Bis(oxazolinyl)phenylrhodium(III) Aqua Complex: Efficiency in Enantioselective Addition of Methallyltributyltin to Aldehydes under Aerobic Conditions

Article abstract of DOI:10.1055/s-2003-41474

A simple and general protocol is described for the enantioselective addition of methallyltributyltin to aldehydes catalyzed by chiral (Phebox)RhCl₂(H₂O) complexes 1 [Phebox = 2,6-bis(oxazolinyl)phenyl]. The reaction can be performed

Full text of DOI:10.1055/s-2003-41474

LETTER
1883
Bis(oxazolinyl)phenylrhodium(III) Aqua Complex: Efficiency in Enantioselec-
tive Addition of Methallyltributyltin to Aldehydes under Aerobic Conditions
B
is(oxazolinyl)phe
u
nylrhodium(
k
III) Aqua Co
i
mplexhiro Motoyama,*1a Hisao Nishiyama1b
School of Materials Science, Toyohashi University of Technology, Tempaku-cho, Toyohashi, Aichi 441-8580, Japan
Fax +81(92)5837819; E-mail: motoyama@cm.kyushu-u.ac.jp
Received 27 July 2003
selective methallyl addition to aldehydes, without the
need for anhyd conditions (Scheme 1).
Abstract: A simple and general protocol is described for the
enantioselective addition of methallyltributyltin to aldehydes
catalyzed by chiral (Phebox)RhCl2(H2O) complexes 1 [Phebox =
2,6-bis(oxazolinyl)phenyl]. The reaction can be performed even
under aerobic conditions to afford the corresponding optically
active homoallylic alcohols in good yields with high enantio-
selectivities (90–99% ee).
1
R1
H
R2
R1
R2
(5 mol%)
+
MS 4Å
CH2Cl2
25 °C
O
OH
SnBu3
Key words: aerobic conditions, allylation, asymmetric catalysis,
rhodium, pincer complex
2: R2 = H
4: R2 = H
3: R2 = Me
5: R2 = Me
Ever since Shaw reported the transition metal complexes
bearing P–C–P type pincer ligands in 1976,2a a variety of
pincer-based complexes have been extensively studied in
terms of not only structural characterization and bonding
properties but also active catalysts in organic synthesis.2 It
is well known that the characteristic features of these
pincer complexes are high degrees of both air- and
thermal stability.
O
O
Bn-1: R = Bn
Cl
s-Bu-1: R = s-Bu
i-Pr-1: R = i-Pr
N
N
Rh
R
R
Cl
O
H
H
Scheme 1
The non-dehydrated procedure for the reaction of benz-
aldehyde and allyltributyltin 2 was examined using 5
mol% of i-Pr-Phebox-derived complex i-Pr-1 in non-dis-
tilled CH2Cl2 in the presence of commercial, non-dried
MS 4A under aerobic conditions at 25 °C. The first, and
obvious, point to notice is that the reaction by this
procedure gives the allylated product 4 without loss of
both the chemical yield and enantioselectivity (Table 1,
entries 1 vs 2). This method is not necessitated by special
techniques and apparatus, therefore, anyone can perform
the reaction easily. We next examined the methallylation
reaction under the same conditions. Although the
reactivity of the methallyltributyltin 3 was relatively low-
er than that of the parent allyltributyltin 2, extension of the
reaction time from 7 hours to 12 hours led to satisfactory
yield. Compared with the allylation reaction catalyzed by
1, enantioselectivity of the methallylated product 5a in-
creased remarkably to 93% ee (entry 3). The best
substituent on the Phebox ligand in terms of the enantio-
selectivity in the methallyl addition reaction proved to be
the i-Pr group (entries 3–5).
