New Applications of Camphor-Derived P,N-Ligands for Asymmetric Pd- and Ir-Catalyzed Reactions

Article abstract of DOI:10.1055/s-2003-42067

Ir-catalyzed asymmetric hydroboration of bicyclic hydrazine 4 in the presence of chiral ligand 1a, leads to bicyclic alcohol 5 after oxidative workup in good yield (76%) and moderate enantioselectivity (71% ee).

Full text of DOI:10.1055/s-2003-42067

2240
LETTER
New Applications of Camphor-Derived P,N-Ligands for Asymmetric Pd- and
Ir-Catalyzed Reactions
New
A
pplicatio
a
ns of Camp
n
hor-Derived
a
P,N-Liga
n
s
ds ri Bunlaksananusorn,a Alejandro Pérez Luna,b Martine Bonin,*b Laurent Micouin,*b Paul Knochel*a
a
Departement Chemie, Ludwig-Maximilians-Universität München, Butenandtstrasse 5–13, Haus F, 81377 München, Germany
Fax +49(89)218077680; E-mail: Paul.Knochel@cup.uni-muenchen.de
b
Laboratoire de Chimie Thérapeutique UMR 8638 associée au CNRS et à l’Université René Descartes, Faculté des Sciences Pharmaceu-
tiques et Biologiques, 4, av. de l’Observatoire, 75270 Paris Cedex 06, France
Received 19 August 2003
PPh2
N
Abstract: Ir-catalyzed asymmetric hydroboration of bicyclic hy-
drazine 4 in the presence of chiral ligand 1a, leads to bicyclic alco-
hol 5 after oxidative workup in good yield (76%) and moderate
enantioselectivity (71% ee).
a
b,c
N
OTf
1a : 70 %
2a
3a : 78 %
Key words: meso-bicyclic hydrazine, Ir-catalyzed hydroboration,
t-BuOK-catalyzed addition, P,N-ligands, asymmetric catalysis
PPh2
N
a
b,c
N
The preparation of new chiral ligands for performing of
metal-catalyzed reactions is an important research field.1
We have recently reported a new synthesis of P,N-ligands
1a,b which proved to be excellent ligands to perform var-
ious iridium-catalyzed hydrogenation reactions.2 Espe-
cially interesting were the hydrogenation of
unfunctionalized stilbenes, which proceeded with up to
96% ee and the first asymmetric iridium-catalyzed asym-
metric hydrogenation of dehydroamino acids with up to
OTf
3b : 85 %
1b : 68 %
2b
Scheme 1 Reagents and conditions: a) Pd(dba)2 (2 mol%), dppf (2
mol%), 2-pyridylzinc bromide, reflux, 12 h; b) t-BuOK (20 mol%),
DMSO, diphenylphosphine oxide, 70 °C, 16 h; c) HSiCl3 (10 equiv),
Et3N (20 equiv), toluene, 120 °C, 16 h.
96.5% ee.2 Herein, we wish to report another application respectively (Scheme 1). We have first investigated the
of ligands 1a,b for the asymmetric hydroboration of asymmetric hydroboration9 of the meso-bicyclic hydra-
meso-bicyclic hydrazines3 as well as the use of ligand zine 4 with catecholborane (CatBH) in the presence of
1a,b for asymmetric Pd-catalyzed allylic substitution.4 [Ir(cod)Cl]2. After H2O2 oxidation the alcohol 5 was ob-
Both ligands 1a,b were readily available from the corre- tained with variable enantioselectivities (Table 1). Bicy-
sponding triflates 2a,b which were obtained from D-(+)- clic alcohol 5 can be readily converted to interesting
camphor and (R)-(+)-nopinone.5 The Pd-catalyzed diaminocyclopentanols of type 6 by a reductive cleavage
Negishi cross-coupling6 of 2a,b with 2-pyridylzinc bro- of the N–N bond and subsequent benzoylation
mide furnished the unsaturated pyridines 3a,b in 78–85% (Scheme 2).3b
yield. The addition of diphenylphosphine oxide in NMP
We found that 1a and 1b are effective ligands for the hy-
droboration of meso-hydrazine 4 providing high conver-
sion in short reaction times (4–6 h). Ligand 1a furnished
or DMSO to 3a,b proceeded readily at 70 °C in the
presence of t-BuOK (20 mol%).7
After the reduction of the intermediate phosphine oxides alcohol 5 with a higher enantioselectivity (58% ee) where-
with HSiCl3 and Et3N in toluene (120 °C, 12 h),8 the de- as 1b provided alcohol 5 with 44% ee at 25 °C (Table 1,
sired ligands 1a,b were obtained in 70% and 68% yields, entries 1 and 2). Performing the hydroboration at 0 °C led
HO
PhOCHN
NHCOPh
a
N
CO2Bn
b
N
CO2Bn
*
N
N
CO2Bn
CO2Bn
OH
4
6
5
Scheme 2 Reagents and conditions: a) i) [Ir(cod)Cl]2 (1 mol%), ligands 1a or 1b (2.1 mol%), catecholborane (2 equiv), THF, 0 °C, ii) 30%
H2O2, NaOH, EtOH; b) i) H2, AcOH, Pt (cat), ii) PhCOCl, pyridine.
SYNLETT 2003, No. 14, pp 2240–2242
0
6
.1
1
.2
0
0
3
Advanced online publication: 07.10.2003
DOI: 10.1055/s-2003-42067; Art ID: G21003ST
© Georg Thieme Verlag Stuttgart · New York

