Highly Diastereoselective Addition of Phenyllithium on cis-Substituted C-Cyclopropylaldimines

Abstract

The addition of phenyllithium to cis-substituted C-cyclopropylaldimines produces in high diastereoselectivity and in good yields anti-(1-aminoalkyl)cyclopropanes as the major isomers.

cyclopropylaldimines - (1-aminoalkyl)cyclopropanes - phenyllithium

References and Notes

For reviews see:

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6

Cyclopropanecarboxaldehydes of type F have been synthesized by PCC oxidation of the corresponding alcohols, which have to be prepared by Simmons-Smith-Furukawa cyclopropanation⁹ of the corresponding cis-alkenes.

7

Synthesis of 4 as Representative Procedure.
All the reactions were performed under an argon atmosphere. To a stirred solution of cis-2-benzyloxymethyl-cyclopropanecarboxaldehyde (0.38 g, 2 mmol) in a 5:1 mixture of dry Et₂O (20 mL) and dry THF (4 mL), was added p-toluidine (0.214 g, 2 mmol). The resulting solution was stirred at r.t. for 4 h. The solvents were removed in vacuo and the residue was dried by azeotropic evaporation to give the pure crude imine 1 which was solubilized in dry Et₂O (15 mL). To this solution, stirred at 0 °C, was added PhLi (2 M in Bu₂O, 1.5 mL, 3 mmol). The resulting light brown solution was stirred from 0 °C to r.t. overnight and then diluted carefully with H₂O (20 mL). The organic layer was separated and the aqueous layer was extracted with CH₂Cl₂ (2 × 30 mL). The combined organic layers were dried over MgSO₄ and filtered. The solvents were removed in vacuo and the residue, which was mainly constituted by one diastereomer (GC-MS analysis showed a ratio anti/syn > 98:2), was purified by flash column chromatography on silica gel (90:10 PE-EtOAc) to provide anti-(1-amino-benzyl)cyclopropane 4 as a yellow oil (0.615 g, 86% yield). IR: 3367 (br), 1615, 1516, 1071, 809, 735, 697 cm^-1.
¹H NMR (CDCl₃): δ = 7.50-7.20 (10 H), 6.82 (d, J = 8.3 Hz, 2 H), 6.30 (m, 2 H), 4.78 (br s, 1 H), 4.43 (s, 2 H), 3.80 (dd, J = 10.2, 5.2 Hz, 1 H), 3.65 (d, J = 9.8 Hz, 1 H), 3.27 (t, J = 10.2 Hz, 1 H), 2.17 (s, 3 H), 1.45-1.20 (2 H), 0.82 (m, 1 H), 0.48 (m, 1 H). ¹³C NMR (CDCl₃): δ = 145.9 (C), 144.6 (C), 138.1 (C), 129.3 (2 CH), 128.7 (2 CH), 128.4 (2 CH), 127.8 (2 CH), 127.6 (CH), 126.9 (CH), 126.5 (C), 126.1 (2 CH), 114.2 (2 CH), 73.3 (CH₂), 70.2 (CH₂), 60.5 (CH), 26.1 (CH), 20.4 (CH₃), 17.1 (CH), 9.0 (CH₂). MS (EI): m/z (rel. int.) = 357 (10) [M⁺], 196 (10), 129 (10), 107 (55), 91 (100).

8 Benkouider A. Bouqaunt J. Pale P. New J. Chem.  2001,  25:  676 

9 Denmark SE. Edwards JP. J. Org. Chem.  1991,  56:  6974