Phospholane-oxazoline ligands for Ir-catalyzed asymmetric hydrogenation

Article abstract of DOI:10.1002/anie.200390251

A new class of chiral phospholane-oxazoline ligands P* was developed for Ir-catalyzed asymmetric hydrogenation (see scheme, e.g. R =Ph; Ar=m-CH₃C₆H₄). High enantioselectivities (up to 99% ee) were obtained for the hydrogenation of methylstilbene derivatives and (E)-β-methylcinnamic esters.

Full text of DOI:10.1002/anie.200390251

Angewandte
Chemie
[8] a) Y. Hoshino, H. Yamamoto, J. Am. Chem. Soc. 2000, 122,
Experimental Section
10452; b) N. Murase, Y. Hoshino, M. Oishi, H. Yamamoto, J.
Org. Chem. 1999, 64, 338; c) Y. Hoshino, N. Murase, M. Oishi, H.
Yamamoto, Bull. Chem. Soc. Jpn. 2000, 73, 1653.
Representative experimental procedure: VO(OiPr)3 (5 mL, 20 mmol)
and hydroxamic acid (26.6 mg, 60 mmol) were dissolved in toluene
(1 mL), stirred for 1 hour, and cooled to 08C. Cumene hydroperoxide
(275 mL, 1.5 mmol) and 3-(1-naphthyl)-3-buten-1-ol (2j) (198 mg,
1.0 mmol) were added at 08C. The reaction mixture was stirred for
10 h, then trimethylphosphite (177 mL, 1.5 mmol) was added at that
temperature. The mixture was allowed to reach room temperature,
then it was extracted with ethyl acetate, dried over sodium sulfate,
and evaporated. The crude product was purified by column chroma-
tography on a silica gel (eluent ethyl acetate/hexane, 1:1) to give 3,4-
[9] The absolute configuration of 3a (3R,4S) was determined by
comparison of the optical rotation with published data.[5b]
[10] The absolute configuration of 3 f (S) was determined by
comparison of the optical rotation of the derivative O-methoxy-
methyl-3,4-epoxy-3-methyl-1-butanol with published data, see:
D. Behnke, L. Henning, M. Findeisen, P. Welzel, D. Müller, M.
Thormann, H.-J. Hofmann, Tetrahedron 2000, 56, 1081.
[11] (Z)-4-Phenyl-3-buten-1-ol (2c) was obtained from trans-styryl-
acetic acid (trans-4-phenyl-3-butenoic acid) and lithium alumi-
num hydride. 3-Phenyl-3-buten-1-ol (2i) was prepared by Heck
reaction according to ref. [12]. The homoallylic alcohols 2e, g, h,
and j were prepared by ene reaction using BF3·OEt2 or Me2AlCl
and formaldehyde according to ref. [14a].
[12] W. Cabri, I. Candiani, A. Bedeschi, J. Org. Chem. 1992, 57, 3558.
[13] a) J.-D. Fourneron, M. Julia, Bull. Soc. Chim. Fr. 1981, II-387;
b) D. Babin, J.-D. Fourneron, M. Julia, Tetrahedron 1981, 37, 1;
c) H. Nemoto, M. Shiraki, M. Nagamochi, K. Fukumoto,
Tetrahedron Lett. 1993, 34, 4939; d) X.-J. Chen, A. Archelas,
R. Furstoss, J. Org. Chem. 1993, 58, 5528.
1
epoxy-3-(1-naphthyl)-1-butanol in 42% yield with 91% ee. H NMR
(300 MHz, CDCl3, 258C, TMS): d = 8.13 (d, J = 8.0 Hz, 1H; Ar-H),
7.90 (d, J = 8.0 Hz, 1H; Ar-H), 7.83 (d, J = 8.0 Hz, 1H; Ar-H), 7.50
(m, 4H; Ar-H), 3.71 (m, 2H; CH2OH), 3.35 (d, J = 6.0 Hz, 1H;
OCH2), 3.00 (d, J = 6.0 Hz, 1H; OCH2), 2.45 (m, 1H; CCH2CH2), 2.29
(m, 1H; CCH2CH2), 1.69 ppm (br, 1H; OH). HPLC analysis
(column: OD-H, Daisel): retention times 44.9 (main peak) and
68.1 min (minor peak) using hexane/2-propanol (40:1) as the eluent at
a flow rate of 1.0 mLminꢀ1. For the epoxy alcohols 3a–e, a saturated
aqueous solution of sodium sulfite instead of trimethylphosphite was
used for quenching the reaction.