Previously, we have reported chiral rhodium(III) aqua
complexes 13 bearing Phebox as an N-C-N pincer ligand
[Phebox = bis(oxazolinyl)phenyl]. We also found that
these aqua complexes 1 acted as novel transition-metal
Lewis acid catalysts for the enantioselective addition of
allyltributyltin to aldehydes3b,c in the presence of dry 4 Å
molecular sieves (MS 4A) under standard conditions such
as in anhyd CH2Cl2 under an argon atmosphere.4
Although the enantioselectivities of the obtained allylated
products were moderate (43–80% ee), these catalysts 1
proved to be air-stable, water-tolerant, and recoverable
chiral transition-metal complexes. Since we expect that
this catalytic system will see wide application for the
above characteristic features, we have been conducting
studies to facilitate the operation employed in such
reactions as much as possible. Most of the asymmetric
reactions using Lewis acid catalysts are performed under
strictly anhyd conditions to prevent the decomposition of
the moisture-sensitive catalysts.5 However, we found that
the present Phebox-Rh(III) complexes 1 catalyze the
reaction, even in CH2Cl2 without distillation and under
aerobic conditions, to afford the methallyl addition
products with excellent enantioselectivities. Here we re-
port the simple procedure for the Rh-catalyzed enantio-
Table 2 summarizes the results obtained for the
methallylation reaction of a variety of aldehydes with 5
mol% of i-Pr-1 in CH2Cl2 solution at 25 °C under aerobic
conditions.6 All reactions resulted in high yields (90–
97%) with both aromatic and aliphatic aldehydes for 12 h,
except in the case of p-chlorobenzaldehyde. Reactivity of
the p-chlorobenzaldehyde was lower than those of the
other aldehydes, however, the chemical yield of 5b
SYNLETT 2003, No. 12, pp 1883–1885
2
9
.0
9
.2
0
0
3
Advanced online publication: 19.09.2003
DOI: 10.1055/s-2003-41474; Art ID: U14803ST
© Georg Thieme Verlag Stuttgart · New York

1884
Y. Motoyama, H. Nishiyama
LETTER
Table 1 Enantioselective Addition of Allyl- and Methallyltribu-
tyltins (2,3) to Benzaldehyde Catalyzed by (Phebox)RhCl2(H2O)
Complexes 1a
(Scheme 2, A and B), which have been proposed
previously.3b,c When the allyltins 2 and 3 approach the
carbonyl re-face through the antiperiplanar B, which
gives the opposite enantiomer, the steric repulsion occurs
between one i-Pr group on the oxazoline rings and the
substituent at the b-position of allyltins (H for 2, and Me
for 3). The steric bulkiness of Me group is expected to be
more important than that of H, therefore,
enantioselectivities of the methallylated products might
increase remarkably.
Entry
Complex Allyltin/
product
Time
Yield
(%)
ee
(%)b
1c
2
i-Pr-1
i-Pr-1
i-Pr-1
s-Bu-1
Bn-1
2/4
7 h
7 h
88
85
95
94
99
51
50
93
92
91
2/4
3
3/5a
3/5a
3/5a
12 h
12 h
12 h
4
5
O
O
O
O
a All reactions were carried out using 0.25 mmol of benzaldehyde,
0.375 mmol (1.5 equiv) of allyltins (2 or 3), and 0.0125 mmol (5
mol%) of 1 in the presence of MS 4 Å (125 mg) in CH2Cl2 (1 mL) at
25 °C.
Cl
Cl
N
N
H
N
N
H
Rh
O
Rh
O
i-Pr
i-Pr
i-Pr
i-Pr
Cl
Cl
b Determined by chiral HPLC analysis (Daicel CHIRALCEL OD-H).
c Previous result under dehydrated conditions.
Me
Me
R1
R1
SnBu3
SnBu3
reached to 82% by prolongation of the reaction time to 24
h (entry 2). The enantioselectivities in all reactions were
achieved over 90% ee for such standard aldehydes.
