Enantioselective hydrogenation of olefins with iridium-phosphanodihydrooxazole catalysts

Full text of DOI:10.1002/(SICI)1521-3773(19981102)37:20<2897::AID-ANIE2897>3.0.CO;2-8

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[16] M. Hoffmann, Synthesis 1988, 62 ± 64.
Crabtreeꢁs catalyst, a cationic iridium complex with a mono-
phosphane and pyridine as ligands.[5] Owing to the remarkable
properties of Crabtreeꢁs catalystÐthat is, the ability to
hydrogenate tri- and tetrasubstituted olefins that do not react
with rhodium± or ruthenium ± phosphane catalystsÐwe de-
cided to study complexes 1 as catalysts for the hydrogenation
of unfunctionalized tri- and tetrasubstituted olefins.
Initial experiments with complex 1a led to encouraging
results. Indeed, the hydrogenation of olefin 3 in CH2Cl2 with
4 mol% of 1a [Eq. (1)] gave a good ee value of 75%, albeit
with moderate conversion (78%, Table 1). Lower catalyst
loadings led to decreased conversion. Preliminary kinetic data
[17] a) Y. Kajihara, K. Koseki, T. Ebata, H. Kodama, H. Matsusita, H.
Hashimoto, Carbohydr. Res. 1994, 264, C1 ± C5; b) Y. Kajihara, K.
Koseki, T. Ebata, H. Kodama, H. Matsusita, H. Hashimoto, J. Org.
Chem. 1995, 60, 5732 ± 5735.
[18] For details of the measurement of the Ki values, see ref. [7a].
[19] Commercially available from Aldrich.
[20] Investigation of inhibition with a recombinant rat liver a(2-3)-
sialyltransferase led to similar results: C. Schaub, Dissertation, in
preparation.
Enantioselective Hydrogenation of Olefins with
Iridium ± Phosphanodihydrooxazole Catalysts
Andrew Lightfoot, Patrick Schnider, and
Andreas Pfaltz*
Enantioselective hydrogenation is one of the most powerful
methods in asymmetric catalysis, with the most versatile
catalysts being rhodium± and ruthenium ± diphosphane com-
plexes.[1] However, with a few exceptions, the range of
substrates is still limited to certain classes of olefins bearing
polar groups that can coordinate to the catalyst. Moreover,
even in standard substrate categories derivatives can be found
that give unsatisfactory enantioselectivities. There are only a
few examples of highly enantioselective hydrogenations of
unfunctionalized olefins.[2, 3] The most impressive results in
this field have been obtained by Buchwald, who used
Brintzingerꢁs chiral titanocene complexes.[3] Although high
ee values were obtained, the low catalyst activity required that
a relatively high catalyst loading (ꢀ5 mol%) was used.
Therefore, the search for new catalysts to fill these methodo-
logical gaps continues.
with (E)-1,2-diphenyl-1-propene as substrate shows a large
initial turnover frequency (TOF) of 41 min (olefin: 0.31m,
catalyst: 0.003m), but as the reaction proceeds the TOF
1
Table 1. Enantioselective hydrogenation of 3 with use of catalysts 1a ± f
[Eq. (1)].
Entry
Cat. (mol%)
Conversion [%]
ee [%]
1
2
3
4
5
6
1a (4)
1b (4)
1c (4)
1d (4)
1e (0.3)
1 f (0.3)
78
98
> 99
57
> 99
> 99
75
90
91
97
70
98
decreases to essentially zero within one hour.[6] Deactivation
has also been observed with Crabtreeꢁs catalyst, which is
explained by the formation of inactive hydride-bridged
trimers.[5] In our case the origin of deactivation is not known,
but traces of water appear to enhance this undesired side
reaction. Thus, the addition of molecular sieves to the above
system gave an increased conversion. Alternatively, running
the reaction under strictly anhydrous conditions, using freshly
dried CH2Cl2 (distilled over CaH2) and standard Schlenk
techniques, allows full conversion to be obtained with 4 mol%
of 1a with the same ee value as before. Analytically pure
product 4 was isolated in essentially quantitative yield by
removal of the solvent and distillation.
We recently reported enantioselective hydrogenation of
imines catalyzed by iridium ± phosphanodihydrooxazole com-
plexes of the type 1 with PF6 as anion.[4] The coordination
environment of the iridium center resembles that in
A systematic study of ligands 2a ± d led to a highly
enantioselective catalyst for the hydrogenation of 3 (Table 1).
Thus, replacement of the isopropyl group of ligand 2a with a
tert-butyl group (2b) increased the ee value to 90%. Alter-
natively, replacement of the diphenylphosphanyl group of 2a
with a bis(o-tolyl)phosphanyl group (2c) increased the ee
value to 91%. The combined use of a tert-butyl group and a
bis(o-tolyl)phosphanyl group (2d) led to the highest enantio-
selectivity (97% ee, 57% conversion with 4 mol% of 1d).
