Pinene-derived monodentate phosphoramidites for asymmetric hydrogenation

Article abstract of DOI:10.1002/ejoc.201500120

Phosphoramidite ligands based on pinene-derived chiral amines have been prepared by a straightforward procedure in good yields. The key step of the synthetic protocol is a stereoselective hydrogenation of annulated pinene-pyridine derivatives leading to (diastereoisomeric) secondary amines that were separated and treated with different chlorophosphites to yield the envisaged phosphoramidites. The absolute configurations of the ligands were assigned on the basis of NMR analyses and corroborated by X-ray diffraction analysis of a borane adduct of a typical ligand. The new ligands were employed in the asymmetric hydrogenation of imines and olefins. The iridium-catalyzed hydrogenation of imines provided up to 81?% ee, whereas in the rhodium-catalyzed hydrogenation of functionalized olefins enantioselectivities of up to 99?% ee were achieved. In this particular application, the different chiral elements of the ligand structure led to synergistic effects and the enantioselectivity is dominated by the chiral diol moiety.

Full text of DOI:10.1002/ejoc.201500120

FULL PAPER
DOI: 10.1002/ejoc.201500120
Pinene-Derived Monodentate Phosphoramidites for Asymmetric Hydrogenation
Christian Schmitz,[a] Walter Leitner,*[a] and Giancarlo Franciò*[a]
Keywords: Asymmetric catalysis / Hydrogenation / Ligand design / Chiral pool / Nitrogen heterocycles / Phosphoramidites
Phosphoramidite ligands based on pinene-derived chiral
amines have been prepared by a straightforward procedure
in good yields. The key step of the synthetic protocol is a
stereoselective hydrogenation of annulated pinene–pyridine
derivatives leading to (diastereoisomeric) secondary amines
that were separated and treated with different chlorophos-
phites to yield the envisaged phosphoramidites. The absolute
configurations of the ligands were assigned on the basis of
NMR analyses and corroborated by X-ray diffraction analysis
of a borane adduct of a typical ligand. The new ligands were
employed in the asymmetric hydrogenation of imines and
olefins. The iridium-catalyzed hydrogenation of imines pro-
vided up to 81% ee, whereas in the rhodium-catalyzed
hydrogenation of functionalized olefins enantioselectivities
of up to 99% ee were achieved. In this particular application,
the different chiral elements of the ligand structure led to
synergistic effects and the enantioselectivity is dominated by
the chiral diol moiety.
which can allow a stereoselective construction of the desired
ligand and result in synergistic effects in catalysis.[8,9]
Among natural products, α-pinene is an attractive candi-
date for ligand synthesis as it is inexpensive, commercially
available in both enantiomeric forms with high optical pu-
rity, and can be easily tailored by (diastereoselective) func-
tionalizations.[9,10] The incorporation of the pinene moiety
into chiral ligands has been exploited in the past. Ligands
possessing N-, O-, and/or P-donor atoms have been de-
Introduction
Transition-metal-catalyzed asymmetric transformations
using chiral ligands belong to the most efficient procedures
for the construction of enantiopure/enriched com-
pounds.[1,2] In this field, the development of novel chiral
ligands is important for new applications and challenging
substrates. Among chiral ligands, phosphorus auxiliaries
are of the utmost importance and have been extensively in-
vestigated over the past few decades.[3,4] Phosphoramidites
have evolved to become a very efficient and versatile class
of ligands and have been successfully used in a variety of
asymmetric transformations, including hydrogenation reac-
tions.[5–7] Their modular and simple synthesis from a diol,
a (secondary) amine, and phosphorus trichloride has al-
lowed for the creation of phosphoramidite libraries.[6a]
Thus, the combination of a chiral diol [(1,1Ј-binaphthal-
ene)-2,2Ј-diol (BINOL) in most cases] and a chiral amine
component offers additional potential for exploiting the co-
operative effects of the different chiral elements and hence
for additional control over enantiodiscrimination/selectivity
in asymmetric catalysis.[6] The chiral information in the
amine moiety of the ligand can be of “synthetic” or “natu-
ral” origin.
Chiral ligands and auxiliaries synthesized from starting
materials from the chiral pool have a long tradition and
have found numerous applications.[2,8] Many of these chiral
starting materials possess multiple stereogenic centers,
[a] Institut für Technische und Makromolekulare Chemie,
RWTH Aachen University,
Worringer Weg 1, 52074 Aachen, Germany
E-mail: leitner@itmc.rwth-aachen.de
francio@itmc.rwth-aachen.de
http://www.tc.rwth-aachen.de
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201500120.
Figure 1. Examples of N,O-, N,S-, and N,P-ligands based on a
pinene–pyridine framework.[12–14]
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C. Schmitz, W. Leitner, G. Franciò
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scribed and employed in various catalytic transforma- tus with singlet oxygen in the presence of acetic anhydride
tions.[11] In particular, bidentate N,O- (1),[12] N,S- (2),[13] and pyridine to give pinocarvone (8) in 85% yield.[15] In
and N,P- (3–6)[14] -ligands containing an annulated pyridine parallel, the pyridinium salts 9a and 9b were prepared by
ring have been reported in the last decade (Figure 1).
treating pyridine with chloroacetone or acetophenone and
Differing from all the approaches exploited up to now, iodine, respectively.[16] The pyridinium salts 9a and 9b were
we envisaged utilising α-pinene to prepare chiral secondary subjected to Kröhnke annulation with pinocarvone (8) and
amines and to use them as novel building blocks for the ammonium acetate to give the pinene–pyridines 10a and
synthesis of phosphoramidite ligands. Herein we report the 10b substituted at the 2-position of the pyridine ring
synthesis of a series of such monodentate phosphoramidites with Me and Ph, respectively, in yields of 58–65%
containing multiple chiral centers and different substituents (Scheme 1).[17,18]
in close spatial proximity to the phosphorus donor atom.
The underlying amines were obtained by a stereoselective
hydrogenation of annulated pinene–pyridine derivatives as
the key synthetic step. The ligands were employed in the
asymmetric hydrogenation of functionalized olefins (Rh-
catalyzed) and imines (Ir-catalyzed), and the steric influence
of the ligand substituents was evaluated as well as the inter-
play of the different chirality elements.
The unsubstituted pinene–pyridine 10c (with R = H) is
not directly accessible by simple Kröhnke annulation and
was synthesized following the reaction sequence shown in
Scheme 2.[19] First, the pyridinium salt 12 was prepared
from pyridine and ethyl 2-bromoacetate (11) and then
treated with pinocarvone (8) to give the pyridone 13. The
latter compound was aromatized to the triflate derivative
14 and finally the triflate group was substituted by a
hydrogen atom to give the unsubstituted pinene–pyridine
10c in an overall yield of 43% (Scheme 2).
The pinene–pyridines 10a–c were then hydrogenated to
the desired pinene–piperidines. This is the key step of the
synthesis because three new stereocenters are generated
within this transformation and up to eight stereoisomers
Results and Discussion
Ligand Synthesis
Enantiopure (1R,5R)-(+)-α-pinene (7) was used as the can be formed. Several heterogeneous hydrogenation cata-
common starting material for the synthesis of all ligands lysts were tested by using Ph-pinene–pyridine 10a as the
L1–L13. Compound 7 was reacted in a photolysis appara- substrate.
Scheme 1. Synthesis of pinene–pyridines by ene reaction and subsequent Kröhnke annulation.
Scheme 2. Synthesis of 10c.
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Pinene-Derived Phosphoramidites for Asymmetric Hydrogenation
Scheme 3. Hydrogenation of pinene–pyridines and the resulting diastereomers.
The first attempts using Rh/C, Rh/Al2O3, Pt/C, PtO2, or phoramidite ligands. The pinene–piperidines were dissolved
Raney Ni (5 mol-%, 120 bar H2, 120 °C) did not lead to the in CH2Cl2 in the presence of NEt3, the solution was cooled
desired product, but to the reduction of the phenyl substitu- to 0 °C, and a solution of (Ra)- or (Sa)-BINOL-PCl (16)[22]
ent to a cyclohexyl group. Even when HBF4 or HOAc were in CH2Cl2 was added dropwise over 15 min. After 1 h at
added as acidic co-catalysts, the reduction of the pyridine 0 °C, the reaction mixture was allowed to warm to room
ring did not occur. Finally, the use of Ru/C or Pd(OH)2/C temperature and then stirred for 2–16 h to allow full conver-
in glacial acetic acid resulted in the successful conversion sion of the chlorophosphite 16. After filtration through a
of Ph-pinene–pyridine 10a into the fully hydrogenated pad of basic alumina, the ligands L1–L10 were obtained in
product Cy-pinene–piperidine 15a as a mixture of two moderate to good yields (49–87%; Scheme 4).[23]
stereoisomers in ratios of 70:30 and 55:45, respectively
(Scheme 3).[20] The diastereomeric mixture could be sepa-
rated either by column chromatography or by fractional
precipitation of the HCl adduct from HOAc/diethyl ether
to give (Sc)- and (Rc)-15a in yields of up to 43 and 28%,
respectively.
The structures of the hydrogenation products were as-
signed by NMR (NOESY) spectroscopy. From the opti-
mized geometries of all eight possible stereoisomers (DFT
calculations: M062X/def2-TZVP), proton distances rel-
evant for establishing the stereochemistry were identified.
The measured NOE interactions match the structures of the
two diastereomers that differ only in the configuration at
the 2-position of the heterocycle (see the Supporting Infor-
mation). Interestingly, the hydrogen atoms have been prefer-
entially delivered to the apparently more hindered face of
the pyridine ring leading to the less-crowded product.
Following the same protocol, Me-pinene–pyridine 10b
was hydrogenated to the corresponding pinene–piperidine
15b by using Pd(OH)2/C in HOAc (Scheme 3). Again, just
two stereoisomers were obtained in a ratio of 60:40, which
were successfully separated by column chromatography and
(Sc)-15b and (Rc)-15b were isolated in yields of 31 and 40%,
respectively. NMR spectroscopic analysis indicated that the
stereoisomers obtained are epimers at C-2 and possess the
same configurations at the remaining chiral centers as Cy-
pinene–piperidines 15a. It is important to note that the
change in CIP priority between the Me- and Cy-substituted
backbones leads to a different nomenclature with respect to
the (Rc) or (Sc) configuration at the chiral center at the 2-
position, although the relative spatial arrangements are
Scheme 4. Synthesis of pinene-derived phosphoramidites.
identical (Scheme 3).
As expected, under the same conditions as above, the
hydrogenation of H-pinene–pyridine 10c led to only a single
For ligand L2, synthesized from H-pinene–piperidine 15c
stereoisomer of 15c in 92% yield. The configurations at the and (Ra)-BINOL-PCl, single crystals of the borane adduct
bridging carbons are identical to those of the pinene–piper- suitable for X-ray analysis were obtained from diethyl ether
idines 15a and 15b.[21]
by slow evaporation at room temperature (Figure 2).
In the solid state, the piperidine ring exhibits a chair con-
The successfully synthesized secondary amines 15a–c
were then used for the synthesis of the envisaged phos- formation and the pinene moiety adopts a half-chair con-
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C. Schmitz, W. Leitner, G. Franciò
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most probably differing in the conformation of the tropo-
isomeric biphenol unit. Consequently, separation was not
feasible.
Scheme 5. Synthesis of phosphoramidites possessing different diol
moieties.
Figure 2. Structure of L2·BH3 in the solid state as determined by
X-ray diffraction analysis.
Application in Asymmetric Hydrogenation
formation. The P1–N1 bond length of 1.6165 Å is relatively
short (Table 1) and the P1–O1 and P1–O2 bond lengths of
1.6310 and 1.6145 Å differ slightly, which is rather unusual
for BINOL-based ligands (Table 1). The dihedral angle of
C1–C10–C11–C20 in the binaphthyl unit is relatively small
(–47.98°), but is still within the expected range (Table 2).
The phosphorus atom shows a nearly perfect tetrahedral
geometry (sum of angles 655.55°) whereas the nitrogen
atom shows a nearly perfect trigonal-planar geometry (sum
of angles 359.70°) and hence has a high degree of sp2-
hybridized character (Table 2). The pinene fragment of the
ligand shows a relatively large spatial distance to the phos-
phorus atom and in particular to the lone pair of the phos-
phorus atom (here coordinated by borane).
Ligands L1–L13 were used in the rhodium-catalyzed
asymmetric hydrogenation of functionalized olefins using
dimethyl itaconate as a benchmark substrate. The catalysts
were prepared in situ from [Rh(cod)2]BF4 and the phos-
phoramidite ligands with a Rh/P ratio of 1:2.05. The results
are shown in Table 3.
Table 3. Asymmetric hydrogenation of dimethyl itaconate.[a]
Entry
Ligand
R
Diol Geometry[b] Conv.[c] [%] ee[d] [%]
Table 1. Selected bond lengths [Å] in L2·BH3.
1
2
3
4
5
6
7
8
L1
L2
L3
L4
L5
L6
L7
L8
L9
L10
L11
L12
L13
L2
L2
L2
L2
H
H
(Sa)
(Ra)
(Sa)
(Ra)
(Sa)
–
–
Ͼ99
Ͼ99
Ͼ99
Ͼ99
Ͼ99
Ͼ99
Ͼ99
Ͼ99
Ͼ99
Ͼ99
Ͼ99
Ͼ99
Ͼ99
99
72 (S)
95 (R)
24 (S)
33 (R)
16 (S)
7 (R)
P1–N1
P1–O1
1.6165
1.6310
P1–O2
P1–B1
1.6145
1.8886
(Sc)-Me
(Sc)-Me
(Rc)-Me
(Rc)-Me (Ra)
(Sc)-Cy
(Sc)-Cy
(Rc)-Cy
(Rc)-Cy
H
H
H
H
H
H
H
A
A
B
B
B
B
A
A
–
–
–
–
–
Table 2. Selected bond angles [°] in L2·BH3.
