1 catalytic asymmetric nozaki- hiyama-kishi reaction: role of organochromium compounds and novel...
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CATALYTIC ASYMMETRIC NOZAKI-HIYAMA-KISHI REACTION: ROLE OF ORGANOCHROMIUM COMPOUNDS
AND NOVEL SALEN LIGANDS
ARKAJYOTI CHAKRABARTY
Prof. Uday Maitra’s GroupDepartment of Organic Chemistry
Indian Institute of Science
GRADUATE COLLOQUIUM
3.12.08
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CONTENTS OF THE TALK
INTRODUCTION TO ORGANOCHROMIUM COMPOUNDS
‘NOZAKI-HIYAMA-KISHI’ REACTION
CATALYTIC AND ENANTIOSELECTIVE VERSION OF ‘NHK’ REACTION
NOVEL SALEN LIGANDS ( I & II ) IN ENANTIOSELECTIVE CATALYSIS
CONCLUSION AND REFERENCES
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ORGANOCHROMIUM COMPOUNDS
Chromium(II) reagents are powerful one electron reducing agents
Cr(II) readily inserts into allyl-, alkenyl-, alkynyl-, propargyl- and aryl halides and sulfonates under aprotic conditions, giving rise to the corresponding organochromium(III) reagents Traces of nickel salts exert a catalytic effect on the formation of the C-Cr(III) bond
Cr3++ e- Cr2+ EO = - 0.408 V
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ORGANOCHROMIUM COMPOUNDS AS NUCLEOPHILES
R- YCrX2
(I I )
R
(I I )
R-CrX2Y
(I I I )E+
R- E
CrX3transmetalation
R- M
CrX2
NHK manifold
A. Furstner, Chem. Rev. 1999, 99, 991-1045
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‘NOZAKI-HIYAMA-KISHI’ REACTION
In Nozaki-Hiyama-Kishi reaction, CrCl2 adds to unsaturated halide to form organochromium(III) compounds, which are used as nucleophiles for coupling with aldehyde
For less reactive substrates such as alkenyl and aryl halides or triflates, doping CrCl2 with catalytic amount of Ni(II) or Mn(0) is a standard trick
The driving force of these reactions is the formation of highly stable O-Cr(III) bond
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TYPICAL EXAMPLES OF NHK REACTIONS
R O +X CrCl2
THF/ 25 OC60- 94 %
R
OH
O
BrO
OO
CrCl2
THF25 oC
CO2CH3
O
O
O
CO2CH3
OH
O
I
HH
TBDMSOO
HH
TBDMSO
CrCl2cat. NiCl2
DMSO25 oC65 %
OHO
A. S. K. Hashmi, J. Prakt. Chem. 1996, 338, 491-495
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NHK REACTIONS CATALYTIC IN CHROMIUM
X
CrX2CrX3CrX3
MnMnX2
CrX2
R
OCrX2
RCHO
Me3SiX
R
OSiMe3
A
B
C
A. Furstner et al. , J. Am. Chem. Soc. 1996, 118, 12349-12357
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ENANTIOSELECTIVE VERSION OF NOZAKI-HIYAMA-KISHI
REACTION
First report of enantioselective NHK reaction involves salen as chiral ligand derived from trans-1,2-diaminocyclohexane
N
OH
tBu
tBu
N
HO
tBu
tBu
H HR R
(R,R)-N,N’-bis(3,5-di-tert-butyl-salicylidene)-1,2-cyclohexanediamine ( I )
A. Umani-Ronchi et al., Angew. Chem. Int. Ed. 1999, 38, 3357-3359
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HOW DOES SALEN ( I ) WORK AS THE CHIRAL LIGAND?
CrCl2
Salen
2 [CrI I(Salen)] [CrI I I(Salen)]X
Mn
MnX2
X(Salen)CrI I I
R
OCrI I I(Salen)
RCHO
Me3SiX
R
OSiMe3
N O
tBu
tBu
N O
tBu
tBu
H
H
CrI I
Cr(Salen)
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ENANTIOSELECTIVE NHK REACTIONS CATALYZED BY [Cr
(salen)] COMPLEX
Cl
Entry R-X Yield [ % ] ee [ %]
1.
2.
3.
67
65
70
84 ( R)
65 ( R)
0
Br
I
CrCl3Mn
CH3CNCrCl2
Salen
Et3N[Cr (Salen)]
RCHO[Cr (Salen)]10 mol %1.
X
X = Cl, Br, I2. Me3SiCl
3. H+
R
OH
RR
OH
OH2 3
Table-1: Enantioselective addition of various allyl halides to PhCHO catalyzed by [Cr(salen)] complex
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ENANTIOSELECTIVE NHK REACTIONS CATALYZED BY [Cr
(salen)] COMPLEX
Entry
R’CHO Yield of 2[ % ]
Yield of 3 [ % ]
ee of 2 [%]
1.
2.
3.
