral (k -P,O)Ir(COD), 7, qui inclut une structure 1-aryl-2,5-dialkylphospholane obtenue a partir du sulfate cyclique
´ ´
´
´
du (2S,5S)-hexane-2,5-diol. La structure du compose 7 a ete confirmee par des techniques de diffraction des rayons X par
ˆ
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un cristal unique. Meme si le compose 7 n’a pas permis d’obtenir d’enantioselectivite dans l’hydroamination intramolecu-
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ˆ
´
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laire d’alcenes non actives portant des chaınes laterales avec des alkylamines secondaires, l’activite de ce produit est com-
`
parable a celle du produit 1.
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Mots-cles : Catalyse, hydroamination, iridium, developpement d’un ligand.
route to nitrogen-containing heterocycles. However, while
catalyst systems employing Brønsted acids,2 rare earth ele-
ments and actinides,3 alkali and alkaline earth metals,4 group
4 metals,5 and groups 8–11 metals6,7 have all proven capable
of mediating the intramolecular hydroamination of such un-
activated aminoalkenes, general methods for promoting the
cyclization of these challenging substrates under mild condi-
tions and with broad substrate scope remain elusive.
We recently reported on the use of [Ir(COD)Cl]2 (COD =
h4-1,5-cyclooctadiene) as a precatalyst for the intramolecu-
lar addition of a variety of secondary alkyl- or aryl-amines
to unactivated alkenes, without the requirement of added li-
gands or cocatalysts7a; notably, this represents one of only a
Introduction
The prevalence of nitrogen-containing moieties in both
naturally occurring and biologically active molecules has
prompted the development of efficient methods for the for-
mation of C–N bonds, including the use of transition-metal
catalysis.1 Notwithstanding the tremendous success of Buch-
wald–Hartwig amination and related cross-coupling chemis-
try,1b,1c the inherent lack of atom economy associated with
such procedures has prompted the development of hydroa-
mination protocols that enable C–N bond formation via the
direct addition of N–H bonds to unsaturated substrates.1d In
particular, intramolecular hydroamination involving N–H
bond addition to an unactivated alkene offers an attractive
Received 25 September 2009. Accepted 17 November 2009. Published on the NRC Research Press Web site at canjchem.nrc.ca on
15 April 2010.
This article is part of a Special Issue dedicated to Professor R. J. Boyd. We dedicate this article to Professor Russ Boyd in recognition of
his widespread contributions to the Department of Chemistry at Dalhousie University as well as to the Canadian chemical community.
K.D. Hesp and M. Stradiotto.1 Department of Chemistry, Dalhousie University, Halifax, NS B3H 4J3, Canada.
R. McDonald. X-Ray Crystallography Laboratory, Department of Chemistry, University of Alberta, Edmonton, AB T6G 2G2, Canada.
1Corresponding author (e-mail: mark.stradiotto@dal.ca).
Can. J. Chem. 88: 700–708 (2010)
doi:10.1139/V09-181
Published by NRC Research Press

Hesp et al.
701
Table 1. Intramolecular hydroamination of unactivated alkenes by secondary alkylamines employ-
ing 1 as a precatalyst.
small number of examples in which late metal catalysts have
been shown to promote the cyclization of such substrates.7
As such, we became interested in identifying alternative
neutral Ir complexes that function as catalysts for the intra-
molecular hydroamination of unactivated aminoalkenes,8 es-
pecially those for which chiral variants could be developed.
Encouraged by our previous observation that the phosphino–
phenolate complex (k2-{2-i-Pr2PC6H4}O)Ir(COD) (1) is a
highly active catalyst for the hydrogenation of substituted al-
kenes under mild conditions,9 we viewed 1 as being an at-
tractive candidate for use in hydroamination chemistry. We
report herein that 1 is a competent catalyst at relatively low
catalyst loadings for the intramolecular hydroamination of a
variety of unactivated alkenes that feature pendant alkyl-
amines. Furthermore, we report on the synthesis and crystal-
lographic characterization of a first-generation chiral variant
of 1, and our efforts to apply this new chiral (k2-
P,O)Ir(COD) complex in intramolecular hydroamination cat-
alysis.10
yield (1H NMR) in the presence of 1.0 mol% 1 in 1,4-diox-
ane at 110 8C over the course of 7 h, with the balance cor-
responding to unreacted 2a (eq. [1]). Under similar
experimental conditions employing catalyst mixtures com-
prised of 0.5 mol% [Ir(COD)Cl]2 and 1.0 mol% of a simple
phosphine ligand including triphenylphosphine, tricyclohex-
ylphosphine or 1,4-bis(diphenylphosphino)butane, negligible
conversion to the desired cyclization product 2b was
achieved. While the use of the Rh variant of 1 under similar
experimental conditions resulted in the consumption of 2a,
multiple products were formed in this reaction with the ma-
jor product corresponding to alkene isomerization within the
starting substrate.
Results and discussion
The utility of 1 as a precatalyst in the hydroamination of a
range of N-alkyl aminoalkenes was surveyed (Table 1). The
cyclization of the parent N-benzyl substrate 2a (Table 1,
In a preliminary test experiment, the cyclization of the
aminoalkene 2a to the pyrrolidine 2b proceeded in a 72%
Published by NRC Research Press

702
Can. J. Chem. Vol. 88, 2010
Fig. 1. A plot of the conversion of 2a to 2b vs time employing 2.5 mol% 1 (1,4-dioxane, 110 8C).
entry 1) as well as para-substituted derivatives featuring
chloride (Table 1, entry 2), methyl ester (Table 1, entry 3),
or methoxy (Table 1, entry 4) substituents, was in each case
achieved in high isolated yield (85%–92%) despite the use
of relatively low catalyst loading (1.0 mol% 1). The steri-
cally hindered N-methylcyclohexyl aminoalkene was also
cyclized (Table 1, entry 5), as were substrates that feature
alternative formulations of mono- and di-substitution on the
linker chain of the aminoalkene substrate (Table 1, entries
6–8). Notably, the results featured in Table 1, entries 6–8,
clearly underscore the importance of the Thorpe–Ingold ef-
fect in promoting these transformations, whereby increased
steric elaboration at the b-carbon enables more facile cyclo-
hydroamination at lower catalyst loadings. The hydroamina-
tion of the hexenylamine substrate featured in Table 1, entry
9, was also achieved in the presence of 1 to afford the cor-
responding piperidine. In surveying more challenging sub-
strates, we turned our attention to the intramolecular
hydroamination of unactivated disubstituted alkenes.