Attempts to further increase the conversion by varying the
reaction conditions and introducing additives, such as iodide,
were met with little success.[7] However, replacement of the
PF6 anion with BARF (tetrakis[3,5-bis(trifluoromethyl)phe-
[*] Prof. Dr. A. Pfaltz, Dr. A. Lightfoot, Dr. P. Schnider
Max-Planck-Institut für Kohlenforschung
Kaiser-Wilhelm-Platz 1, D-45470 Mülheim an der Ruhr (Germany)
Fax: (‡49)208-306-2992
E-mail: pfaltz@mpi-muelheim.mpg.de
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nyl]borate, 5)[8] had a dramatic effect on the conversion and
allowed a reduction in the catalyst loading to typically less
than 1 mol%. For example, in a concentrated solution (4m)
(E)-1,2-diphenyl-1-propene was hydrogenated with 70% ee
(>99% conversion) with 0.05 mol% of 1e. Similar weakly
coordinating anions such as 6[9] (0.1 mol% of catatyst,
65% ee, >99% conversion) and 7[10] (0.1 mol% of catalyst,
60% ee, 84% conversion) also gave active catalysts, whereas
all other anions tested (SbF6 , BF4 , BPh4 , TfO , halides)
resulted in much lower activity. Curiously, the catalysts with
BARF as counterion appear to be tolerant of traces of
moisture, and the reaction solutions can be prepared in the air
without specially dried solvents. The initial TOF of the
catalysts with BARF as counterion is even higher than that of
Figure 1. Substrates for hydrogenation with catalysts 1a ± g along with
catalyst amounts, ee values, and conversions.
1
the hexafluorophosphate complexes (70 ± 135 min , olefin 8:
0.31m, 1e: 0.003m).
The most efficient catalyst in this series proved to be 1 f,
which gave high conversions and yields as well as good to
excellent ee values for a number of trisubstituted olefins
(Figure 1). Until now, unfunctionalized olefins of this type
could not be hydrogenated with high enantioselectivity using
other catalysts at such low loading (0.1 ± 0.5 mol%). (Z)-1,2-
Diarylolefins are unreactive towards this catalyst, whereas
both (E)- and (Z)-2-(4-methoxyphenyl)-2-butene (11 and 12,
respectively) gave high conversions but only moderate ee
values. The major enantiomer derived from the Z isomer was
found to be opposite to that obtained for the E isomer. The
allylic acetate 13 was also hydrogenated with high ee value.
Even the tetrasubstituted olefin 14 could be hydrogenated in
high yield, and with remarkable enantioselectivity for this
type of substrate, using complex 1g, which was the best
catalyst in this case. Allyl alcohols and a,b-unsaturated esters,
on the other hand, gave only low conversion with the BARF
complexes 1e and 1 f. For these classes of substrates, the
hexafluorophosphate complex 1d proved to be a superior
catalyst. Thus, 16 was hydrogenated efficiently with 1 mol%
of 1d (96% ee, 95% conversion), demonstrating that these
complexes provide an alternative to the ruthenium/BINAP
system.[11] The same catalyst was successfully employed in the
enantioselective synthesis of the artificial fragrance lilial
(Scheme 1).[12] The allyl alcohol 17[13] was hydrogenated in the
presence of 2 mol% of 1d to give 95% of the corresponding
alcohol with 94% ee. Oxidation with pyridinium chlorochro-
mate (PCC) led to lilial in 56% yield.
Scheme 1. Synthesis of lilial. PCC ˆ pyridinium chlorochromate.
We have demonstrated that cationic iridium complexes
with chiral phosphanodihydrooxazoles are efficient catalysts
for the enantioselective hydrogenation of olefins. The com-
plexes are air-stable and easy to handle. Depending on the
counterion, BARF or hexafluorophosphate, certain unfunc-
tionalized aryl-substituted olefins or allyl alcohols can be
hydrogenated in high yields and with excellent enantioselec-
tivities.
Experimental Section
1 f: To a two-necked flask fitted with a condenser was added 2d[14] (400 mg,
0.96 mmol), [{Ir(cod)Cl}2] (324 mg, 0.48 mmol), and CH2Cl2 (10 mL). The
deep red mixture was heated under Ar to reflux for 1 h, until thin layer
chromatography (TLC; silica gel, CH2Cl2) indicated that 2d had been
consumed. After the mixture was cooled to room temperature, Na[BARF]
(1.31 g, 1.5 mmol) was added followed by H2O (10 mL), and the resulting
two-phase mixture was stirred vigorously for 10 min. Counterion exchange
from the chloride (Rf ˆ 0) to BARF (Rf ˆ 0.95) was indicated by TLC
(silica gel, CH2Cl2). The layers were separated, and the aqueous layer was
extracted with further portions of CH2Cl2 (2 Â 10 mL). The combined
organic extracts were washed with H2O (10 mL) and evaporated. The
residue was taken up in EtOH (10 mL) and crystallized by the slow
addition of H2O (1 mL) to give 1 f (935 mg, 62%) as a dark orange solid.