[14] a) B. B. Snider, D. J. Rodini, T. C. Kirk, R. Cordova, J. Am.
Chem. Soc. 1982, 104, 555; b) A. T. Blomquist, R. J. Himics, J.
Org. Chem. 1968, 33, 1156; c) R. J. Crawford, W. F. Erman, C. D.
Broaddus, J. Am. Chem. Soc. 1972, 94, 4298.
Received: September 24, 2002 [Z50233]
[15] 9: [a]2D5 = ꢀ54.9 (c = 1.27 in ethanol);[13d] 13C NMR (300 MHz,
CDCl3, 258C, TMS): d = 133.9, 131.3, 124.6, 120.6, 74.1, 42.9,
40.1, 31.0, 26.9, 25.6, 23.3, 23.2, 23.0, 22.0, 17.6 ppm.
[1] a) R. A. Sheldon, J. A. Kochi, Metal-Catalyzed Oxidations of
OrganicCompounds , Academic Press, New York, 1981; b) Or-
ganicSyntheses by Oxidation with Metal Compounds (Eds.: W. J.
Mijs, C. R. H. I. De Jonge), Plenum, New York, 1986; c) M.
[16] 9’: [a]2D5 = ꢀ61.4 (c = 1.70 in ethanol), ꢀ69 (c = 1.3 in ethanol);[13d]
13C NMR (300 MHz, CDCl3, 258C, TMS): d = 133.9, 131.8, 124.7,
120.9, 74.4, 43.4, 39.4, 31.1, 26.2, 25.8, 24.1, 24.0, 23.5, 22.4,
17.8 ppm.
´
Hudlicky, Oxidations in OrganicChemistry, American Chemical
Society, Washington, DC, 1990; d) E. N. Jacobsen in Compre-
hensive OrganometallicChemistry II, Vol. 12 (Eds.: E. W. Abel,
F. G. A. Stone, G. Wilkinson), Elsevier Science, Oxford, 1995,
p. 1097.
[2] For selected recent reviews of the asymmetric epoxidation of
functionalized alkenes, see: a) R. A. Johnson, K. B. Sharpless in
CatalyticAsymmetricSynthesis , 2nd ed. (Ed.: I. Ojima), Wiley-
VCH, New York, 2000, p. 231; b) T. Katsuki in Comprehensive
AsymmetricCatalysis I–III, Vol. 2 (Eds.: E. N. Jacobsen, A.
Pfaltz, H. Yamamoto), Springer, Berlin, 1999, p. 621; c) T.
Katsuki, V. S. Martin, Org. React. 1996, 48, 1.
Catalytic Asymmetric Hydrogenation
Phospholane–Oxazoline Ligands for Ir-Catalyzed
Asymmetric Hydrogenation**
[3] For selected recent reviews of the asymmetric epoxidation of
a,b-unsaturated carbonyl compounds, see: a) V. K. Aggarwal in
Comprehensive AsymmetricCatalysis I–III, Vol. 2 (Eds.: E. N.
Jacobsen, A. Pfaltz, H. Yamamoto), Springer, Berlin, 1999,
p. 679; b) M. J. Porter, J. Skidmore, Chem. Commun. 2000, 1215.
[4] For selected reviews of the asymmetric epoxidation of unfunc-
tionalized alkenes, see: a) V. Schurig, F. Betschinger, Chem. Rev.
1992, 92, 873; b) K. A. Jörgensen, Chem. Rev. 1989, 89, 431; c) T.
Katsuki in CatalyticAsymmetricSynthesis , 2nd ed. (Ed.: I.
Ojima), Wiley-VCH, New York, 2000, p. 287; d) E. N. Jacobsen,
M. H. Wu in Comprehensive AsymmetricCatalysis I–III, Vol. 2
(Eds.: E. N. Jacobsen, A. Pfaltz, H. Yamamoto), Springer,
Berlin, 1999, p. 649.