Whereas the efficient cyclization of a 1,1-disubstituted sub-
strate was achieved by use of 1 (Table 1, entry 10), under
our standard catalytic conditions, this catalyst proved un-
reactive toward aminoalkenes featuring unstrained 1,2-sub-
stituted olefins or those lacking substituents on the tethering
chain that facilitate the cyclization process, as well as pri-
mary amine substrates. In comparison to the catalytic per-
formance of [Ir(COD)Cl]2,7a longer reaction times were
needed when using 1 to achieve similar levels of conversion
for the substrates featured in Table 1, entries 1–6; for 2a, as
well as the N-methylcyclohexyl aminoalkene substrate
(Table 1, entry 5), significantly higher Ir loadings were also
required when using 1. Otherwise, the catalytic performance
of 1 in the cyclization of N-alkyl aminoalkenes was found to
be competitive with that of [Ir(COD)Cl]2, and in the case of
the more challenging substrates featured in Table 1, entries
8–10, 1 proved to be superior to [Ir(COD)Cl]2 on the basis
of Ir loading, reaction time, and isolated yield.
catalyst loadings were needed for 1 relative to [Ir(COD)Cl]2
to achieve similarly high levels of conversion in the cycliza-
tion of 2a to 2b, we examined the conversion versus time
profile for this transformation employing 1 (2.5 mol% Ir,
1,4-dioxane, 110 8C; Fig. 1). Notably, a pronounced induc-
tion period (~3 h) was observed under these conditions; by
comparison, high conversion to 2b was achieved after 3 h
by using only 0.5 mol% [Ir(COD)Cl]2 under similar condi-
tions in the absence of an induction period.7a Variable-
temperature 1H and 31P NMR studies (25–100 8C) of an
equimolar mixture of 1 and 2a, either without precondition-
ing or following preconditioning for 3 h at 110 8C, revealed
the presence of only 1 and 2a, as well as small quantities of
2b at elevated temperatures. While we are presently unable
to comment definitively regarding the mechanism of hydro-
amination mediated by 1, these spectroscopic observations
appear to preclude a mechanism in which dissociation of
the P,O ligand from Ir is responsible for the observed induc-
tion period. Mechanistic investigations regarding the cycli-
zation of 2a and related substrates by each of 1 and
[Ir(COD)Cl]2 are ongoing in our laboratory.
The late metal catalyzed enantioselective intramolecular
hydroamination of unactivated alkenes featuring pendant al-
kylamines has yet to be reported in the literature.10 Given
the desirable catalytic performance of 1, and encouraged by
reports documenting the Ir-mediated enantioselective inter-
molecular hydroamination of activated alkenes,11 we sought
to construct a chiral variant of 1. In consideration of the dii-
sopropylphosphino present in 1, we elected to employ a
structurally similar k2-P,O phenylene ligand featuring the 1-
aryl-2,5-dialkylphospholane scaffold.12 Preparation of the
target ligand precursor 6 was carried out by adapting previ-
ously published methods.12a,13 As outlined in Scheme 1, the
installation of the chiral phospholane fragment required ini-
tial treatment of the methoxymethyl (MOM) protected phe-
nol 3 with n-BuLi and P(NMe2)2Cl, followed by in situ
methanolysis and reduction with LiAlH4 to afford the pri-
mary phosphine 4. Using the procedure established by Burk
Having observed that longer reaction times and higher
Published by NRC Research Press

Hesp et al.
703
Fig. 2. ORTEP diagram for 7 is shown with 50% displacement el-
Scheme 1. Synthesis of the new chiral (k2-P,O)Ir(COD) complex 7.
Reagents and conditions: (a) n-BuLi, Et2O, –78 8C ? 25 8C, 16 h;
P(NMe2)2Cl, Et2O, –78 8C ? 25 8C, 3 h; MeOH, 50 8C, 3 h;
LiAlH4, Et2O, 25 8C, 48 h (36% from 3). (b) n-BuLi, THF, 25 8C,
1.5 h; (2S,5S)-2,5-hexanediol cyclic sulfate, THF, 25 8C, 2 h;
n-BuLi, THF, 25 8C, 2 h, (68% from 4). (c) 5 mol/L HCl (aq.),
THF, 50 8C, 16 h; 7 mol/L NH4OH (aq.), Et2O, 25 8C, 5 h, (73%
from 5). (d) [Ir(COD)Cl]2, NEt3, THF, 25 8C, 2 h, 68%.
lipsoids; selected hydrogen atoms have been removed for clarity.