Elemental analysis calcd for C67H54BF24IrNOP: C 50.96, H 3.45, N 0.89;
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found: C 51.11, H 3.46, N 0.92; m.p. 200 ± 2038C (decomp); [a]589
ˆ
160
[1] R. Noyori, Asymmetric Catalysis in Organic Synthesis, Wiley, New
York, 1994, pp. 16 ± 94; H. Tayaka, T. Ohta, R. Noyori in Catalytic
Asymmetric Synthesis (Ed.: I. Ojima), VCH, New York, 1993, pp. 1 ±
39; A. Pfaltz, Methods Org. Chem. (Houben-Weyl), 4th ed., Vol. E21,
1995, chap. 2.5.1.2.1/2, pp. 4334 ± 4359.
[2] R. L. Halterman, K. P. C. Vollhardt, M. E. Welker, D. Bläser, R.
Boese, J. Am. Chem. Soc. 1987, 109, 8105 ± 8107; V. P. Conticello, L.
Brard, M. A. Giardello, Y. Tsuji, M. Sabat, C. L. Stern, T. J. Marks, J.
Am. Chem. Soc. 1992 114, 2761 ± 2762; M. A. Giardello, V. P.
(CDCl3, c ˆ 0.2, 238C); 1H NMR (300 MHz, CDCl3): d ˆ 0.46 (brs, 9H;
tBu), 1.43 (m, 2H; CH2 (COD)), 1.92 (m, 2H; CH2 (COD)), 2.15 ± 2.33 (m,
8H; 2Me, CH2 (COD)), 2.99 (brs, 3H; CH, CH2 (COD)), 3.37 (brs, 1H;
CH (COD)), 3.85 (m, 1H; CH2O), 4.21 (t, J ˆ 9.45 Hz, 1H, CHN), 4.45 (m,
1H; CH2O), 4.64 (m, 1H; CH (COD)), 4.75 (brs, 1H; CH (COD)), 6.37 (m,
1H; arom. H), 6.78 (m, 1H; arom. H), 6.96 (m, 1H; arom. H), 7.11 ± 7.17 (m,
4H; arom. H), 7.24 ± 7.37 (m, 4H; arom. H), 7.43 (s, 4H; BARF), 7.52 (m,
2H; arom. H), 7.63 (s, 8H; BARF), 8.13 ± 8.08 (m, 1H; arom. CH); 31P
NMR (100 MHz, CDCl3): d ˆ 11.0.
Â
Conticello, L. Brard, M. R. Gagne, T. J. Marks, J. Am. Chem. Soc.
1994, 116, 10241 ± 10254.
Hydrogenation of 3. To a 35-mL autoclave with magnetic stirrer was added
1 f (1.6 mg, 0.001 mmol, 0.3 mol%), 3 (74 mg, 0.33 mmol), and CH2Cl2
(0.3 mL). The autoclave was sealed and pressurized to 50 bar with H2, and
the mixture was stirred for 2 h. The CH2Cl2 solvent was removed and
replaced with heptane (3 mL), and the solution passed through a short plug
of silica (0.5 cm) to remove the metal salts. Analysis by gas chromatography
(GC) indicated 99.8% conversion into 4. Kugelrohr distillation (130 ±
1408C/0.04 mbar) afforded 4 as a clear oil (75 mg, 99%). The reaction of
4 mmol of 3 and 0.3 mol% of 1 f gave the same results. HPLC (Chiralcel
[3] R. D. Broene, S. L. Buchwald, J. Am. Chem. Soc. 1993, 115, 12569 ±
12570.
 Ã
[4] P. Schnider, G. Koch, R. Pretot, G. Wang, F. M. Bohnen, C. Krüger, A.
Pfaltz, Chem. Eur. J. 1997, 3, 887 ± 891.
[5] R. H. Crabtree, Acc. Chem. Res. 1979, 12, 331 ± 338.
[6] D. Blackmond, T. Rosner, Max-Planck-Institut für Kohlenforschung,
unpublished results.
[7] For the effect of additives upon iridium-catalyzed hydrogenation of
imines, see Y. N. C. Chan, D. Meyer, J. A. Osborn, J. Chem. Soc.
Chem. Commun. 1990, 869 ± 871; T. Morimoto, K. Achiwa, Tetrahe-
dron: Asymmetry 1995, 6, 2661 ± 1664; K. Tani, J.-I. Onouchi, T.
Yamagata, Y. Kataoka, Chem. Lett. 1995, 955 ± 956; F. Spindler, B.
