Download Catalytic asymmetric carbonyl addition reactions catalysed by group

Catalytic asymmetric carbonyl addition reactions catalysed by group 10 metals
The addition of a nucleophilic species to the
carbonyl group is one of the most important
methodology for carbon-carbon bond construction
and various solutions have been offered to
achieve an asymmetric version.
OH
O
+
R1
M(Ni, Pd, Pt)*
Nu
R1
R2
*
R2
Nu
Among those, recourse to group 10 transition elements has received growing attention only in recent years.
This letter briefly highlights the use of chiral Ni-, Pd- and Pt-derived complexes in the transformation portrayed in
general terms in the Scheme above.
Asymmetric Aldol-type condensation 1-4
Asymmetric Aldol-type condensation has been realised in the presence of several Pt(II) and Pd(II) complexes with C-2
symmetry.
Thus, the cationic complex prepared in situ by
reaction of 1 with AgOTf catalysed the
condensation of benzaldehyde with methyl αisocyanoacetate in CH2Cl2 at rt to give a mixture of
trans/cis 2-oxazoline 3 (EWG = CO2Me ; trans/cis :
70/30) in up to 65% ee for the major trans
diastereomer. Similarly, cationic aqua complexes 2
catalysed the condensation of benzaldehyde with
tosMIC in THF at rt to give the sole trans 2oxazoline 3 (EWG = Tos) with 57% ee (M = Pd) and
68% ee (M = Pt), respectively .
EWG
Ph-CHO
+
O
O
Ph3P
Pt
O
O
O
O
PPh3
N
M
Cl
H
Hünig's base
(10-12 mol %)
cat* (1.5-2 mol %)
N C
Ph
EWG
HO
C
Ph
O
N
N
H
M = Pt, Pd
2
1
O
BF4
EWG
N
3
CH
Asymmetric Mukaiyama aldol condensation of acetophenone silyl enol ether with benzaldehyde to give aldol
product 4 was achieved in up to 71% ee in the presence of 5 mol% of the cationic complex generated from PdCl2(R)-binap 5 and AgOTf in wet DMF in the presence of 4Å molecular sieves.
cat* (5 mol %)
23°C, 16h
OSiMe3
Ph
+
Ph-CHO
O
OSiMe3
Ph
96%
Ph
PPh2
PPh2
4
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. PdCl2
5
Page 1/1
Asymmetric ene-reaction 5-6
The palladium dicationic complex 6 was shown to catalyse the ene reaction of 1,1-disubstituted and trisubstituted
olefins with ethyl glyoxylate to give α-hydroxy-esters (e.g. 8) in excellent chemical yields and with enantioselectivities
ranging from 73 to 88%. The same reaction could also be executed at –50°C in CH2Cl2 with equal efficiency (85%
ee) in the presence of the complex (2 mol%) prepared in situ by reaction of 7 with AgOTf, and pentafluorophenol as
an additive.
2
2SbF6
P(tol) 2
P(tol) 2
MeO
PAr2
MeO
PAr2
. PdCl2
. Pd(CH3CN)2
7 Ar = p-tert-Bu-Ph
6
10 mol% 6
O
+
O
H
Et
Cl(CH2)2Cl/tol :1/2
O
OH
CO2Et
97%
8 88% ee
Asymmetric cyclisation of ω–formyl-1,3-dienes 7
Nickel-catalysed cyclisation of 1,3-diene and tethered aldehyde groups has been realised
in an asymmetric manner by using a catalytic amount of chiral phosphorane 9 in the
presence of silanes. For instance, cyclisation of prochiral diene-aldehyde 10 using
Ni(cod)2 and ligand 9 in the presence of (EtO)3SiH in a polar solvent (DMF or CH3CN)
afforded a mixture of cyclisation products 11 (73% ee) and 12 in a ratio of 50 :1. Use of
other silanes and non-polar solvents (THF, toluene) gave less satisfying results both in
term of chimioselectivity (ratio 11 :12) and enantioselectivity.
MeO2C
CHO
MeO2C
10
Ni(cod)2 (10 mol %)
9 (20 mol %)
(EtO)3SiH 4 equiv.