[5] a) S. Ikegami, T. Katsuki, M. Yamaguchi, Chem. Lett. 1987, 83;
b) B. E. Rossiter, K. B. Sharpless, J. Org. Chem. 1984, 49, 3707;
c) J. K. Karjalainen, O. E. Hormi, D. C. Sherrington, Tetrahe-
dron: Asymmetry 1998, 9, 3895.
[6] F. Freeman in OrganicSyntheses by Oxidation with Metal
Compounds (Eds.: W. J. Mijs, C. R. H. I. De Jonge), Plenum,
New York, 1986, p. 1.
Wenjun Tang, Weimin Wang, and Xumu Zhang*
Although a lot of progress has been made in Rh- or Ru-
catalyzed asymmetric hydrogenation, Ir-catalyzed asymmet-
ric hydrogenation is relatively unexplored.[1] Pfaltz and co-
workers first reported several Ir-phosphinooxazoline com-
plexes as catalysts for asymmetric hydrogenation. With
leading efforts by Pfaltz and co-workers,[2] and Burgess and
[*] Prof. X. Zhang, W. Tang, Dr. W. Wang
Department of Chemistry, The Pennsylvania State University
University Park, PA16802 (USA)
Fax: (+1)814-863-8403
E-mail: xumu@chem.psu.edu
[7] The asymmetric epoxidation of allylic alcohols using vanadium
and an optically active hydroxamic acid was first reported by
K. B. Sharpless in 1977: R. C. Michaelson, R. E. Palermo, K. B.
Sharpless, J. Am. Chem. Soc. 1977, 99, 1990.
[**] This work was supported by the National Institute of Health.
Supporting information for this article is available on the WWW
under http://www.angewandte.org or from the author.
Angew. Chem. Int. Ed. 2003, 42, No. 8
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Communications
co-workers,[3] Ir-catalyzed asymmetric hydrogenation has
H
O
N
H
c
b
a
been realized for some functionalized and nonfunctionalized
olefins. However, since Ir-catalyzed asymmetric hydrogena-
tion is still highly substrate dependent, the development of
new efficient chiral ligands for Ir-catalyzed hydrogenation is a
continuing challenge. Herein we report a new class of chiral
N,Pligands, the phospholane–oxazolines 6 (Scheme 1), for Ir-
catalyzed asymmetric hydrogenation. Excellent enantiosele-
citivities have been obtained in hydrogenation of methylstil-
bene derivatives and b-methylcinammic esters.
COOH
P
P
P
tBu
R
S
S
tBu
S
tBu
10a–f
8
9
+
H
P
O
N
7a: R = iPr
7b: R = tBu
7c: R = Ph
7d: R = Bn
7e: R = iBu
BARF–
R
R
Ir
tBu
H
O
N
d
P
R
+
H
Ir
O
N
tBu
Ph
Ph
O
7f: R = iPr
O
BARF–
P
O
P
O
6a–f
O
N
tBu
O
N
N
O
PAr2
O
PAr2
N
Ph
R
Ph
R
Scheme 2. Synthesis of phospholane–oxazoline ligands 6. a) nBuLi,
(ꢀ)-sparteine, CO2, ꢀ788C, recrystallization, 71% ee!100% ee, 40%;
b) 1. amino alcohol, EDC, HOBT, DMF, 708C; 2. MsCl, CH2Cl2, 70–
80%; c) Raney Ni, CH3CN, 80–95%; d) [{Ir(cod)Cl}2], NaBARF, 50–
70%. EDC=N-(3-dimethylaminopropyl)-N’-ethylcarbodiimide hydro-
chloride, HOBT=1-hydroxybenzotriazole, cod=1,5-cyclooctadiene,
BARF=tetrakis[3,5-bis(trifluoromethyl)phenyl]borate, MsCl=methane-
sulfonyl chloride.
2
3
1
R2 R2
O
H
O
O
O
PAr2
N
N
PAr2
P
N
R
R
R1
tBu
5
6
4
Scheme 1. N,P Ligands for enantioselective Ir-catalyzed hydrogenation.
alcohols by using EDC/HOBT as the reagents proceeded
smoothly to yield the coupling products, which were sub-
sequently treated with MsCl to form the oxazoline com-
pounds 10. Desulfurization of 10 using Raney Ni[11] provided a
set of phospholane–oxazoline ligands 6 in excellent yields.
