Helicene-based phosphite ligands in asymmetric transition-metal catalysis: Exploring Rh-catalyzed hydroformylation and Ir-catalyzed allylic amination

Article abstract of DOI:10.1002/ejoc.201100259

Starting from the optically pure [6]helicene-like alcohol(P,3S)-3-methyl-4- (4-methylphenyl)-1,3,6,7-tetrahydrobenzo[c]benzo[5,6]phenanthro[4,3-e] oxepin-14-ol, four helical phosphites were prepared from the corresponding chlorophosphites. These ligands containing parent or substituted 1,3,2-dioxaphospholan-2-yl or dibenzo[d,f][1,3,2]dioxaphosphepin-6-yl moieties were applied to the asymmetric hydroformylation of terminal alkenes catalyzed by Rh(acac)(CO)₂ and the asymmetric allylic amination of cinnamyl-type carbonates catalyzed by [Ir(cod)Cl]₂. The helical phosphite containing the dibenzo[d,f][1,3,2]dioxaphosphepin-6-yl group was most successful in the asymmetric hydroformylation of styrene, leading to moderate enantiomeric excess values (up to 32 % ee), high regioselectivity in favor of the branched product, and mostly high conversion, whereas the helical ligand containing the 4,4,5,5-tetramethyl-1,3,2-dioxaphospholan-2-yl fragment was most effective in asymmetric allylic aminations, exhibiting high enantioselectivity (up to 94 % ee), excellent regioselectivity in favor of the branched products, and good reactivity. This study represents the first use of helicene-like ligands in asymmetric reactions, including hydroformylation and allylic amination, and the promising results indicate the potential of the helicene moieties as chiral inductors. Copyright

Full text of DOI:10.1002/ejoc.201100259

FULL PAPER
DOI: 10.1002/ejoc.201100259
Helicene-Based Phosphite Ligands in Asymmetric Transition-Metal Catalysis:
Exploring Rh-Catalyzed Hydroformylation and Ir-Catalyzed Allylic Amination
[
a]
[a]
[b]
[b]
Zuzana Krausová, Petr Sehnal, Bojan P. Bondzic, Serghei Chercheja,
[b]
[a]
ˇ
[a]
[a]
Peter Eilbracht,* Irena G. Stará,* David Saman, and Ivo Starý*
Keywords: Asymmetric catalysis / Helical structures / P ligands / Hydroformylation / Amination
Starting from the optically pure [6]helicene-like alcohol
styrene, leading to moderate enantiomeric excess values (up
P,3S)-3-methyl-4-(4-methylphenyl)-1,3,6,7-tetrahydrobenzo- to 32%ee), high regioselectivity in favor of the branched
c]benzo[5,6]phenanthro[4,3-e]oxepin-14-ol, four helical product, and mostly high conversion, whereas the helical li-
(
[
phosphites were prepared from the corresponding chloro- gand containing the 4,4,5,5-tetramethyl-1,3,2-dioxaphos-
phosphites. These ligands containing parent or substituted
,3,2-dioxaphospholan-2-yl or dibenzo[d,f][1,3,2]dioxaphos-
phepin-6-yl moieties were applied to the asymmetric hydro-
formylation of terminal alkenes catalyzed by Rh(acac)(CO)
and the asymmetric allylic amination of cinnamyl-type carb-
onates catalyzed by [Ir(cod)Cl] . The helical phosphite con-
pholan-2-yl fragment was most effective in asymmetric al-
lylic aminations, exhibiting high enantioselectivity (up to
94%ee), excellent regioselectivity in favor of the branched
products, and good reactivity. This study represents the first
use of helicene-like ligands in asymmetric reactions, includ-
ing hydroformylation and allylic amination, and the promis-
ing results indicate the potential of the helicene moieties as
chiral inductors.
1
2
2
taining the dibenzo[d,f][1,3,2]dioxaphosphepin-6-yl group
was most successful in the asymmetric hydroformylation of
Introduction
metric catalysis. Indeed, the efficiency of chirality induction
by using helical ligands has virtually been unexplored. This
fact can be illustrated by the limited number of examples
Myriads of chiral ligands have successfully been explored
in asymmetric transition-metal catalysis.[ In the quest to
reach the highest enantioselectivity, turnover frequency, cat-
alyst lifetime, and effective recycling, the chiral ligands
screened in homogeneous catalysis have been of virtually
unlimited diversity. When classifying ligands by the type of
the element(s) of chirality comprised, practically all of them
are molecules exhibiting central, axial, or planar chirality.
Among them, a gradually increasing group of “privileged
1]
[11]
[12]
for which ligands derived from helicenes are explored.
After it was originally prepared by Brunner et al. in racemic
[13]
form,
Reetz et al. pioneered the utilization of optically
[14]
active PHelix (1, Figure 1) in a Rh-catalyzed asymmetric
hydrogenation of the ester of itaconic acid (reaching up to
[14]
3
9%ee). Helical diphosphane 1 was used by Reetz et al.
in the Pd-catalyzed kinetic resolution of a racemic allylic
substrate (obtaining up to Ͼ99%ee for the starting material
[
2,3]
ligands”
plays a pivotal role. Ligand “blockbusters”, for
[15]
and up to 86%ee for the substitution product).
Soai et
[
4]
[5]
[6]
example, DuPhos, BINAP, Solvias ferrocenes, salen li-
[16]
[17]
al.
and later Soai, Maiorana et al.
reported remark-
[
7]
[8]
gands, and phosphoramidite ligands (vide infra), have
able asymmetric induction by unfunctionalized helicenes,
for example, 2, or thiahelicenes, for example, 3, in the enan-
tioselective addition of diisopropylzinc to pyrimidine-5-
carbaldehyde (in conjunction with asymmetric autocataly-
sis, achieving up to 95%ee with 2 or 99%ee with 3). Katz
et al. successfully used [5]HELOL (4) in the addition of
diethylzinc to aromatic aldehydes (receiving up to
gained remarkable fame and glory,[
9,10]
thus documenting
the exceptionality of “priviledged ligands” as well as the
usefulness of the chirality elements mentioned above.
Keeping the focus on ligand scaffolds, the remaining type
of chirality, that is, helicity, has rarely been used in asym-
[
18]
[
a] Institute of Organic Chemistry and Biochemistry,
Academy of Sciences of the Czech Republic,
Flemingovo nám. 2, 166 10 Prague 6, Czech Republic
Fax: +420-220-183-133
81%ee). In this case, however, the helicene ligand exhib-
its mixed chirality, as 4 contains two helical aromatic units
linked by a single bond, which introduces a chirality axis
typical for 1,1Ј-biaryls. Furthermore, Yamaguchi et al.
studied helicene phosphites, for example, 5, being a medley
of three types of chirality: helical, axial, and central.[
They observed a significant effect of matched/mismatched
helical and axial chirality on the stereochemical outcome of
the Rh-catalyzed enantioselective hydrogenation of di-
E-mail: stara@uochb.cas.cz
stary@uochb.cas.cz
b] Universität Dortmund,
[
19]
Otto-Hahn-Strasse 6, 44221 Dortmund, Germany
Fax: +49-231-755-5363
E-mail: peter.eilbracht@uni-dortmund.de
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201100259.
Eur. J. Org. Chem. 2011, 3849–3857
© 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
3849

P. Eilbracht, I. G. Stará, I. Starý et al.
FULL PAPER
methyl itaconate (monitoring up to 96%ee). Recently, Tak- selectivity in the kinetic resolution of chiral secondary
enaka et al. used helical pyridine N-oxides 6–8 as organoca- alcohols (reaching a selectivity factor of up to 116).[
talysts in a desymmetrization of meso-epoxides (reaching Thus, to the best of our knowledge, there are no other ex-
23]
[
20a,20b]
up to 94%ee)
and the enantioselective propar- amples of true helicene-based ligands that are used in asym-
gylation of aldehydes with allenyltrichlorosilane (receiving metric transition-metal catalysis or organocatalysis.
[
20c]
up to 96%ee).