˚
Selected interatomic distances (A): Ir—P 2.2797(7), Ir—O
2.0163(18), Ir—C21 2.114(3), Ir—C22 2.131(3), Ir—C25 2.167(3),
Ir—C26 2.193(3), P—C2 1.824(3), O—C1 1.343(3).
et al.12b for the construction of phospholane moieties, suc-
cessive treatment of 4 with 1 equiv. n-BuLi, followed by
1 equiv. (2S,5S)-2,5-hexanediol cyclic sulfate, and then an
additional 1 equiv. of n-BuLi provided the protected inter-
mediate 5, which was converted to the phosphinoenolate 6
upon exposure to aqueous HCl followed by workup with
aqueous NH4OH. Treatment of 6 with 0.5 equiv. [Ir(COD)Cl]2
and NEt3 afforded 7 as an analytically pure, isolable orange
solid (68% from 6; 12% from 3). The connectivity in 7 was
established by use of NMR spectroscopic and X-ray crystal-
lographic techniques (Fig. 2, Table 2). The structural fea-
tures in 7 compare well with those found in 1,9 including
the observed Ir–P and Ir–O distances (2.2797(7) and
Table 2. Crystallographic data for 7.
Empirical formula
Formula weight
C28H44IrOP
619.80
0.42 Â 0.29 Â 0.24
Orange, prism
Orthorhombic
P212121
10.5353 (10)
12.8694 (12)
19.3425 (18)
2622.5 (4)
4
Crystal dimensions (mm3)
Color, habit
Crystal system
Space group
˚
a (A)
˚
b (A)
˚
c (A)
3
˚
V (A )
Z
Range of transmission
2q limit (8)
0.3701–0.2201
54.96
˚
˚
2.0163(18) A, respectively; cf. 2.289(1) and 2.028(3) A in
1, respectively), as well as the observation that in 7 the
Collection ranges
–13 £ h £ 13
–16 £ k £ 16
–24 £ l £ 25
22846
5986
0.0240
˚
Ir–alkene distances trans to P (2.167(3) and 2.193(3) A) are
statistically longer than the Ir–alkene distances trans to O
˚
(2.114(3) and 2.131(3) A), which is in keeping with the
Total data collected
Independent reflections
Rint
greater trans influence anticipated for a phosphine fragment
relative to an alkoxy donor on Ir. Unfortunately, despite
maintaining a catalytic activity profile similar to 1 in the hy-
droamination of 2a and related substrates, the chiral com-
plex 7 was incapable of inducing any enantioselectivity in
the resulting cyclization product (e.g., 2b) over a range of
reaction conditions (1–5 mol% 7, 80–110 8C).
Observed reflections
5652
Data / restraints / parameters 5986 / 0 / 280
Absolute structure parameter 0.000 (5)
Goodness-of-fit
1.063
0.0190
0.0453
1.534, –0.262
2
2
R1 [Fo ‡ 2s(Fo )]
2
2
wR2 [Fo ‡ –3s(Fo )]
-3
˚
Largest peak, hole (e A )
Summary and conclusion
In summary, (k2-{2-i-Pr2PC6H4}O)Ir(COD) (1) is an ef-
fective precatalyst for the intramolecular hydroamination of
unactivated alkenes with pendant secondary alkylamines,
providing either pyrrolidine or piperidine heterocycles in
the absence of competing alkene isomerization. We have
also succeeded in establishing a synthetic pathway to 7: a
chiral relative of 1 that features a 1-aryl-2,5-dialkylphospho-
lane structure derived from (2S,5S)-2,5-hexanediol cyclic
sulfate. While 7 failed to provide enantioselectivity in this
hydroamination chemistry, the activity of 7 was found to be
comparable to that of 1. Future studies will focus both on
preparing alternative chiral variants of 1, as well as on ex-
ploring the mechanism of hydroamination processes medi-
ated by (k2-P,O)Ir(COD) species to guide the design of
increasingly effective catalysts.
Published by NRC Research Press

704
Can. J. Chem. Vol. 88, 2010
dissolved in anhydrous methanol and was heated in an oil
bath at 50 8C for 3 h. Subsequent removal of the solvent af-
forded a colorless oil that was dissolved in diethyl ether
(10 mL). The ethereal solution was added dropwise to a
Schlenk tube containing LiAlH4 (0.60 g, 15.6 mmol) in di-
ethyl ether (7 mL). The resulting green solution was mag-
netically stirred at ambient temperature for 48 h. The
reaction mixture was quenched with degassed distilled H2O
followed by filtration through a filter stick to remove the
solids. The diethyl ether layer was dried over Na2SO4. Sub-
sequent filtration and removal of the solvent afforded 4 as a
light brown oil, which when purified by vacuum distillation
at 80–90 8C (10–3 Torr) was obtained as a colorless oil that
was used without further purification (1.21 g, 4.28 mmol,
Experimental
General considerations
All manipulations were conducted in the absence of oxy-
gen and water under an atmosphere of dinitrogen, either by
use of standard Schlenk methods or within an MBraun glo-
vebox apparatus, utilizing glassware that was oven-dried
(130 8C) and evacuated while hot prior to use. The nondeu-
terated solvents, tetrahydrofuran, diethyl ether, dichlorome-
thane, benzene, hexanes, and pentane, were deoxygenated
and dried by sparging with dinitrogen gas, followed by pas-
sage through a double-column solvent purification system
purchased from MBraun Inc. Tetrahydrofuran, diethyl ether,
and dichloromethane were purified over two alumina-packed
columns, while benzene, hexanes, and pentane were purified
over one alumina-packed column and one column packed
with copper-Q5 reactant. 1,4-Dioxane (Sigma-Aldrich) was
dried over Na/benzophenone followed by distillation under
an atmosphere of dinitrogen; anhydrous 1,4-dioxane used as
received from Sigma-Aldrich provided inferior results.
Chloroform-d1 (Cambridge Isotopes) was used as received.