(Sa)
(Ra)
(Sa)
(Ra)
(Ra)
(R,R)
24 (S)
2 (S)
P1–N1–C31
P1–N1–C21
C21–N1–C31
O1–P1–O2
O1–P1–N1
124.09
119.30
116.31
99.97
O1–P1–B1
O2–P1–B1
N1–P1–B1
N1–P1–O2
108.21
116.80
117.19
99.93
9
49 (S)
16 (R)
77 (R)
11 (S)
4 (R)
95 (R)
83 (R)
94 (R)
95 (R)
10
11
12
13
14[e]
15[e,f]
113.45
C1–C10–C11–C20
–47.98
(Ra)
(Ra)
(Ra)
(Ra)
Then the diol moiety was varied by using the pinene–
piperidine 15c as the common amine. The chloro phos- 16[g]
phites of (Ra)-H8-BINOL, (R,R)-TADDOL, and of a tro-
Ͼ99
98
98
–
–
17[h]
poisomeric biphenol (generated in situ) were treated with
15c following the procedure described above. The envisaged
ligands L11–L13 were obtained in yields of 58–87%
(Scheme 5). The 31P{1H} NMR spectrum (CDCl3, room
temp.) of L13 shows two peaks at δ = 144.4 and 150.6 ppm
in a ratio of 87:13. The 31P-31P EXSY NMR measurements
[a] Substrate: 3 mmol, substrate/Rh/L = 1000:1:2.05, CH2Cl2:
2 mL, p(H2) = 40 bar, room temp., t = 16 h. [b] In analogy to
Scheme 4. [c] Determined by GC. [d] Determined by chiral GC. [e]
t = 1 h. [f] In MeOH. [g] Substrate/Rh = 10000:1. [h] p(H2) =
10 bar, t = 1 h.
All the ligands formed active Rh catalysts for this trans-
confirmed that the two peaks are in exchange, which indi- formation and full conversion was achieved with all the cat-
cates the presence in solution of interconverting isomers alyst systems under the standard conditions. The enantio-
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Pinene-Derived Phosphoramidites for Asymmetric Hydrogenation
selectivity was very strongly dependent on the amine moiety Table 4. Rhodium-catalyzed asymmetric hydrogenation of pro-
chiral olefins using [Rh(cod)(L2)2]BF4.[a]
of the ligand, with the axial chirality at the diol moiety
having a dominating steering effect determining in most
cases the preferred configuration of the product formed.
Cooperative effects between the pinene skeleton and the
BINOL moiety were observed for ligands L1 and L2 based
on the 2-unsubstituted amine 15c. While a moderate
enantioselectivity of 72% ee (S) was obtained with L1
(Table 3, entry 1), the matched diastereomer L2 led to 95%
ee of the opposite enantiomer (R) (entry 2).
Surprisingly, the additional steric bulk caused by substit-
uents at the 2-position of the pinene–piperidine moiety in
L3–L10 had a very negative influence on the enantio-
selectivity regardless of the configuration of the stereocen-
ter. Considering the spatial orientation of the respective
substituents, the ligands with geometry A gave higher ee
values than the ligands with geometry B (Table 3, entries 3–
10).
The three ligands L11–L13 based on the most promising
amine moiety 15c did not lead to improved results. In par-
ticular, L11 bearing (Ra)-H8-BINOL gave a lower ee than
the related (Ra)-BINOL-based L2 (77 vs. 95% ee, respec-
tively), and almost racemic products were obtained with
(R,R)-TADDOL and the biphenol-based ligands L12 and
L13 (Table 3, entries 11–13).
[a] Substrate: 1.5 mmol, substrate/Rh = 1000:1, CH2Cl2: 2 mL,
p(H2) = 20 bar, room temp., t = 14 h. [b] Determined by H NMR
spectroscopy. [c] Determined by chiral GC or HPLC. [d] In MeOH.
[e] Substrate/Rh = 100:1.
1
The activity and productivity of the Rh/L2 system were
investigated further. At a 0.1 mol-% catalyst loading, full obtained (Table 4, entry 6). Finally,
a high enantio-
conversion was achieved within 1 h corresponding to a selectivity of 99% (S) was achieved in the hydrogenation of
TOF of Ն1000 h–1 (Table 3, entry 14). Almost full conver- 1-(dimethoxyphosphoryl)vinyl benzoate by using 1 mol-%
sion (TON 9800) at the same level of enantioselectivity of the catalyst (Table 4, entry 7). To the best of our knowl-
could be obtained by reducing the catalyst loading to edge this is the highest enantioselectivity ever reported for
0.01 mol-% (Table 3, entry 16). When MeOH was used as this substrate using monodentate ligands.
the reaction solvent, the enantioselectivity was slightly re-
Next, the Ir-catalyzed hydrogenation of prochiral imines
duced (Table 3, entry 15).[24] A reduced hydrogen pressure was investigated by using the phosphoramidites L1 and L2.
of 10 bar did not affect the enantioselectivity (Table 3, en- The catalytic systems were generated in situ from [Ir(cod)-
try 17).
Cl]2 and the respective ligand in an iridium/phosphorus ra-
The substrate scope was explored by using the isolated tio of 1:2.1. Iodine (5 mol-%) was used as an activator. The
catalyst complex [Rh(cod)(L2)2]BF4 prepared from results are summarized in Table 5. In the hydrogenation of
[Rh(cod)acac], HBF4·Et2O, and L2.[25] The results of the N-(1-phenylethylidene)aniline, full conversion was obtained
substrate screening are summarized in Table 4.
with both ligands. While L2 led to the (S) enantiomer with
The asymmetric hydrogenation using [Rh(cod)(L2)2]BF4 70% ee, the use of L1 gave a higher ee of 74% of the oppo-
led to full conversion for all the substrates tested. In the site enantiomer (R) (Table 5, entries 1 and 2). Thus, in con-
case of dimethyl itaconate, the use of the isolated catalyst trast to the Rh-catalyzed olefin hydrogenation reaction, the
gave the same enantioselectivity as the in situ generated cat- two diastereomers L1 and L2 led to similar levels of
alyst (Table 3, entry 2 vs. Table 4, entry 1). Methyl 2-acet- enantioselectivity and, again, the enantiodiscrimination is
amidoacrylate was hydrogenated with 95% ee (S) (Table 4, largely dominated by the configuration of the BINOL moi-
entry 2), whereas a slightly lower enantiomeric excess of ety.
88% (S) was achieved with the corresponding free acid 2-
The scope of the Ir/L1/I2 system was evaluated for a
acetamidoacrylic acid (Table 4, entry 3). The enantio- series of acyclic imines containing additional functional
selectivity obtained in this hydrogenation might be nega- groups. In comparison with N-(1-phenylethylidene)aniline,
tively affected by the use of MeOH as solvent, which is an increased steric demand around the C=N bond, either
necessary due to solubility constraints of the substrate in at the carbon (Ar1 = o-tolyl) or the nitrogen (Ar2 = 2-
CH2Cl2. In the hydrogenation of methyl (Z)-acetamido- naphthyl), led to slightly reduced enantioselectivity
cinnamate, an enantiomeric excess of 96% (S) was achieved (Table 5, entries 3 and 4). When both groups were present
(Table 4, entry 4), whereas a lower enantioselectivity of 49% in the substrate, a significantly lower conversion was also
ee (S) was obtained for N-(1-phenylvinyl)acetamide obtained (Table 5, entry 5). Electron-withdrawing fluoro or
(Table 4, entry 5). Using 1-trifluoromethylvinyl acetate as chloro substituents at the para position of Ar1 led to lower
substrate, a good enantiomeric excess of 95% (S) was again enantiomeric excesses of 65 and 55% (Table 5, entries 6 and
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Table 5. Ir-catalyzed asymmetric hydrogenation of acyclic imines.[a]
The pinene–piperidines were then treated with different
diols to give 13 structurally different phosphoramidite li-
gands, which were evaluated in asymmetric catalysis. In the
rhodium-catalyzed asymmetric hydrogenation of differently
functionalized olefins, L2 comprising the most simple
piperidine derivative and the (Ra)-BINOL moiety proved to
be the most efficient ligand leading to high enantiomeric
excesses of up to 99%, a TOF of Ն1000 h–1, and a TON of
9800. The diastereomeric counterpart L1 bearing the (Sa)-
BINOL gave the highest enantioselectivities in the iridium-
catalyzed asymmetric hydrogenation of acyclic imines with
ee values of up to 81%.
This investigation has shown that α-pinene is a useful
chiral starting material for the synthesis of phosphoramid-
ites with multiple stereogenic centers and the right combi-
nation of different chiral and structural elements has pro-
vided two valuable ligands for metal-catalyzed asymmetric
hydrogenation reactions.
Entry Ligand Ar1
Ar2
Conv.[b] [%]
ee[c] [%]
1
2
3
4
5
6
7
8
L1
L2
L1
L1
L1
L1
L1
L1
L1
L1
L1
Ph
Ph
Ph
Ph
Ph
2-MeC6H4
Ph
2-MeC6H4
Ph
Ͼ99
Ͼ99
Ͼ99
92
77
96
74 (R)
70 (S)
72 (–)
63 (–)
60 (–)
65 (–)
81 (+)
–
2-naphthyl
2-naphthyl
4-FC6H4
Ph
2-naphthyl
4-MeOC6H4 4-MeOC6H4
4-MeOC6H4
4-MeOC6H4
65
Ͻ10
Ͼ99
Ͼ99
Ͼ99
9
10
11
63 (+)
55 (–)
63 (+)
4-ClC6H4
4-ClC6H4
Ph
4-MeOC6H4
[a] Substrate: 0.5 mmol, substrate/Ir/L/I2 = 100:1:2.1:5, toluene:
2 mL, p(H2) = 40 bar, room temp., t = 14 h. [b] Determined by GC
1
or H NMR spectroscopy. [c] Determined by chiral GC or chiral
HPLC.
Experimental Section
General: All reactions and manipulations were performed using
standard Schlenk techniques or in a glovebox under argon. 1H, 13C,
and 31P NMR spectra were recorded with Bruker AV 600 (600,
150, and 243 MHz, respectively), AV 400 (400, 100, and 162 MHz,
respectively), and Bruker AV 300 (300, 75, and 121 MHz, respec-
tively) spectrometers. The chemical shifts are referenced to residual
solvent peaks (1H, 13C NMR) or H3PO4 85% as external standard
(31P NMR). Mass spectra were recorded with a Finnigan MAT
8200 (MS + HRMS-EI) or Bruker FTICR-Apex III (HRMS-ESI)
spectrometer. Optical rotations were measured with a Jasco P-1020
10), whereas an electron-donating p-methoxy substituent in
Ar2 resulted in an increased enantioselectivity of 81% ee
(+) with a reduced conversion of 65% (Table 5, entry 7).
The reactivity of the substrate dramatically decreased when
both the 2-naphthyl group (Ar1) and the p-methoxyphenyl
(Ar2) were present (Table 5, entry 8). In contrast, p-methoxy
substituents in both Ar1 and Ar2 led to full conversion and
a moderate enantiomeric excess of 63% (+) (Table 5, en-
try 9). The combination of an electron-donating p-methoxy
substituent in Ar2 and an electron-withdrawing chloro sub- polarimeter. The concentrations used for measuring specific rota-
stituent in Ar1 again resulted in full conversion and 63% ee
tions are given as g per 100 mL. CH2Cl2, toluene, and n-pentane
were dried with alumina and molecular sieves with a solvent purifi-
(+) (Table 5, entry 11).
cation system from Innovative Technology. THF, diethyl ether, and
NEt3 were distilled from KOH and dried with molecular sieves.
PCl3 was freshly distilled. CDCl3, CD2Cl2, and C6D6 were degassed
Conclusions
through freeze–pump–thaw cycles and stored over molecular sieves.
All solvents and compounds were stored over molecular sieves un-
Chiral secondary amines derived from pinene have been
der argon. The following compounds were synthesized according
synthesized and used as novel building blocks for the prepa-
to literature procedures: (Ra)- and (Sa)-BINOL-PCl (16),[22] (R)-
ration of a small library of monodentate phosphoramidites,
H8-BINOL-PCl,[26] (R,R)-TADDOL-PCl,[27] 1-(2-oxo-2-phenyl-
which has been evaluated in the asymmetric hydrogenation
of prochiral olefins and imines. The underlying amine com-
ponents were synthesized from enantiopure α-pinene by a
Schenk–ene reaction followed by Kröhnke annulation and
subsequent hydrogenation of the pyridine ring as the key
step of the synthetic protocol. The hydrogenation of the
annulated pyridines bearing H, Me, or Ph at C-2 was cata-
lyzed by Pd(OH)2/C (or Ru/C) and proceeded stereoselec-
tively at the two carbon atoms at the ring junctures, whereas
the chirality at C-2 was not controlled. Thus, the chirality
embedded in the pinene scaffold is effective in directing the
stereochemistry of the hydrogenation reaction. The re-
sulting Me- and Cy-substituted diastereomers were easily
separated either by column chromatography or crystalli-
zation of the hydrochloride derivatives. The structures of
the novel pinene–piperidines were elucidated by means of
NMR spectroscopy (NOESY) and confirmed in the solid
state by X-ray diffraction analysis.
ethyl)pyridinium iodide (9a),[16b] 1-(2-oxopropyl)pyridinium chlor-
ide (9b),[16c] 1-(2-ethoxy-2-oxoethyl)pyridinium bromide (12),[19a]
(1S,9S)-10,10-dimethyl-5-phenyl-6-azatricyclo[7.1.1.02,7]undeca-
2,4,6-triene (10a).[17c] Silica gel (SiO2 60, 0.04–0.063 mm, 230–
400 mesh) and basic alumina (Al2O3 90 basic, pH 8.5–10.5, 0.063–
0.2 mm) were purchased from Roth. All other chemicals were pur-
chased from Sigma–Aldrich, ABCR, TCI, or AlfaAesar and used
as received.