MeO2C
CH3CN, -30°C, 8h
MeO2C
83%
OSi(OEt)3
+
Me
11
Me
P
Me
Ph
9
OSi(OEt)3
MeO2C
MeO2C
12
Desymmetrisation of a cyclic anhydride 8
Desymmetrisation of anhydride 13
Ni(cod)2 (10 mol %)
conducted in the presence of diethylzinc
14 (12 mol %)
(1.2-1.5 equiv.), Ni(cod)2 (10 mol %), pO
H
ZnEt2, 1.5 equiv.
trifluoromethylstyrene (0.2 equiv.) and
O
chiral phosphino-oxazoline ligand 14 (12
THF, 0°C, 3h
mol %) in THF afforded the γ-keto acid 15
85%
H
O
in up to 79% ee. Use of CHIRAPHOS as
the ligand provided higher ee (88%) but
13
the chemical yield of the transformation
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H O
OH
Et
H
15
O
PPh2 N
O
14
Page 2/2
Asymmetric Nozaki-Hiyama-Kishi reaction 9
The Cr(III) / sulfonamide ligand complex 16, in the presence of TMSCl and Mn(0), was found to catalyse the Ni/Cr
mediated Nozaki-Hiyama-Kishi coupling reaction (e.g. formation of R-17 in c.a. 86 % ee). The same conditions were
applied to prepare a fragment of the marine natural product halochondrin B, a new anti-cancer drug candidate.
O
N
OMe
N Cr(Cl)2(THF)
SO2Me 16
Ph
CHO +
Me
I
16(10 mol %)
NiCl2 (10 mol %)
Mn (2 equiv.)
TMSCl (2 equiv.)
LiCl (2 equiv.)
NEt3.HCl(20 mol %)
OH
Ph
EtCN, rt
17
Asymmetric reductive coupling of alkynes and aldehydes 10-12
Nickel-catalysed intermolecular reductive coupling (exclusive cis-addition) of aryl-C≡C-alkyl
alkynes with aldehydes can be accomplished in the presence of a catalytic amount of the
commercially available (+)-(neomenthyl)-diphenylphosphine 18 (NMDPP) to give
trisubstituted allylic alcohols with excellent regioselectivity and in up to 96% ee. Variation of
the alkyne substituents are tolerated and branched aldehydes provide the best results. The
tranformation of allylic alcohols to α-hydroxy ketones further enhanced the synthetic utility of
the reaction (e.g. 19 →20).
Ph
NHBoc
+
OHC
Me
Me
Ni(cod)2 (10 mol %)
(+)-NMDPP (20 mol %)
Et3B (200 mol %)
Me
Me
Me
(+)-NMDPP 18
OH
Ph
AcOEt:DMI 1/1
Me
O
Me
Ni(cod)2 (10 mol %)
(R)- 21 (10 mol %)
BEt3 (2 equiv.)
Me
+
H
22
Me
Me
OHC
OTBS
AcOEt, 16h, rt
23
OH
BocHN
O
O
P
Fe
Me
Ph
(R)-21
H OTMS
OH
Me
OTBS
H
24
Me
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Me
Me
Me
20 (96% ee)
19 (96% ee)
Chiral ligand 18 was less suited to promote the reductive coupling of alkyl-C≡C-alkyl alkynes
with aldehydes in good enantioselectivities. In that case, a catalyst incorporating the Pferrocenylphosphine ligand (R)-21 gave encouraging results. As an illustration, nickel-catalysed
reaction of alkyne 22 with aldehyde 23 in the presence of ligand (R)-21 afforded mainly adduct
24 (70% combined chemical yield) which was next transformed to (-)-terpestacin, a
sesterterpene exhibiting anti-angiogenesis activity.
H OTMS
O3
Me
BocHN
60%
PPh2
2
Page 3/3
References
1. Ozawa, F.; Kubo, A.; Matsumoto, Y.; Hayashi, T, Nishioka, E.; Yanagi, K.; Moriguchi, K-I. Organometallics, 1993,
12, 4188-4196.
2. Gorla, F.; Togni, A.; Venanzi, L. M.; Albinati, A., Lianza, F. Organometallics, 1994, 13, 1607-1616.
3. Motoyama, Y.; Kawakami, H.; Shimozono, K.; Aoki, K.; Nishiyama, H. Organometallics, 2002, 21, 3408-3416.
4. Sodeoka, M.; Ohrai, K.; Shibasaki, M. J. Org. Chem. 1995, 60, 2648-2649.
5. Hao, J.; Hatano, M.; Mikami, K. Org. Lett. 2000, 2, 4059-4062.
6. Koh, J. H.; Larsen, A. O.; Gagné, M. R. Org. Lett. 2001, 3, 1233-1236.
7. Sato, Y.; Saito, N.; Mori, M. J. Am. Chem. Soc. 2000, 122, 2371-2372.
8. Bercot, E.A.; Rovis, T. J. Am. Chem. Soc. 2002, 124, 174-175.
9. Choi, H-W.; Nakajima, K.; Demeke, D.; Kang, F-A.; Jun, H-S,; Wan, Z-K.; Kishi, Y. Org. Lett., 2002, 4, 4435-4438.
10. Miller, K. M.; Huang, W-S.; Jamison, T. F. J. Am. Chem. Soc. 2003, 125, 3442-3443.
11. Colby, E. A.; Jamison, T. F. J. Org. Chem. 2003, 68, 156-166.
12. Chan, J.; Jamison, T. F. J. Am. Chem. Soc. 2003, 125, 11514-11515.
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