LETTER
New Applications of Camphor-Derived P,N-Ligands
2241
Table 1 Enantioselective Ir-Catalyzed Hydroboration of the meso-Hydrazine 4 in the Presence of Ligands1a,b
Entry
L*
Molarity
0.25
0.25
0.25
0.25
0.25
0.25
0.1
Solvent
THF
Temp (°C)
Yield (%)a
%eeb,c
58
1
2
3
4
5
6
7
8
9
1a
25
25
25
–20
25
0
57
1b
THF
67
44
1a
THF
61 (54)c
–
71 (52)d
–
1a
THF
1a
toluene
DME
THF
30
65
1a
63
67
1a
0
56
62
1a
0.6
THF
0
76
71
(R,S)-Josiphos
0.6
THF
0
61
64e
a Yield of analytically pure products.
b The enantioselectivity was determined by chiral HPLC (Chiracel AD: i-PrOH:n-hexane, 20:80, flow: 0.8 mL/min).
c The absolute configuration of the major enantiomer with 1a has been established to be (1S,4R,5R).
d Results in parentheses were obtained using 1 equivalent of CatBH.
e The absolute configuration of the major enantiomer has been established to be (1S,4R,5R).3a
to a further improvement of the enantioselectivity provid- malonate in the presence of [Pd(C3H5)Cl]2 (1–2.5 mol%)
ing alcohol 5 with 71% ee and 61% yield (entry 3). On and the new P,N-ligands 1a,b under standard conditions.
lowering the reaction temperature further (–20 °C), no We found that both ligands gave good enantioselectivi-
significant reaction occurred (entry 4). Using toluene as ties. Thus, the reaction with benzylamine under standard
solvent led to a lower conversion (30% yield) and 65% ee conditions provided the desired allylic amine 8 in 95%
(entry 5) whereas change to DME provided alcohol 5 in yield and 87% ee using the ligand 1b (2 mol%). Similarly,
63% yield and 67% ee (entry 6). In order to improve the substitution with dimethylmalonate provided the expected
reaction yield we increased the concentration (compare product 9 in the presence of ligand 1a (5 mol%) in 75%
entries 3, 7 and 8) and obtained our best result with a 0.6 yield and 96% ee (Scheme 3).
M solution of bicycle 4 (76% yield, 71% ee, entry 8).
Lowering the amount of CatBH from 2 equivalents to 1
equivalent in order to avoid an eventual uncatalyzed race-
In summary, we have reported the use of the new modular
ligands 1a,b for Ir-catalyzed asymmetric hydroboration
and Pd(0)-catalyzed allylation. Further applications of
mic hydroboration did not succeed and resulted in 54%
this new family of ligands are currently underway in our
yield and 52% ee (entry 3). Compared to previous studies
laboratories.11
using (R,S)-Josiphos,3a the use of the new ligand 1a repre-
sents an improvement of yield and a slight improvement
in enantioselectivity (from 68% ee to 71% ee).
Acknowledgement
We thank the Fonds der Chemischen Industrie for financial support.
We thank the BASF AG, Bayer Chemicals, Chemetall GmbH for
generous gifts of chemicals. APL thanks CNRS and DAAD for a
grant.
Next, we have used ligands 1a,b to perform palladium-
catalyzed allylation reactions. We examined the Pd(0)-
catalyzed amination of 1,3-diphenylallyl acetate 7 with
benzylamine as well as the reaction of 7 with dimethyl
NHBn
OAc
[Pd(C3H5)Cl]2 (1 mol %)
Ph
8 : 95 %; 87 % ee
Ph
+
BnNH2
Ph
Ph
L* 1b (2 mol %)
7
toluene, r.t., 12 h
MeO2C
CO2Me
OAc
[Pd(C3H5)Cl]2 (2.5 mol %)
CH2(CO2Me)2 + Ph
Ph
Ph
9 : 75 %; 96 % ee
Ph
L* 1a (5 mol %), r.t., 1 h
KOAc (5 mol %), CH2Cl2
BSA (3 equiv)
7
Scheme 3
Synlett 2003, No. 14, 2240–2242 © Thieme Stuttgart · New York