67
41
42
16
40
0
78 ( R )
77 ( R )
89 ( R )
Me
CHO
CHO
F
CHO
Table-2: Enantioselective addition of allyl chloride to aldehyde catalyzed by
Cr (salen) complex
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SYN DIASTEREOSELECTIVE ADDITION PROMOTED BY CHIRAL Cr(salen)
COMPLEX
ArCH2OCrCl2 10%
Salen 20 %Mn, Me3SiCl
H+
Ar
OH
Me
syn:anti = 65 : 35 / 85 : 15
ee = 82- 90 %
Br
Hypothetical open transition state for the addition of crotyl bromide to ArCHO
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A BRIEF EXPLANATION This syn diasteroselective addition is unique as normally aldehydes react with stereogenic allylchromium reagents to afford homoallylic alcohols with excellent degree of anti
selectivity
A cyclic Zimmerman-Traxler transition state is thought to be involved in this reaction
Two molecules of Cr-salen complexes are involved in the transition state
A. Umani Ronchi et al. , Polyhedron 2000, 19, 537-539
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LIMITATIONS OF SALEN LIGAND ( I ) IN ENANTIOSELECTIVE NHK
REACTION
The substrate spectrum is fairly narrow
Ally bromide and iodide were found to add with only moderate ( 52 % ee ) or no selectivity to benzaldehyde
Using this asymmetric NHK process, enantiomerically enriched allylic alcohols can not be generated starting
from vinylic halides
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HOW TO SURPASS THE CURRENT LIMITATIONS?
Modification of the chiral diamine backbone of the salen ligand can lead to better catalytic properties in NHK reactions
A chiral diamine having a larger nitrogen-atom separation may prove to be useful building block for a highly enantioselective catalyst in the asymmetric NHK reaction
Ar
N
Ar
N
H HR R
Salen ( I )
A Highly Enatioselective Catalyst
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A NOVEL SALEN LIGAND ( II ) BASED ON DIANANE
S S
N N
OH
tBu
tBu HO
tBu
tBu
(S,S)- 2
C2 AXI S
This chiral salen ligand has the advantages of possessing C2 symmetry and having a rigid hydrocarbon backbone and the separation between nitrogen atom is larger which
plays an important role in improving the catalytic properties
Ian Paterson et al. , Angew. Chem Int. Ed. 2003, 42, 1032-1035
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ENANTIODIVERGENT SYNTHESIS OF (S,S)-2 AND (R,R)-2
HCO2H
reflux84 %
OCHO
OHCO
J ones reagent
44 %
O
O rac
(1) NH2OH.HCl EtOH, reflux, 1h(2) NiCl2, NaBH4 MeOH,- 35 OC to - 20 oC, 1h 70- 75 %
(3)TsCl, NEt3, CH2Cl2 - 78 oC to rt
NHTs
NHTs
rac
1. Preparative HPLC
2. Li, NH3, - 33 OC 80 min, 85 %
S S
R R
NH2 NH2
NH2 NH2(S,S)
(R,R)
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ENANTIODIVERGENT SYNTHESIS OF (S,S)-2 AND (R,R)-2
( CONTD...)
S S
NH2NH2
(S,S)
S S
N N
OH
tBu
tBu HO
tBu
tBu
(S,S)- 2
CHO
OH
tButBu
MeOHRT, 30 min76- 81 %
R R
NH2NH2
(R,R)
CHO
OH
tButBu
MeOHRT, 30 min76- 81 %
N
OH
tBu
tBu HO
tBu
tBu
(R,R)- 2
R R
N
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CATALYTIC PERFOMANCE OF (S,S)-2
Entry Aldehyde Halide Product ee ( % ) Yield ( % )
1 90 72
2 31 Not Determined
3 79 76
4 54 78
5 64 Not Determined
Ph
O
H
Ph
O
H
Ph
O
H
Ph
O
H
Ph
O
H
Br
I
Cl
Cl
Cl
Ph
OH
Ph
OH
Ph
OH
Ph
OH
Ph
OH
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CATALYTIC PERFOMANCE OF (S,S)-2 ( CONTD…..)
Entry Aldehyde Halide Product ee ( % ) Yield ( % )
6. 92 69
7. 75 59
8. 61 54
Br
I
OTf
PMBO H
O
PMBO H
O
PMBO H
O
PMBO
OH
PMBO
OH
R*
PMBO
OH
R*
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SALIENT FEATURES OF THE CATALYTIC PERFOMANCE OF (S,S)-2
The addition of allyl bromide to benzaldehyde proceeded with high enantioselectivity ( 90 %) and good yield ( 72 % )
THF proved to be the best solvent for these catalytic asymmetric reactions and catalyst concentration of 0.025 M gave the best results
In contrast to salen ligand 1, ligand 2 was able to effect an enantioselective addition of allyl iodide
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SALIENT FEATURES OF THE CATALYTIC PERFOMANCE OF (S,S)-2 ( CONTD…)
Using this ligand, it was possible to synthesise alylic alcohols
in enantioselective fashion from vinyl iodides and triflates
Presence of 2 mol % of NiII was required for these coupling
reactions to occur efficiently
Vinyl halide gave 59 % yield with 75 % ee
Vinyl triflate gave 61 % ee
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CONCLUSION
Organochromium reagents take part as nucleophiles in versatile C-C bond forming reaction involving wide range of functionality
The novel salen ligands ( I & II ) play important role in catalytic and enantioselective Nozaki-Hiyama-Kishi reactions
The DIANANE-based salen ligands, (S,S)-II and (R,R)-II promote the asymmetric additions of allyl iodide and vinyl halides and triflates with useful levels of enatioselectivity
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REFERENCES
1. A. Frustner, Chem. Eur. J. 1998, 4, 567-570
2. C. Chen, K. Tagami, Y. Kishi, J. Org. Chem. 1995, 60, 5386-5387
3. M. Bandini, P.G. Cozzi, A. Umani-Ronchi, Chem. Commun. 2002, 919-927
4. R. T. Hawkins, R. S. Hsu, S. G. Wood, J. Org. Chem. 1978, 43, 4648-4650
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THANK YOU
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