Moreover, they applied helical 2-amino-
In addition to the helical ligands discussed so far, newly
pyridinium ions 9 and 10 as hydrogen-bond donors to an emerging family of monodentate phosphites 13, phosphin-
acid-catalyzed asymmetric Friedel–Crafts reaction, re- ites 14, and phosphoramidites 15 (Figure 2) derived from
porting high enantioselectivities up to 96%ee.[ We have BINOL can definitely not be neglected. Soon after the inde-
21]
[
24]
demonstrated the organocatalytic activity of parent 2-aza- pendent discovery by Reetz et al. (cf. 13),
Pringle et al.
in 2000 that such
Re- compounds are excellent chiral ligands in Rh-catalyzed ole-
[
25]
[26]
[
6]helicene 11 in asymmetric acyl transfer reactions to de- (cf. 14),
and Feringa et al. (cf. 15)
[
22]
scribe a moderate selectivity factor (of up to 10).
cently, Carbery et al. developed helicene DMAP Lewis base fin hydrogenations, they started to attract considerable at-
catalyst 12, which exhibited excellent reactivity as well as tention (owing to their chirality induction efficiency, versa-
tility, facile availability, and possibility to apply new combi-
[
8]
natorial approaches to asymmetric catalysis). Despite the
fact that the axially chiral 2,2Ј-dihydroxy-1,1Ј-binaphthyl
moiety is embodied in their scaffolds, they can also be
[
27]
viewed as hetero[5]helicene counterparts, having a 1,3,2-
dioxaphosphepine unit incorporated into the helical back-
bone.
Figure 2. Helicene congeners used in asymmetric catalysis.
Apparently, helically chiral ligands can serve as effective
chiral inducers in asymmetric catalysis, competing success-
fully against “traditional” ligands possessing central, axial,
or planar chirality. As the former have not been systemati-
cally studied and, accordingly, their potential has not been
fully explored, further effort in this direction is required.
Results and Discussion
In conjunction with the progress in the synthesis of heli-
cenes and their congeners based on general triyne [2+2+2]
cyclotrimerization methodology, we already attempted the
preparation of possible ligands such as racemic 3-diphenyl-
[
28]
phosphanyl[6]helicene 16
and optically pure 1-aza[6]-
[
29]
helicene 17 and 2-aza[6]helicene 11.
Even though they
have not yet been used in asymmetric transition-metal catal-
ysis, we have demonstrated the ability of these compounds
to form intriguing complexes with silver. Recently, we estab-
lished the basis of the diastereoselective synthesis of
[
27a–27d]
helicene-like molecules.
Having developed reliable
access to optically pure alcohol 18 (Figure 3) on a prepara-
[
27b]
tive scale,
we could attempt the exploitation of this
unique helical scaffold in asymmetric catalysis. We have
proposed that placement of a coordinating group on the
most sterically congested position of the helical backbone
Figure 1. Helical ligands used in asymmetric catalysis.
850
3
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Eur. J. Org. Chem. 2011, 3849–3857

Helicene-Based Phosphite Ligands in Asymmetric Transition-Metal Catalysis
(i.e., C-1 of the terminal benzene ring) would lead, after
metal coordination, to the well-defined chiral environment
of the reaction center and, accordingly, to a considerably
large enantiomeric excess value for the reaction studied. In
this paper, we report on the preparation of a series of new
helical phosphites 23–26 (Scheme 1) derived from alcohol
18, which we subsequently explored in Rh-catalyzed hydro-
formylation and Ir-catalyzed allylic amination reactions.
Figure 3. Helical phosphane rac-16, azahelicene (+)-(P)-17 and he-
lical alcohol (+)-(P,S)-18 with its X-ray structure.[
27b]
Synthesis of Helical Phosphites
The asymmetric synthesis of alcohol (+)-(P,S)-18 was re-
[
27b]
cently published.
It employs optically pure (S)-but-3-yn-
Scheme 1. Synthesis of helical phosphites 23–26. Reagents and con-
ditions: (a) (+)-(P,S)-18 (1.0 equiv.), NaH (2.5–4.0 equiv.), chloro-
phosphite 19–22 (1.6 equiv.), THF, 0 °C to room temp., 2 h.
2
-ol as a chiral building block, which is commercially avail-
able in both enantiomeric forms. Although the methyl ether
of (+)-(P,S)-18 can undergo thermal epimerization to reach
the equilibrium (P,S)/(M,S) = 87:13; the barrier of
2
7.7 kcal/mol to the (P,S)Ǟ(M,S) process (26.4 kcal/mol C junction between the helicene platform and a phosphite
[27b]
for the backward one)
is high enough to prevent any moiety is flexible to some extent. While the rotation around
configurational scrambling at room temperature or at ele- the O–C bond (Figure 4, a) is limited because of steric
vated temperatures for a limited period of time. reasons, the rotation of the phosphite moiety around the P–
The preparation of each helical phosphite 23–26 was a O bond (Figure 4, b) is less restricted. In 23, there are two
single-step operation (Scheme 1). After optimizing the reac- resolved methylene signals of the 1,3,2-dioxaphospholane
tion conditions, we found that sodium alcoholate generated unit in the 13C NMR spectrum (63.70 and 63.72 ppm), indi-
from optically pure (+)-(P,S)-18 reacted smoothly with cating a partially restricted rotation around the P–O bond
commercially available chlorophosphites 19 and 20 or chlo- (Figure 4, b). Similarly, the 4,4,5,5-tetramethyl-1,3,2-dioxa-
[
30]
[31]
rophosphites 21
and 22,
whose syntheses have been phospholane unit in 24 displays non-equivalency of the
1
13
described in the literature. The formation of phosphites four methyl groups in the H and C NMR spectra (1.00,
3
1
1
could be easily monitored by P{ H} NMR spectroscopy, 1.12, 1.14, 1.24 ppm and 24.08, 24.95, 25.34, 25.85 ppm,
as the conversion of chlorophosphites into phosphites was respectively). The presence of an axially chiral di-
indicated by a significant shift in the signal of the phos- benzo[d,f][1,3,2]dioxaphosphepine unit in 25 raises the
phorus atom (for the chemical shifts of phosphorus atoms question of its configuration. As there is only one set of
1
13
in chlorophosphites 19–22 and phosphites 23–26, see the signals in the H and C NMR spectra, either rapid in-
Supporting Information).[
30–33]
Phosphites 23–26 were ob- terconversion between the (R ) and (S ) atropoisomers or
a
a
tained in moderate to good yields, reflecting in this way preferential formation of only one of them (cf. Waldvogel
[
31]
their stability during the workup and subsequent fast fil- et al. ) should occur along with free rotation of the phos-
tration through a pad of silica. phite moiety around the P–O bond (Figure 4, b). Similarly,
The conformational behavior of phosphites 23–26 re- 26 displays one set of signals except for the resolved signals
1
13
quires more detailed analysis. The (P,S) helicene platform of the two methoxy groups in the H and C NMR spectra
is well defined, because it is rather rigid. However, the P–O– (3.81, 4.00 ppm and 55.58, 55.77 ppm, respectively) and two
Eur. J. Org. Chem. 2011, 3849–3857
© 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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3851

P. Eilbracht, I. G. Stará, I. Starý et al.
FULL PAPER
quaternary carbon atoms of the tert-butyl groups in the 13
C
30a. After other optimizations, we monitored the best
NMR spectrum (34.98, 35.17 ppm). Such features might be stereochemical outcome of an asymmetric hydroformyl-
attributed to a partially hindered revolution of the phos- ation of styrene 27 (32%ee) when the reaction was per-
phite moiety around the P–O bond (Figure 4, b).
formed in the presence of Rh(acac)(CO) (0.5 mol-%) and
2
25 (1.25 mol-%) in toluene under partial pressure of CO
(
40 bar) and H (40 bar) at 40 °C (Table 1, Entry 7). The
2
I
hydroformylation of 4-chlorostyrene (28) under Rh cataly-
sis with ligands 23–26 was found to proceed with excellent
regioselectivity and a low or moderate enantioselectivity to
[
37,38]
afford 31a
(Table 1, Entries 9–12). Similar to the hy-
droformylation of 27, helical phosphite 25 was most effec-
tive in chirality induction (20%ee). The hydroformylation
Figure 4. Conformational freedom of phosphites 23–26.
[
37b]
of vinyl acetate 29 to afford 32a
differed from the above-
mentioned examples in several aspects (Table 1, Entries 13–
1
2
6). Electronically rich terminal alkene 29 was reactive like
7 and 28 (with ligands 23 and 25; Table 1, Entries 13 and
Rh-Catalyzed Hydroformylation
The hydroformylation of alkenes under transition-metal 15) or slightly less reactive (with ligands 24 and 26; Table 1,
catalysis represents an ideal chemical process from the point Entries 14 and 16), which resulted in conversions around
of view of atom economy as well as the exploitation of inex- 70% within the 20-hour reaction period. As for 29, the ace-
[
34]
pensive feedstock. Terminal olefins are uniformly used as tone medium and the higher-ligand loading (5 mol-%) were
substrates for asymmetric hydroformylation reactions along found to be superior to toluene and a lower loading of the
with rhodium catalysts and chiral (bis)phosphane/(bis)- ligand, respectively, in terms of reaching higher regioselec-
[
34,35]
phosphite ligands.
