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tation of Pineno-Salen Type Ligand for Enantioselective Nozaki-H
Ajam C. Shaikh and Chinpiao Chen
Introduction
Department of Chemistry, National Dong Hwa University, Soufeng, Hualien 97401,
Taiwan, Republic of China.
The formation of carbon-carbon bonds is one of the most widely studied areas in organic synthesis. One
class of carbon-carbon bond forming reactions involves the nucleophilic addition of vinyl or allyl organometallics
to aldhydes, yielding allylic or homoallylic alcohols. The stereochemical
unpredictability of these allyl and vinyl organometallics often limit their
use in natural products synthesis, restricting their role to early synthetic
steps where functionality is typically unlimited. The Nozaki-Hiyama
reaction was first reported in the late 1970’s1 and has proven to be a
highly versatile procedure for the formation of C-C bonds involving the
nucleophilic addition to carbonyl compounds with intermediacy of
organochromium(III) reagents. The reports by Fürstner2 and Shi3, with
catalytic amounts of chromium, are of considerable interest. In fact,
Cr(II) or Cr(II)/Ni(II) mediated reactions are unique in terms of scope
and chemoselectivity.
Results and Discussion
In the course of our work, several types of chiral ligands were tested in the reaction of allylchromium complexes with benzaldehyde, but best results were obtained by ligand 1. The chiral organometallic allyl-Cr (pineno-salen)
complex was prepared in situ by adding solution of 15 mol% of 1 to the THF solution of 5
mol% anhydrous CrCl3 and Mn followed by treatment with allyl bromide. Subsequent
treatment of benzaldehyde and trimethylsilyl choride at room temperature yielded 95% of
product with 71% of the enantioselectivity. Further optimization of reaction conditions by
lowering down the amount of ligand 1 from 15 mol% to 5 mol% showed promising results
with increased enantioselectivity and yield up to 77% and 97% respectively. Low
temperature conditions found to be hampering to the yield as well as asymmetric induction
to the product. Therefore applicability of this protocol to the substrates carrying various
functional groups have been proposed with 5 mol% of ligand 1, 5 mol% of CrCl3 and 1.5 eq. of allyl bromide with
substrates at room temperature. Notably, outcomes of this condition were exciting, which are stipulated in the
following Table.1.
Table.1 Enantioselective addition of allyl bromide to aldehydes catalyzed by ligand 1
Entry
Substrate
(-R)
Temp. (oC)
Time (h)
Ligand
(mol%)
Yield (%)
Ee (%)
1
m-CN
RT
20
5
61
57
2
H
RT
20
5
97
77
3
o-Me
RT
20
5
93
65
4
p-Cl
RT
20
5
55
66
5
o-OMe
RT
20
5
84
54
Conclusions
In summary, we have prepared a new type of pineno-salen ligand 1, which promote efficient and good
enantioselective catalytic Nozaki-Hiyama reactions. Notably, generality and functional-group compatibility of this
catalytic carbon–carbon bond-forming process is one of the salient features of this protocol.
References
1) Okude, Y.; Hirano, S.; Hiyama, T.; Nozaki, H. J. Am. Chem. Soc. 1977, 99, 3179; 2) Fürstner, A. Chem. Rev.
1999, 99, 991; 3) Fürstner, A.; Shi, N. J. Am. Chem. Soc. 1996, 118, 12349.