General Procedure for the Synthesis of Ligands: The pinene–piper-
idine derivatives 15a–c (1.0 equiv.) were dissolved in CH2Cl2
(10 mL). The solution was cooled to 0 °C and triethylamine
(3.0 equiv.) was added. After 10 min a solution of the chlorophos-
phite 16 (1.0 equiv.) in CH2Cl2 (5 mL) was added dropwise during
15 min. The reaction mixture was stirred at 0 °C for 30 min and for
a further 5 h at room temperature. The solvent was removed under
reduced pressure and the residue redissolved in THF (8 mL). The
solution was filtered through a pad of basic alumina and rinsed
with THF (8 mL). Removal of the solvent under reduced pressure
yielded the desired product as a white powder.
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Pinene-Derived Phosphoramidites for Asymmetric Hydrogenation
General Procedure for the Catalytic Hydrogenation of Dimethyl It-
aconate Using in situ Generated Catalysts: A solution of the respec-
tive ligand (6.15 μmol, 2.05 equiv.) in CH2Cl2 (1 mL) was added to
a solution of [Rh(cod)2]BF4 (1.22 mg, 3.0 μmol, 1.0 equiv.) in
CH2Cl2 (1 mL). The mixture was stirred for 15 min at room tem-
perature and then transferred under argon to a 10 mL stainless-
steel autoclave equipped with a glass inlet and magnetic stirring
bar and charged with dimethyl itaconate (474.5 mg, 3.0 mmol,
1.000 equiv.). After stirring for 10 min, the autoclave was pressur-
ized with hydrogen and the mixture stirred for 14 h at room tem-
perature. Further details and modifications of the conditions are
given in Table 3. After carefully releasing the pressure, the reaction
mixture was filtered through a short plug of silica and analyzed by
NMR spectroscopy and chiral GC.
14 h. The yellow solution was diluted with CH2Cl2 (250 mL) and
washed carefully with a saturated aqueous NaHCO3 solution (3ϫ
150 mL) until the aqueous phase stayed basic. Then the organic
phase was washed with 10% aqueous hydrochloric acid (2ϫ
75 mL) until the aqueous phase stayed acidic. Finally, the organic
phase was washed with a saturated aqueous CuSO4 solution
(75 mL) and NaCl solution (150 mL) and dried over MgSO4. The
solvent was removed under reduced pressure keeping the tempera-
ture below 30 °C to prevent polymerization of the product. The
brown oily residue was distilled under vacuum (5 mbar) by using a
Vigreux column to give the product as a colorless liquid, yield
12.7 g (84.6 mmol, 85%). 1H NMR (400 MHz, CDCl3): δ = 0.77
(s, 3 H, CH3), 1.25 (d, JH,H = 10.4 Hz, 1 H, CH2), 1.33 (s, 3 H,
CH3), 2.17 (m, 1 H, CH), 2.48 (m, 1 H, CH2), 2.59–2.69 (m, 2 H,
CH2), 2.74 (t, JH,H = 6.0 Hz, 1 H, CH), 4.97 (d, JH,H = 1.7 Hz, 1
H, C=CH2), 5.90 (d, JH,H = 1.7 Hz, 1 H, C=CH2) ppm. 13C{1H}
NMR (100 MHz, CDCl3): δ = 21.4 (CH3), 25.9 (CH3), 32.3 (CH2),
38.5 (CH), 40.7 (Cq), 42.4 (CH2), 48.1 (CH), 117.2 (CH2), 149.0
(Cq), 199.6 (C=O) ppm. The analytical data are in accordance with
the literature.[15a,19a]
General Procedure for the Catalytic Hydrogenation of C=C Double
Bonds Using [Rh(cod)(L2)2]BF4: A solution of [Rh(cod)(L2)2]BF4
(1.9 mg, 1.5 μmol, 1.0 equiv.) in CH2Cl2 or MeOH (1 mL) was
transferred under argon to a 10 mL stainless-steel autoclave
equipped with a glass inlet, a magnetic stirring bar and containing
the desired substrate (1.5 mmol, 1.000 equiv.). After stirring for
10 min, the autoclave was pressurized with hydrogen and the mix-
ture stirred for the indicated time at room temperature. Further
details and modifications of the conditions are given in Table 4.
After carefully releasing the pressure, the reaction mixture was fil-
tered through a short plug of silica and analyzed by NMR spec-
troscopy and chiral GC or HPLC. The absolute configurations of
the hydrogenation products were assigned by comparison of their
signs of optical rotation with those reported in the literature.
(1S,9S)-5,10,10-Trimethyl-6-azatricyclo[7.1.1.02,7]undeca-2,4,6-tri-
ene (10b): 1-(2-Oxopropyl)pyridinium chloride (9b; 10.43 g,
60.8 mmol, 1.5 equiv.) was dissolved in glacial acetic acid. Ammo-
nium acetate (40.0 g, 520 mmol, 12.8 equiv.) was added and the
mixture was heated to 130 °C and stirred until it became clear.
Then (1S,5S)-6,6-dimethyl-2-methylenebicyclo[3.1.1]heptan-3-one
(8; 6.1 g, 40.5 mmol, 1.0 equiv.) was added and the brownish reac-
tion mixture was heated at reflux for 16 h. After cooling to room
temperature, the brown solution was diluted with water (100 mL)
and basified by the addition of a 15 m sodium hydroxide solution.
The aqueous phase was extracted with ethyl acetate (4ϫ100 mL)
and the combined organic extracts were diluted with CH2Cl2
(500 mL). The organic layers were washed with water (3ϫ 100 mL)
and brine (100 mL), and dried with Na2SO4. The solvent was re-
moved under reduced pressure to give a brownish residue which
was subjected to column chromatography (pentane/ethyl acetate,
2:1, Rf = 0.38). The product was obtained as a light-yellow liquid,
General Procedure for the Catalytic Hydrogenation of C=N Double
Bonds: A solution of the ligand (10.5 μmol, 2.1 equiv.) in toluene
(1 mL) was added to a solution of [Ir(cod)Cl]2 (1.68 mg, 2.5 μmol,
0.5 equiv.) in toluene (1 mL). The mixture was stirred for 15 min
at room temperature and then added to the substrate (0.5 mmol,
100 equiv.) and iodine (6.4 mg, 25 μmol, 5.0 equiv.). After stirring
for 10 min the solution was transferred under argon to a 10 mL
stainless-steel autoclave, equipped with a glass inlet and a magnetic
stirring bar. The autoclave was pressurized with hydrogen and the
mixture stirred for 14 h at room temperature. Further details are
given in Table 5. After carefully releasing the pressure, all the vola-
tiles were removed under reduced pressure. The residue was ana-
lyzed by NMR spectroscopy and in the case of incomplete conver-
sion purified by column chromatography. The enantiomeric excess
was determined by chiral GC or HPLC.
yield 4.38 g (23.4 mmol, 58%). [α]2D8 = 57.0 (c = 0.5, CH2Cl2). H
1
NMR (400 MHz, CDCl3): δ = 0.62 (s, 3 H, CH3), 1.23 (d, JH,H
9.3 Hz, 1 H, CH2), 1.37 (s, 3 H, CH3), 2.40 (tt, JH,H = 6.0, JH,H
=
=
2.9 Hz, 1 H, CH), 2.49 (s, 3 H, CH3), 2.60–2.71 (m, 1 H, CH, 1 H,
CH2), 3.06 (d, JH,H = 2.8 Hz, 2 H, CH2), 6.80 (d, JH,H = 7.6 Hz, 1
H, Ar), 7.07 (d, JH,H = 7.6 Hz, 1 H, Ar) ppm. 13C{1H} NMR
(100 MHz, CDCl3): δ = 21.1 (CH3), 24.0 (CH3), 25.9 (CH3), 32.0
(CH2), 36.4 (CH2), 39.3 (Cq), 40.1 (CH), 46.0 (CH), 119.4 (CH,
Ar), 133.2 (CH, Ar), 138.4 (Cq, Ar), 154.8 (Cq, Ar), 155.8 (Cq,
Ar) ppm. MS (EI): m/z (%) = 186 (24), 172 (38), 158 (17), 157 (11),
146 (15), 145 (15), 144 (100), 143 (27), 132 (10), 131 (12), 77 (11).
HRMS (ESI): calcd. for C13H18N+ [M + H]+ 188.14338; found
188.14346.
(8S,10S)-10,10-Dimethyl-6-azatricyclo[7.1.1.02,7]undeca-2,4,6-triene
(10c): Formic acid (1.0 mL, 26.0 mmol, 2.5 equiv.) was added drop-
wise to a solution of (5S,7S)-5,6,7,8-tetrahydro-6,6-dimethyl-5,7-
methanoquinolin-2-yl trifluoromethanesulfonate (14; 3.32 g,
10.3 mmol, 1.0 equiv.), Pd(OAc)2 (47 mg, 0.21 mmol, 0.02 equiv.),
1,1Ј-bis(diphenylphosphanyl)ferrocene (233 mg, 0.42 mmol,
0.04 equiv.), and triethylamine (4.3 mL, 31.0 mmol, 3.0 equiv.) in
(1S,5S)-6,6-Dimethyl-2-methylenebicyclo[3.1.1]heptan-3-one (8): In
a photolysis apparatus (DEMA, UV apparatus 13/11, 300 mL total
volume), (1R,5R)-(+)-α-pinene (7; 15.9 mL, 100 mmol, 1.0 equiv.)
was dissolved in CH2Cl2 (130 mL). Acetic acid anhydride (14.2 mL,
150 mmol, 1.5 equiv.), pyridine (12.9 mL, 160 mmol, 1.6 equiv.), 4-
(dimethylamino)pyridine (DMAP; 245 mg, 2.0 mmol, 0.02 equiv.),
and 5,10,15,20-tetraphenyl-21H,23H-porphyrin (123 mg, 0.2 mmol,
0.002 equiv.) were added. The UV apparatus was equipped with a
reflux condenser with a drying tube (CaCl2) at the top. The reac-
tion vessel was cooled to –10 °C by a cryostat. The deep-purple
reaction mixture was stirred for 10 min and a slow stream of pres-
surized air was purged through the reaction mixture under vigorous
stirring from the bottom of the reaction vessel to give small
bubbles. The Hg lamp (Philips HPK 125) of the UV apparatus, DMF (40 mL). The reaction mixture was stirred overnight at 60 °C.
which was cooled by a cryostat at –15 °C, was switched on and the After cooling to room temperature, the reaction mixture was
reaction mixture stirred at the maximal rate (1200 rpm) for 40 h. quenched by the addition of water (20 mL) and extracted with di-
When full conversion was achieved (TLC monitoring, pentane/
ethyl acetate, 9:1), the Hg lamp and the pressurized air were
switched off and the reaction mixture stirred at 5 °C for another
ethyl ether (4 ϫ 50 mL). The combined organic extracts were
washed with brine (50 mL) and dried with Na2SO4. The solvent
was removed under reduced pressure and the brownish-orange resi-
Eur. J. Org. Chem. 2015, 2889–2901
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2895

C. Schmitz, W. Leitner, G. Franciò
FULL PAPER
due subjected to column chromatography (pentane/ethyl acetate,
110.3 (CH, Ar), 136.1 (CH, Ar), 142.0 (Cq, Ar), 152.8 (Cq, Ar),
156.1 (Cq, Ar) ppm. The analytical data are in accordance with the
4:1 to 1:1, Rf = 0.37) to give the product as a colorless liquid, yield
1
1.56 g (9.0 mmol, 87%). H NMR (400 MHz, CDCl3): δ = 0.62 (s, literature.[19a]
3 H, CH3), 1.25 (d, JH,H = 9.5 Hz, 1 H, CH2), 1.39 (s, 3 H, CH3),
(1R,2S,7R,9S)-5-Cyclohexyl-10,10-dimethyl-6-azatricyclo-
2.35 (m, 1 H, CH), 2.66 (dt, JH,H = 9.4, JH,H = 5.6 Hz, 1 H, CH2),
2.73 (t, JH,H = 5.7 Hz, 1 H, CH), 3.10 (d, JH,H = 2.5 Hz, 2 H,
CH2), 6.95 (m, 1 H, Ar), 7.16 (m, 1 H, Ar), 8.33 (m, 1 H, Ar) ppm.