Despite the significant effort re-
cently devoted to the further development of asymmetric
Table 1. The asymmetric hydroformylation of alkenes 27–29.[a]
[
36]
hydroformylations,
the question of the chirality induc-
tion efficiency by helical ligands has so far remained unan-
swered.
Accordingly, we decided to screen the regioselectivity and
I
enantioselectivity of the Rh -catalyzed hydroformylation of
terminal alkenes 27–29 in the presence of helical phosphites
23–26 (Table 1). We started with the hydroformylation of
the model substrate styrene (27) to find the conditions
where the widely used catalyst Rh(acac)(CO) in combina-
2
tion with phosphites 23–26 is sufficiently active but where
the reaction proceeds under mild enough conditions to pre-
vent any undesired side reaction of the starting material or
products (i.e., hydrogenation, isomerization, polymeriza-
tion, aldol condensation). The test experiments showed that
Branched/linear [c] ee [%][d]
Entry Alkene
Ligand
Product
(% conv.)
[b]
1
2
3
27
27
27
27
27
27
27
27
28
28
28
28
29
29
29
29
23
24
25
25
30 (96)
30 (93)
30 (96)
30 (98)
30 (99)
30 (97)
30 (99)
30 (96)
31 (98)
31 (96)
31 (98)
31 (97)
32 (98)
32 (70)
32 (99)
32 (69)
91:9
92:8
93:7
94:6
98:2
94:6
n.d.
95:5
99:1
97:3
98:2
98:2
5 (S)
7 (S)
29 (S)
24 (S)
18 (S)
16 (S)
32 (S)
0
6 (S)
6 (S)
20 (S)
11 (S)
4 (S)
25 (S)
15 (S)
0
[
e]
I
4
5
6
the reaction catalyzed by the Rh –25 (1:2.5) system went to
[
e]
e]
[h]
[f]
25
completion at 50 °C within 20 h (with a yield of 97%),
whereas at room temperature the reaction slowed signifi-
cantly (with a yield of 50%). For the initial hydrofor-
mylation experiments in toluene, we choose the partial pres-
[
[g]
25
7
25
26
23
8
9
[
f]
[i]
[i]
[
f]
1
0
24
25
26
23
24
25
26
sure of CO and H to be 10:10 bar (in the case of 27, re-
2
[f]
[f]
[f]
[f]
[f]
[f]
1
1
gioselectivity can be affected by changing the CO/H partial
2
1
2
pressure only at high temperature). Employing helical li-
gands 23–26, the hydroformylation of 27 proceeded with 14
[j]
13
67:33
91:9
92:8
[j]
[j]
1
5
high regioselectivity (up to 95:5) in favor of branched prod-
[j]
[
36a]
16
86:14
uct 30a
with enantiomeric excess values ranging from 0
[a] Rh(acac)(CO)
2
(1 mol-%), (P,S)-ligand (2.5 mol-%), toluene,
(10 bar), 50 °C, 20 h. [b] Determined by GC
Chrompack DB-1701 column) by using dodecane as internal stan-
dard. [c] Determined by GC. [d] The enantiomeric excess value of
to 29% (Table 1, Entries 1–3, 8). Although ligand 25 exhib-
ited a moderate level of chirality induction, ligands 23, 24,
and 26 were ineffective in this regard. By changing the sol-
CO (10 bar), H
(
2
vent from toluene to dichloromethane, the moderate the branched isomer was determined by GC (Beta Dex 225 column
enantioselectivity was found to drop slightly (Table 1, En- by Supelco), the absolute configuration of the prevailing enantio-
I
mer is given in parentheses; for the assignment of the absolute con-
try 4). To examine the effect of the Rh -to-ligand ratio, we
figuration, see ref.[
ligand. [g] 10 mol-% of the ligand. [h] Rh(acac)(CO)
ligand (1.25 mol-%), toluene, CO (40 bar), H (40 bar), 40 °C, 20 h.
37,38]
. [e] In dichloromethane. [f] 5 mol-% of the
(0.5 mol-%),
changed this proportion from 1:2.5 to 1:5 and 1:10 (Table 1,
Entries 4–6). However, we observed that a higher loading
of the ligand led to a lower enantiomeric excess value of [i] Determined by H NMR spectroscopy. [j] In acetone.
2
2
1
3
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© 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Helicene-Based Phosphite Ligands in Asymmetric Transition-Metal Catalysis
tivity and enantioselectivity. In the case of the hydrofor- Table 2. Asymmetric allylic amination of allyl carbonates 33 and
[a]
34.
mylation of 29, ligand 24 was the most effective in chirality
induction to provide branched product 32a with a moderate
enantiomeric excess value (25%ee) and with high regiose-
lectivity (Table 1, Entry 14).
Ir-Catalyzed Allylic Amination
The fact that secondary allylamines can advantageously
be utilized in the synthesis of natural products raises the
question of how to prepare these valuable building blocks
in a nonracemic form. Recently, significant progress has
been achieved in transition-metal catalyzed asymmetric al-
I
lylic aminations, where chiral Ir complexes have played a
[
39]
prominent role.
phoramidites
Axially chiral BINOL-derived phos-
have been identified as privileged ligands
to generate a catalytically active species after the coordina-
[
40]
I
[41]
tion of Ir followed by base-induced C–H activation. The
high regioselectivity (in favor of the branched isomer) and
enantioselectivity that are usually observed, the detailed
mechanistic insight, along with the simplicity of the reac-
tion protocol make asymmetric allylic aminations an at-
tractive synthetic tool. Although various chiral ligands have
been examined, the helical ones are still awaiting applica-
tion in this reaction.
To examine the regioselectivity and enantioselectivity of
2
[a] [Ir(cod)Cl] (1.0 mol-%), (P,S)-ligand (2.0 mol-%), amine (1.3–
asymmetric allylic aminations in the presence of [Ir(cod)- 1.6 equiv.), THF, 50 °C, 2 h to 3 d. [b] Isolated. [c] Determined by
1
H NMR spectroscopy. [d] Determined by HPLC (Chiracel OD-H
Cl]2 and helical phosphites 23–26, we treated cinnamyl
[
42]
[43]
column by Daicel), the absolute configuration or the sense of op-
carbonate 33 and (pyridinyl)allyl carbonate 34 with a
tical rotation of the prevailing enantiomer is given in parentheses;
primary (benzylamine) or secondary amine (pyrrolidine, pi-
[37]
for the assignment of the absolute configuration, see ref.
[e] In
peridine, or morpholine; Table 2). Initial experiments with dichloromethane at 35 °C. [f] Determined by HPLC (Chiracel OJ-
1
3
3 and benzylamine carried out in THF at 50 °C showed H column by Daicel). [g] Determined by H NMR spectroscopy
with a TFAE shift reagent.
that the use of ligand 24 resulted in a high enantiomeric
[
40b]
excess value of 35a
erate enantioselectivity and 23 was ineffective in this regard
Table 2, Entries 1, 2 and 4). We observed excellent regiose-
(93%ee), whereas 25 provided mod-
(
lectivity in favor of branched product 35a, but the yields 37b), whose enantiomeric excess was high when using phos-
were typically low. Ligand 26 completely impeded the reac- phite 24 (91%ee) or 23 (79%ee) but low with phosphite 25
tion and, therefore, was not further tested (Table 2, En- (Table 2, Entries 10, 12, and 13). As described above, the
try 5).
use of THF led to a diminished yield of 37a; whereas the
We found that the problem with the low reactivity could enantioselectivity remained unaffected (Table 2, Entry 11
be resolved simply by replacing THF with dichloromethane. vs. 12). The reaction of the pyridine analogue 34 of cinn-
Indeed, performing the reaction with 24 in this solvent at amyl carbonate 33 with piperidine in dichloromethane pro-
3
5 °C led to a comparable enantioselectivity (90%ee), but vided the best results, as the use of phosphite 24 led to
the preparative yield was significantly increased (95%; excellent regioselectivity (only branched product 38a[
Table 2, Entry 3). The reaction of 33 with pyrrolidine as was detected), high enantioselectivity (94%ee), and a good
nucleophile in dichloromethane followed the trends men- yield (Table 2, Entry 15). Similarly to the examples men-
43a]
tioned above. Here, we observed the exclusive formation of tioned above, phosphites 23 and 25 were less successful, as
branched product 36a[
40b,43a]
in the presence of phosphites they yielded only a moderate enantiomeric excess value of
23–25, but only 24 gave rise to a high enantioselectivity (up 38a (Table 2, Entries 14 and 16). The efficiency of phosphite
to 92%ee), whereas 23 and 25 provided moderate and no 24 within the series 23–26 leading to the best enantio-
enantiomeric excess, respectively (Table 2, Entries 6, 8, and selectivities along with predominantly the highest reactivi-
9). Similarly, dichloromethane was found to be superior to ties regardless of the substrate and N nucleophile used
THF in terms of the reactivity of 33 (Table 2, Entry 7 vs. might be related to its proposed C–H activation to generate
[
41]
8
). Like pyrrolidine, morpholine reacted with 33 in dichlo- a catalytically active P–C-chelated iridium species (owing
romethane to afford predominantly branched product to the presence of the CH groups in the dioxaphospholanyl
3
7a[
40b,44]
(accompanied by a small amount of linear isomer moiety).