Pugin, H.-P. Jalett, H.-P. Buser, U. Pittelkow, H.-U. Blaser, Chem. Ind.
(Dekker) 1996, 68, 153 ± 168.
OJ, iPrOH/heptane 5/95, 0.5 mLmin 1, 208C, 254 nm): tR (R) ˆ 15.6 min, tR
1
(S) ˆ 20.3 min, 98% ee; [a]589
ˆ
94.4 (CH2Cl2, c ˆ 2.93, 238C); H NMR
(200 MHz, CDCl3): d ˆ 1.21 (d, 3H; J ˆ 8.3 Hz, Me), 2.67 ± 3.01 (m, 3H;
CH, CH2), 3.77 (s, 3H; OMe), 6.81 (d, 2H; J ˆ 8.8 Hz, arom. H), 7.07 ± 7.26
(m, 7H; arom. H); 13C NMR (75 MHz, CDCl3): d ˆ 21.0 (Me), 40.7 (CH),
45.1 (CH2), 55.5 (OMe), 113.9, 126.1, 128.2, 128.4, 129.5 (arom. CH), 139.5,
141.3, 158.3 (arom. C).
[8] H. Nishida, N. Takada, M. Yoshimura, T. Sonoda, H. Kobayashi, Bull.
Chem. Soc. Jpn. 1984, 57, 2600 ± 2604.
HPLC analysis of the hydrogenation products from 8 ± 13 and 15 ± 17
(0.5 mLmin 1, 208C, 254 nm): 8 (Chiralcel OJ, iPrOH/heptane 1/99): tR ˆ
12.6 min (major enantiomer), 20.6 min (minor enantiomer); 9 (Chiralcel
OJ, iPrOH/heptane 1/99): 12.9/15.7 min; 10 (Chiralcel OJ, iPrOH/heptane
5/95): 12.1/17.3 min; 11 (Chiralcel OD-H, iPrOH/heptane 0.01/99.99): 15.3/
13.9 min; 12 (Chiralcel OD-H, iPrOH/heptane 0.01/99.99): 14.1/16.0 min;
13 was hydrolyzed (MeOH/K2CO3), and the resulting alcohol was analyzed
(Chiralcel OD-H, iPrOH/heptane 5/95, 408C): 17.4/15.1 min; 15 (Chiralcel
OB-H, iPrOH/heptane 0.5/99.5): 18.4/21.4 min; 16 (Chiralcel OD-H,
iPrOH/heptane 5/95, 508C), 16.4/14.6 min; 17 (Chiralcel OD-H, iPrOH/
heptane 5/95, 408C): 18.0/15.6 min. Analysis by GC of the hydrogenation
product from 14 (20% tBu b-CD, 80% OV1701, 25 m, 0.5 bar H2, 50 ±
1808C, 18min 1): tR ˆ 52.4 min (major enantiomer), 51.2 min (minor
enantiomer).
[9] G. H. Zhang, T. Imato, Y. Asano, T. Sonoda, H. Kobayashi, N.
Ishibashi, Anal. Chem. 1990, 62, 1644 ± 1648.
[10] A. G. Massey, A. J. Park, J. Organomet. Chem. 1962, 2, 245 ± 250.
[11] H. Takaya, T. Ohta, N. Sayo, H. Kumobayashi, S. Akutagawa, S. Inoue,
I. Kasahara, R. Noyori, J. Am. Chem. Soc. 1987, 109, 1596 ± 1597,
4129.
[12] ªFlavours and Fragrancesº: K. Bauer, D. Garbe, H. Surberg in
Ullmannꢀs Encyclopedia of Industrial Chemistry, Vol. A11, VCH,
Weinheim, 1988, pp. 141 ± 250; D. Enders, H. Dyker, Liebigs Ann.
Chem. 1990, 1107 ± 1110.
[13] Prepared by stereoselective Horner± Wadsworth ± Emmons olefina-
tion (I. Paterson, K.-S. Yeung, J. B. Smaill, Synlett 1993, 774 ± 776),
followed by reduction of the a,b-unsaturated ester (E. J. Corey, H. A.
Kirst, J. A. Katzenellenbogen, J. Am. Chem. Soc. 1970, 92, 6314 ±
6319).
Received: May 27, 1998 [Z11908IE]
German version: Angew. Chem. 1998, 110, 3047 ± 3050
[14] Prepared by the directed ortho lithiation method: G. Koch, G. C.
 Ã
Lloyd-Jones, O. Loiseleur, A. Pfaltz, R. Pretot, S. Schaffner, P.
Keywords: asymmetric catalysis ´ dihydrooxazoles ´ hydro-
genations ´ iridium ´ N ligands ´ P ligands
Schnider, P. von Matt, Recl. Trav. Chim. Pays-Bas. 1995, 114,
206 ± 210.
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