Transcript catalytic asymmetric nozaki-hiyama-kishi reaction

CATALYTIC ASYMMETRIC NOZAKIHIYAMA-KISHI REACTION: ROLE OF
ORGANOCHROMIUM COMPOUNDS
AND NOVEL SALEN LIGANDS
GRADUATE COLLOQUIUM
ARKAJYOTI CHAKRABARTY
3.12.08
Prof. Uday Maitra’s Group
Department of Organic Chemistry
Indian Institute of Science
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CONTENTS OF THE TALK
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INTRODUCTION TO ORGANOCHROMIUM COMPOUNDS
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‘NOZAKI-HIYAMA-KISHI’ REACTION
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CATALYTIC AND ENANTIOSELECTIVE VERSION OF ‘NHK’
REACTION
NOVEL SALEN LIGANDS ( I & II ) IN ENANTIOSELECTIVE
CATALYSIS
CONCLUSION AND REFERENCES
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ORGANOCHROMIUM COMPOUNDS
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Chromium(II) reagents are powerful one electron reducing
agents
Cr(II) readily inserts into allyl-, alkenyl-, alkynyl-, propargyland 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
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ORGANOCHROMIUM COMPOUNDS
AS NUCLEOPHILES
A. Furstner, Chem. Rev. 1999, 99, 991-1045
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‘NOZAKI-HIYAMA-KISHI’ REACTION
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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
A. S. K. Hashmi, J. Prakt. Chem. 1996, 338, 491-495
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NHK REACTIONS CATALYTIC IN
CHROMIUM
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
(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?
Cr(Salen)
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ENANTIOSELECTIVE NHK REACTIONS
CATALYZED BY [Cr (salen)] COMPLEX
Table-1: Enantioselective addition of various allyl halides to PhCHO catalyzed
by [Cr(salen)] complex
Entry
R-X
Yield [ % ]
ee [ %]
1.
67
84 ( R)
2.
65
65 ( R)
3.
70
0
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ENANTIOSELECTIVE NHK REACTIONS
CATALYZED BY [Cr (salen)] COMPLEX
Table-2: Enantioselective addition of allyl chloride to aldehyde catalyzed by
Cr (salen) complex
Entry
R’CHO
Yield of 2
[ % ]
Yield of 3
[ % ]
ee of 2
[%]
1.
67
16
78 ( R )
2.
41
40
77 ( R )
3.
42
0
89 ( R )
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SYN DIASTEREOSELECTIVE ADDITION
PROMOTED BY CHIRAL Cr(salen) COMPLEX
Hypothetical open transition state for
the addition of crotyl bromide to ArCHO
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A BRIEF EXPLANATION
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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
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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?
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Modification of the chiral diamine backbone of the salen
ligand can lead to better catalytic properties in NHK reactions
A Highly
Enatioselective Catalyst
Salen ( I )
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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
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A NOVEL SALEN LIGAND ( II ) BASED
ON DIANANE
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
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ENANTIODIVERGENT SYNTHESIS OF
(S,S)-2 AND (R,R)-2 ( CONTD...)
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CATALYTIC PERFOMANCE OF (S,S)-2
Entry Aldehyde
Halide
Product
ee ( % )
Yield ( % )
1
90
72
2
31
3
79
76
4
54
78
5
64
Not Determined
Not Determined
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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
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SALIENT FEATURES OF THE CATALYTIC
PERFOMANCE OF (S,S)-2
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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…)
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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
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Vinyl halide gave 59 % yield with 75 % ee
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Vinyl triflate gave 61 % ee
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CONCLUSION
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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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