Especially, the ee of the (E)-cinnamaldehyde-derived
product 5f recorded a value of 99% (entry 6). In all of the
cases, methallyltributyltin 3 attacks the si face of the
aldehyde’s C=O planes,7 it is the same p-face selectivity
as in the case of allyltributyltin 2.3b,c
A
B
si-face attack
re-face attack
R1
R1
OH
OH
Scheme 2
The reason why the methallylated products 5 show much
higher enantioselectivities than the allylated ones is
explained by the antiperiplanar transition states
The main features of the present catalytic system are as
follows: 1) there is no need to use anhyd solvent and dry
MS 4 Å, and inert atmospheres; 2) the procedure is
straightforward because the reaction can be performed by
simply mixing substrates and the catalyst i-Pr-1 at room
temperature (low reaction temperatures are not required);
3) chiral Lewis acid i-Pr-1 can be easily recovered9 in high
yield by column chromatography; 4) various optically
active homoallylic alcohols can be provided with high
enantioselectivity (up to 99% ee), and the absolute stereo-
chemistry of the methallylated products can also be
predicted. Hence, this simple procedure should be broadly
applicable in asymmetric organic synthesis.10
Table 2 Enantioselective Addition of Methallyltributyltin 3 to Var-
ious Aldehydes Catalyzed by (i-Pr-Phebox)RhCl2(H2O) Complex i-
Pr-1a
Entry Aldehyde
Prod- Yield ee
Config.c
uct
5a
5b
5c
5d
5e
5f
(%)
95
82
97
95
92
90
95
(%)b
1
2d
3
4
5
6
7
PhCHO
93
(–)-S
(–)-S
(–)-S
(–)-S
(+)-R
(–)-S
(–)-S
4-ClC6H4CHO
4-MeOC6H4CHO
2-furyl-CHO
90
94
92
Acknowledgement
PhCH2CH2CHO
(E)-PhCH=CHCHO
(E)-n-PrCH=CHCHO
91
This work was partly supported by a Grant-in-Aid for Scientific
Research from the Ministry of Education, Culture, Sports, Science
and Technology, Japan, by a Research Grant for Young Faculties
from Toyohashi University of Technology, and by the Tatematsu
Foundation. We are grateful to Professor Dr. Akira Yanagisawa of
Chiba University for helpful discussion.
99
5g
94e
a All reactions were carried out using 0.25 mmol of aldehyde, 0.325
mmol (1.5 equiv) of methallyltributyltin 3 and 0.0125 mmol (5
mol%) of chiral catalyst i-Pr-1 in 1 mL of CH2Cl2 in the presence of
4 Å molecular sieves (125 mg) at 25 °C for 12 h.
b Determined by chiral HPLC analysis.
References
c Assignment by comparison of the sign of optically rotation with re-
ported value.
(1) (a) New address: Institute for Materials Chemistry and
Engineering, Kyushu University, Kasuga, Fukuoka 816-
8580, Japan. (b) New address: Department of Applied
Chemistry, Graduate School of Engeering, Nagoya
University, Chikusa, Nagoya 464-8603, Japan.
d 24 h.
e Determined after converting to the benzoate.
Synlett 2003, No. 12, 1883–1885 © Thieme Stuttgart · New York

LETTER
Bis(oxazolinyl)phenylrhodium(III) Aqua Complex
1885
(2) (a) Moulton, C. J.; Shaw, B. L. J. Chem. Soc., Dalton Trans.
1976, 1020. (b) Reviews: Rietveld, M. H. P.; Grove, D. M.;
van Koten, G. New J. Chem. 1997, 21, 751. (c) Albrecht,
M.; van Koten, G. Angew. Chem. Int. Ed. 2001, 40, 3750.
(d) van der Boom, M. E.; Milstein, D. Chem. Rev. 2003, 103,
1759. (e) Singleton, J. T. Tetrahedron 2003, 59, 1837.
(3) (a) Motoyama, Y.; Makihara, N.; Mikami, Y.; Aoki, K.;
Nishiyama, H. Chem. Lett. 1997, 951. (b) Motoyama, Y.;
Narusawa, H.; Nishiyama, H. Chem. Commun. 1999, 131.
(c) Motoyama, Y.; Okano, M.; Narusawa, H.; Makihara, N.;
Aoki, K.; Nishiyama, H. Organometallics 2001, 20, 1580.