C6D6 (Cambridge Isotopes Laboratories) was degassed by
using three freeze-pump-thaw cycles and then dried over 3
1
4
36%). H NMR (C6D6) d: 7.46 (d, JHH = 2.5 Hz, 1H, Ar-
3
4
H), 7.41 (d of d, JPH = 7.0 Hz, JHH = 2.5 Hz, 1H, Ar-H),
1
4.96 (s, 2H, CH2 (MOM)), 3.97 (d, JPH = 202.1 Hz, 2H,
–PH2), 3.40 (s, 3H, CH3 (MOM)), 1.48 (s, 9H, C(CH3)3),
1.23 (s, 9H, C(CH3)3). 13C{1H} NMR (C6D6) d: 155.7 (d,
JPC = 10.9 Hz, Ar-quaternary), 145.4 (d, JPC = 3.0 Hz, Ar-
quaternary), 141.9 (d, JPC = 1.5 Hz, Ar-quaternary), 130.7
2
(d, JPC = 7.4 Hz, Ar-CH), 124.5 (Ar-CH), 123.0 (d, JPC
=
4
11.4 Hz, Ar-quaternary), 98.8 (d, JPC = 7.9 Hz, CH2
(MOM)), 56.2 (d, JPC = 1.5 Hz, CH3 (MOM)), 34.6 (d,
2JPC = 0.75 Hz, C(CH3)3)), 33.5 (C(CH3)3), 30.5 (C(CH3)3),
30.3 (C(CH3)3). 31P{1H} NMR (C6D6) d: –128.6.
˚
A molecular sieves. All solvents used within the glovebox
˚
were stored over activated 4 A molecular sieves. Purification
of NEt3 was achieved by stirring over KOH for 7 d, fol-
lowed by distillation; the distilled NEt3 was then refluxed
over CaH2 for 3 d under dinitrogen, followed by distillation.
Complex 1,9 P(NMe2)2Cl,14 (2S,5S)-2,5-hexanediol cyclic
sulfate,12b N-benzyl-2,2-diphenylpent-4-en-1-amine,7f N-
(4-chlorobenzyl)-2,2-diphenylpent-4-en-1-amine,2a methyl
4-[(2,2-diphenylpent-4-enylamino)methyl]benzoate,7f N-(4-me-
thoxybenzyl)-2,2-diphenylpent-4-en-1-amine,2a N-(cyclohex-
ylmethyl)-2,2-diphenylpent-4-en-1-amine,7d (1-allylcyclohexyl)-
N-benzylmethanamine,7f N-benzyl-2,2-dimethylpent-4-en-1-
amine,7f N-benzyl-2-isopropylpent-4-en-1-amine,7f N-benzyl-
2,2-diphenylhex-5-en-1-amine,7d and N-benzyl-4-methyl-2,2-
diphenylpent-4-en-1-amine15 were synthesized according to
literature procedures. The synthetic route to 6 starting from
3 was carried out in accordance with previously published
methods.13 [Ir(COD)Cl]2 (Strem) was dried in vacuo for
~24 h prior to use. All other reagents were used as received.
1H, 13C, and 31P NMR characterization data were collected
at 300 K on a Bruker AV-500 spectrometer operating at
500.1, 125.8, and 202.5 MHz (respectively) with chemical
shifts reported in parts per million downfield of SiMe4. Ele-
mental analyses were performed by Canadian Microanalyti-
cal Service Ltd., Delta, BC, Canada.
Preparation of 5
To a magnetically stirred solution of 4 (0.244 g,
0.860 mmol) in THF (5 mL) was added a 1.45 mol/L solu-
tion of n-BuLi in hexanes (0.600 mL, 0.860 mmol). The re-
action mixture went from colorless to yellow in appearance
and was magnetically stirred at ambient temperature for
1.5 h, followed by the addition of a THF (2 mL) solution of
(2S,5S)-2,5-hexanediol cyclic sulfate (0.156 g, 0.860 mmol).
The reaction went colorless and was magnetically stirred at
ambient temperature for 2 h followed by the addition of a
1.45 mol/L solution of n-BuLi in hexanes (0.60 mL,
0.860 mmol). The mixture went yellow and remained that
color for the subsequent 2 h of magnetic stirring. The sol-
vent and other volatiles were removed in vacuo affording
an off-white solid that was washed with pentane (2 Â
3 mL) to effect the precipitation of a gelatinous white solid,
which was separated by filtration through Celite. The re-
maining solvent was removed in vacuo affording 5 as a yel-
low oil that was used without further purification (0.215 g,
0.59 mmol, 68%). 1H NMR (C6D6) d: 7.53 (d, JHH
=
=
4
5
2.0 Hz, 1H, Ar-H), 7.39 (m, 1H, Ar-H), 5.81 (t, JPH
5
4.0 Hz, 1H, CH2 (MOM)), 5.11 (d, 1H, JPH = 3.5 Hz, 1H,
CH2 (MOM)), 3.56 (s, 3H, CH3 (MOM)), 2.62 (m, 1H, CH
(phospholane)), 2.27 (m, 1H, CH (phospholane)), 2.13 (m,
1H, CH2 (phospholane)), 1.84 (m, 1H, CH2 (phospholane)),
1.57 (s, 9H, C(CH3)3), 1.41 (m, 1H, CH2 (phospholane)),
Preparation of 4
To
a magnetically stirred solution of 3 (3.96 g,
12.0 mmol) in diethyl ether (10 mL) at –78 8C was added
4.1 mL of a 2.9 mol/L solution of n-BuLi in hexanes, which
effected the precipitation of a white solid. The resulting
mixture was magnetically stirred for 16 h followed by cool-
ing to –78 8C and the dropwise addition of ClP(NMe2)2
(1.9 mL, 12.0 mmol). The reaction mixture was warmed to
ambient temperature and was magnetically stirred for 3 h.
