Asymmetric 1,3-Dipolar Cycloaddition Reactions of Nitrile Oxides Catalyzed by Chiral Binaphthyldiimine-Ni(II) Complexes

Abstract

Asymmetric cycloaddition reactions between several nitrile oxides and 3-(2-alkenoyl)-2-oxazolidinones and 2-(2-alkenoyl)-3-pyrazolidinone derivatives were carried out in the presence of chiral binaphthyldiimine (BINIM)-Ni(II) complexes as catalysts. Using (R)-BINIM-4(3,5-xylyl)-2QN-Ni(II) complex (30 mol %), good regioselectivity (4-Me/5-Me = 85:15) along with high enantioselectivity (96% ee) of the 4-Me adduct were obtained for the reaction between isolable 2,4,6-trimethylbenzonitrile oxide and 3-crotonoyl-5,5-dimethyl-2-oxazolidinone. Substituted and unsubstituted benzonitrile oxides and aliphatic nitrile oxides, which were generated from the corresponding hydroximoyl chloride in the presence of MS 4A, were reacted with 3-crotonoyl-5,5-dimethyl-2-oxazolidinone, 5,5-dimethyl-3-(2-pentenoyl)-2-oxazolidinone, 5,5-dimethy-3-[3-(ethoxycarbonyl)propenoyl]-2-oxazolidinone, 1-benzyl-2-crotonoyl-5,5-dimethyl-3-pyrazolidinone, and 1-benzyl-2-[3-(ethoxycarbonyl)propenoyl]-5,5-dimethy-3-pyrazolidinone in the presence of (R)-BINIM-4Ph-2QN-Ni(II) or (R)-BINIM-4(3,5-xylyl)-2QN-Ni(II) complexes (10-30 mol %) as catalysts to give the corresponding cycloadducts in high yields, with high regioselectively (4-R/5-R = 85:15-99:1) and with moderate to high enantioselectivities (42-95% ee) of the 4-R adducts. Higher enantioselectivities and regioselectivities were obtained for the reactions using pyrazolidinone derivatives as the dipolarophiles. For the cycloadditions of 2-(2-alkenoyl)-1-benzyl-5,5-dimethyl-3-pyrazolidinones catalyzed by (R)-BINIM-4(3,5-xylyl)-2QN-Ni(II) complex (30 mol %), the enantioselectivity varied from 75% to 95% ee. The reactions between several nitrile oxides and 2-acryloyl-1-benzyl-5,5-dimethyl-3-pyrazolidinone in the presence of (R)-BINIM-4(3,5-xylyl)-2QN-Ni(II) complex (10 mol %) resulted in enantioselectivities (79-91% ee) that exceed those of previously reported enantioselective cycloadditions of acrylic acid derivatives. Furthermore, studies using a molecular modeling program using PM3 calculations were carried out to gain insight into the mechanisms of the asymmetric induction.

4.22 Intermolecular 1,3-Dipolar Cycloadditions of Alkenes, Alkynes, and Allenes

“…89 Recently, Suga and coworkers have disclosed a novel synthetic protocol featuring BINIM-Ni(II) complexes as chiral Lewis acid catalysts for the asymmetric cycloadditions of nitrile oxide (Scheme 87). 90 The nitrile oxides were generated from the corresponding hydroximoyl chloride 166 in the presence of MS 4 Å. The best result, in terms of enantioselectivity (96% ee), was achieved for the reaction of isolable 2,4,6-trimethylbenzonitrile oxide 167 and 3-crotonoyl-5,5-dimethyl-2-oxazolidinone 168a as the dipolarophile.…”

The Future of Catalysis by Chiral Lewis Acids

“…A major limitation that remains to the uses of nitrones in cycloaddition reactions is access to C-alkyl nitrones and reactivity/selectivity with those that are ketone derivatives. Dipolar cycloaddition reactions of nitrile oxides have received far less attention than those of nitrones [111][112][113]. By using a chiral N,N 0 -dioxideÀnickel (II) complex as a catalyst, good regioselectivities and excellent enantioselectivities were obtained in the 1,3-dipolar cycloaddition reaction of nitrile oxides with 3-arylidene-oxindoles (Scheme 23) [102].…”

Recent Advances in Nitrile Oxide Cycloadditions. Synthesis of Isoxazolines

“…Slow addition of the dipole was essential for obtaining higher enantioselectivities. Enantiomeric excess of up to 93% was achieved when 4-trifluoromethyl benzonitrile oxide was used as the dipole at -20 ºC ( Suga et al [64] have recently reported nitrile oxide cycloaddition to electron deficient olefins using a chiral nickel catalyst. The nitrile oxide was generated in situ by the dehydration of corresponding hydroximoyl chloride using molecular sieves.…”