13C{1H} NMR (100 MHz, CDCl3): δ = 21.1 (CH3), 25.9 (CH3),
31.8 (CH2), 36.3 (CH2), 39.3 (Cq), 40.1 (CH), 46.3 (CH), 120.2
(CH, Ar), 132.7 (CH, Ar), 141.7 (Cq, Ar), 146.5 (CH, Ar), 156.7
(Cq, Ar) ppm. The analytical data are in accordance with the litera-
ture.[19c]
[7.1.1.02,7]undecane (15a): The pinene–pyridine derivative 10a
(4.99 g, 20.0 mmol, 1.0 equiv.) and dry Pd(OH)2/C (702 mg,
1.0 mmol, 20% Pd, 0.05 equiv.) were placed in a 75 mL stainless-
steel autoclave with a glass inlet and stirring bar under argon. Gla-
cial acetic acid (30 mL) was added and the autoclave pressurized
with 90 bar hydrogen. The reaction mixture was stirred at 120 °C
under isobaric conditions for 3 d. After cooling to room tempera-
ture the pressure was released and the reaction mixture filtered
through a pad of Celite. Concentrated hydrochloric acid (5 mL)
was added to the light-yellow solution and the mixture stirred for
1 h. The following section gives two alternatives for the purification
and isolation of the two diastereomeric products of the reaction.
(5S,7S)-5,6,7,8-Tetrahydro-6,6-dimethyl-5,7-methanoquinolin-
2(1H)-one (13): Ammonium acetate (74.0 g, 960 mmol, 10.0 equiv.)
and 1-(2-ethoxy-2-oxoethyl)pyridinium bromide (12; 26.0 g,
105.6 mmol, 1.1 equiv.) were suspended in dry n-butanol. (1S,5S)-
6,6-Dimethyl-2-methylenebicyclo[3.1.1]heptan-3-one (8; 14.4 g,
96.0 mmol, 1.0 equiv.) and piperidine (1.9 mL, 19.2 mmol,
0.2 equiv.) were added sequentially to the yellow solution. The re-
sulting red solution was heated at reflux for 2 h and glacial acetic
acid (11.0 mL, 192.0 mmol, 2.0 equiv.) was added. The reaction
mixture was then heated at reflux for 18 h at 140 °C. After cooling
to room temperature the mixture was neutralized by the addition
of a 2 m aqueous sodium hydroxide solution and extracted with
ethyl acetate (4 ϫ 100 mL). The combined organic layers were
washed with brine (100 mL) and dried with Na2SO4. The solvent
was removed under reduced pressure and the brownish residue sub-
jected to column chromatography (pentane/diethyl ether/acetone/
methanol, 45:30:22:3, Rf = 0.22) to yield the product as a colorless
solid, yield 10.23 g (54.1 mmol, 56 %). 1H NMR (400 MHz,
CDCl3): δ = 0.70 (s, 3 H, CH3), 1.26 (d, JH,H = 9.4 Hz, 1 H, CH2),
1.37 (s, 3 H, CH3), 2.28 (m, 1 H, CH), 2.57 (t, JH,H = 5.6 Hz, 1 H,
CH), 2.63 (dt, JH,H = 9.5, JH,H = 5.5 Hz, 1 H, CH2), 2.95 (m, 2 H,
CH2), 6.33 (d, JH,H = 8.9 Hz, 1 H, Ar), 7.15 (d, JH,H = 8.9 Hz, 1
H, Ar), 14.02 (br. s, 1 H, NH) ppm. 13C{1H} NMR (100 MHz,
CDCl3): δ = 21.0 (CH3), 25.9 (CH3), 31.4 (CH2), 32.7 (CH2), 39.4
(CH), 40.2 (Cq), 44.1 (CH), 114.8 (CH, Ar), 124.8 (Cq, Ar), 141.2
(CH, Ar), 142.3 (Cq, Ar), 165.6 (C=O) ppm. The analytical data
are in accordance with the literature.[19a,19b]
Method A: Diethyl ether (15 mL) was added dropwise to the acidic
solution to give a colorless precipitate [(Rc)-15aH+Cl–] which was
collected by filtration and dried under high vacuum. The addition
of an additional amount of ether (15–20 mL) led to the precipi-
tation of a mixture of the two diastereomers, which was also col-
lected. The mother liquor, containing predominantly the (Sc)-dia-
stereomer, was concentrated to a volume of about 8–10 mL. Slow
addition of small portions of diethyl ether (5 mL each) again re-
sulted in the precipitation of diastereomeric mixtures and finally in
the precipitation of pure (Sc)-15aH+Cl–, which was collected by
filtration and dried under high vacuum to give a colorless powder.
To improve the yield, the diastereomeric mixtures obtained were
redissolved in glacial acetic acid and subjected to the same process
as described above. To obtain the desired amines, the hydrochloride
adducts were suspended in diethyl ether (30 mL) and saturated
aqueous Na2CO3 solution (20 mL) and stirred overnight. Extrac-
tion with diethyl ether (3ϫ 30 mL), drying over Na2SO4, and re-
moval of the solvent gave the products as light-yellow liquids that
slowly crystallized upon standing.
Method B: All the volatiles were removed under reduced pressure.
Diethyl ether (30 mL) and a saturated aqueous Na2CO3 solution
(30 mL) were added to the residual colorless powder. The suspen-
sion was stirred overnight at room temperature. The aqueous phase
was extracted with diethyl ether (3ϫ 30 mL) and the combined
organic layers washed with brine (20 mL) and dried with Na2SO4.
The solvent was removed under reduced pressure to give a light-
yellow liquid (5.16 g, 19.7 mmol, 99%), which was subjected to col-
umn chromatography (basic alumina, pentane/ethyl acetate, 9:1).
Both diastereomers were collected after removal of the solvent un-
der reduced pressure as colorless liquids that slowly crystallized
upon standing.
(5S,7S)-5,6,7,8-Tetrahydro-6,6-dimethyl-5,7-methanoquinolin-2-yl
Trifluoromethanesulfonate (14): Triethylamine (9.0 mL, 64.8 mmol,
1.2 equiv.) was added to a solution of (5S,7S)-5,6,7,8-tetrahydro-
6,6-dimethyl-5,7-methanoquinolin-2(1H)-one (13; 10.2 g,
54.0 mmol, 1.0 equiv.) in CH2Cl2 (200 mL) and the solution was
cooled to –45 °C. Trifluoromethanesulfonic acid anhydride
(13.6 mL, 81.0 mmol, 1.5 equiv.) was added dropwise during
30 min leading to a deep-red solution. After stirring at –45 °C for
1 h, the solution turned brownish and then was allowed to slowly
warm to room temperature. The reaction mixture was stirred over-
night and then quenched by the addition of water (20 mL) and an
aqueous NaHCO3 solution (100 mL, 2 m). The mixture was ex-
tracted with CH2Cl2 (3ϫ 100 mL) and the combined organic ex-
(2S,4aS,5R,7S,8aR)-2-Cyclohexyl-6,6-dimethyldecahydro-5,7-meth-
anoquinoline [(Sc)-15a]: Yield method A: 1.66 g (6.35 mmol, 32%);
method B: 2.25 g (8.6 mmol, 43%). [α]2D8 = 29.0 (c = 0.5, CH2Cl2).
1H NMR (400 MHz, C6D6): δ = 0.92–1.08 (m, 2 H, CH2), 1.09–
tracts washed with brine (100 mL) and dried with Na2SO4. The 1.24 (m, 3 H, CH3, 5 H, CH2, 1 H, CH), 1.28–1.38 (m, 3 H, CH3,
solvent was removed under reduced pressure and the residue sub-
jected to column chromatography (pentane/ethyl acetate, 19:1, Rf
1 H, CH2), 1.53 (m, 1 H, CH2), 1.58–1.80 (m, 6 H, CH2), 1.87–
2.01 (m, 1 H, CH2, 3 H, CH), 2.23–2.35 (m, 2 H, CH2), 2.39 (dt,
= 0.42) to give the product as a light-yellow oil, yield 15.89 g
JH,H = 9.1, JH,H 5.2 Hz, 1 H, CH), 3.10 (dt, JH,H = 9.5, JH,H =
1
(49.5 mmol, 92%). H NMR (400 MHz, CDCl3): δ = 0.64 (s, 3 H, 4.8 Hz, 1 H, CH) ppm. 13C{1H} NMR (100 MHz, C6D6): δ = 22.6
CH3), 1.27 (d, JH,H = 9.9 Hz, 1 H, CH2), 1.42 (s, 3 H, CH3), 2.38
(CH3), 24.1 (CH2), 26.9 (CH2), 27.0 (CH2), 27.1 (CH2), 27.3 (CH2),
(m, 1 H, CH), 2.71 (dt, JH,H = 9.7, JH,H = 5.6 Hz, 1 H, CH2), 2.83 28.4 (CH3), 28.8 (CH2), 29.1 (CH2), 31.5 (CH2), 36.1 (CH2), 39.4
(t, JH,H = 5.6 Hz, 1 H, CH), 3.08 (d, JH,H = 2.7 Hz, 2 H, CH2), (Cq), 41.6 (CH), 43.9 (CH), 45.2 (CH), 47.0 (CH), 48.3 (CH), 58.3
6.86 (d, JH,H = 8.0 Hz, 1 H, Ar), 7.37 (d, JH,H = 8.0 Hz, 1 H,
(CH) ppm. MS (EI): m/z (%) = 179 (13), 178 (100), 82 (27), 67 (12),
Ar) ppm. 13C{1H} NMR (100 MHz, CDCl3): δ = 20.2 (CH3), 24.8 55 (14), 41 (17). HRMS (ESI): calcd. for C18H32N+ [M +
(CH3), 30.6 (CH2), 35.1 (CH2), 38.3 (Cq), 38.7 (CH), 44.7 (CH), H]+ 262.25293; found 262.25241.
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Pinene-Derived Phosphoramidites for Asymmetric Hydrogenation
(2R,4aS,5R,7S,8aR)-2-Cyclohexyl-6,6-dimethyldecahydro-5,7-meth-
anoquinoline [(Rc)-15a]: Yield method A: 1.48 g (5.7 mmol, 28%);
method B: 1.00 g (3.82 mmol, 19%). [α]2D8 = 41.2 (c = 0.5, CH2Cl2).
1.6 Hz, 1 H, CH), 1,81–1.99 (m, 1 H, CH2, 2 H, CH), 2.10 (m, 1
H, CH2), 2.36 (m, 1 H, CH2), 3.12 (m, 1 H, CH), 3.21 (dt, JH,H
=
9.0, JH,H = 1.8 Hz, 1 H, CH) ppm. 13C{1H} NMR (100 MHz,
1H NMR (400 MHz, CDCl3): δ = 0.83 (s, 3 H, CH3), 0.85–0.95 (m, CDCl3): δ = 20.4 (CH3), 21.9 (CH3), 24.4 (CH2), 26.1 (CH2), 26.4
3 H, CH2), 1.05–1.40 (m, 6 H, CH2, 1 H, CH), 1.22 (s, 3 H, CH3), (CH3), 30.3 (CH2), 36.1 (CH2), 38.8 (CH), 39.1 (Cq), 40.9 (CH),
1.44–1.52 (m, 1 H, CH2), 1.65–1.70 (m, 2 H, CH2), 1.71–1.79 (m,
41.6 (CH), 46.7 (CH), 47.2 (CH) ppm. MS (EI): m/z (%) = 192
2 H CH2, 1 H, CH), 1.82–1.91 (m, 2 H, CH2, 1 H, CH), 1.94–1.99 (12), 190 (56), 174 (13), 164 (24), 148 (25), 146 (12), 139 (18), 138
(m, 1 H, CH), 2.04–2.11 (m, 1 H, CH2), 2.32 (ddt, JH,H = 14.0, (17), 136 (12), 134 (27), 133 (20), 132 (15), 131 (24), 124 (12), 120
JH,H = 9.2, JH,H = 2.0 Hz, 1 H, CH2), 2.59 (q, JH,H = 8.8 Hz, 1 H,
(25), 119 (14), 117 (18), 108 (15), 107 (18), 106 (17), 105 (30), 96
(12), 95 (13), 94 (18), 93 (28), 92 (13), 91 (49), 86 (100), 82 (12), 81
CH), 3.15 (dt, JH,H = 8.7, JH,H = 1.5 Hz, 1 H, CH) ppm. 13C{1H}
NMR (100 MHz, CDCl3): δ = 20.5 (CH3), 24.3 (CH2), 25.7 (CH2), (19), 80 (15), 79 (42), 78 (13), 77 (39), 69 (20), 67 (32), 65 (16).
26.2 (CH2), 26.3 (CH2), 26.4 (CH3), 26.6 (CH2), 26.7 (CH2), 29.4 HRMS (ESI): calcd. for C13H24N+ [M + H]+ 194.19033; found
(CH2), 30.3 (CH2), 36.2 (CH2), 38.8 (CH), 39.2 (Cq), 41.0 (CH), 194.19022.
42.1 (CH), 42.6 (CH), 46.7 (CH), 57.4 (CH) ppm. MS (EI): m/z
(%) = 179 (43), 178 (100), 165 (20), 133 (11), 119 (16), 108 (10),
(1R,2S,7R,9S)-10,10-Dimethyl-6-azatricyclo[7.1.1.02,7]undecane
(15c): The pinene–pyridine derivative 10c (3.47 g, 20.0 mmol,
107 (11), 105 (12), 93 (22), 91 (23), 83 (12), 82 (63), 81 (18), 80 (15),
1.0 equiv.) and dry Pd(OH)2/C (702 mg, 1.0 mmol, 20 % Pd,
79 (22), 77 (8), 69 (10), 67 (24), 55 (36), 41 (39). HRMS (ESI):
0.05 equiv.) were placed in a 75 mL stainless-steel autoclave with a
glass inlet and stirring bar under argon. Glacial acetic acid (30 mL)
calcd. for C18H32N+ [M + H]+ 262.25293; found 262.25250.
was added and the autoclave pressurized with 90 bar hydrogen. The
reaction mixture was stirred at 120 °C under isobaric conditions
for 3 d. After cooling to room temperature the pressure was re-
leased and the reaction mixture filtered through a pad of Celite.