The resulting white solid was removed by filtration through
a filter stick and from the remaining solution the diethyl
ether was removed, which afforded a colorless oil that was
3
3
1.33 (d of d, JPH = 19.0 Hz, JHH = 6.0 Hz, 3H, CH3 (phos-
pholane)), 1.31 (s, 9H, C(CH3)3), 1.25 (m, 1H, CH2 (phos-
3
3
pholane)), 0.93 (d of d, JPH = 9.5 Hz, JHH = 7.0 Hz, 3H,
CH3 (phospholane)). 13C{1H} NMR (C6D6) d: 156.6 (d,
2JPC = 18.5 Hz, Ar-quaternary), 144.4 (Ar-quaternary),
141.6 (d, JPC = 0.9 Hz, Ar-quaternary), 130.0 (d, JPC
31.6 Hz, Ar-quaternary), 127.3 (d, JPC = 2.3 Hz, Ar-CH),
=
2
3
124.4 (Ar-CH), 98.7 (d, JPC = 21.0 Hz, CH2 (MOM)), 56.2
Published by NRC Research Press

Hesp et al.
705
2
(d, JPC = 1.9 Hz, CH3 (MOM)), 35.9 (d, JPC = 2.4 Hz, CH2
C(CH3)3), 1.39 (s, 9H, C(CH3)3), 1.35 (m, 1H, CH2 (phos-
pholane)), 1.12 (d of d, JPH = 17.5 Hz, JHH = 7.5 Hz, 3H,
2
3
3
(phospholane)), 35.3 (d, JPC = 2.3 Hz, CH2 (phospholane)),
2
34.6 (d, JPC = 1.1 Hz, C(CH3)3), 34.1 (d, JPC = 14.7 Hz, CH
CH3 (phospholane)), 1.03 (m, 1H, CH2 (phospholane)), 0.93
2
3
3
(phospholane)), 33.7 (C(CH3)3), 33.6 (d, JPC = 10.9 Hz, CH
(d of d, JPH = 14.5 Hz, JHH = 7.0 Hz, 3H, CH3 (phospho-
lane)). 13C{1H} NMR (C6D6) d: 176.6 (d, JPC = 18.7 Hz, Ar-
quaternary), 137.1 (d, JPC = 6.7 Hz, Ar-quaternary), 136.7
(d, JPC = 8.8 Hz, Ar-quaternary), 126.6 (d, JPC = 2.0 Hz,
Ar-CH), 125.0 (Ar-CH), 116.8 (d, JPC = 45.1 (Ar-quater-
(phospholane)), 30.7 (C(CH3)3), 30.2 (C(CH3)3), 20.4 (d,
3JPC = 35.5 Hz, CH3 (phospholane)), 15.0 (d, JPC = 0.9 Hz,
3
CH3 (phospholane)). 31P{1H} NMR (C6D6) d: 2.3.
2
2
nary), 92.5 (d, JPC = 12.7 Hz, CH (COD)), 91.5 (d, JPC
=
Preparation of 6
5.4 Hz, CH (COD)), 51.4 (CH (COD)), 45.9 (CH (COD)),
To a magnetically stirred solution of 5 (0.382 g,
1.05 mmol) in THF (10 mL) was added 5 mol/L HCl (aq.)
(5 mL) followed by heating at 50 8C in an oil bath for
16 h. Subsequent removal of the solvent afforded a white
solid that was suspended in diethyl ether (10 mL) followed
by the addition of 7 mol/L NH4OH (aq.) (5 mL), which
caused the solution to become homogeneous. The solution
was magnetically stirred for 5 h at ambient temperature fol-
lowed by removal of the solvent and extraction of the resi-
due into pentane (3 Â 3 mL). Upon removal of the pentane
in vacuo, 6 was obtained as a colorless oil that was used
1
39.1 (d, JPC = 43.4 Hz, CH (phospholane)), 35.7 (CH2
2
(phospholane)), 35.3 (d, JPC = 4.9 Hz, CH2 (phospholane)),
3
3
34.0 (d, JPC = 2.9 Hz, CH2 (COD)), 33.5 (d, JPC = 2.8 Hz,
1
CH2 (COD)), 33.1 (C(CH3)3), 33.0 (d, JPC = 30.3 Hz, CH
(phospholane)), 31.1 (C(CH3)3), 29.0 (C(CH3)3), 28.2 (d,
3
3JPC = 2.3 Hz, CH2 (COD)), 28.1 (d, JPC = 2.0 Hz, CH2
2
(COD)), 21.7 (C(CH3)3), 16.4 (d, JPC = 8.2 Hz, CH3 (phos-
2
pholane)), 13.9 (d, JPC = 1.6 Hz, CH3 (phospholane)).
31P{1H} NMR (C6D6) d: 40.1. Anal. calcd. for C28H44IrOP:
C 54.23, H 7.16, N 0.00; found: C 54.44, H 7.52, N < 0.3.
Crystals suitable for X-ray crystallographic analysis were
grown from a concentrated solution of 7 in pentane at –
35 8C.