3
Eur. J. Org. Chem. 2011, 3849–3857
© 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
3853

P. Eilbracht, I. G. Stará, I. Starý et al.
FULL PAPER
2
1,[30] 22,[31] 33,[42] and 34[43] were synthesized according to pro-
Conclusions
cedures in the literature.
Here we have described the synthesis of four new [6]hel-
icene-related phosphites (+)-(P,S)-23–26 starting from op-
tically pure helical alcohol (+)-(P,S)-18 and corresponding
(
+)-(P,3S)-14-(1,3,2-Dioxaphospholan-2-yloxy)-3-methyl-4-(4-meth-
ylphenyl)-1,3,6,7-tetrahydrobenzo[c]benzo[5,6]phenanthro[4,3-e]ox-
epine (23): A Schlenk flask was charged with NaH (80% suspension
in mineral oil, 24 mg, 1.014 mmol, 3.8 equiv.) and put under an
chlorophosphites 19–22. We have applied these helically
I
chiral phosphites to the asymmetric Rh -catalyzed hydro- atmosphere of argon. THF (1 mL) was added, and the stirred sus-
I
formylation of terminal alkenes and to asymmetric Ir -cata- pension was cooled to 0 °C. A solution of (+)-(P,3S)-18 (100 mg,
lyzed allylic aminations. Ligand (+)-(P,S)-25 containing the 0.213 mmol) in THF (1.5 mL) was added dropwise. The reaction
mixture was stirred at 0 °C for 15 min, then warmed slowly to room
temperature and stirred for 45 min. Subsequently, the mixture was
cooled again to 0 °C and phosphorochloridite 19 (30 μL,
biphenyl-2,2Ј-diol fragment in the phosphite moiety was the
most successful ligand in asymmetric hydroformylation re-
actions, leading to moderate enantiomeric excess values (up
to 32%ee in the hydroformylation of 27), high regioselectiv-
ity in favor of the branched products, and mostly high con-
versions. In contrast, ligand (+)-(P,S)-24 containing the
pinacol fragment in the phosphite moiety was most effective
0.342 mmol, 1.6 equiv.) was added dropwise. The reaction mixture
was warmed slowly to room temperature over 3 h, after which tri-
ethylamine (300 μL) was added. The solvent was removed in vacuo,
and the crude product was purified by chromatography on silica
3
gel (cyclohexane/diethyl ether/acetone, 80:10:10 + 3% Et N) to af-
2
2
in an asymmetric allylic amination, exhibiting high enantio- ford (+)-(P,3S)-23 (90 mg, 76%) as an amorphous solid. [α]5
=
89
1
selectivity (up to 94%ee in the amination of the cinnamyl- +369 (c = 0.09, CH Cl ). H NMR (500 MHz, CDCl ): δ = 0.62
2
2
3
type substrates), excellent regioselectivity in favor of the (d, J = 7.1 Hz, 3 H), 2.43 (s, 3 H), 2.73–2.81 (m, 1 H), 2.87–2.94
(
1
m, 1 H), 3.08–3.15 (m, 2 H), 3.76–3.86 (m, 4 H), 4.74 (d, J =
1.4 Hz, 1 H), 5.01 (d, J = 11.4 Hz, 1 H), 5.31 (q, J = 7.1 Hz, 1
H), 6.36 (dd, J = 8.1, 1.3 Hz, 1 H), 6.73 (ddd, J = 8.6, 6.7, 1.4 Hz,
H), 6.90 (dd, J = 8.1, 7.5 Hz, 1 H), 7.03 (ddd, J = 8.1, 6.7, 1.2 Hz,
H), 7.11 (dd, J = 7.5, 1.3 Hz, 1 H), 7.18 (dq, J = 8.6, 1.0, 1.0,
.0 Hz, 1 H), 7.28 (m, 2 H), 7.40 (d, J = 1.1 Hz, 1 H), 7.40 (m, 2
branched products, and good reactivity. This study repre-
sents the first use of helicene-like ligands in asymmetric re-
actions such as hydroformylation and allylic amination. The
promising results indicate the potential of the helicene
moieties as chiral inductors, whose use in asymmetric catal-
ysis has remained rather unexplored.
1
1
1
H), 7.42 (d, J = 8.0 Hz, 1 H), 7.56 (dd, J = 8.1, 1.4 Hz, 1 H), 7.63
1
3
(
(
(
3
d, J = 8.0 Hz, 1 H) ppm. C NMR (126 MHz, CDCl ): δ = 21.21
q), 22.53 (q), 30.55 (t), 30.70 (t), 63.70 (t), 63.72 (t), 67.87 (t), 72.40
d), 119.75 (d), 123.59 (d), 123.79 (d), 124.53 (d), 125.56 (d), 125.93
Experimental Section
General: 1H and 13C NMR spectra were measured at 499.88 and
(d), 127.02 (d), 127.39 (d), 128.92 (s), 128.92 (d), 128.99 (2 d),
29.28 (d), 132.40 (s), 132.60 (s), 132.84 (s), 133.61 (s), 134.05 (s),
135.56 (s), 136.67 (s), 138.70 (s), 138.73 (s), 138.94 (s), 140.58 (s),
1
1
25.71 MHz, respectively, in CDCl
3
with TMS as an internal stan-
dard. P NMR spectra were measured at 121.50 or 161.98 MHz
in CDCl with H PO as an external standard. HMBC experiments
31
3
1
1
41.32 (s), 147.70 (s) ppm. P NMR (162 MHz, CDCl
3
): δ =
3
3
4
1
27.25 (s) ppm. IR (CCl ): ν˜ = 3053 (m), 1622 (vw, sh.), 1612 (w),
4
were set up for JC,H = 5 Hz. For the correct assignment of both
the 1H and 13C NMR spectra of the key compounds, COSY,
1596 (w, sh.), 1587 (w), 1578 (w), 1514 (m), 1465 (s), 1438 (m),
1
1
1
380 (m, sh.), 1368 (s), 1303 (w, sh.), 1293 (m), 1277 (m), 1249 (s),
238 (m), 1213 (m), 1181 (m), 1159 (m, sh.), 1138 (w), 1110 (w),
090 (vs), 1073 (s), 1037 (m, sh.), 1022 (m), 1012 (s), 888 (m), 863
HMQC, and HMBC experiments were performed. The IR spectra
were measured in CCl . The APCI mass spectra were recorded by
4
using a ZQ micromass mass spectrometer (Waters) equipped with
an ESCi multimode ion source and controlled by MassLynx soft-
ware. Methanol was used as the solvent. Accurate mass measure-
ments were obtained by APCI MS. Optical rotations were mea-
(
5
3
+
w), 847 (m), 837 (m), 822 (vs), 729 (m), 701 (w), 565 (w), 545 (w),
–
1
+
29 (w), 492 (w) cm . MS (APCI): m/z = 559 [M + H] , 526, 451,
91, 317, 301, 282, 254. HRMS (APCI): calcd. for C36 P [M
32 4
H O
+
H] 559.2038; found 559.2031.
2 2
sured in CH Cl by using an Autopol IV (Rudolph Research Ana-
lytical) instrument. For gas chromatographic analyses, a Carlo
Erba HRGC Mega2 Series MFC 800 chromatograph with a Carlo
Erba EL 580 flame-ionization detector (FID) was used with do-
decane as an internal standard. Separations were performed on a
Chrompack DB-1701 column (25 m ϫ0.32 mm ϫ1.0 mm). En-
antiomeric excess values were determined with a GC Beta Dex 225
column from Supelco or by HPLC with a Chiracel OD-H
(+)-(P,3S)-3-Methyl-4-(4-methylphenyl)-14-[(4,4,5,5-tetramethyl-
1,3,2-dioxaphospholan-2-yl)oxy]-1,3,6,7-tetrahydrobenzo[c]benzo-
[5,6]phenanthro[4,3-e]oxepine (24): A Schlenk flask was charged
with NaH (80% suspension in mineral oil, 24 mg, 1.014 mmol,
3.8 equiv.) and put under an atmosphere of argon. THF (1 mL) was
added, and the stirred suspension was cooled to 0 °C. A solution of
(+)-(P,3S)-18 (100 mg, 0.213 mmol) in THF (1.5 mL) was added
(
250ϫ4.6 mm) or a Chiracel OJ-H (250ϫ4.6 mm) column by dropwise. The reaction mixture was stirred at 0 °C for 15 min, then
1
Daicel using heptane/2-propanol as the mobile phase or by
H
warmed slowly to room temperature and stirred for 45 min. Sub-
sequently, the mixture was cooled again to 0 °C and phosphoroch-
loridite 20 (54 μL, 0.342 mmol, 1.6 equiv.) was added dropwise. The
reaction mixture was warmed slowly to room temperature over 2 h,
after which triethylamine (300 μL) was added. The solvent was re-
moved in vacuo, and the crude product was purified by chromatog-
raphy on silica gel (cyclohexane/diethyl ether/acetone, 80:10:10 +
NMR spectroscopy by using TFAE as a shift reagent. Commer-
cially available, reagent-grade materials were used as received.