The corresponding iridium complexes 7a–f were synthesized
in good yields according to standard procedures.[2a] Although
the iridium complexes 7a–f are slightly air-sensitive, they can
be stored under nitrogen for a long period of time without
deterioration. To investigate the influence of the relative
configuration of the chirality in the oxazoline ring, and the
chiralities in the phospholane ring, two diastereomeric ligands
6a and 6 f (R = iPr) were synthesized. A series of ligands 6a–f
were also synthesized to study the influence of R in the
oxazoline ring.
To test the effectiveness of the new chiral N,Pligands,
iridium complexes 7a–f were used as catalysts for asymmetric
hydrogenation of methylstilbene derivatives.[12] The hydro-
genations were carried out at room temperature under 50 bar
of pressure using CH2Cl2 as the solvent. All the reactions
proceeded to completion in the presence of 1 mol% of an
iridium complex. The diastereomeric complexes 7a and 7 f led
to hydrogenation products with different configuration (Ta-
ble 1), which indicated that the chirality in the oxazoline ring
of the ligand determined the configuration of the product.
Iridium complex 7a was favored over 7b for the reaction, as a
higher ee value (91%) was obtained (Table 1, entries 1 and 6).
Among the Ir complexes with different steric bulk (7a–e,
Table 1, entries 1–5), the highest ee value (95%) was obtained
with 7c, which has a phenyl group on the oxazoline ring. The
enantiomeric excess of the product is comparable to those
reported by Pfalz et al[2a] with an Ir–PHOX system. With 7c as
the catalyst, another two substituted methylstilbene deriva-
After the development of phosphinooxazoline ligands
(PHOX, 1) for Ir-catalyzed asymmetric hydrogenation,[2a]
Pfaltz and others have continued their efforts for the search
of new efficient N,Pligands (Scheme 1). Various N,Pligands
such as TADDOL-phosphite–oxazoline (2),[2b] PyrPHOX
(3),[2d] and phosphinite-oxazoline (4),[2e,f,g] were subsequently
developed by Pfalz and co-workers. Burgess and co-workers
also reported JM-Phos (5)[3a,b] and imidazolylidene-oxazoli-
ne.[3c] These ligands expanded the reaction scope of Ir-
catalyzed asymmetric hydrogenation. The closely related
Crabtree's catalyst, [Ir(cod)(Py)PCy3]PF6 (cod = 1,5-cyclooc-
tadiene, Py = pyridine, Cy = cyclohexyl), is an efficient achiral
catalyst for the hydrogenation of tri- or tetrasubstituted
olefins.[4] Since an electron-rich phosphane PCy3 is used in this
system, we aimed to develop a new class of chiral N,Pligands
6 with an electron-rich phosphorus center to match the
electronic properties of Crabtree's catalyst. It is noteworthy
that these phospholane–oxazoline ligands not only have a
stereogenic center in the oxazoline ring but also at the
phosphorus center.[5] The structure of 6 is modular since the
oxazoline ring can vary with an array of R groups.
We reported the synthesis of an efficient chiral bisphos-
pholane ligand, TangPhos, from 1-tert-butyl-phospholane 1-
sulfide 8 in only three steps.[6] Phospholane–oxazolines 6 can
also be synthesized easily from 8 in four steps (Scheme 2).
Selective deprotonation of 8 by n-butyllithium in the presence
of (ꢀ)-sparteine[7] followed by reaction with CO2 provided
acid 9 with 72% ee.[8,9] Recrystallization of the acid from
ethanol yielded the enantiomerically pure 9 in 40% yield.[15]
The absolute configuration of 9 was confirmed by its X-ray
structure analysis.[10] The condensation of 9 with chiral amino
944
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Chemie
Table 1: Ir-catalyzed asymmetric hydrogenation of methylstilbene deriv-
atives.