Concentrated hydrochloric acid (5 mL) was added to the light-yel-
low solution and the mixture stirred for 1 h. The solution was con-
centrated to a volume of 5 mL and diethyl ether (15 mL) was added
to give a colorless precipitate. The precipitate was collected by fil-
tration, washed with diethyl ether, and dried under high vacuum.
Diethyl ether (30 mL) and a saturated aqueous sodium carbonate
solution (20 mL) were added to the residual colorless powder. The
suspension was stirred for 3 h at room temperature and extracted
with diethyl ether (3ϫ 30 mL). The combined organic extracts were
washed with brine (20 mL) and dried with sodium sulfate. The sol-
vent was removed under reduced pressure to give the product as a
colorless liquid, yield 3.31 g (18.46 mmol, 92%). [α]2D8 = –20.2 (c =
0.5, CH2Cl2). 1H NMR (400 MHz, CDCl3): δ = 0.78 (s, 3 H, CH3),
1.14 (s, 3 H, CH3), 1.19 (m, 1 H, CH2), 1.26 (d, JH,H = 10.0 Hz, 1
H, CH2), 1.29–1.49 (m, 3 H, CH2, 1 H, NH), 1.58–1.70 (m, 1 H,
CH2, 1 H, CH), 1.81 (m, 1 H, CH), 1.93 (m, 1 H, CH), 2.06 (m, 1
H, CH2), 2.33 (ddt, JH,H = 14.2, JH,H = 9.5, JH,H = 2.2 Hz, 1 H,
CH2), 2.71 (ddd, J = 12.7, J = 9.2, JH,H = 4.3 Hz, 1 H, CH2), 2.92
(m, 1 H, CH2, 1 H, CH) ppm. 13C{1H} NMR (100 MHz, CDCl3):
δ = 20.5 (CH3), 21.0 (CH2), 22.9 (CH2), 26.4 (CH3), 26.7 (CH2),
36.2 (CH2), 37.4 (CH), 39.3 (Cq), 40.9 (CH), 42.7 (CH2), 47.1 (CH),
48.4 (CH) ppm. MS (EI): m/z (%) = 110 (10), 83 (100), 82 (24), 68
(16), 41 (16). HRMS (ESI): calcd. for C12H22N+ [M + H]+
180.17468; found 180.17470.
(4aS,5R,7S,8aR)-2,6,6-Trimethyldecahydro-5,7-methanoquinoline
(15b): The pinene–pyridine derivative 10b (1.87 g, 10.0 mmol,
1.0 equiv.) and dry Pd(OH)2/C (351 mg, 0.5 mmol, 20 % Pd,
0.05 equiv.) were placed in a 75 mL stainless-steel autoclave with a
glass inlet and stirring bar under argon. Glacial acetic acid (30 mL)
was added and the autoclave pressurized with 90 bar hydrogen. The
reaction mixture was stirred at 120 °C under isobaric conditions
for 3 d. After cooling to room temperature the pressure was re-
leased and the reaction mixture filtered through a pad of Celite.
Concentrated hydrochloric acid (5 mL) was added to the light-yel-
low solution and the mixture stirred for 1 h. All the volatiles were
removed under reduced pressure. To the residual colorless powder
was added ether (30 mL) and a saturated aqueous sodium carb-
onate solution (20 mL). The suspension was stirred overnight at
room temperature. The aqueous phase was extracted with diethyl
ether (3ϫ 30 mL) and the combined organic layers washed with
brine (20 mL) and dried with sodium sulfate. The solvent was re-
moved under reduced pressure to give a light-yellow liquid (1.86 g,
9.6 mmol, 96%), which was subjected to column chromatography
(silica, toluene/ethanol, 6:1). Both diastereomers could be collected
as colorless liquids from the observed fractions after removal of
the solvent under reduced pressure.
(2R,4aS,5R,7S,8aR)-2,6,6-Trimethyldecahydro-5,7-methanoquinol-
ine [(Rc)-15b]: Yield 770.1 mg (3.98 mmol, 40%). [α]2D8 = 49.2 (c =
0.5, CH2Cl2). 1H NMR (400 MHz, CDCl3): δ = 1.07 (s, 3 H, CH3),
1.11 (d, JH,H = 6.4 Hz, 3 H, CH3), 1.15 (m, 1 H, CH), 1.18 (s, 3
H, CH3), 1.21 (m, 1 H, CH2), 1.32 (m, 1 H, CH2), 1.51–1.63 (m, 2
H, CH2), 1.76–1.92 (m, 1 H, CH2, 2 H, CH), 2.01 (m, 1 H, CH2),
2.25 (m, 1 H, CH2), 2.37 (m, 1 H, CH2), 2.78 (m, 1 H, CH), 3.30
(dt, JH,H = 10.0, JH,H = 6.0 Hz, 1 H, CH) ppm. 13C{1H} NMR
(100 MHz, CDCl3): δ = 22.5 (CH2), 22.8 (CH3), 24.1 (CH3), 27.9
(CH3), 30.1 (CH2), 30.9 (CH2), 34.8 (CH2), 39.0 (Cq), 40.8 (CH),
41.8 (CH), 46.4 (CH), 48.1 (CH), 48.2 (CH) ppm. MS (EI): m/z
(%) = 192 (12), 190 (50), 155 (41), 151 (18), 146 (27), 137 (21), 136
(18), 124 (16), 122 (20), 121 (18), 111 (22), 109 (40), 108 (17), 107
(18), 99 (90), 98 (49), 97 (21), 95 (22), 91 (23), 83 (100), 81 (25), 80
(11), 79 (24), 77 (29), 71 (20), 70 (80), 69 (37), 67 (20), 65 (14).
HRMS (ESI): calcd. for C13H24N+ [M + H]+ 194.19033; found
194.19029.
(4aS,5R,7S,8aR)-1-[(11bS)-Dinaphtho(2,1-d:1Ј,2Ј-f)[1,3,2]dioxa-
phosphepin-4-yl]-6,6-dimethyldecahydro-5,7-methanoquinoline (L1):
Compound L1 was synthesized following the general procedure for
ligand synthesis starting from (1R,2S,7R,9S)-10,10-dimethyl-6-aza-
tricyclo[7.1.1.02,7]undecane (15c; 2.0 mmol, 1.0 equiv.) and (11bS)-
4-chlorodinaphtho[2,1-d:1Ј,2Ј-f][1,3,2]dioxaphosphepine [(Sa)-16;
2.0 mmol, 1.0 equiv.]. The product was obtained as a colorless so-
lid, yield 831.2 mg (1.684 mmol, 84%). [α]2D8 = 356.8 (c = 0.5,
CH2Cl2). 1H NMR (400 MHz, CDCl3): δ = 0.87 (s, 3 H, CH3),
1.22 (s, 3 H, CH3), 1.32–1.61 (m, 5 H, CH2), 1.80 (m, 1 H, CH),
1.93 (m, 1 H, CH), 2.12–2.37 (m, 3 H, CH2, 1 H, CH), 2.78 (m, 2
H, CH2), 4.22 (m, 1 H, CH), 7.16–7.52 (m, 8 H, Ar), 7.84–7.97 (m,
4 H, Ar) ppm. 13C{1H} NMR (100 MHz, CDCl3): δ = 21.6 (CH3),
(2S,4aS,5R,7S,8aR)-2,6,6-Trimethyldecahydro-5,7-methanoquinol-
ine [(Sc)-15b]: Yield 599.3 mg (3.10 mmol, 31%). [α]2D8 = 22.3 (c =
23.5 (CH2), 25.2 (CH2), 27.7 (CH3), 29.9 (CH2), 34.9 (d, JC,P
=
0.5, CH2Cl2). 1H NMR (400 MHz, CDCl3): δ = 0.83 (s, 3 H, CH3), 12.0 Hz, CH2), 35.3 (d, JC,P = 5.2 Hz, CH), 39.1 (Cq), 39.2 (d, JC,P
0.95 (m, 1 H, CH2), 1.09 (d, JH,H = 6.5 Hz, 3 H, CH3), 1.20 (s, 3
H, CH3), 1.24–1.44 (m, 4 H, CH2), 1.68 (dt, JH,H = 5.7, JH,H
= 2.7 Hz, CH2), 41.4 (CH), 48.2 (d, JC,P = 32.2 Hz, CH), 48.4
(CH), 122.0 (d, JC,P = 2.0 Hz, Cq, Ar), 122.2 (d, JC,P = 1.3 Hz, CH,
=
Eur. J. Org. Chem. 2015, 2889–2901
© 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
2897

C. Schmitz, W. Leitner, G. Franciò
FULL PAPER
Ar), 122.3 (CH, Ar), 124.0 (d, JC,P = 5.1 Hz, Cq, Ar), 124.4 (CH,
1.5 Hz, Cq, Ar), 149.9 (Cq, Ar), 150.3 (d, JC,P = 9.5 Hz, Cq,
Ar), 124.6 (CH, Ar), 125.9 (CH, Ar), 126.0 (CH, Ar), 127.0 (2 CH, Ar) ppm. 31P{1H} NMR (162 MHz, CDCl3): δ = 143.9 ppm. MS
Ar), 128.1 (CH, Ar), 128.3 (CH, Ar), 129.5 (CH, Ar), 130.2 (CH, (EI): m/z (%) = 279 (11), 191 (17), 176 (13), 167 (20), 149 (60), 148
Ar), 130.5 (Cq, Ar), 131.3 (Cq, Ar), 132.7 (Cq, Ar), 132.8 (d, JC,P
= 1.1 Hz, Cq, Ar), 149.7 (Cq, Ar), 150.0 (d, JC,P = 6.9 Hz, Cq,
Ar) ppm. 31P{1H} NMR (162 MHz, CDCl3): δ = 146.9 ppm. MS
(EI): m/z (%) = 279 (32), 205 (16), 179 (14), 178 (81), 167 (63), 150
(16), 149 (92), 138 (13), 113 (14), 112 (17), 111 (78), 110 (20), 109
(10), 96 (42), 91 (11), 84 (19), 83 (100), 82 (52), 81 (14), 79 (12).
HRMS (ESI): calcd. for C32H32NO2P+ [M]+ 493.21707; found
493.21743.
(10), 97 (100), 82 (35). HRMS (ESI): calcd. for C33H34NO2P+
[M]+ 507.23217; found 507.23247.
(2S,4aS,5R,7S,8aR)-1-[(11bR)-Dinaphtho(2,1-d:1Ј,2Ј-f)[1,3,2]dioxa-
phosphepin-4-yl]-2,6,6-trimethyldecahydro-5,7-methanoquinoline
(L4): Compound L4 was synthesized following the general pro-
cedure for ligand synthesis starting from (2S,4aS,5R,7S,8aR)-2,6,6-
trimethyldecahydro-5,7-methanoquinoline [(Sc)-15b; 1.0 mmol,
1.0 equiv.] and (11bR)-4-chlorodinaphtho[2,1-d:1Ј,2Ј-f][1,3,2]di-
oxaphosphepine [(Ra)-16; 1.0 mmol, 1.0 equiv.]. The product was
obtained as a colorless solid, yield 425.4 mg (0.838 mmol, 84%).
(4aS,5R,7S,8aR)-1-[(11bR)-Dinaphtho(2,1-d:1Ј,2Ј-f)[1,3,2]dioxa-
phosphepin-4-yl]-6,6-dimethyldecahydro-5,7-methanoquinoline (L2):
Compound L2 was synthesized following the general procedure for
ligand synthesis starting from (1R,2S,7R,9S)-10,10-dimethyl-6-aza-
tricyclo[7.1.1.02,7]undecane (15c; 2.0 mmol, 1.0 equiv.) and (11bR)-
4-chlorodinaphtho[2,1-d:1Ј,2Ј-f][1,3,2]dioxaphosphepine [(Ra)-16;
2.0 mmol, 1.0 equiv.]. The product was obtained as a colorless so-
lid, yield 860.8 mg (1.744 mmol, 87%). [α]2D8 = –266.9 (c = 0.5,
1
[α]2D8 = –267.8 (c = 0.5, CH2Cl2). H NMR (400 MHz, CDCl3): δ
= 0.72–0.98 (m, 2 H), 1.00–1.38 (m, 9 H), 1.43–1.88 (m, 6 H), 1.95–
2.19 (m, 3 H), 3.30 (m, 1 H), 3.89 (m, 1 H), 7.17–7.39 (m, 6 H,
Ar), 7.44 (d, JH,H = 8.7 Hz, 1 H, Ar), 7.50 (d, JH,H = 8.7 Hz, 1 H,
Ar), 7.85–7.96 (m, 4 H, Ar) ppm. 13C{1H} NMR (100 MHz,
CDCl3): δ = 20.3 (CH3), 20.8 (d, JC,P = 7.7 Hz, CH2), 21.6 (d, JC,P
= 19.8 Hz, CH3), 26.1 (CH2), 27.2 (CH3), 39.0 (m, CH2), 40.3 (Cq),
41.2 (2 CH), 45.8 (CH), 45.9 (CH), 47.8 (m, CH), 48.1 (m, CH2),
121.6 (Cq, Ar), 122.4 (d, JC,P = 1.8 Hz, CH, Ar), 122.5 (CH, Ar),
124.1 (d, JC,P = 5.7 Hz, Cq, Ar), 124.2 (CH, Ar), 124.6 (CH, Ar),
125.8 (CH, Ar), 125.9 (CH, Ar), 127.0 (CH, Ar), 127.1 (CH, Ar),
128.1 (CH, Ar), 128.2 (CH, Ar), 129.5 (CH, Ar), 130.2 (CH, Ar),
130.4 (Cq, Ar), 131.3 (Cq, Ar), 132.8 (d, JC,P = 1.7 Hz, Cq, Ar),
132.9 (Cq, Ar), 150.2 (Cq, Ar), 150.5 (d, JC,P = 6.0 Hz, Cq,
Ar) ppm. 31P{1H} NMR (162 MHz, CDCl3): δ = 145.5 (br. s) ppm.