Dichloromethane was distilled from calcium hydride under an at-
mosphere of argon, and THF was freshly distilled from sodium/
benzophenone under an atmosphere of nitrogen. TLC was per-
formed on Silica gel 60 F254 coated aluminum sheets (Merck); spots
were detected by using a solution of Ce(SO
P(Mo (2%) in sulfuric acid (10%) or a solution (2.5%) of
NH SCN/CoCl (3:1) in water. Flash chromatography was per-
formed on Silica gel 60 (0.040–0.063 mm, Fluka). Rh(acac)(CO)
4
)
2
·4H
2
O (1%) and
3% Et
solid. [α]589 = +543 (c = 0.16, CH
CDCl ): δ = 0.60 (d, J = 7.1 Hz, 3 H), 1.00 (s, 3 H), 1.12 (s, J =
1.6 Hz, 3 H), 1.14 (s, J = 4.2 Hz, 3 H), 1.24 (s, 3 H), 2.43 (s, 3 H),
2.75 (dddd, J = 15.2, 13.9, 3.8, 1.0 Hz, 1 H), 2.82–2.91 (m, 1 H),
3
N) to afford (+)-(P,3S)-24 (110 mg, 84%) as an amorphous
2
2
1
H
3
3
O
10
)
4
2 2
Cl ). H NMR (500 MHz,
4
2
3
2
,
, 19, 20, and 27–29 were purchased; (+)-(P,S)-18,[
27b]
[
Ir(cod)Cl]
2
3854
www.eurjoc.org
© 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2011, 3849–3857

Helicene-Based Phosphite Ligands in Asymmetric Transition-Metal Catalysis
2
(
7
.82–2.91 (m, 1 H), 3.21 (br. dt, J = 15.0, 15.0, 4.5 Hz, 1 H), 4.74
d, J = 11.5 Hz, 1 H), 5.03 (d, J = 11.5 Hz, 1 H), 5.30 (q, J =
.1 Hz, 1 H), 6.36 (ddt, J = 8.0, 1.9, 0.7, 0.7 Hz, 1 H), 6.73 (ddd,
J = 8.4, 6.7, 1.4 Hz, 1 H), 6.90 (dd, J = 8.0, 7.4 Hz, 1 H), 7.01
ddd, J = 8.1, 6.7, 1.2 Hz, 1 H), 7.10 (ddt, J = 7.4, 1.9, 0.7, 0.7 Hz,
H), 7.19 (dq, J = 8.4, 1.0, 1.0, 1.0 Hz, 1 H), 7.27 (m, 2 H), 7.39
(vs), 1379 (m, sh.), 1368 (s), 1205 (vs), 1184 (vs), 1138 (m), 1116
(m), 1097 (s), 1089 (vs), 1074 (s), 1036 (s), 1024 (m), 1011 (m), 890
(s, sh.), 864 (vs), 815 (vs), 708 (s), 570 (w), 559 (w), 545 (m), 528
–
1
+
(m), 493 (w) cm . MS (APCI): m/z = 683 [M + H] , 665, 369, 316,
36 4
H O
P [M + H]+ 683.2351;
(
1
288. HRMS (APCI): calcd. for C46
found 683.2330.
(
(
m, 1 H), 7.38 (d, J = 1.0 Hz, 1 H), 7.39 (d, J = 8.0 Hz, 1 H), 7.53
ddt, J = 8.1, 1.4, 0.6, 0.6 Hz, 1 H), 7.59 (br. d, J = 8.0 Hz, 1 H)
(+)-(P,3S)-14-[(4,8-Di-tert-butyl-2,10-dimethoxydibenzo[d,f][1,3,2]-
13
ppm. C NMR (126 MHz, CDCl
3
): δ = 21.21 (q), 22.65 (q), 30.56 dioxaphosphepin-6-yl)oxy]-3-methyl-4-(4-methylphenyl)-1,3,6,7-tetra-
(
t), 30.82 (t), 67.92 (t), 72.46 (d), 121.02 (d), 123.46 (d), 123.58 (d), hydrobenzo[c]benzo[5,6]phenanthro[4,3-e]oxepine (26): A solution of
1
1
24.49 (d), 125.57 (d), 126.32 (d), 126.99 (d), 127.15 (d), 128.84 (d),
28.96 (s), 128.96 (2 d), 129.20 (d), 132.33 (s), 132.89 (2 s), 134.11
3,3Ј-di-tert-butyl-5,5Ј-dimethoxybiphenyl-2,2Ј-diol
(200 mg,
0.558 mmol) in toluene (2 mL), triethylamine (310 μL, 2.232 mmol,
4.0 equiv.), and phosphorus trichloride (290 μL, 3.348 mmol,
6.0 equiv.) was heated at reflux for 2 h. The excess amount of phos-
phorus trichloride was distilled off to give phosphorochloridite 22
(
(
s), 134.16 (s), 135.48 (s), 136.57 (s), 138.62 (s), 138.81 (s), 139.16
31
s), 140.62 (s), 141.10 (s), 147.52 (s) ppm. P NMR (162 MHz,
): δ = 134.98 (s) ppm. IR (CCl ): ν˜ = 1612 (vw), 1595 (w,
sh.), 1589 (w), 1576 (w, sh.), 1514 (w), 1465 (m), 1438 (w), 1383 (w,
sh.), 1375 (m), 1368 (w, sh.), 1237 (w), 1213 (w), 1181 (m), 1112 toluene): δ = 204.21 (s) ppm. A Schlenk flask was charged with
w), 1090 (m), 1073 (w), 1023 (w), 1009 (m), 881 (m), 865 (w, sh.), NaH (60% suspension in mineral oil, 13 mg, 0.534 mmol,
46 (w), 821 (m), 729 (w), 701 (w), 565 (w), 545 (w), 529 (w), 497 2.5 equiv.) and put under an atmosphere of argon. THF (2 mL) was
CDCl
3
4
3
1
8
(137 g, 58%) as an amorphous solid. P NMR (162 MHz, [D ]-
(
8
–1
+
(w) cm . MS (APCI): m/z = 615 [M + H] , 469, 451, 366, 301,
added, and the stirred suspension was cooled to 0 °C. A solution
P [M + H] 615.2664; of (+)-(P,3S)-18 (100 mg, 0.213 mmol) in THF (2 mL) was added
dropwise. The reaction mixture was stirred at 0 °C for 10 min then
+
252. HRMS (APCI): calcd. for C40
H
40
O
4
found 615.2642.
warmed slowly to room temperature and stirred for 3 h. Sub-
sequently, the mixture was cooled again to 0 °C and phosphoroch-
(
+)-(P,3S)-14-(Dibenzo[d,f][1,3,2]dioxaphosphepin-6-yloxy)-3-
methyl-4-(4-methylphenyl)-1,3,6,7-tetrahydrobenzo[c]benzo[5,6]phen- loridite 22 (135 mg, 0.320 mmol, 1.5 equiv.) in THF (1.5 mL) was
anthro[4,3-e]oxepine (25): A solution of 2,2Ј-biphenol (10 g,
.054 mol) in phosphorus trichloride (30 mL) was heated at reflux
for 2 h. The excess amount of phosphorus trichloride was distilled
off. The residue was purified by vacuum distillation (b.p. 183–
added dropwise. The reaction mixture was warmed slowly to room
temperature over 2 h, after which triethylamine (300 μL) was
added. The solvent was removed in vacuo and the crude product
was purified by chromatography on silica gel (cyclohexane/diethyl
0
1
86 °C at 0.7 Torr) to give phosphorochloridite 21 (10.10 g, 75%)
ether, 90:10 with 3% Et N) to afford (+)-(P,3S)-26 (82 mg, 45%)
as an amorphous solid. [α]5 = +98 (c = 0.05, CH Cl ). H NMR
89 2 2
3
31
22
1
as an oil. P NMR (162 MHz, [D
8
]toluene): δ = 180.64 (s) ppm.