two diastereomeric catalysts 7a and 7 f (R = iPr) led to
products with different configurations (Table 2, entries 1
and 6). The highest enantiomeric excess (98%) was obtained
when 7c was used as the catalyst (Table 2, entry 3). We
therefore used 7c as the catalyst for hydrogenation of a series
of substituted (E)-b-methylcinnamic esters. Avariety of chrial
3-arylbutyric esters were thus obtained in excellent enantio-
meric excesses (95–99%) regardless of the substitution
pattern on the phenyl ring (Table 2, entries 7–12). The
electronic properties of the substrates did not have a
significant influence on the enantioselectivities. Substrates
with a 2-naphthyl group and a 1-naphthyl group also gave
high ee values (Table 2, entries 13, 14). To our knowledge,
these are highest enantioselectivities to date for asymmetric
hydrogenation of b-methylcinnamic esters. Asymmetric hy-
drogenation of a (Z)-b-methylcinnamic ester led to a product
with a different configuration, and a lower enantiomeric
excess was obtained (entries 8 and 15).
In conclusion, we have developed a new class of phos-
pholane–oxazoline ligands for Ir-catalyzed asymmetric hydro-
genation. Excellent reactivities and enantioselectivities were
obtained in the hydrogenation of methylstilbene derivatives
and (E)-b-methylcinnamic esters. Since the phospholane–
oxazoline ligands can be easily synthesized, these ligands are
promising for the synthesis of chiral arenes and 3-arylbutyric
esters.[15]
1 mol% 7a–f
50 bar H2
*
CH2Cl2, RT
X
X
Entry[a]
Substrate
X
Catalyst
ee [%][b]
Config.[c]
1
2
3
4
5
6
7
8
8
8
8
8
8
8
9
10
H
H
H
H
H
H
7a
7b
7c
7d
7e
7 f
7c
7c
91
81
95
89
75
77
91
90
R
R
R
R
R
S
R
R
OMe
Cl
[a] See Supporting Information for experimental details. [b] The enatio-
meric excesses were determined by chiral HPLC (Chiralcel OJH). [c] The
absolute configuration was assigned by comparison of the observed
optical rotation with reported data.
tives were also subjected to hydrogenation and ee values over
90% were obtained (entry 7 and 8).
Asymmetric hydrogenation of b-methylcinnamic esters
can directly form chiral 3-arylbutyric esters. The reduction
products of 3-arylbutyric esters (i.e. chiral 3-arylbutanols) are
important intermediates for the synthesis of aromatic sesqui-
terpenes of the bisabolane family.[13] Pfaltz and co-workers
applied the iridium phosphinite–oxazoline system to the
asymmetric hydrogenation of ethyl b-methylcinnamate ester
and obtained the desired product in 94% ee.[2f] We used the
iridium complexes 7a–f for hydrogenation of (E)-b-methyl-
cinnamic esters, which can be easily synthesized by using the
Heck reaction from aryl halides and crotonic esters.[14] Methyl
(E)-b-methylcinnamate was selected as the substrate to
screen different iridium catalysts (Table 2, entries 1–6). The
Received: October 2, 2002 [Z50283]
[1] For recent reviews, see: a) T. Ohkuma, M. Kitamura, R. Noyori
in CatalyticAsymmetricSynthesis (Ed.: I. Ojima), Wiley-VCH,
Weinheim, 2000, p. 1; b) J. M. Brown in Comprehensive Asym-
metricCatalysis (Eds.: E. N. Jacobsen, A. Pfaltz, H. Yamamoto),
Springer, Berlin, 1999, p. 121; c) R. L. Halterman in Compre-
hensive AsymmetricCatalysis (Eds.: E. N. Jacobsen, A. Pfaltz, H.
Yamamoto), Springer, Berlin, 1999,
p. 183.
[2] a) A. Lightfoot, P. Schnider, A.
Table 2: Ir-catalyzed asymmetric hydrogenation of b-methylcinnamic esters.
1 mol% 7a–f
Pfaltz, Angew. Chem. 1998, 110,
3047 – 3050; Angew. Chem. Int. Ed.
50 bar H2
COOCH3
1998, 37, 2897 – 2899; b) R. Hilgraf,
A. Pfaltz, Synlett 1999, 1814 – 1816;
c) D. G. Blackmond, A. Lightfoot,
A. Pfaltz, T. Rosner, P. Schnider, N.
Zimmermann, Chirality 2000, 12,
442 – 449; d) P. G. Cozzi, N. Zim-
mermann, R. Hilgraf, S. Schaffner,
A. Pfaltz, Adv. Synth. Catal. 2001,
343, 450 – 454; e) J. Blankenstein,
A. Pfaltz, Angew. Chem. 2001, 113,
4577 – 4579; Angew. Chem. Int. Ed.