MS (EI): m/z (%) = 411 (10), 279 (15), 268 (12), 191 (11), 176 (10),
167 (30), 149 (81), 98 (12), 97 (100), 83 (11), 82 (66), 81 (10).
HRMS (ESI): calcd. for C33H34NO2P+ [M]+ 507.23217; found
507.23231.
1
CH2Cl2). H NMR (400 MHz, CDCl3): δ = 0.21 (br. s, 3 H, CH3),
1.03 (s, 3 H, CH3), 1.10 (d, J = 10.0 Hz, 1 H, CH2), 1.35–1.79 (m,
5 H, CH2, 2 H, CH), 2.04–2.19 (m, 2 H, CH2, 1 H, CH), 2.51 (m,
1 H, CH2), 3.20 (m, 1 H, CH2), 4.01 (m, 1 H, CH), 7.12–7.20 (m,
2 H, Ar), 7.26–7.40 (m, 5 H, Ar), 7.44–7.49 (m, 1 H, Ar), 7.79–
7.91 (m, 4 H, Ar) ppm. 13C{1H} NMR (100 MHz, CDCl3): δ =
21.1 (CH3), 26.1 (CH2), 26.4 (CH2), 28.4 (CH3), 31.6 (CH2), 34.2
(d, JC,P = 3.5 Hz, CH), 37.3 (d, JC,P = 2.3 Hz, CH2), 38.2 (Cq),
39.9 (d, JC,P = 25.9 Hz, CH2), 41.6 (CH), 46.2 (d, JC,P = 15.9 Hz,
CH) 48.9 (CH), 122.0 (CH, Ar), 122.2 (d, JC,P = 1.2 Hz, CH, Ar),
122.4 (d, JC,P = 2.0 Hz, Cq, Ar), 124.0 (d, JC,P = 4.9 Hz, Cq, Ar),
124.4 (CH, Ar), 124.7 (CH, Ar), 125.9 (CH, Ar), 126.0 (CH, Ar),
126.8 (CH, Ar), 127.0 (CH, Ar), 128.2 (CH, Ar), 128.3 (CH, Ar),
129.7 (CH, Ar), 130.2 (CH, Ar), 130.8 (Cq, Ar), 131.3 (Cq, Ar),
132.8 (Cq, Ar), 132.9 (Cq, Ar), 149.8 (Cq, Ar), 149.9 (Cq, Ar) ppm.
31P{1H} NMR (162 MHz, CDCl3): δ = 148.3 ppm. MS (EI): m/z
(%) = 279 (60), 167 (89), 150 (29), 149 (100), 113 (26), 112 (18),
111 (11), 104 (11), 83 (56), 71 (44), 70 (48). HRMS (ESI): calcd.
for C32H32NO2P+ [M]+ 493.21707; found 493.21774.
(2R,4aS,5R,7S,8aR)-1-[(11bS)-Dinaphtho(2,1-d:1Ј,2Ј-f)[1,3,2]dioxa-
phosphepin-4-yl]-2,6,6-trimethyldecahydro-5,7-methanoquinoline
(L5): Compound L5 was synthesized following the general pro-
cedure for ligand synthesis starting from (2R,4aS,5R,7S,8aR)-2,6,6-
trimethyldecahydro-5,7-methanoquinoline [(Rc)-15b; 1.0 mmol,
1.0 equiv.] and (11bS)-4-chlorodinaphtho[2,1-d:1Ј,2Ј-f][1,3,2]di-
oxaphosphepine [(Sa)-16; 1.0 mmol, 1.0 equiv.]. The product was
obtained as a colorless solid, yield 316.7 mg (0.624 mmol, 62%).
(2S,4aS,5R,7S,8aR)-1-[(11bS)-Dinaphtho(2,1-d:1Ј,2Ј-f)[1,3,2]dioxa-
phosphepin-4-yl]-2,6,6-trimethyldecahydro-5,7-methanoquinoline
(L3): Compound L3 was synthesized following the general pro-
cedure for ligand synthesis starting from (2S,4aS,5R,7S,8aR)-2,6,6-
trimethyldecahydro-5,7-methanoquinoline [(Sc)-15b; 1.0 mmol,
1.0 equiv.] and (11bS)-4-chlorodinaphtho[2,1-d:1Ј,2Ј-f][1,3,2]di-
oxaphosphepine [(Sa)-16; 1.0 mmol, 1.0 equiv.]. The product was
obtained as a colorless solid, yield 350.8 mg (0.691 mmol, 69%).
1
[α]2D8 = 305.8 (c = 0.5, CH2Cl2). H NMR (400 MHz, CDCl3): δ =
0.78–0.89 (m, 1 H), 1.07 (s, 3 H, CH3), 1.09 (s, 3 H, CH3), 1.14–
1.28 (m, 2 H), 1.32 (d, JH,H = 7.1 Hz, 3 H, CH3), 1.40 (m, 1 H),
1.56 (m, 1 H), 1.69 (m, 2 H), 1.80 (m, 1 H), 1.90–2.09 (m, 3 H),
3.64 (m, 1 H), 3.99 (m, 1 H), 7.19–7.44 (m, 7 H, Ar), 7.53 (d, JH,H
= 8.7 Hz, 1 H, Ar), 7.84–7.92 (m, 3 H, Ar), 7.95 (d, JH,H = 8.8 Hz,
1 H, Ar) ppm. 13C{1H} NMR (100 MHz, CDCl3): δ = 20.5 (CH2),
22.2 (d, JC,P = 4.0 Hz, CH3), 23.5 (CH3), 24.7 (CH2), 28.7 (CH3),
31.9 (d, JC,P = 3.0 Hz, CH2), 33.6 (CH2), 39.4 (CH), 40.4 (Cq), 41.5
(CH), 45.1 (d, JC,P = 3.0 Hz, CH), 46.1 (d, JC,P = 43.5 Hz, CH),
47.1 (CH), 121.7 (d, JC,P = 1.9 Hz, Cq, Ar), 122.1 (CH, Ar), 122.2
(d, JC,P = 1.4 Hz, CH, Ar), 124.0 (d, JC,P = 5.1 Hz, Cq, Ar), 124.3
(CH, Ar), 124.6 (CH, Ar), 125.9 (CH, Ar), 126.0 (CH, Ar), 126.9
(CH, Ar), 127.0 (CH, Ar), 128.1 (CH, Ar), 128.3 (CH, Ar), 129.3
(CH, Ar), 130.2 (CH, Ar), 130.6 (Cq, Ar), 131.3 (Cq, Ar), 132.7
(Cq, Ar), 132.8 (d, JC,P = 1.3 Hz, Cq, Ar), 149.8 (Cq, Ar), 150.2 (d,
JC,P = 5.0 Hz, Cq, Ar) ppm. 31P{1H} NMR (162 MHz, CDCl3): δ
= 149.9 ppm. MS (EI): m/z (%) = 412 (23), 411 (88), 316 (11), 315
(44), 268 (33), 252 (10), 167 (16), 149 (47), 124 (14), 110 (11), 97
(100), 82 (45). HRMS (ESI): calcd. for C33H34NO2P+ [M]+
507.23217; found 507.23213.
1
[α]2D8 = 342.5 (c = 0.5, CH2Cl2). H NMR (400 MHz, CDCl3): δ =
0.72 (s, 3 H, CH3), 0.78–0.91 (m, 2 H), 1.13 (d, JH,H = 6.6 Hz, 3
H, CH3), 1.20 (s, 3 H, CH3), 1.22–1.30 (m, 1 H), 1.55 (dq, J = 12.8,
J = 4.0 Hz, 1 H), 1.67–1.78 (m, 2 H), 1.82–1.89 (m, 1 H), 1.94–
2.03 (m, 2 H), 2.17–2.28 (m, 2 H), 3.54 (m, 1 H), 3.92 (m, 1 H),
7.16–7.28 (m, 3 H, Ar), 7.34–7.40 (m, 3 H, Ar), 7.44 (d, JH,H
=
6.4 Hz, 1 H, Ar), 7.46 (d, JH,H = 6.4 Hz, 1 H, Ar), 7.88 (m, 3 H,
Ar), 7.94 (d, JH,H = 8.8 Hz, 1 H, Ar) ppm. 13C{1H} NMR
(100 MHz, CDCl3): δ = 20.6 (CH3), 21.5 (d, JC,P = 6.2 Hz, CH3),
24.8 (CH2), 26.0 (d, JC,P = 9.7 Hz, CH2), 26.4 (CH3), 29.2 (d, JC,P
= 34.4 Hz, CH2), 30.8 (CH2), 38.8 (CH), 40.0 (d, JC,P = 2.6 Hz,
Cq), 41.4 (CH), 45.5 (CH), 45.7 (CH), 47.2 (CH), 121.3 (d, JC,P
=
2.8 Hz, Cq, Ar), 122.4 (d, JC,P = 1.8 Hz, CH, Ar), 122.8 (CH, Ar),
124.0 (d, JC,P = 5.5 Hz, Cq, Ar), 124.2 (CH, Ar), 124.6 (CH, Ar),
125.7 (CH, Ar), 125.9 (CH, Ar), 127.1 (CH, Ar), 127.2 (CH, Ar),
128.1 (CH, Ar), 128.3 (CH, Ar), 129.2 (CH, Ar), 130.3 (CH, Ar), (2R,4aS,5R,7S,8aR)-1-[(11bR)-Dinaphtho(2,1-d:1Ј,2Ј-f)[1,3,2]dioxa-
130.4 (Cq, Ar), 131.3 (Cq, Ar), 132.8 (Cq, Ar), 132.9 (d, JC,P phosphepin-4-yl]-2,6,6-trimethyldecahydro-5,7-methanoquinoline
=
2898
www.eurjoc.org
© 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2015, 2889–2901

Pinene-Derived Phosphoramidites for Asymmetric Hydrogenation
(L6): Compound L6 was synthesized following the general pro-
cedure for ligand synthesis starting from (2R,4aS,5R,7S,8aR)-2,6,6-
trimethyldecahydro-5,7-methanoquinoline [(Rc)-15b; 1.0 mmol,
1.0 equiv.] and (11bR)-4-chlorodinaphtho[2,1-d:1Ј,2Ј-f][1,3,2]di-
oxaphosphepine [(Ra)-16; 1.0 mmol, 1.0 equiv.]. The product was
obtained as a colorless solid, yield 298.5 mg (0.588 mmol, 59%).
1.0 mmol, 1.0 equiv.]. The product was obtained as a colorless so-
lid, yield 405.3 mg (0.704 mmol, 70 %). 1H NMR (400 MHz,
CDCl3): δ = 0.88–1.99 (m, 6 H, CH3, 16 H, CH2, 4 H, CH), 2.09–
2.41 (m, 2 H, CH2), 2.97 (m, 1 H, CH), 3.15 (m, 1 H, CH), 7.10–
7.46 (m, 8 H, Ar), 7.76–7.91 (m, 4 H, Ar) ppm. 13C{1H} NMR
(100 MHz, CDCl3): δ = 21.0 (CH2), 23.4 (CH3), 25.4 (CH2), 26.3
(CH2), 26.5 (CH2), 26.6 (CH2), 27.4 (CH2), 29.0 (CH3), 30.5 (CH2),
1
[α]2D8 = –258.3 (c = 0.5, CH2Cl2). H NMR (400 MHz, CDCl3): δ
= 0.86 (m, 1 H), 1.11 (d, JH,H = 7.0 Hz, 3 H, CH3), 1.17 (s, 3 H, 31.0 (CH2), 32.7 (CH2), 38.6 (d, JC,P = 4.9 Hz, CH), 40.0 (d, JC,P
CH3), 1.20–1.52 (m, 5 H), 1.72 (d, J = 10.2 Hz, 1 H), 1.83–2.08 (m, = 2.5 Hz, CH), 40.9 (Cq), 41.6 (CH), 45.3 (d, JC,P = 27.3 Hz, CH),
5 H), 2.15 (m, 1 H), 2.32 (m, 1 H), 3.35 (m, 1 H), 4.35 (m, 1 H),
7.19–7.32 (m, 3 H, Ar), 7.36–7.44 (m, 4 H, Ar), 7.53 (d, JH,H
47.5 (CH), 55.4 (d, JC,P = 19.3 Hz, CH), 121.5 (Cq, Ar), 122.4 (CH,
Ar), 122.5 (CH, Ar), 124.1 (Cq, Ar), 124.2 (CH, Ar), 124.6 (CH,
=
8.8 Hz, 1 H, Ar), 7.85–7.93 (m, 3 H, Ar), 7.97 (d, JH,H = 8.8 Hz, Ar), 125.7 (CH, Ar), 125.9 (CH, Ar), 127.2 (2 CH, Ar), 128.1 (CH,
1 H, Ar) ppm. 13C{1H} NMR (100 MHz, CDCl3): δ = 20.6 (CH3), Ar), 128.3 (CH, Ar), 129.1 (CH, Ar), 130.2 (CH, Ar), 130.4 (Cq,
21.8 (CH2), 23.6 (CH2), 25.6 (CH3), 28.8 (CH3), 31.2 (CH2), 34.9 Ar), 131.3 (Cq, Ar), 132.8 (Cq, Ar), 132.9 (Cq, Ar), 149.4 (Cq, Ar),
(CH2), 39.9 (d, JC,P = 6.7 Hz, CH), 40.8 (Cq), 41.6 (CH), 44.5 (CH),
150.0 (Cq, Ar) ppm. 31P{1H} NMR (162 MHz, CDCl3): δ =
45.8 (d, JC,P = 45.4 Hz, CH), 47.6 (CH), 121.8 (d, JC,P = 2.0 Hz, 146.1 ppm. HRMS (ESI): calcd. for C38H43NO2P+ [M + H]+
Cq, Ar), 122.2 (CH, Ar), 122.4 (d, JC,P = 1.7 Hz, CH, Ar), 124.1 576.30259; found 576.30291.