A Schlenk flask was charged with NaH (60% suspension in mineral
oil, 43 mg, 1.79 mmol, 4.0 equiv.) and put under an atmosphere of
argon. THF (1 mL) was added, and the stirred suspension was co-
oled to 0 °C. A solution of (+)-(P,3S)-18 (125 mg, 0.267 mmol) in
THF (2 mL) was added dropwise. The reaction mixture was stirred
at 0 °C for 15 min then warmed slowly to room temperature and
stirred for 3 h. Subsequently, the mixture was cooled again to 0 °C
and phosphorochloridite 21 (107 mg, 0.427 mmol, 1.6 equiv.) in
THF (1 mL) was added dropwise. The reaction mixture was
warmed slowly to room temperature over 2 h, after which triethyl-
amine (300 μL) was added. The solvent was removed in vacuo, and
the crude product was purified by chromatography on silica gel
(500 MHz, CDCl ): δ = 0.62 (d, J = 7.1 Hz, 3 H), 1.06 (s, 18 H),
2.44 (s, 3 H), 2.58 (m, 2 H), 2.64 (m, 2 H), 3.81 (s, 3 H), 4.00 (s, 3
3
H), 4.82 (d, J = 11.3 Hz, 1 H), 5.09 (d, J = 11.3 Hz, 1 H), 5.38 (q,
J = 7.1 Hz, 1 H), 6.69 (d, J = 3.1 Hz, 1 H), 6.75 (ddd, J = 8.4, 6.8,
1.4 Hz, 1 H), 6.82 (d, J = 3.1 Hz, 1 H), 7.02 (ddd, J = 8.0, 6.8,
1.2 Hz, 1 H), 7.03 (br. t, J = 7.4 Hz, 1 H), 7.09 (br. d, J = 7.3 Hz,
1 H), 7.21 (dd, J = 7.5, 1.0 Hz, 1 H), 7.25 (s, 1 H), 7.28 (m, 1 H),
7.28 (br. dq, J = 8.4, 1.0, 1.0, 1.0 Hz, 1 H), 7.29 (br. d, J = 8.0 Hz,
1 H), 7.36 (d, J = 8.1 Hz, 1 H), 7.38 (m, 1 H), 7.49 (br. d, J =
1
3
8.1 Hz, 1 H) ppm. C NMR (126 MHz, CDCl ): δ = 21.20 (q),
3
22.75 (q), 30.80 (t), 30.83 (t), 30.90 (q), 34.98 (s), 35.17 (s), 55.58
(q), 55.77 (q), 67.93 (t), 72.26 (d), 112.17 (d), 112.93 (d), 114.08
(q), 114.53 (d), 123.19 (d), 123.61 (d), 125.36 (d), 125.36 (d), 125.99
(d), 127.08 (d), 127.36 (d), 128.33 (d), 128.39 (s), 128.93 (2 d),
129.32 (d), 131.96 (s), 132.38 (s), 132.39 (s), 134.39 (s), 134.66 (s),
135.12 (s), 136.60 (s), 138.17 (s), 138.77 (s), 138.86 (s), 139.18 (s),
(
2
3
cyclohexane/diethyl ether, 90:10 + 3% Et N) to afford (+)-(P,3S)-
22
5 (133 mg, 73%) as an amorphous solid. [α]589 = +264 (c = 0.16,
1
2 2 3
CH Cl ). H NMR (500 MHz, CDCl ): δ = 1.27 (d, J = 7.1 Hz, 3
H), 3.06 (s, 3 H), 3.30–3.41 (m, 2 H), 5.40 (d, J = 11.5 Hz, 1 H),
.68 (d, J = 11.5 Hz, 1 H), 5.94 (q, J = 7.1 Hz, 1 H), 7.27 (m, 1
H), 7.27 (dd, J = 8.2, 1.7 Hz, 1 H), 7.38 (ddd, J = 8.5, 6.8, 1.4 Hz,
3
1
5
141.02 (s), 142.37 (s), 142.81 (s), 155.34 (s), 155.81 (s) ppm.
P
NMR (162 MHz, CDCl ): δ = 142.85 (s) ppm. IR (CCl ): ν˜ = 3052
3
4
1
1
H), 7.61 (dd, J = 8.2, 7.5 Hz, 1 H), 7.67 (ddd, J = 8.1, 6.8, 1.2 Hz,
H), 7.73 (m, 1 H), 7.78 (m, 2 H), 7.78 (d, J = 8.6 Hz, 1 H), 7.79
(w), 2835 (w), 1590 (m), 1513 (w), 1481 (w), 1463 (m), 1447 (m),
1436 (m), 1411 (s), 1394 (w), 1380 (w, sh.), 1364 (m), 1203 (vs),
–
1
(dd, J = 7.5, 1.7 Hz, 1 H), 7.81 (ddt, J = 8.5, 1.2, 0.5, 0.5 Hz, 1 H),
1187 (m), 1088 (m), 1032 (m), 1024 (w), 883 (s), 860 (m) cm . MS
+
7
1
0
.89 (s, 1 H), 7.92 (m, 1 H), 7.96 (m, 2 H), 8.05 (dd, J = 7.6, 1.7 Hz, (APCI): m/z = 855 [M + H] , 745, 583, 451, 421, 405, 391, 279.
+
H), 8.19 (ddt, J = 8.1, 1.4, 0.6, 0.6 Hz, 1 H), 8.25 (dt, J = 8.6,
56 56 6
HRMS (APCI): calcd. for C H O P [M + H] 855.3815; found
.6, 0.6 Hz, 1 H) ppm. 13C NMR (126 MHz, CDCl
): δ = 21.20
3
855.3803.
(q), 22.50 (q), 30.36 (t), 30.42 (t), 67.82 (t), 72.40 (d), 119.40 (d),
1
1
1
1
1
1
21.48 (d), 122.05 (d), 123.63 (d), 123.71 (d), 124.67 (d), 124.89 (d),
25.39 (d), 125.44 (d), 127.11 (d), 127.73 (d), 128.85 (d), 128.91 (s), Rh(acac)(CO)
29.00 (d), 129.09 (d), 129.47 (d), 129.83 (d), 131.83 (s), 132.34 (s), (2 mL) in a vial was added ligand (+)-(P,3S)-25 (0.019 mmol,
Typical Procedure for Hydroformylation: To
a solution of
2
(1 mg, 0.004 mmol, 1 mol-%) in dichloromethane
32.70 (s), 133.30 (s), 134.25 (s), 135.43 (s), 136.69 (s), 138.66 (s),
38.98 (s), 139.46 (s), 140.80 (s), 141.24 (s), 148.00 (s), 148.62 (s),
5 mol-%). The solution was stirred for 5 min and then charged with
styrene 27 (40 mg, 0.384 mmol) and dodecane (20 mg, 0.117 mmol,
49.14 (s) ppm. 31P NMR (162 MHz, CDCl
): δ = 142.33 (s) ppm. 30 mol-%). The vial was transferred to an autoclave, pressurized
): ν˜ = 3070 (m, sh.), 3053 (m), 1620 (w), 1601 (m), 1586 with CO (10 bar) and H (10 bar), and heated to 50 °C for 20 h.
m), 1576 (m), 1568 (m), 1513 (s), 1500 (s), 1476 (vs), 1468 (s), 1437 Then the autoclave was cooled down to room temperature, de-
3
IR (CCl
(
4
2
Eur. J. Org. Chem. 2011, 3849–3857
© 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
3855

P. Eilbracht, I. G. Stará, I. Starý et al.
FULL PAPER
pressurized, flushed with argon, and opened to obtain a sample of
product 30 for GC analysis.
166–176; c) A. Rajca, M. Miyasaka in Functional Organic Ma-
terials (Eds.: T. J. J. Müller, U. H. F. Bunz), Wiley-VCH,
Weinheim, 2007, pp. 547–581; d) A. Urbano, Angew. Chem. Int.
Ed. 2003, 42, 3986–3989; e) H. Hopf in Classics in Hydrocarbon
Chemistry: Syntheses, Concepts, Perspectives, Wiley-VCH,
Weinheim, 2000, pp. 323–330; f) T. J. Katz, Angew. Chem. Int.
Ed. 2000, 39, 1921–1923; g) G. Oremek, U. Seiffert, A. Janecka,
Chem.-Ztg. 1987, 111, 69–75; h) F. Vögtle, Fascinating Mole-
cules in Organic Chemistry, Wiley, New York, 1992, pp. 156–
Typical Procedure for Asymmetric Allylic Amination: A Schlenk
flask was charged with [Ir(cod)Cl] (6.4 mg, 0.010 mmol, 1 mol-%),
2
ligand (+)-(P,3S)-24 (0.020 mmol, 2 mol-%), and flushed with ar-
gon. The materials were dissolved in THF (0.3 mL), and the reac-
tion mixture was stirred at 50 °C for 30 min. Benzylamine (135 μL,
1.230 mmol, 1.26 equiv.) was added by syringe. The reaction mix-
180; i) K. P. Meurer, F. Vögtle, Top. Curr. Chem. 1985, 127, 1–
76; j) W. H. Laarhoven, W. J. C. Prinsen, Top. Curr. Chem.