2001, 40, 4445 – 4447; f) F. Menges,
A. Pfaltz, Adv. Synth. Catal. 2002,
344, 40 – 44; g) Closely related li-
gands have been recently applied in
Pd-catalyzed allylic alkylation: G.
Jones, C. J. Richards, Tetrahedron
Lett. 2001, 42, 5553 – 5555.
COOCH3
*
Ar
Ar
CH2Cl2, RT
Entry[a]
Substrate
Ar
Catalyst
ee [%][b]
Config.[c]
1
2
3
4
5
6
7
8
11
11
11
11
11
11
12
13
14
15
16
17
18
19
(Z)-13
Ph
Ph
Ph
Ph
Ph
Ph
p-F-C6H4
p-Cl-C6H4
p-CH3-C6H4
p-OCF3-C6H4
p-OCH3-C6H4
m-CH3-C6H4
1-naphthyl
2-naphthyl
p-Cl-C6H4
7a
7b
7c
7d
7e
7 f
7c
7c
7c
7c
7c
7c
7c
7c
7c
94
91
98
92
95
93
95
98
97
97
97
99
98
95
80
R
R
R
R
R
S
R
R
R
R
R
R
R
R
S
9
10
11
12
13
14
15
[3] a) D.-R. Hou, J. H. Reibenspies, K.
Burgess, J. Org. Chem. 2001, 66,
206 – 215; b) D.-R. Hou, J. Reibens-
pies, T. J. Colacot, K. Burgess,
[a] See Supporting Information for experimental details. [b] The enantiomeric excesses were determined
by chiral HPLC (Chiralcel OJH) or chiral GC (Chiralselect 1000). [c] The absolute configurations were
assigned by comparison of the observed optical rotation with reported data or by analogy.
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945

Communications
Chem. Eur. J. 2001, 7, 5391 – 5400; c) M. T. Powell, D.-R. Hou,
Allylation of Aldehydes
M. C. Perry, X. Cui, K. Burgess, J. Am. Chem. Soc. 2001, 123,
8878 – 8879.
A Highly Practical and Enantioselective Reagent
for the Allylation of Aldehydes**
[4] R. H. Crabtree, Acc. Chem. Res. 1979, 12, 331 – 338.
[5] Helmchen reported a P-chiral Phox ligand for Pd-catalyzed
allylic alkylation, see: S. Kudis, G. Helmchen, Angew. Chem.
1998, 110, 3210 – 3212; Angew. Chem. Int. Ed. 1998, 37, 3047 –
3050.
Katsumi Kubota and James L. Leighton*
[6] a) W. Tang, X. Zhang, Angew. Chem. 2002, 114, 1682 – 1684;
Angew. Chem. Int. Ed. 2002, 41, 1612 – 1614; b) W. Tang, X.
Zhang, Org. Lett. 2002, 4, 4159 – 4161.
[7] a) D. Hoppe, F. Hintze, P, Tebben, M. Paetow, H. Ahrens, J.
Schwerdtfeger, P. Sommerfeld, J. Haller, W. Guarnieri, S.
Kolczewski, T. Hense, I. Hoppe, Pure Appl. Chem. 1994, 66,
1479 – 1486, and references therein; b) P. Beak, S. T. Kerrick, S.
Wu, J. Chu, J. Am. Chem. Soc. 1994, 116, 3231 – 3239, and
references therein.
[8] Asymmetric deprotonation of phosphane sulfides or phosphane
boranes have been reported, see: a) A. R. Muci, K. R. Campos,
D. A. Evans, J. Am. Chem. Soc. 1995, 117, 9075 – 9076; b) T.
Imamoto, J. Watanabe, W. Yoshiyuki, H. Masuda, H. Yamada,
H. Tsuruta, S, Matsukawa, K. Yamaguchi, J. Am. Chem. Soc.
1998, 120, 1635 – 1636.