(d, JC,P = 5.0 Hz, Cq, Ar), 124.3 (CH, Ar), 124.7 (CH, Ar), 125.8
(CH, Ar), 125.9 (CH, Ar), 127.1 (2 CH, Ar), 128.2 (CH, Ar), 128.3
(CH, Ar), 129.4 (CH, Ar), 130.2 (CH, Ar), 130.5 (Cq, Ar), 131.3
(2R,4aS,5R,7S,8aR)-2-Cyclohexyl-1-[(11bS)-dinaphtho(2,1-d:1Ј,
2Ј-f)[1,3,2]dioxaphosphepin-4-yl]-6,6-dimethyldecahydro-5,7-meth-
anoquinoline (L9): Compound L9 was synthesized following
the general procedure for ligand synthesis starting from
(Cq, Ar), 132.7 (Cq, Ar), 132.8 (d, JC,P = 1.7 Hz, Cq, Ar), 149.9
(Cq, Ar), 150.3 (d, JC,P = 6.0 Hz, Cq, Ar) ppm. 31P{1H} NMR
(2R,4aS,5R,7S,8aR)-2-cyclohexyl-6,6-dimethyldecahydro-5,7-meth-
(162 MHz, CDCl3): δ = 148.7 ppm. MS (EI): m/z (%) = 412 (17),
anoquinoline [(Rc)-15a; 1.0 mmol, 1.0 equiv.] and (11bS)-4-chloro-
411 (64), 332 (29), 315 (34), 268 (53), 267 (13), 239 (26), 167 (12),
dinaphtho[2,1-d:1Ј,2Ј-f][1,3,2]dioxaphosphepine [(Sa)-16
149 (36), 124 (18), 123 (14), 110 (12), 98 (12), 97 (100), 96 (11), 82
(1.0 mmol, 1.0 equiv.]. The work-up by filtration through basic alu-
(65), 79 (10), 70 (20). HRMS (ESI): calcd. for C33H34NO2P+ [M]+
mina was skipped due to decomposition. After removal of the sol-
vent from the crude reaction mixture the product was obtained as
507.23217; found 507.23225.
(2S,4aS,5R,7S,8aR)-2-Cyclohexyl-1-[(11bS)-dinaphtho(2,1-d:1Ј,2Ј-f)-
[1,3,2]dioxaphosphepin-4-yl]-6,6-dimethyldecahydro-5,7-methano-
quinoline (L7): Compound L7 was synthesized following the
general procedure for ligand synthesis starting from
(2S,4aS,5R,7S,8aR)-2-cyclohexyl-6,6-dimethyldecahydro-5,7-meth-
anoquinoline [(Sc)-15a; 1.0 mmol, 1.0 equiv.] and (11bS)-4-chloro-
dinaphtho[2,1-d:1Ј,2Ј-f][1,3,2]dioxaphosphepine [(Sa)-16; 1.0 mmol,
1.0 equiv.]. The product was obtained as a light-yellow solid, yield
a light-yellow solid, yield 283.2 mg (0.492 mmol, 49%). Purity: The
ligand was prone to decomposition during the work-up procedure.
The purity was about 85%, as estimated by 1H NMR spectroscopy.
1H NMR (400 MHz, CDCl3): δ = 0.26 (br. s, 3 H, CH3), 0.78 (m,
2 H, CH2), 0.94–1.27 (m, 6 H), 1.36–1.81 (m, 14 H), 1.93–2.10 (m,
3 H, CH2), 2.81 (m, 1 H, CH), 3.79 (dq, J = 9.9, J = 5.3 Hz, 1 H,
CH), 7.10–7.18 (m, 3 H, Ar), 7.24 (d, JH,H = 8.5 Hz, 1 H, Ar), 7.30
(m, 2 H, Ar), 7.41 (m, 2 H, Ar), 7.79–7.90 (m, 4 H, Ar) ppm.
13C{1H} NMR (100 MHz, CDCl3): δ = 20.5 (CH2), 25.5 (CH3),
358.1 mg (0.622 mmol, 62%). [α]2D8 = 200.7 (c = 0.5, CH2Cl2). H
1
NMR (400 MHz, CDCl3): δ = 0.80–1.98 (m, 6 H, CH3, 15 H, CH2, 26.2 (CH2), 26.4 (2 CH2), 26.5 (CH2), 26.8 (CH3), 27.0 (CH2), 30.4
4 H, CH), 2.03–2.46 (m, 3 H, CH2), 3.26 (m, 1 H, CH), 3.53 (m, (CH2), 30.5 (d, JC,P = 1.4 Hz, CH2), 32.4 (CH2), 39.1 (CH), 39.3
1 H, CH), 7.09–7.48 (m, 8 H, Ar), 7.72–7.90 (m, 4 H, Ar) ppm.
(CH), 40.3 (Cq), 41.5 (CH), 46.8 (d, JC,P = 8.1 Hz, CH), 47.9 (CH),
13C{1H} NMR (100 MHz, CDCl3): δ = 21.1 (CH2), 23.2 (CH3), 56.9 (d, JC,P = 44.7 Hz, CH), 121.3 (Cq, Ar), 122.3 (CH, Ar), 123.1
24.6 (CH2), 26.4 (CH2), 26.5 (2 CH2), 27.7 (d, JC,P = 3.3 Hz, CH2), (CH, Ar), 124.1 (Cq, Ar), 124.2 (CH, Ar), 124.5 (CH, Ar), 125.7
28.8 (CH3), 30.6 (CH2), 30.8 (CH2), 32.3 (CH2), 39.0 (d, JC,P
7.4 Hz, CH), 39.6 (CH), 40.4 (Cq), 41.4 (CH), 44.9 (d, JC,P
=
=
(CH, Ar), 125.9 (CH, Ar), 127.0 (CH, Ar), 127.1 (CH, Ar), 127.9
(CH, Ar), 128.2 (CH, Ar), 129.1 (CH, Ar), 130.3 (CH, Ar), 130.4
7.8 Hz, CH), 47.0 (CH), 56.9 (d, JC,P = 45.7 Hz, CH), 121.5 (d, (Cq, Ar), 131.2 (Cq, Ar), 132.8 (Cq, Ar), 132.9 (d, JC,P = 1.4 Hz, Cq,
JC,P = 4.8 Hz, Cq, Ar), 122.1 (CH, Ar), 122.4 (CH, Ar), 124.1 (d,
JC,P = 5.1 Hz, Cq, Ar), 124.3 (CH, Ar), 124.6 (CH, Ar), 125.9 (2
CH, Ar), 126.9 (CH, Ar), 127.1 (CH, Ar), 128.0 (CH, Ar), 128.3
Ar), 150.0 (Cq, Ar), 150.3 (Cq, Ar) ppm. 31P{1H} NMR (162 MHz,
CDCl3): δ = 149.1 (br.) ppm. MS (EI): m/z (%) = 259.3 (21), 255.3
(19), 220.3 (53), 205.2 (12), 200.2 (21), 179.2 (20), 178.2 (100), 177.2
(CH, Ar), 129.3 (CH, Ar), 130.1 (CH, Ar), 130.5 (Cq, Ar), 131.3 (23), 176.2 (31), 149.1 (18), 93.2 (10), 91.2 (12), 83.2 (15), 82.2 (27),
(Cq, Ar), 132.7 (Cq, Ar), 132.8 (Cq, Ar), 149.8 (Cq, Ar), 150.4 (d,
81.2 (14), 79.2 (13). HRMS (ESI): calcd. for C38H42NO2P+ [M]+
JC,P = 4.7 Hz, Cq, Ar) ppm. 31P{1H} NMR (162 MHz, CDCl3): δ 575.29477; found 575.29456.
= 150.8 ppm. MS (EI): m/z (%) = 332.1 (36), 268.2 (30), 267.1 (14),
(2R,4aS,5R,7S,8aR)-2-Cyclohexyl-1-[(11bR)-dinaphtho(2,1-d:1Ј,
260.3 (10), 259.3 (42), 244.3 (13), 239.2 (23), 218.3 (12), 216.3 (11),
204.3 (52), 179.2 (27), 178.2 (100), 177.2 (34), 176.2 (40), 165.2 (21),
162.2 (15), 149.1 (22), 134.2 (13), 108.2 (13), 95.2 (14), 94.2 (10),
93.2 (12), 91.2 (14), 83.2 (14), 82.2 (57), 81.2 (18), 79.2 (17). HRMS
(ESI): calcd. for C38H42NO2P+ [M]+ 575.29477; found 575.29467.
2Ј-f)[1,3,2]dioxaphosphepin-4-yl]-6,6-dimethyldecahydro-5,7-meth-
anoquinoline (L10): Compound L10 was synthesized following
the general procedure for ligand synthesis starting from
(2R,4aS,5R,7S,8aR)-2-cyclohexyl-6,6-dimethyldecahydro-5,7-meth-
anoquinoline [(Rc)-15a; 1.0 mmol, 1.0 equiv.] and (11bR)-4-chloro-
(2S,4aS,5R,7S,8aR)-2-Cyclohexyl-1-[(11bR)-dinaphtho(2,1-d:1Ј, dinaphtho[2,1-d:1Ј,2Ј-f][1,3,2]dioxaphosphepine [(Ra)-16;
2Ј-f)[1,3,2]dioxaphosphepin-4-yl]-6,6-dimethyldecahydro-5,7-meth-
anoquinoline (L8): Compound L8 was synthesized following
the general procedure for ligand synthesis starting from
(2S,4aS,5R,7S,8aR)-2-cyclohexyl-6,6-dimethyldecahydro-5,7-meth-
anoquinoline [(Sc)-15a; 1.0 mmol, 1.0 equiv.] and (11bR)-4-chloro-
dinaphtho[2,1-d:1Ј,2Ј-f][1,3,2]dioxaphosphepine [(Ra)-16;
1.0 mmol, 1.0 equiv.]. The product was obtained as a colorless so-
lid, yield 448.5 mg (0.779 mmol, 78 %). 1H NMR (400 MHz,
CDCl3): δ = 0.71–0.84 (m, 3 H, CH3, 2 H, CH2), 0.94–1.79 (m, 3
H, CH3, 13 H, CH2, 3 H, CH), 1.93 (m, 2 H, CH2), 2.23 (m, 1 H,
CH2), 2.63 (m, 1 H, CH), 3.13 (m, 1 H, CH), 7.03–7.20 (m, 3 H,
Ar), 7.25–7.45 (m, 5 H, Ar), 7.71–7.89 (m, 4 H, Ar) ppm. 13C{1H}
Eur. J. Org. Chem. 2015, 2889–2901
© 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
2899

C. Schmitz, W. Leitner, G. Franciò
FULL PAPER
NMR (100 MHz, CDCl3): δ = 20.6 (CH2), 26.2 (2 CH2), 26.3 (CH, Ar), 126.9 (CH, Ar), 127.0 (2 CH, Ar), 127.1 (5 CH, Ar),
(CH3), 26.4 (CH2), 26.5 (CH2), 26.6 (CH2), 28.6 (d, JC,P = 2.2 Hz, 127.3 (CH, Ar), 127.5 (2 CH, Ar), 127.6 (2 CH, Ar), 128.0 (2 CH,
CH2), 29.7 (CH3), 30.5 (CH2), 31.0 (CH2), 38.6 (d, JC,P = 5.5 Hz, Ar), 128.7 (CH, Ar), 128.8 (CH, Ar), 129.1 (2 CH, Ar), 141.8 (Cq,
CH), 40.9 (CH), 41.3 (CH), 41.5 (Cq), 46.6 (CH), 47.5 (CH), 57.2
(d, JC,P = 11.8 Hz, CH), 122.4 (CH, Ar), 122.5 (CH, Ar), 122.6
Ar), 142.6 (d, JC,P = 1.2 Hz, Cq, Ar), 146.9 (d, JC,P = 1.3 Hz, Cq,
Ar), 147.3 (Cq, Ar) ppm. 31P{1H} NMR (162 MHz, CDCl3): δ =
(Cq, Ar), 124.2 (CH, Ar), 124.6 (CH, Ar), 125.7 (CH, Ar), 125.9 138.7 ppm. MS (EI): m/z (%) = 577.3 (10), 478.3 (29), 420.2 (30),
(CH, Ar), 126.9 (Cq, Ar), 127.0 (CH, Ar), 127.1 (CH, Ar), 128.0 242.1 (10), 238.1 (14), 237.1 (78), 236.1 (15), 208.1 (13), 207.1 (44),
(CH, Ar), 128.1 (d, JC,P = 22.1 Hz, Cq, Ar), 128.2 (CH, Ar), 129.3
(CH, Ar), 130.1 (CH, Ar), 130.3 (d, JC,P = 16.8 Hz, Cq, Ar), 131.3
(Cq, Ar), 132.8 (Cq, Ar), 149.4 (Cq, Ar), 149.9 (Cq, Ar) ppm.
