Stereochemistry of the Menthyl Grignard Reagent: Generation, Composition, Dynamics, and Reactions with Electrophiles.

Menthyl Grignard reagent 1 from either menthyl chloride (2) or neomenthyl chloride (3) consists of menthylmagnesium chloride (la), neomenthyl-magnesium chloride (1b), trans-p-menthane (4), 2-menthene (8), 3-menthene (9), and Wurtz coupling products including symmetrical bimenthyl 13. The diastereomeric ratio 1a/1b was determined in situ by C-13 NMR or after D2O quenching by H-2 NMR analysis. Hydrolysis of the C Mg bond proceeds with retention of configuration at C-1. The kinetic ratio la/lb from Grignard reagent generation (dr 59:41 at 50 degrees C in THF) is close to the thermodynamic ratio (56:44 at 50 degrees C in THF). Carboxylation of 1 at-78 degrees C separates diastereomers 1a/b to give the anion of menthanecarboxylic acid (19) from la, which combines with unreactive lb to give neomenthylmagnesium menthanecarboxylate (1b(1)). The kinetics of epimerization for the menthyl/neomenthylmagnesium system was analyzed (Delta H-double dagger = 98.5 kJ/mol, Delta S-double dagger =-113 J/mol.K for 1b(I) -> 1a(I)). Reactions of 1 with phosphorus electrophiles proceed stereoconvergently at C-1 of 1a/b to give predominantly menthyl-configured substitution products: PCl3 and 2 equiv of 1 give Men(2)PCl (6), which hydrolyzes to dimenthylphosphine P-oxide (7), whereas Ph2PCl with 1 equiv of 1 gave Pmenthyldiphenylphosphine oxide (27) after workup in air.