(d) Motoyama, Y.; Koga, Y.; Nishiyama, H. Tetrahedron
2001, 57, 853. (e) Motoyama, Y.; Shimozono, K.; Aoki, K.;
Nishiyama, H. Organometallics 2002, 21, 1684.
Et2O, and this solution was treated with a mixture of 1 N HCl
(5 mL) and solid KF (ca. 0.5 g) at r.t. for 30 min. The
resultant precipitate was filtered off, the filtrate was dried
over MgSO4 and concentrated under reduced pressure.
Purification by silica gel chromatography (hexane–Et2O =
3:1, then EtOAc as eluent for recovering i-Pr-1) gave
homoallylic alcohol, the enantioselectivity was determined
by chiral HPLC analysis. 5a: Daicel CHIRALCEL OD-H,
UV Detector 254 nm, hexane–i-PrOH = 20:1, flow rate 0.5
mL/min. tR = 13.1 min (S), 14.6 min (R); 5b: Daicel
CHIRALCEL OJ, UV Detector 254 nm, hexane–i-PrOH =
30:1, flow rate 0.5 mL/min. tR = 16.9 min (S), 19.1 min (R);
5c: Daicel CHIRALCEL OD-H, UV Detector 230 nm,
hexane–i-PrOH = 30:1, flow rate 0.5 mL/min. tR = 20.9 min
(R), 22.9 min (S); 5d: Daicel CHIRALCEL OD-H, UV
Detector 230 nm, hexane–i-PrOH = 40:1, flow rate 0.5 mL/
min. tR = 18.1 min (S), 19.1 min (R); 5e: Daicel
CHIRALCEL OD-H, UV Detector 254 nm, hexane–i-PrOH
= 20:1, flow rate 0.5 mL/min. tR = 13.5 min (S), 19.2 min (R);
5f: Daicel CHIRALCEL OD-H, UV Detector 254 nm,
hexane–i-PrOH = 20:1, flow rate 1.0 mL/min. tR = 10.9 min
(R), 20.8 min (S); 5g: The %ee was determined after
converting to the benzoate ester. Daicel CHIRALPAK AD,
UV Detector 254 nm, hexane–i-PrOH = 200:1, flow rate 0.5
mL/min. tR = 9.4 min (R), 11.2 min (S).
(f) Motoyama, Y.; Koga, Y.; Kobayashi, K.; Aoki, K.;
Nishiyama, H. Chem.–Eur. J. 2002, 8, 2968.
(g) Motoyama, Y.; Kawakami, H.; Shimozono, K.; Aoki, K.;
Nishiyama, H. Organometallics 2002, 21, 3408. (h) Also
see: Motoyama, Y.; Nishiyama, H. In Latest Frontiers of
Organic Synthesis; Kobayashi, Y., Ed.; Research Signpost:
India, 2002, 1.
(4) In the presence of MS 4 Å, this catalytic reaction was
slightly accelerated but the enantioselectivity was not
changed, see ref.3b
(5) For examples of chiral Lewis acid-catalyzed reactions in
water-containing solvents, see: (a) Diels–Alder reaction:
Mikami, K.; Kotera, O.; Motoyama, Y.; Sakaguchi, H.
Synlett 1995, 975. (b) Also see: Otto, S.; Engberts, J. B. F.
N. J. Am. Chem. Soc. 1999, 121, 6798. (c) Aldol reaction:
Kobayashi, S.; Nagayama, S.; Busujima, T. Tetrahedron
1999, 55, 8739. (d) Also see: Nagayama, S.; Kobayashi, S.
J. Am. Chem. Soc. 2000, 122, 11531. (e) Also see:
Kobayashi, S.; Hamada, T.; Nagayama, S.; Manabe, K. Org.
Lett. 2001, 3, 165. (f) Also see: Yamashita, Y.; Ishitani, H.;
Shimizu, H.; Kobayashi, S. J. Am. Chem. Soc. 2002, 124,
3292. (g) Allylation of aldehydes: Loh, T.-P.; Zhou, J.-R.