1
without further purification (0.246 g, 0.767 mmol, 73%). H
4
NMR (C6D6) d: 7.72 (d, JPH = 13.5 Hz, 1H, OH), 7.52 (d,
4JHH = 2.0 Hz, 1H, Ar-H), 7.27 (m, 1H, Ar-H), 2.53 (m, 1H,
CH (phospholane)), 2.05 (m, 2H, CH and CH2 (phospho-
lane)), 1.78 (m, 1H, CH2 (phospholane)), 1.60 (s, 9H,
C(CH3)3), 1.53 (m, 1H, CH2 (phospholane)), 1.32 (s, 9H,
Representative procedure for the intramolecular
hydroamination of unactivated alkenes by secondary
alkylamines catalyzed by 1
3
3
C(CH3)3), 1.15 (d of d, JPH = 19.5 Hz, JHH = 7.0 Hz, 3H,
To a screw-capped vial containing 2a (82 mg, 0.25 mmol)
and a stir-bar was added 0.220 mL of a stock solution of 1
(5.8 mg in 1.000 mL of 1,4-dioxane) and 0.280 mL of 1,4-
dioxane (total reaction volume = 0. 5 mL). The vial was
sealed under N2 with a cap containing a PTFE septum and,
once all the material had dissolved, was removed from the
glovebox and was placed in a temperature-controlled alumi-
num heating block set at 110 8C. After 16 h of magnetic stir-
ring, the vial was removed from the temperature-controlled
aluminum heating block, cooled to ambient temperature,
diluted with CH2Cl2 (2 mL), and was washed with brine
(2 Â 2 mL). The organic extracts were combined, dried
over Na2SO4, and concentrated. The resulting residue
was purified by flash column chromatography on silica gel
(hexanes/EtOAc = 20:1) to yield 2b as a white solid
(74 mg, 0.23 mmol, 92%) that afforded analytical data in
agreement with data reported in the literature.7f
CH3 (phospholane)), 1.12 (m, 1H, CH2 (phospholane)), 0.79
3
3
(d of d, JPH = 11.5 Hz, JHH = 7.0 Hz, 3H, CH3 (phospho-
lane)). 13C{1H} NMR (C6D6) d: 156.8 (d, JPC = 19.4 Hz, Ar-
quaternary), 140.4 (Ar-quaternary), 134.4 (Ar-quaternary),
2
134.3 (d, JPC = 15.8 Hz, Ar-quaternary), 126.9 (d, JPC
=
2
2.1 Hz, Ar-CH), 124.9 (Ar-CH), 36.5 (d, JPC = 4.2 Hz,
CH2 (phospholane)), 36.4 (CH2 (phospholane)), 35.8 (d,
1JPC = 4.8 Hz, CH (phospholane)), 34.4 (C(CH3)3), 33.5
1
(C(CH3)3), 33.2 (d, JPC = 5.7 Hz, CH (phospholane)), 30.8
2
(C(CH3)3), 28.8 (C(CH3)3), 19.6 (d, JPC = 31.7 Hz, CH3
(phospholane)), 13.8 (CH3 (phospholane)). 31P{1H} NMR
(C6D6) d: –25.6.
Preparation of 7
To a magnetically stirred solution of [Ir(COD)Cl]2
(0.14 g, 0.20 mmol) in THF (2 mL) was added a THF
(2 mL) solution of 6 (0.13 g, 0.41 mmol). After 3 h of mag-
netic stirring, NEt3 (57 mL, 0.41 mmol) was added, which
resulted in an immediate color change from yellow-orange
to bright orange. After 2 h of magnetic stirring at ambient
temperature, 31P NMR analysis of the reaction mixture con-
firmed the consumption of 6 and the quantitative formation
of a new product (7). The solvent and other volatiles were
removed in vacuo and the residual solid was extracted into
pentane (3 Â 2 mL). Subsequent removal of the solvent af-
1-Benzyl-2-methyl-4,4-diphenylpyrrolidine (Table 1,
entry 1)
The indicated compound was purified by flash chromato-
graphy on silica gel (EtOAc/hexanes = 20:1) in a 92% yield
(74 mg) as a white solid.7f 1H NMR (CDCl3) d: 7.53–7.19
(m, 15H), 4.21 (d, J = 13.5 Hz, 1H), 3.77 (d, J = 9.5 Hz,
1H), 3.38 (d, J = 13.5 Hz, 1H), 3.07–2.89 (m, 3H), 2.34 (d
of d, J = 13.0, 8.0 Hz, 1H), 1.29 (d, J = 6.5 Hz, 3H).
13C{1H} NMR (CDCl3) d: 150.6, 148.7, 140.1, 128.6, 128.2,
128.1, 127.8, 127.4, 127.2, 126.7, 125.8, 125.4, 66.4, 59.6,
58.0, 52.5, 48.0, 19.5.
forded 7 as an analytically pure orange solid (0.17 g,
4
0.28 mmol, 68%). 1H NMR (C6D6) d: 7.57 (d, JHH
=
=
3
3
2.0 Hz, 1H, Ar-H), 7.05 (d of d, JPH = 8.5 Hz, JHH
2.5 Hz, 1H, Ar-H), 5.36 (m, 2H, 2 x CH (COD)), 3.56 (m,
1H, CH (COD)), 3.13 (m, 1H, CH (COD)), 2.54 (m, 1H, CH
(phospholane)), 2.27 (m, 3H, CH2 (COD) and CH (phospho-
lane)), 2.13 (m, 2H, CH2 (COD)), 1.88 (m, 2H, CH2
(COD)), 1.83 (m, 1H, CH2 (phospholane)), 1.78 (m, 1H,
CH2 (phospholane)), 1.72 (m, 2H, CH2 (COD)), 1.70 (s, 9H,
1-(4-Chlorobenzyl)-2-methyl-4,4-diphenylpyrrolidine
(Table 1, entry 2)
The indicated compound was purified by flash chroma-
tography on silica gel (n-pentane/Et2O = 30:1) in an 86%
Published by NRC Research Press

706
Can. J. Chem. Vol. 88, 2010
yield (78 mg) as a white solid.2a 1H NMR (CDCl3) d: 7.43–7.17
(m, 14H), 4.12 (d, J = 13.5 Hz, 1H), 3.71 (d, J = 10.0 Hz,
1H), 3.33 (d, J = 13.5 Hz, 1H), 3.05–2.89 (m, 2H), 2.87 (d,
J = 9.5 Hz, 1H), 2.33 (d of d, J = 12.5, 7.9 Hz, 1H), 1.26 (d,
J = 6.5 Hz, 3H). 13C{1H} NMR (CDCl3) d: 150.4, 148.6,
138.6, 132.4, 129.8, 128.3, 128.1, 127.8, 127.3, 127.1,
125.8, 125.5, 66.3, 59.6, 57.2, 52.5, 47.8, 19.5.
tography on silica gel (hexanes/EtOAc = 20:1) in a 86%
yield (44 mg) as a colorless oil.7f 1H NMR (CDCl3) d:
7.39–7.23 (m, 5H), 4.05 (d, J = 14.5 Hz, 1H), 3.15 (d, J =
13.5 Hz, 1H), 2.67 (d, J = 9.0 Hz, 1H), 2.59 (m, 1H), 1.98
(d, J = 9.0 Hz, 1H), 1.76 (d of d, J = 12.0, 7.5 Hz, 1H), 1.35
(d of d, J = 12.5, 9.0 Hz, 1H), 1.19 (d, J = 6.0 Hz, 3H), 1.11
(s, 3H), 1.01 (s, 3H). 13C{1H} NMR (CDCl3) d: 140.1,
128.7, 128.0, 126.5, 68.4, 59.7, 58.0, 49.1, 35.4, 30.9, 29.2,
19.4.