2242
T. Bunlaksananusorn et al.
LETTER
(5) McMurry, J. E.; Scott, W. J. Tetrahedron Lett. 1983, 24,
References
979.
(1) (a) Noyori, R. Asymmetric Catalysis in Organic Synthesis;
Wiley: New York, 1994. (b) Ohkuma, T.; Kitamura, M.;
Noyori, R. In Catalytic Asymmetric Synthesis; Ojima, I., Ed.;
Wiley-VCH: Weinheim, 2000, 1. (c) Brown, J. M. In
Comprehensive Asymmetric Catalysis; Jacobsen, E. N.;
Pflatz, A.; Yamamoto, H., Eds.; Springer: Berlin, 1999,
121. (d) Togni, A.; Halterman, R. L. Metallocenes, Vol. 2;
Wiley-VCH: Weinheim, 1998, 685. (e) Beller, M.; Eckert,
M. Angew. Chem. Int. Ed. 2000, 39, 1010; Angew. Chem.
2000, 112, 1027.
(6) (a) Negishi, E.-I. Acc. Chem. Res. 1982, 15, 340.
(b) Negishi, E.-I. In Metal-Catalyzed Cross Coupling
Reactions; Diederich, F.; Stang, P. J., Eds.; Wiley-VCH:
Weinheim, 1998, Chap. 1. (c) Erdik, E. Tetrahedron 1992,
48, 9577.
(7) (a) Rodriguez, A. L.; Bunlaksananusorn, T.; Knochel, P.
Org. Lett. 2000, 2, 3285. (b) Bunlaksananusorn, T.;
Rodriguez, A. L.; Knochel, P. Chem. Commun. 2001, 745.
(c) Bunlaksananusorn, T.; Knochel, P. Tetrahedron Lett.
2002, 43, 5817.
(2) Bunlaksanusorn, T.; Polborn, K.; Knochel, P. Angew. Chem.
Int. Ed. 2003, 42, Angew. Chem. 3941; 2003, 115, 4071.
(3) (a) Pérez Luna, A.; Bonin, M.; Micouin, L.; Husson, H.-P. J.
Am. Chem. Soc. 2002, 124, 12098. (b) Pérez Luna, A.;
Ceschi, M.-A.; Bonin, M.; Micouin, L.; Husson, H.-P.;
Gougeon, S.; Estenne-Bouhtou, G.; Marabout, B.; Sevrin,
M.; George, P. J. Org. Chem. 2002, 67, 3522.
(4) (a) Helmchen, G.; Pfaltz, P. Acc. Chem. Res. 2000, 33, 336.
(b) Togni, A.; Bieler, N.; Burckhardt, C.; Köllner, C.; Pioda,
G.; Schneider, R.; Schnyder, A. Pure Appl. Chem. 1999, 71,
1531. (c) Loiseleur, O.; Hayashi, M.; Keenan, M.; Schmees,
N.; Pflatz, A. J. Organomet. Chem. 1999, 576, 16.
(d) Roesky, P. W. Heteroatom Chem. 2002, 13, 514.
(e) Von Matt, P.; Loiseleur, O.; Koch, G.; Pfaltz, A.;
Lefeber, C.; Feucht, T.; Helmchen, G. Tetrahedron:
Asymmetry 1994, 5, 573. (f) Dawson, G. J.; Williams, J. M.
J.; Coote, S. J. Tetrahedron: Asymmetry 1995, 6, 2535.
(g) Hou, D.-R.; Reibenspies, J.; Colacot, T. J.; Burgess, K.
Chem.–Eur. J. 2001, 7, 5391. (h) Lightfoot, A.; Schnider,
P.; Pfaltz, A. Angew. Chem. 1998, 110, 3047; Angew. Chem.
Int. Ed. 1998, 37, 2897.
(8) Uozumi, Y.; Hayashi, T. J. Am. Chem. Soc. 1991, 113, 9887.
(9) Männig, D.; Nöth, H. Angew. Chem. Int. Ed. 1985, 24, 878;
Angew. Chem. 1985, 97, 854.
(10) Schnyder, A.; Togni, A.; Wiesli, U. Organometallics 1997,
16, 255.
(11) [Ir(COD)Cl]2 (3.4 mg, 5 mol, 1 mol%), ligand 1a (4.2 mg,
11 mol, 2.1 mol%) and 4 (182 mg, 0.5 mmol) were placed
under Ar in a flame-dried Schlenk tube. THF (0.85 mL) was
degassed at –50 °C and added to the mixture at this
temperature. The reaction was stirred at r.t. for 30 min and
cooled to 0 °C. Catecholborane (0.11 mL, 1 mmol) was
added at 0 °C and stirred for 4 h. EtOH (0.5 mL), 3 M NaOH
(0.85 mL) and 30% H2O2 (0.5 mL) were added and stirred at
25 °C for 16 h. The reaction mixture was extracted with
EtOAc (3 × 10 mL). The organic phase was washed with 1
M NaOH (5 × 10 mL), brine, dried over MgSO4 and
concentrated in vacuo. The crude product was purified by
flash chromatography (50% EtOAc in cyclohexane),
affording (1S,4R,5R)-5 (145 mg, 76%, 71% ee) as a colorless
liquid. The ee value was determined by HPLC [Chiralcel
AD, n-hexane–i-PrOH, 80:20, 0.8 mL/min, 220 nm): tr (min)
= 14.6 (1S,4R,5R), 16.4 (1R, 4S,5S)].
Synlett 2003, No. 14, 2240–2242 © Thieme Stuttgart · New York