Owing mainly to the prevalence of secondary alcohols in
bioactive natural products, chemists have developed many
moderately to highly enantioselective chiral reagents[1] and
catalytic systems[2] for the allylation of aldehydes. In terms of
practical utility, an ideal reagent should 1. be readily prepared
in both enantiomeric forms, 2. be a stable/storable solid that
can be prepared in bulk and employed at will by using only
trivial procedures, 3. possess a good safety profile both for the
user and environmentally, and 4. be generally effective in
terms of both efficiency and enantioselectivity. Herein we
report a new reagent that almost completely satisfies all of
these conditions.
[9] Asymmetric deprotonation of a phospholane–borane complex
was reported by Kobayashi, see: S. Kobayashi, N. Shiraishi,
W. W.-L. Lam, K. Manabe, Tetrahedron Lett. 2001, 42, 7303 –
7306.
[10] CCDC-193670 contains the supplementary crystallographic data
for this paper. These data can be obtained free of charge via
www.ccdc.cam.ac.uk/conts/retrieving.html (or from the Cam-
bridge Crystallographic Data Centre, 12 Union Road, Cam-
bridge CB21EZ, UK; fax: (+ 44)1223-336-033; or deposit@
ccdc.cam.ac.uk). We thank Dr. H. Yennawar for solving the
crystal structure.
[11] S. R. Gilbertson, Z. Fu, Org. Lett. 2001, 3, 161 – 164.
[12] For Ti-catalyzed asymmetric hydrogenation, see: R. D. Broene,
S. L. Buchwald, J. Am. Chem. Soc. 1993, 115, 12569 – 12570.
[13] a) C. Fuganti, S. Serra, A. Dulio, J. Chem. Soc. Perkin Trans. 1
1999, 279 – 282; b) C. Fuganti, S. Serra, J. Chem. Soc. Perkin
Trans. 1 2000, 3758 – 3764; c) A. I. Meyers, D. Stoianova, J. Org.
Chem. 1997, 62, 5219 – 5221.
Based on our discovery that silicon—constrained in a five-
membered ring by 1,2-diols, 1,2-aminoalcohols and 1,2-
diamines—possesses Lewis acidity sufficient for clean, un-
catalyzed allylation of aldehydes, we recently described the
pseudoephedrine-derived strained silacycle 1 as a reagent for
the enantioselective allylation of aldehydes (Scheme 1).[3]
Whereas this reagent is trivially prepared and employed,
and the enantioselectivities for aliphatic aldehydes are good
(87–89% ee, typically), they are unacceptably low for aro-
matic and conjugated aldehydes (60–81% ee, typically). This
reagent thus falls short of ideal mainly in terms of condition 4
(see above). Also reported were preliminary data regarding
reagent 2, which was found to provide improved enantiose-
lectivity, but also low reactivity. We therefore initiated a full
investigation into the potential of the diamine-based system.
[14] A. F. Littke, G. C. Fu, J. Am. Chem. Soc. 2001, 123, 6989 – 7000.
[15] The Supporting Information contains the experimental details,
and spectroscopic data of all the new ligands, their Ir complexes,
new substrates, and new hydrogenation products.
Ph
O
N
O
OH
toluene
Si
+
+
Ph
Ph
H
H
-10 °C
2 h
Ph
Ph
Cl
Me
84%; 88% ee
Me
(S,S)-1
Ph
N
O
OH
toluene
72 h
Si
Cl
N
58%; 95% ee
Ph
(R,R)-2
Scheme 1. Reagents for asymmetric allylation.
[*] Prof. J. L. Leighton, K. Kubota
Department of Chemistry
Columbia University
New York, NY 10027 (USA)
Fax: (+1)212-932-1289
E-mail: leighton@chem.columbia.edu
[**] Financial support was provided by the Sumitomo Corp. (postdoc-
toral support of K.K.). We thank Merck Research Laboratories for
generous financial support. J.L.L. is a recipient of a Pfizer Award for
Creativity in Organic Chemistry.
Supporting information for this article is available on the WWW
under http://www.angewandte.org or from the author.
946
ꢀ 2003 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
1433-7851/03/4208-0946 $ 20.00+.50/0
Angew. Chem. Int. Ed. 2003, 42, No. 8