Methyl 4-(2-methyl-4,4-diphenylpyrrolidin-1-ylmethyl)-
benzoate (Table 1, entry 3)
1-Benzyl-2-methyl-4-isopropylpyrrolidine (Table 1,
entry 8)
The indicated compound was purified by flash chroma-
tography on silica gel (n-pentane/Et2O = 8:1) in a 85% yield
(82 mg) as a colorless oil.7f 1H NMR (CDCl3) d: 8.07 (d, J =
8.0 Hz, 2H), 7.50 (d, J = 8.5 Hz, 2H), 7.35–7.15 (m, 10H),
4.16 (d, J = 14.0 Hz, 1H), 3.98 (s, 3H), 3.68 (d, J = 10.0 Hz,
1H), 3.39 (d, J = 13.5 Hz, 1H), 3.02–2.88 (m, 2H), 2.86 (d,
J = 10.0 Hz, 1H), 2.31 (d of d, J = 13.0, 7.5 Hz, 1H), 1.23
(d, J = 5.5 Hz, 3H). 13C{1H} NMR (CDCl3) d: 167.1, 150.3,
148.5, 145.7, 129.6, 128.7, 128.4, 128.1, 127.8, 127.3,
127.1, 125.8, 125.5, 66.4, 59.7, 57.7, 52.6, 51.9, 47.8, 19.5.
The indicated compound was obtained in 87% yield with
1
a diastereomeric ratio of 1.3:1 on the basis of H NMR us-
ing 1,4-bis(trifluoromethyl)benzene as an internal standard.7f
1-Benzyl-2-methyl-5,5-diphenylpiperidine (Table 1,
entry 9)
The indicated compound was purified by flash chroma-
tography on silica gel (hexanes/EtOAc = 20:1) in a 85%
yield (73 mg) as a colorless oil.7d 1H NMR (CDCl3) d:
7.46–7.14 (m, 15H), 4.13 (d, J = 13.5 Hz, 1H), 3.43 (d, J =
12.5 Hz, 1H), 3.21 (d, J = 13.5 Hz, 1H), 3.60–2.50 (m, 3H),
2.25 (m, 1H), 1.70 (m, 1H), 1.45 (m, 1H), 1.21 (d, J =
6.0 Hz, 3H). 13C{1H} NMR (CDCl3) d: 148.6, 146.7, 139.4,
129.5, 128.4, 128.0, 127.9, 127.6, 127.0, 126.9, 125.6,
125.3, 61.0, 58.9, 56.1, 46.5, 34.2, 31.0, 18.6.
1-(4-Methoxybenzyl)-2-methyl-4,4-diphenylpyrrolidine
(Table 1, entry 4)
The indicated compound was purified by flash chroma-
tography on silica gel (n-pentane/Et2O = 15:1) in a 87%
yield (77 mg) as a colorless oil.2a 1H NMR (CDCl3) d: 7.29
(m, 1H), 7.00–6.95 (m, 2H), 4.13 (d, J = 13.0 Hz, 1H), 3.90
(s, 3H), 3.74 (d, J = 10.0 Hz, 1H), 3.30 (d, J = 13.0 Hz,
1H), 3.02 (d of d, J = 13.0, 7.5 Hz, 1H), 2.96–2.85 (m,
2H), 2.30 (d of d, J = 13.0, 7.5 Hz, 1H), 1.27 (d, J =
6.0 Hz, 3H). 13C{1H} NMR (CDCl3) d: 158.5, 150.6, 148.7,
132.0, 129.6, 128.1, 127.8, 127.4, 127.2, 125.7, 125.3,
113.5, 66.3, 59.5, 57.2, 55.2, 52.4, 48.0, 19.5.
1-Benzyl-2–2-dimethyl-4,4-diphenylpyrrolidine (Table 1,
entry 10)
The indicated compound was purified by flash chroma-
tography on silica gel (EtOAc/hexanes = 20:1) in a 92%
yield (78 mg) as a white solid.15 1H NMR (CDCl3) d: 7.52–
7.20 (m, 15H), 3.73 (s, 2H), 3.41 (s, 2H), 2.74 (s, 2H), 1.26
(s, 6H). 13C{1H} NMR (CDCl3) d: 149.7, 140.9, 128.5,
128.1, 127.8, 127.2, 126.7, 125.4, 6.1, 60.4, 54.4, 52.4,
51.6, 25.1.
1-Cyclohexylmethyl-2-methyl-4,4-diphenylpyrrolidine
(Table 1, entry 5)
The indicated compound was purified by flash chroma-
tography on silica gel (hexanes/EtOAc = 8:1) in a 89% yield
(75 mg) as a white solid.7d 1H NMR (CDCl3) d: 7.38–7.21
(m, 9H), 7.16 (m, 1H), 3.87 (d, J = 9.5 Hz, 1H), 2.87 (d of
d, J = 13.0, 7.5 Hz, 1H), 2.82 (d, J = 10.0 Hz, 1H), 2.66 (m,
1H), 2.56 (m, 1H), 2.18–2.03 (m, 3H), 1.82–1.63 (m, 4H),
1.53 (m, 1H), 1.36–1.15 (m, 3H), 1.10 (d, J = 6.0 Hz, 3H),
1.02–0.87 (m, 2H). 13C{1H} NMR (CDCl3) d: 151.3, 148.9,
128.1, 127.8, 127.6, 127.3, 125.7, 125.4, 67.6, 61.4, 60.3,
52.8, 48.1, 37.3, 32.2, 31.9, 26.9, 26.3, 26.1, 19.6.