Tetrahedron Lett. 2000, 41, 5261. (h) Mannich-type
reaction: Kobayashi, S.; Hamada, T.; Manabe, K. J. Am.
Chem. Soc. 2002, 124, 5640. (i) Also see: Li, C.-J.; Chan,
T.-H. Organic Reactions in Aqueous Media; John Wiley &
Sons: New York, 1997. (j) Organic Synthesis in Water;
Grieco, P. A., Ed.; Blackie Academic and Professional:
London, 1998. (k) Kobayashi, S. In Lanthanides: Chemistry
and Use in Organic Synthesis; Kobayashi, S., Ed.; Springer:
Berlin, 1999, 63. (l) Kobayashi, S.; Manabe, K. Acc. Chem.
Res. 2002, 35, 209.
(6) General Procedure for the Catalytic Enantioselective
Addition of Methallyltributyltin 3 to Aldehydes
Catalyzed by i-Pr-1. To a suspension of MS 4A (125 mg)
in CH2Cl2 (1 mL) were added (i-Pr-Phebox)RhCl2(H2O)
complex i-Pr-1 (6.1 mg, 0.0125 mmol, 5 mol%), aldehyde
(0.25 mmol) and methallyltributyltin (0.375 mmol, 1.5
equiv) at 25 °C. After stirring the reaction mixture for 12 h
at that temperature, the reaction mixture was concentrated
under reduced pressure. The residue was dissolved 5 mL of
(7) 5a: [a]D23 –48.7 (c 0.63, Et2O); lit.8a [a]D20 –19.70° (c 9.90,
Et2O) for 40% ee (S); 5b: [a]D22 –44.5 (c 0.77, benzene);
lit.8b [a]D21 –40.4° (c 3.15, benzene) for 88% ee (S); 5c:
[a]D23 –67.9 (c 0.99, CHCl3); 5d: [a]D21 –49.2° (c 0.61,
CHCl3); 5e: [a]D22 +15.8° (c 0.85, CHCl3); lit.8b [a]D23 +16.6
(c 2.66, CHCl3) for 67% ee (R); 5f: [a]D22 –19.4 (c 0.26,
benzene); lit.8c [a]D +19.0 (c 1.44, benzene) for 84% ee (R);
5g: [a]D20 –3.30 (c 0.79, benzene); lit.8c [a]D +4.04 (c 1.93,
benzene) for 77% ee (R).
(8) (a) Hoffmann, R. W.; Herold, T. Chem. Ber. 1981, 114, 375.
(b) Minowa, N.; Mukaiyama, T. Bull. Chem. Soc. Jpn. 1987,
60, 3697. (c) Ishihara, K.; Mouri, M.; Gao, Q.; Maruyama,
T.; Furuta, K.; Yamamoto, H. J. Am. Chem. Soc. 1993, 115,
11490.
(9) Other examples of the recoverable chiral complexes are as
follows.: (a) Ru complex for the cyclopropanation:
Nishiyama, H.; Itoh, Y.; Matsumoto, H.; Park, S.-B.; Itoh, K.
J. Am. Chem. Soc. 1994, 116, 2223. (b) Ru complex for the
oxidation of sulfides: Schenk, W. A.; Dürr, M. Chem.–Eur.
J. 1997, 3, 713. (c) Ru complex for the Diels–Alder
reaction: Kündig, E. P.; Saudan, C. M.; Bernardinelli, G.
Angew. Chem. Int. Ed. 1999, 38, 1220. (d) Ni complex for
the 1,3-dipolar cycloaddition: Kanemasa, S.; Oderaotoshi,
Y.; Sakaguchi, S.; Yamamoto, H.; Tanaka, J.; Wada, E.;
Curran, D. P. J. Am. Chem. Soc. 1998, 120, 3074.
(10) Very recently, Portnoy reported the solid-supported Phebox-
Rh complexes and its application as heterogeneous catalysts
for the allylation of aldehydes, see: Weissberg, A.; Portnoy,
M. Chem. Commun. 2003, 1538.
Synlett 2003, No. 12, 1883–1885 © Thieme Stuttgart · New York