Methyl (4R,5R)-(E)-3-(1,3-Dimethyl-4,5-diphenyl-2-imidazolidinyl)propenoate

[135212-29-2]  · C21H24N2O2  · Methyl (4R,5R)-(E)-3-(1,3-Dimethyl-4,5-diphenyl-2-imidazolidinyl)propenoate  · (MW 336.47)

(a chiral synthetic equivalent of methyl (E)-4-oxo-2-butenoate)

Physical Data: colorless needles (MeOH); mp 109-110 °C; [a]23D +45.0° (c 0.6, CHCl3);1 IR, 1H NMR, 13C NMR, MS spectral data, and X-ray structural data are also available.1

Solubility: very sol dichloromethane, chloroform, ethyl acetate, acetone; sol methanol, ethanol; hardly sol hexane.

Analysis of Reagent Purity: chiral HPLC.1

Preparative Methods: both the (4R,5R) and (4S,5S) compounds are readily available by condensation of optically active 1,2-bis(methylamino)-1,2-diphenylethanes2 with methyl (E)-4-oxo-2-butenoate.3

Pyrrolidine Synthesis.

The lithium (Z)-enolate of methyl N-benzylideneglycinate undergoes a cycloaddition rapidly at -78 °C with methyl (4R,5R)-(E)-3-(1,3-dimethyl-4,5-diphenyl-2-imidazolidinyl)propenoate (1) to give pyrrolidine-2,4-dicarboxylate in quantitative yield and as a single stereoisomer (eq 1).1 Removal of the chiral auxiliary from the cycloadduct can be readily performed by treatment with conc Sulfuric Acid in MeOH at rt to produce the optically pure pyrrolidine-2,4-dicarboxylate bearing an acetal substituent at the 3-position.

Asymmetric Nitrile Oxide Cycloadditions.

Although the dipolar cycloadditions of nitrile oxides with (1) are poor both in reactivity and regioselectivity, regioisomeric isoxazolines are obtained as single diastereomers (eq 2).4 Removal of the chiral auxiliary can again be performed by an acetal exchange reaction under reflux in MeOH in the presence of H2SO4.

Related a,b-Unsaturated Esters.

Similar a,b-unsaturated esters bearing a heterocyclic chiral auxiliary of a-amino acid origin at the b-position are known and have been utilized in asymmetric synthesis. Effective asymmetric conjugate additions of cuprates to (2),5 (3),6 and (5),7 epoxidations of (3),8 and dipolar cycloadditions of (2)9 have been reported. Although oxazolidine (4)10 is only obtained as an 86:14 equilibrating mixture of stereoisomers, reactions with the lithium (Z)-enolate of methyl N-benzylideneglycinate (see Ethyl N-Benzylideneglycinate) are exclusively diastereoselective.

1. Kanemasa, S.; Hayashi, T.; Tanaka, J.; Yamamoto, H.; Sakurai, T. JOC 1991, 56, 4473.
2. Mangeney, P.; Grojean, F.; Alexakis, A.; Normant, J. F. TL 1988, 29, 2675.
3. Bohlmann, F.; Inhoffen, E. CB 1956, 89, 1276.
4. Kanemasa, S.; Hayashi, T.; Yamamoto, H.; Wada, E.; Sakurai, T. BCJ 1991, 64, 3274.
5. (a) Asami, M.; Mukaiyama, T. CL 1979, 569. (b) Mukaiyama, T. T 1981, 37, 4111.
6. (a) Bernardi, A.; Cardani, S.; Poli, G.; Scolastico, C. JOC 1986, 51, 5041. (b) Bernardi, A.; Cardani, S.; Pilati, T.; Poli, G.; Scolastico, C. JOC 1988, 53, 1600.
7. Alexakis, A.; Sedrani, R.; Mangeney, P. TL 1990, 31, 345.
8. Cardani, S.; Bernardi, A.; Colombo, L.; Gennari, C.; Scolastico, C.; Venturini, I. T 1988, 44, 5563.
9. Kanemasa, S.; Yamamoto, H. TL 1990, 31, 3633.
10. Kanemasa, S.; Yamamoto, H.; Wada, E.; Sakurai, T.; Urushido, K. BCJ 1990, 63, 2857.

Shuji Kanemasa

Kyushu University, Kasuga, Japan

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