Crystallographic characterization of 7
Crystallographic data were obtained at 193 ( 2) K on a
Bruker PLATFORM/SMART 1000 CCD diffractometer us-
˚
ing a graphite-monochromated Mo Ka (l = 0.71073 A) radi-
ation, employing a sample that was mounted in inert oil and
transferred to a cold gas stream on the diffractometer. Pro-
grams for diffractometer operation, data collection, and data
reduction were supplied by Bruker. SADABS was employed
as the absorption correction method. The structure was
solved by use of a Patterson search/structure expansion and
refinement was carried out by use of full-matrix least-
2-Benzyl-3-methyl-2-aza-spiro[4,5]decane (Table 1,
entry 6)
squares procedures (on F2) with R1 based on Fo ‡ 2s(Fo )
2
2
The indicated compound was purified by flash chroma-
tography on silica gel (hexanes/EtOAc = 20:1) in a 85%
yield (52 mg) as a colorless oil.7f 1H NMR (CDCl3) d:
7.40–7.24 (m, 5H), 4.06 (d, J = 13.0 Hz, 1H), 3.14 (d, J =
13.5 Hz, 1H), 2.82 (d, J = 9.5 Hz, 1H), 2.54 (m, 1H), 1.91
(d, J = 9.5 Hz, 1H), 1.80 (d of d, J = 12.0, 7.0 Hz, 1H),
1.56–1.27 (m, 11H), 1.19 (d, J = 6.0 Hz, 3H). 13C{1H}
NMR (CDCl3) d: 140.0, 128.6, 128.0, 126.5, 66.6, 59.0,
58.0, 47.0, 39.3, 39.2, 38.5, 26.1, 23.6, 23.5, 19.3.
2
2
and wR2 based on Fo ‡ –3s(Fo ). All hydrogen atoms were
added at calculated positions and refined by use of a riding
model employing isotropic displacement parameters based
on the isotropic displacement parameter of the attached
atom. The near-zero final refined value of the absolute struc-
ture parameter (0.000(5)) supported that the correct absolute
structure had been chosen.16 See the Supplementary data
section for information on obtaining the complete supple-
mentary crystallographic data for this paper. The thermal el-
lipsoid plot of 7 was generated by use of ORTEP-3 for
Windows.17
1-Benzyl-2,4,4-trimethylpyrrolidine (Table 1, entry 7)
The indicated compound was purified by flash chroma-
Published by NRC Research Press

Hesp et al.
707
C. S.; Kozak, J. A.; Schafer, L. L. Angew. Chem. Int. Ed.
2007, 46 (3), 354. doi:10.1002/anie.200603017.; (e) Lee, A.
V.; Schafer, L. L. Eur. J. Inorg. Chem. 2007, 2245, and refs.
cited therein. doi:10.1002/ejic.200700036.
Supplementary data
Supplementary data for this article are available on the
journal Web site (canjchem.nrc.ca). CCDC 744698 contains
the X-ray data in CIF format for this manuscript. These data
can be obtained, free of charge, via www.ccdc.cam.ac.uk/
conts/retrieving.html (Or from the Cambridge Crystallo-
graphic Data Centre, 12 Union Road, Cambridge CB2 1EZ,
UK; fax +44 1223 336033; or deposit@ccdc.cam.ac.uk).
(6) (a) For examples involving the late metal-mediated addition
of secondary amides, carbamates, or ureas to unactivated
olefins, see: Cochran, B. M.; Michael, F. E. J. Am. Chem.
Soc. 2008, 130 (9), 2786. doi:10.1021/ja0734997. PMID:
18254623.; (b) Cochran, B. M.; Michael, F. E. Org. Lett.
2008, 10 (2), 329. doi:10.1021/ol702891p. PMID:18154298.;
(c) Komeyama, K.; Morimoto, T.; Takaki, K. Angew. Chem.
Int. Ed. 2006, 45 (18), 2938. doi:10.1002/anie.200503789.;
(d) Michael, F. E.; Cochran, B. M. J. Am. Chem. Soc. 2006,
128 (13), 4246. doi:10.1021/ja060126h. PMID:16568997.;
(e) Bender, C. F.; Widenhoefer, R. A. Chem. Commun.
(Camb.) 2006, 4143. doi:10.1039/b608638a. PMID:
17024275.; (f) Bender, C. F.; Widenhoefer, R. A. Org. Lett.
Acknowledgement
Acknowledgment is made to Dalhousie University (Hal-
ifax, NS) and the Natural Sciences and Engineering Re-
search Council of Canada (including a Discovery Grant for
M. S. and a Canada Graduate Scholarship for K. D. H.).
We also thank Dr. Michael Lumsden (Nuclear Magnetic
Resonance Research Resource (NMR-3), Dalhousie Univer-
sity) for assistance in the acquisition of NMR data.
2006,
8
(23), 5303. doi:10.1021/ol062107i. PMID:
17078703.; (g) Zhang, J.; Yang, C.-G.; He, C. J. Am. Chem.
Soc. 2006, 128 (6), 1798. doi:10.1021/ja053864z. PMID:
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alkenes
in
good
yields
with
excellent
´
(11) (a) Dorta, R.; Egli, P.; Zu¨rcher, F.; Togni, A. J. Am. Chem.
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