1984, 125, 63–130.
ture was stirred at room temperature for 5 min, and then a solution
of cinnamyl methyl carbonate (33; 188 mg, 0.978 mmol) in THF
(0.3 mL) was added dropwise. The reaction mixture was warmed
[
12] Helicenes were also used in stoichiometric asymmetric reac-
tions as chiral auxiliaries (in diastereoselective reduction of α-
keto esters, ene reaction, and atrolactic synthesis) or chiral rea-
gents (in hydroxyamination and epoxidation of olefins). For
more details, see: a) B. Ben Hassine, M. Gorsane, J. Pecher,
R. H. Martin, Bull. Soc. Chim. Belg. 1987, 96, 801–808; b) B.
Ben Hassine, M. Gorsane, F. Geerts-Evrard, J. Pecher, R. H.
Martin, D. Castelet, Bull. Soc. Chim. Belg. 1986, 95, 557–566;
c) B. Ben Hassine, M. Gorsane, J. Pecher, R. H. Martin, Bull.
Soc. Chim. Belg. 1986, 95, 547–556; d) B. Ben Hassine, M. Gor-
sane, J. Pecher, R. H. Martin, Bull. Soc. Chim. Belg. 1985, 94,
to 50 °C and stirred for 2 d. Subsequently, the solvent was removed
in vacuo. 1H NMR spectroscopic analysis of the residual crude
mixture indicated the ratio of branched 35a to linear 35b to be
Ͼ97:3. The crude product was then purified by chromatography on
silica gel (cyclohexane/ethyl acetate, 90:10 + 0.5% Et N) to afford
3
branched 35a (64 mg, 25%) as an oil.
Supporting Information (see footnote on the first page of this arti-
cle): The chemical shifts of the phosphorus atoms in chlorophos-
1
13
31
phites 19–22 and phosphites 23–26; H, C, and P NMR spectra
of (+)-(P,3S)-23–26; GC or HPLC analyses of racemic and enanti-
oenriched 30a–32a, 35a–38a on chiral columns.
759–769; e) B. Ben Hassine, M. Gorsane, J. Pecher, R. H. Mar-
tin, Bull. Soc. Chim. Belg. 1985, 94, 597–603.
13] A. Terfort, H. Görls, H. Brunner, Synthesis 1997, 79–86.
14] M. T. Reetz, E. W. Beuttenmüller, R. Goddard, Tetrahedron
Lett. 1997, 38, 3211–3214.
[
[
Acknowledgments
[
[
[
[
15] M. T. Reetz, S. Sostmann, J. Organomet. Chem. 2000, 603, 105–
109.
This research was supported by the Czech Science Foundation un-
der Grant No. 203/09/1766, by the Ministry of Education, Youth
and Sports of the Czech Republic under Project No. LC512 (the
Centre for Biomolecules and Complex Molecular Systems), and by
the Institute of Organic Chemistry and Biochemistry, Academy of
Sciences of the Czech Republic (this work is part of the Research
Project Z4 055 0506).
16] I. Sato, R. Yamashima, K. Kadowaki, J. Yamamoto, T. Shib-
ata, K. Soai, Angew. Chem. Int. Ed. 2001, 40, 1096–1098.
17] T. Kawasaki, K. Suzuki, E. Licandro, A. Bossi, S. Maiorana,
K. Soai, Tetrahedron: Asymmetry 2006, 17, 2050–2053.
18] S. D. Dreher, T. J. Katz, K.-C. Lam, A. L. Rheingold, J. Org.
Chem. 2000, 65, 815–822.
[19] D. Nakano, M. Yamaguchi, Tetrahedron Lett. 2003, 44, 4969–
4971.
[
20] a) J. Chen, N. Takenaka, Chem. Eur. J. 2009, 15, 7268–7276;
b) N. Takenaka, R. S. Sarangthem, B. Captain, Angew. Chem.
Int. Ed. 2008, 47, 9708–9710; c) J. Chen, B. Captain, N. Tak-
enaka, Org. Lett. 2011, 13, 1654–1657.
[
1] E. N. Jacobsen, A. Pfaltz, H. Yamamoto (Eds.), Comprehensive
Asymmetric Catalysis, Springer, Berlin, 1999 along with Sup-
plements 1 and 2 (2004).
2] Q.-L. Zhou (Ed.), Privileged Chiral Ligands and Catalysts,
Wiley, Hoboken, 2011.
[
[
[
[
[
[
[
[
21] N. Takenaka, J. Chen, B. Captain, R. S. Sarangthem, A. Chan-
drakumar, J. Am. Chem. Soc. 2010, 132, 4536–4537.
3] For “privileged chiral catalysts”, see T. P. Yoon, E. N. Ja-
cobsen, Science 2003, 299, 1691–1693.
4] a) I. C. Lennon, C. J. Pilkington, Synthesis 2003, 1639–1642; b)
M. J. Burk, Acc. Chem. Res. 2000, 33, 363–372; c) M. J. Burk, J.
Am. Chem. Soc. 1991, 113, 8518–8519.
22] M. Sˇ ámal, J. Mí sˇ ek, I. G. Stará, I. Starý, Collect. Czech. Chem.
Commun. 2009, 74, 1151–1159.
23] M. R. Crittall, H. S. Rzepa, D. R. Carbery, Org. Lett. 2011, 13,
1250–1253.
24] M. T. Reetz, G. Mehler, Angew. Chem. Int. Ed. 2000, 39, 3889–
[
5] a) R. Noyori, Angew. Chem. Int. Ed. 2002, 41, 2008–2022; b)
A. Miyashita, A. Yasuda, H. Takaya, K. Toriumi, T. Ito, K.
Toriumi, T. Ito, J. Am. Chem. Soc. 1980, 102, 7932–7934.
6] a) H.-U. Blaser, B. Pugin, F. Spindler, M. Thommen, Acc.
Chem. Res. 2007, 40, 1240–1250; b) R. G. Arrayás, J. Adrio,
J. C. Carretero, Angew. Chem. Int. Ed. 2006, 45, 7674–7715; c)
H. U. Blaser, W. Brieden, B. Pugin, F. Spindler, M. Studer, A.
Togni, Top. Catal. 2002, 19, 3–16; d) A. Togni, Chimia 1996,
3890.
25] C. Claver, E. Fernandez, A. Gillon, K. Heslop, D. J. Hyett, A.
Martorell, A. G. Orpen, P. G. Pringle, Chem. Commun. 2000,
961–962.
[
[26] M. van den Berg, A. J. Minnaard, E. P. Schudde, J. van Esch,
A. H. M. de Vries, J. G. de Vries, B. L. Feringa, J. Am. Chem.
Soc. 2000, 122, 11539–11540.
5
0, 86–93.
7] a) E. M. McGarrigle, D. G. Gilheany, Chem. Rev. 2005, 105,
563–1602; b) W. Zhang, J. L. Loebach, S. R. Wilson, E. N.
[27] Helicenes are defined as polycyclic aromatic compounds con-
sisting of all-ortho-fused benzene or heteroarene (e.g., thio-
phene) rings. However, modification of the helicene skeleton
can go further, displacing one or more five/six-membered ar-
enes by five/six/seven-membered, partially saturated car-
bocycles or heterocycles. Such molecules can be referred to as
helicene-like structures, as they usually keep the molecular
shape of the parent helicenes. For representative examples, see:
a) A. Andronova, F. Szydlo, F. Teplý, M. Tobrmanová, A. Vo-
[
1
Jacobsen, J. Am. Chem. Soc. 1990, 112, 2801–2803.
[
[
[
[
8] J. F. Teichert, B. L. Feringa, Angew. Chem. Int. Ed. 2010, 49,
2486–2528.
9] K. Mikami, M. Lautens (Eds.), New Frontiers in Asymmetric
Catalysis, Wiley, Hoboken, 2007.
10] A. Börner (Ed.), Phosphorus Ligands in Asymmetric Catalysis,
Wiley-VCH, Weinheim, 2008.
ˇ
lot, I. G. Stará, I. Starý, L. Rulí sˇ ek, D. Saman, J. Cva cˇ ka, P.
11] For selected reviews, see: a) I. G. Stará, I. Starý in Science of
Synthesis (Eds: J. S. Siegel, Y. Tobe), Thieme, Stuttgart, 2010,
vol. 45b, pp. 885–953; b) I. Starý, I. G. Stará in Strained Hydro-
carbons (Ed.: H. Dodziuk), Wiley-VCH, Weinheim, 2009, pp.