31P{1H} NMR (162 MHz, CDCl3): δ = 144.6 ppm. HRMS (ESI):
calcd. for C38H43NO2P+ [M + H]+ 576.30259; found 576.30284.
180.1 (18), 179.1 (100), 178.1 (34), 167.1 (15), 165.1 (10), 105.1 (11).
HRMS (ESI): calcd. for C43H49NO4P+ [M + H]+ 674.33937; found
674.33862.
(4aS,5R,7S,8aR)-1-(4,8-Di-tert-butyl-2,10-dimethoxydibenzo[d,f]-
[1,3,2]dioxaphosphepin-6-yl)-6,6-dimethyldecahydro-5,7-methano-
quinoline (L13): Compound L13 was synthesized following the ge-
neral procedure for ligand synthesis from (1R,2S,7R,9S)-10,10-di-
methyl-6-azatricyclo[7.1.1.02,7]undecane (15c; 2.0 mmol, 1.0 equiv.)
and 4,8-di-tert-butyl-6-chloro-2,10-dimethoxydibenzo[d,f][1,3,2]di-
oxaphosphepine (2.0 mmol, 1.0 equiv., generated in situ). The prod-
uct was obtained as a colorless solid, yield 653.9 mg (1.156 mmol,
(4aS,5R,7S,8aR)-6,6-Dimethyl-1-[(11bR)-8,9,10,11,12,13,14,15-
octahydrodinaphtho(2,1-d:1Ј,2Ј-f)[1,3,2]dioxaphosphepin-4-yl]deca-
hydro-5,7-methanoquinoline (L11): Compound L11 was synthesized
following the general procedure for ligand synthesis starting
from (1R,2S,7R,9S)-10,10-dimethyl-6-azatricyclo[7.1.1.02,7]-
undecane (15c; 1.0 mmol, 1.0 equiv.) and (11bR)-4-chloro-
8,9,10,11,12,13,14,15-octahydrodinaphtho[2,1-d:1Ј,2Ј-f]-[1,3,2]di-
oxaphosphepine (1.0 mmol, 1.0 equiv.). The product was obtained
1
58%). H NMR (400 MHz, CDCl3, major isomer): δ = 0.91 (s, 3
H, CH3), 1.11–1.48 (m, 21 H CH3, 5 H, CH2), 1.69 (m, 1 H, CH2,
1 H, CH), 1.89 (m, 1 H, CH), 2.10 (m, 3 H, CH2), 2.41 (m, 1 H,
CH), 2.60 (m, 1 H, CH), 2.88 (m, 1 H, CH2), 3.73 (s, 3 H, OCH3),
3.74 (s, 3 H, OCH3), 6.60 (d, JH,H = 2.7 Hz, 1 H, Ar), 6.63 (d,
JH,H = 3.0 Hz, 1 H, Ar), 6.88 (m, 2 H, Ar) ppm. 13C{1H} NMR
(100 MHz, CDCl3, major isomer): δ = 21.5 (CH3), 24.5 (CH2), 25.6
(CH2), 27.4 (CH3), 29.7 (CH2), 30.7 (3 CH3), 30.8 (3 CH3), 31.0
(d, JC,P = 4.0 Hz, CH), 35.3 (Cq), 35.4 (Cq), 37.1 (d, JC,P = 7.1 Hz,
CH2), 39.2 (Cq), 41.3 (m, CH2), 41.4 (m, CH), 41.5 (m, CH), 48.1
(CH), 55.6 (2 OCH3), 112.2 (CH, Ar), 112.6 (CH, Ar), 114.0 (CH,
Ar), 114.2 (CH, Ar), 133.3 (d, JC,P = 3.6 Hz, Cq, Ar), 133.6 (d, JC,P
as a colorless solid, yield 362.2 mg (0.722 mmol, 72%). [α]2D7
=
1
–150.9 (c = 0.5, CH2Cl2). H NMR (400 MHz, CDCl3): δ = 0.56
(s, 3 H, CH3), 1.14 (s, 3 H, CH3), 1.18 (m, 1 H, CH2), 1.41–1.79
(m, 2 H, CH, 12 H, CH2), 2.04–2.29 (m, 1 H, CH, 4 H, CH2),
2.52–2.87 (m, 8 H, CH2), 3.26 (m, 1 H, CH2), 3.83 (m, 1 H, CH),
6.88 (m, 1 H, Ar), 7.00 (m, 3 H, Ar) ppm. 13C{1H} NMR
(100 MHz, CDCl3): δ = 21.7 (CH3), 22.5 (CH2), 22.6 (CH2), 22.7
(CH2), 22.8 (CH2), 26.3 (CH2), 26.5 (CH2), 27.6 (CH2), 27.8 (CH2),
28.5 (CH3), 29.0 (CH2), 29.1 (CH2), 31.7 (CH2), 34.0 (CH), 37.3
(CH2), 38.1 (Cq), 40.2 (d, JC,P = 36.1 Hz, CH2), 41.5 (CH), 45.2
(d, JC,P = 6.3 Hz, CH), 49.0 (CH), 118.3 (CH, Ar), 118.6 (d, JC,P
= 2.1 Hz, CH, Ar), 127.8 (d, JC,P = 1.3 Hz, Cq, Ar), 128.8 (CH,
Ar), 129.1 (CH, Ar), 129.2 (d, JC,P = 4.4 Hz, Cq, Ar), 132.7 (Cq,
Ar), 133.7 (d, JC,P = 1.0 Hz, Cq, Ar), 137.3 (Cq, Ar), 137.8 (d, JC,P
= 1.3 Hz, Cq, Ar), 147.9 (d, JC,P = 3.2 Hz, Cq, Ar), 149.0 (Cq,
= 3.3 Hz, Cq, Ar), 142.1 (Cq, Ar), 142.4 (Cq, Ar), 143.1 (d, JC,P
=
4.0 Hz, Cq, Ar), 144.2 (d, JC,P = 3.6 Hz, Cq, Ar), 154.8 (Cq, Ar),
154.9 (Cq, Ar) ppm. 31P{1H} NMR (162 MHz, CDCl3): δ = 144.4
(major, 87%), 150.6 (minor, 13%) ppm.
Ar) ppm. 31P{1H} NMR (162 MHz, CDCl3): δ = 140.9 ppm. MS [Rh(cod)(L2)2]BF4:
(EI): m/z (%) = 355.2 (26), 354.2 (99), 233.1 (56), 210.2 (22), 211.2 20.6 μL, 81.6 μmol, 1.02 equiv.) was added to a solution of [Rh(co-
A solution of HBF4·diethyl ether (54%,
(15), 208.2 (100). HRMS (ESI): calcd. for C32H41NO2P+ [M + d)(acac)] (24.8 mg, 80.0 μmol, 1.0 equiv.) in CH2Cl2 (5 mL) and the
H]+ 502.28694; found 502.28629.
resulting yellow-orange solution stirred for 20 min at room tem-
perature. A solution of (4aS,5R,7S,8aR)-1-[(11bR)-dinaphtho(2,1-
d:1Ј,2Ј-f)[1,3,2]dioxaphosphepin-4-yl]-6,6-dimethyldecahydro-5,7-
methanoquinoline (L2; 79.8 mg, 161.6 μmol, 2.02 equiv.) in CH2Cl2
(2 mL) was added and the solution stirred for 1.5 h at room tem-
perature. All the volatiles were removed under reduced pressure,
the residue was redissolved in CH2Cl2 (1 mL) and then added drop-
wise to vigorously stirred n-pentane (25 mL). A yellow precipitate
formed. The supernatant was removed and the yellow solid washed
with n-pentane (2ϫ 10 mL) and diethyl ether (2ϫ 10 mL). The
solid was dried under vacuum (1ϫ 10–3 mbar) to yield the desired
Rh complex as a yellow-orange powder, yield 78.5 mg (61.1 μmol,
(4aS,5R,7S,8aR)-1-[(3aR,8aR)-2,2-Dimethyl-4,4,8,8-tetraphenyl-
tetrahydro[1,3]dioxolo[4,5-e][1,3,2]dioxaphosphepin-6-yl]-6,6-dimeth-
yldecahydro-5,7-methanoquinoline (L12): Compound L12 was syn-
thesized following the general procedure for ligand synthesis start-
ing from (3aR,8aR)-6-chloro-2,2-dimethyl-4,4,8,8-tetraphenyltetra-
hydro[1,3]dioxolo[4,5-e][1,3,2]dioxaphosphepine (2.0 mmol,
1.0 equiv.) and (1R,2S,7R,9S)-10,10-dimethyl-6-azatri-
cyclo[7.1.1.02,7]undecane (15c; 2.0 mmol, 1.0 equiv.). The product
was obtained as a colorless solid, yield 1.172 g (1.740 mmol, 87%).
1
[α]2D9 = –53.3 (c = 0.5, CH2Cl2). H NMR (400 MHz, CDCl3): δ =
0.24 (s, 3 H, CH3), 1.10 (s, 3 H, CH3),1.26 (s, 3 H, CH3), 1.29 (d,
JH,H = 10.4 Hz, 1 H, CH2), 1.33 (s, 3 H, CH3), 1.52–1.70 (m, 4 H,
CH2), 1.80–1.93 (m, 2 H, CH, 1 H, CH2), 2.19 (m, 1 H, CH2), 2.32
(m, 1 H, CH, 1 H, CH2), 2.98 (m, 1 H, CH2), 3.40 (m, 1 H, CH2),
4.52 (m, 1 H, CH), 4.73 (d, JH,H = 8.5 Hz, 1 H, CH), 5.17 (dd,
JH,H = 8.5, JH,P = 3.2 Hz, 1 H, CH), 7.16–7.30 (m, 12 H, Ar), 7.44
(d, JH,H = 8.1 Hz, 2 H, Ar), 7.48 (d, JH,H = 8.1 Hz, 2 H, Ar), 7.61
(d, JH,H = 8.0 Hz, 2 H, Ar), 7.77 (d, JH,H = 8.1 Hz, 2 H, Ar) ppm.
13C{1H} NMR (100 MHz, CDCl3): δ = 21.9 (CH3), 25.1 (CH2),
25.2 (CH3), 26.3 (CH2), 27.6 (CH3), 28.3 (CH3), 31.1 (CH2), 34.9
(d, JC,P = 2.6 Hz, CH), 36.4 (d, JC,P = 7.3 Hz, CH2), 38.7 (Cq),
40.4 (d, JC,P = 23.5 Hz, CH2), 41.7 (CH), 45.8 (d, JC,P = 15.9 Hz,
CH), 48.8 (CH), 81.2 (d, JC,P = 8.4 Hz, Cq), 81.3 (Cq), 82.4 (d, JC,P
1
76%). H NMR (400 MHz, CDCl3): δ = –0.51 (br. s, 6 H, CH3),
0.61 (s, 6 H, CH3), 0.69–2.67 (m, 26 H, CH2, 8 H, CH), 2.92 (m,
2 H, CH2), 5.50–5.97 (m, 4 H, CH), 7.17–7.52 (m, 16 H, Ar), 7.84–
8.12 (m, 8 H, Ar) ppm. 31P{1H} NMR (162 MHz, CDCl3): δ =
140.4 (d, JP,Rh = 238.0 Hz) ppm. HRMS (ESI pos.): calcd. for
C72H76N2O4P2Rh+ [M – BF4]+ 1197.43299; found 1197.43403.
CCDC-1038409 (for L2·BH3) contains the supplementary crystal-
lographic data for this paper. These data can be obtained free of
charge from The Cambridge Crystallographic Data Centre via
www.ccdc.cam.ac.uk/data_request/cif.
Supporting Information (see footnote on the first page of this arti-
= 20.8 Hz, CH), 82.7 (d, JC,P = 3.7 Hz, CH), 111.3 (Cq), 126.8 cle): 1H, 13C, and 31P NMR spectra of all new key intermediates
2900
www.eurjoc.org
© 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2015, 2889–2901

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[20] Further experiments indicated that the hydrogenation of the
phenyl ring is favored over hydrogenation of the pyridine ring.
[21] The structures and configurations of the stereocenters were
confirmed in the solid state by single-crystal X-ray diffraction
analysis of the hydrochloride 15cH+ Cl–. Owing to the poor
quality of the crystals obtained, the refinement of the structure
resulted in R1 = 0.1177, wR2 = 0.2761, GOF = 1.280, Flack X
parameter 0.05 and is therefore not suitable for reproduction,
but included in the Supporting Information.
Acknowledgments
The authors thank Julia Wurlitzer and Hannelore Eschmann for
GC and HPLC measurements, Florian Strassl for experimental as-
sistance, Ghazi Ghattas for the provision of imines, Dr. Andreas
Uhe for DFT calculations, the group of Prof. Ulli Englert for the
acquisition of raw X-ray diffraction data, Dr. Markus Hölscher for
crystal structure analysis, and Johnson Matthey for the donation
of metal precursors.
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Received: January 26, 2015
Published Online: March 17, 2015
Eur. J. Org. Chem. 2015, 2889–2901
© 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
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