Exploitation of Pineno-Salen Type Ligand for Enantioselective Nozaki-Hiyama Reaction

1. Exploitation of Pineno-Salen Type Ligand for Enantioselective Nozaki-Hiyama Reaction Ajam C. Shaikh and Chinpiao Chen Department of Chemistry, National Dong Hwa University, Soufeng, Hualien 97401, Taiwan, Republic of China. Introduction 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 allylorganometallics to aldhydes,yielding allylic or homoallylic alcohols. The stereochemical unpredictability of these allyl and vinyl organometallics often limittheir 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 intermediacyof organochromium(III) reagents. The reports by Fürstner2 and Shi3, with catalytic amounts of chromium, are of considerable interest. In fact, Cr(II)orCr(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 complex- es 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 carryingvarious 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.1Enantioselective addition of allyl bromide to aldehydes catalyzed by ligand1 1 m-CN RT 20 5 61 57 2 H RT 20 5 77 97 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 • 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.