Fiedler, P. Vojtí sˇ ek, Collect. Czech. Chem. Commun. 2009, 74,
189–215; b) P. Sehnal, Z. Krausová, F. Teplý, I. G. Stará, I.
ˇ
Starý, L. Rulí sˇ ek, D. Saman, I. Císa rˇ ová, J. Org. Chem. 2008,
73, 2074–2082; c) I. Starý, I. G. Stará, Z. Alexandrová, P.
3856
www.eurjoc.org
© 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2011, 3849–3857

Helicene-Based Phosphite Ligands in Asymmetric Transition-Metal Catalysis
ˇ
Sehnal, F. Teplý, D. Saman, L. Rulí sˇ ek, Pure Appl. Chem. 2006,
8, 495–499; d) I. G. Stará, Z. Alexandrová, F. Teplý, P. Sehnal,
R. I. McDonald, G. W. Wong, R. P. Neupane, S. S. Stahl, C. R.
Landis, J. Am. Chem. Soc. 2010, 132, 14027–14029; k) A. L.
Watkins, C. R. Landis, J. Am. Chem. Soc. 2010, 132, 10306–
10317.
7
ˇ
I. Starý, D. Saman, M. Bud eˇ sˇ ínský, J. Cva cˇ ka, Org. Lett. 2005,
7
, 2547–2550; e) I. G. Stará, Z. Alexandrová, F. Teplý, P.
ˇ
Sehnal, I. Starý, D. Saman, M. Bud eˇ sˇ ínský, J. Cva cˇ ka, Collect.
Czech. Chem. Commun. 2003, 68, 917–930; f) I. G. Stará, I.
[37] Absolute configurations of products 30a, 32a, and 35a were
assigned by comparing the sign of their optical rotation with
data known from the literature: a) For (+)-(S)-30a, see: T. Hay-
ashi, M. Konishi, M. Fukushima, T. Mise, M. Kagotani, M.
Tajika, M. Kumada, J. Am. Chem. Soc. 1982, 104, 180–186; b)
for (–)-(S)-32a, see: N. Sakai, S. Mano, K. Nozaki, H. Takaya,
J. Am. Chem. Soc. 1993, 115, 7033–7034; c) for (+)-(S)-35a,
see: J. S. Yadav, A. Bandyopadhyay, B. V. S. Reddy, Tetrahedron
Lett. 2001, 42, 6385–6388. Optical rotation of (R)- or (S)-
enantiomers of 31a and 36a–38a have not been published.
[38] The enantiomeric excess value of 31a was determined by chiral
GC analysis of the corresponding alcohol: a) Y. Yan, X. Zhang,
J. Am. Chem. Soc. 2006, 128, 7198–7202; b) U. Nettekoven,
P. C. J. Kamer, M. Widhalm, P. W. N. M. van Leeuwen, Orga-
nometallics 2000, 19, 4596–4607.
ˇ
ˇ
Starý, A. Kollárovi cˇ , F. Teplý, S. Vysko cˇ il, D. Saman, Tetrahe-
dron Lett. 1999, 40, 1993–1996; g) I. G. Stará, I. Starý, A.
Kollárovi cˇ , F. Teplý, D. Saman, M. Tichý, J. Org. Chem. 1998,
3, 4046–4050.
ˇ
6
ˇ
ˇ
[
[
28] F. Teplý, I. G. Stará, I. Starý, A. Kollárovi cˇ , D. Saman, S. Vys-
ko cˇ il, P. Fiedler, J. Org. Chem. 2003, 68, 5193–5197.
29] J. Mí sˇ ek, F. Teplý, I. G. Stará, M. Tichý, D. Saman, I. Císa-
ˇ
rˇ ová, P. Vojtí sˇ ek, I. Starý, Angew. Chem. Int. Ed. 2008, 47,
3188–3191.
[
[
[
[
30] C. Vallée, Y. Chauvin, J.-M. Basset, C. C. Santini, J.-C. Gal-
land, Adv. Synth. Catal. 2005, 347, 1835–1847.
31] I. M. Malkowsky, M. Nieger, O. Kataeva, S. R. Waldvogel,
Synthesis 2007, 773–778.
32] N. L. H. L. Broeders, L. H. Koole, H. M. Buck, J. Am. Chem.
Soc. 1990, 112, 7475–7482.
[39] For reviews, see: a) G. Helmchen, A. Dahnz, P. Dübon, M.
Schelwies, R. Weihofen, Chem. Commun. 2007, 675–691; b) G.
Helmchen in Iridium Complexes in Organic Synthesis (Eds.:
L. A. Oro, C. Claver), Wiley-VCH, Weinheim, 2009, pp. 211–
250; c) R. Takeuchi, S. Kezuka, Synthesis 2006, 3349–3366; d)
H. Miyabe, Y. Takemoto, Synlett 2005, 1641–1655.
[40] a) F. Lopez, T. Ohmura, J. F. Hartwig, J. Am. Chem. Soc. 2003,
125, 3426–3427; b) T. Ohmura, J. F. Hartwig, J. Am. Chem.
Soc. 2002, 124, 15164–15165.
[41] a) J. A. Raskatov, S. Spiess, C. Gnamm, K. Brödner, F. Rom-
inger, G. Helmchen, Chem. Eur. J. 2010, 16, 6601–6615; b) D.
Markovi c´ , J. F. Hartwig, J. Am. Chem. Soc. 2007, 129, 11680–
11681; c) A. Leitner, S. Shekhar, M. J. Pouy, J. F. Hartwig, J.
Am. Chem. Soc. 2005, 127, 15506–15514; d) C. A. Kiener, C.
Shu, C. Incarvito, J. F. Hartwig, J. Am. Chem. Soc. 2003, 125,
14272–14273.
33] a) A. Granata, D. S. Argyropoulos, J. Agric. Food Chem. 1995,
4
3, 1538–1544; b) A. Zwierzak, Can. J. Chem. 1967, 45, 2501–
2512.
[
34] P. W. N. M. Van Leeuwen, C. Claver, Rhodium-Catalysed Hy-
droformylation, Kluwer Academic, Dordrecht, 2000.
[
35] For reviews, see: a) A. Gual, C. Godard, S. Castillón, C. Claver,
Tetrahedron: Asymmetry 2010, 21, 1135–1146; b) J. Klosin,
C. R. Landis, Acc. Chem. Res. 2007, 40, 1251–1259 and refer-
ences cited therein; c) B. Breit, W. Seiche, Synthesis 2001, 1–
36.
[
36] For recent examples, see: a) A. L. Watkins, C. R. Landis, Org.
Lett. 2011, 13, 164–167; b) X. Zhang, B. Cao, S. Yu, X. Zhang,
Angew. Chem. Int. Ed. 2010, 49, 4047–4050; c) X. Zhang, B.
Cao, Y. Yan, S. Yu, B. Ji, X. Zhang, Chem. Eur. J. 2010, 16,
871–877; d) G. M. Noonan, C. J. Cobley, T. Lebl, M. L. Clarke,
[42] J. Lehmann, G. C. Lloyd-Jones, Tetrahedron 1995, 51, 8863–
Chem. Eur. J. 2010, 16, 12788–12791; e) G. M. Noonan, D.
Newton, C. J. Cobley, A. Suárez, A. Pizzano, M. L. Clarke,
Adv. Synth. Catal. 2010, 352, 1047–1054; f) S. Chercheja, S. K.
Nadakudity, P. Eilbracht, Adv. Synth. Catal. 2010, 352, 637–
8874.
[43] a) B. P. Bondzic, A. Farwick, J. Liebich, P. Eilbracht, Org. Bio-
mol. Chem. 2008, 6, 3723–3731; b) C. Welter, R. M. Moreno,
S. Streiff, G. Helmchen, Org. Biomol. Chem. 2005, 3, 3266–
3268.
643; g) A. Gual, C. Godard, S. Castillón, C. Claver, Adv. Synth.
Catal. 2010, 352, 463–477; h) J. Mazuela, O. Pàmies, M. Dié-
guez, L. Palais, S. Rosset, A. Alexakis, Tetrahedron: Asymmetry
[44] A. M. Schmidt, P. Eilbracht, J. Org. Chem. 2005, 70, 5528–
5535.
2
010, 21, 2153–2157; i) A. D. Worthy, C. L. Joe, T. E. Light-
Received: February 24, 2011
Published Online: May 12, 2011
burn, K. L. Tan, J. Am. Chem. Soc. 2010, 132, 14757–14759; j)
Eur. J. Org. Chem. 2011, 3849–3857
© 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
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