J. Huang et al. / Tetrahedron Letters 46 (2005) 7831–7834
7833
Further investigation of the reaction using ligands 3–8
showed that pressure and temperature only slightly
affect the enantioselectivity in most cases, although the
reaction rates varied (Table 1). For example, when
TangPhos (8) was used, the eeÕs decreased from 92%,
To demonstrate the application of the asymmetric hyd-
roformylation, the synthesis of R-exo-norbornylamine
was carried out: The crude hydroformylated product
of norbornylene in toluene was directly oxidized to the
carboxylic acid (21). Amide (22) was formed via acid
chloride and quenching with ammonia. Hofmann reac-
tion of 22 gave the corresponding exo-norbornylamine
9
0%, and 87% as temperature/pressure increased from
1
20 psi/23 °C, 500 psi/50 °C, and 100 psi/60 °C, respec-
1
2
tively. The rest of the ligands behaved irregularly toward
the changes of temperature and pressure. When Tang-
Phos (8) was used at room temperature, the eeÕs were
consistently 92–93% for experiments where the pressures
were varied from 30 psi up to 500 psi. Among several
solvents tested, all gave the same ee of the product,
but the less polar toluene was superior in terms of reac-
tion rate. This solvent effect is probably due to the com-
petitive association to the active catalytic site of Rh
complex between the substrate and the more polar sol-
vents. In practice, the catalyst precursor was generated
tosylate (24) using KoserÕs reagent (PhI(OH)OTs, 23)
in high chemical yield (overall 71% from norbornylene)
with full retention of enantiomeric purity. This process
provides a convenient and scalable access to the highly
enantiomerically pure exo-norbornylamine that is other-
1
3
wise difficult to obtain (Scheme 1).
In summary, a catalytic system for highly enantio-
selective hydroformylation of [2.2.1]-bicyclic olefins
was discovered based on ligand screening. When Tang-
Phos was used, eeÕs in the range of 56–93% were
observed. Further mechanistic studies are planned and
insights gained will be used to guide the design of more
8
in situ and used directly. It was found that the ratio
of Rh/L from anywhere 1 to 2 did not change the out-
come of the reaction.
1
4
efficient catalysts.
A variety of olefins were tested with the current catalytic
protocol utilizing three ligands (5, 7, and 8). Interest-
References and notes
. (a) Agbossou, F.; Carpentier, J.-F.; Mortreux, X. Chem.
Rev. 1995, 95, 2485; (b) Gladiali, S.; Bayon, J. C.; Claver,
C. Tetrahedron: Asymmetry 1995, 6, 1453; (c) Nozaki, K.;
Ojima, I. In Catalytic Asymmetric Catalysis, 2nd ed.;
Ojima, I., Ed.; Wiley-VCH: New York, 2000; p 429.
. Consiglio, G.; Nefkens, S. C. A.; Borer, A. Organomet-
allics 1991, 10, 2046.
3. (a) Sakai, S.; Mano, S.; Nozaki, K.; Takaya, H. J. Am.
Chem. Soc. 1993, 115, 7033; (b) Nozaki, K.; Sakai, N.;
Nanno, T.; Higashijima, T.; Mano, S.; Horuchi, T.;
Takaya, H. J. Am. Chem. Soc. 1997, 119, 3313; (c)
Nozaki, K.; Itoi, Y.; Shibahara, F.; Shirakawa, E.; Ohta,
T.; Takaya, H.; Hiyama, T. J. Am. Chem. Soc. 1998, 120,
ingly, this series of C -symmetric ligands seemed to only
2
1
favor the [2.2.1]-bicyclic olefins under relatively mild
conditions. For example, [2.2.1]-bicyclic olefins (Table
2
) gave quantitative formation of the corresponding
aldehyde in moderate to excellent eeÕs (55–92% ee)
9
and exo-selectivity. For compounds, which have no
2
functionality, a flat aryl ring or an endo moiety gave
exclusively exo-products. One exception is the hydro-
formylation of the exo-anhydride (13), which gave
1
0
approximately 25/75 exo/endo selectivity. Moderate
eeÕs for meso bicyclic hydrazine (Cbz- (15) and Boc-
(
17) derivatives) are probably due to the interference
of the flexible protective groups. The current results
are very attractive because these hydrazine products
can be useful building blocks after reductive cleavage
4
051; (d) Nozaki, K.; Matsuo, T.; Shibahara, F.; Hiyama,
T. Adv. Synth. Catal. 2001, 343, 61.
4
. In the process of preparation of this manuscript, a
communication on asymmetric hydroformylation of ole-
fins appeared using newly designed ligands: Clark, T. P.;
Landis, C. R.; Freed, S. L.; Klosin, J.; Abboud, K. A.
J. Am. Chem. Soc. 2005, 127, 5040.
1
1
of the N–N bond. It is worth noting that asymmetric
hydroformylation of the benchmark styrene was very
slow and showed lower enantioselectivities under the
same conditions. Much harsher conditions (e.g.,
8
00 psi/70 °C, 120 h) were employed for styrene but still
5. (a) Parrinello, G.; Deschenaux, R.; Stille, J. K. J. Org.
Chem. 1986, 51, 4189; (b) Parrinello, G.; Stille, J. K.
J. Am. Chem. Soc. 1987, 109, 7122; (c) Lu, S.; Li, X.;
Wang, A. Catal. Today 2000, 63, 531.
no satisfactory results were obtained (44% conversion
and 76% ee). Also, the product was not detected for
the closely related [2.2.2]-bicyclic system under the cur-
rent conditions.
1
c
6
. BINAPHOS, the well-known chiral ligand for asymmet-
ric hydroformylation, gave only 70% ee under the same
conditions.
7
. Tang, W.; Zhang, X. Angew. Chem., Int. Ed. 2002, 41,
TangPhos
1
612.
Rh(acac)(CO)2
OHC
3
1
8
.
P NMR studies showed instant substitution of phos-
Toluene, CO/H2
6
phine for CO in benzene-d .
1
2
9. The absolute structure of 2 was determined by the
Cat.TEMPO
NaClO2
comparison of optical rotation of the corresponding acid
with the literature. The structure of 10 was determined
1
) (COCl) , DMF, CH Cl
2
2
2
5b
HO2C
by X-ray analysis of single crystal. The structures of the
rest of the aldehydes were proposed by analogy of 2 and
Toluene,
2
) NH4OH
9%
9
0% over two steps
21
9
1
0.
PhI(OH)OTs (23)
0%
H2NOC
TsOH N
10. Even when PCy was used to prepare the racemic
3
3
8
reference, the same exo/endo distribution was observed.
The assignments are arbitrary.
2
2
24
1
1. Asymmetric hydroboration of such substrates was
reported recently: (a) Luna, A. P.; Bonin, M.; Micouin,
Scheme 1.
Huang, Jinkun
