The resolution of trans-2,2-dichloro-3-methylcyclopropanecarboxylic acid via crystallization of its salts with (+)- and (−)-α-phenylethylamine, and the transformation of the resulting enantiomers into (R)- and (S)-dimethyl 2-methylsuccinates

Chiral methyl trans-2,2-dichloro-3-methylcyclopropanecarboxylate upon exposure to thiophenolate nucleophile

“…[1][2][3][4][5][6][7][8][9][10][11] These compounds are excellent building blocks due to their availability in high enantiomeric purity, simple techniques of preparation, and a substantial synthetic potential of the cyclopropane ring. [12][13][14][15] For example, they were utilized in the asymmetric synthesis of pyrethroids 1,2 and other natural products, 3,4 stereoregular oligocyclopropanes, 5 chiral biaryls, 6 and liquid crystals.…”

“…7 In a recent article we efficiently resolved racemic trans-2,2-dichloro-3-methylcyclopropanecarboxylic acid into enantiomers 1. 10 Further, the chiral acid (1R,3S)-1 was used in the construction of the methyl branched chain of the pine sawfly sex pheromone. 11 β-Halogen atoms in esters, amides or nitriles of 1 may easily be substituted with nucleophiles and this property gives an additional method of functionalization of cyclopropane compounds.…”

“…[16][17][18][19][20] Recently, numerous examples of stereoselective substitution in monobromocyclopropanes with heteroatomic nucleophiles have been described. 21,22 In continuation of our research, 10,11 the substitution of halogens by thiophenoxy groups in the chiral acids 1 has become the object of investigation. The stereochemistry of the dithiocyclopropanes obtained and the process of the cyclopropane ring opening were studied.…”

“…An alternative route to optically pure acids 5 could be realized via the resolution of the racemic acid but this attempt appeared to be less effective. In view of our previous results, 10 when individual enantiomers of acid 1 had been easily obtained from racemate by crystallization of the (R)-and (S)-α-phenylethylamine salts, the same procedure was applied to acid 5. First, racemic acid 5 was obtained from correspondent ester (±)-2, as well as chiral (1R,3S)-5 (Scheme 3).…”

“…Finally, the process of the ring cleavage of dithiocyclopropanes obtained was investigated, because the derivatives of acids 5, as well as acids 1, could be the precursors of useful 1,4-bifunctional chiral compounds with an isopentane skeleton. 10,11 Ester (1RS,3S)-4, as described above, demonstrates high stability during long-term heating under basic conditions (Scheme 1), but similar gem-diphenylthiocyclopropyl ketones are known to be easily transformed into S-phenylalkanethioate or ketene diphenylthioacetals under acidic catalysis. 23,24 The experiments showed that ester (1RS,3S)-4 was unreactive in aqueous formic acid and even in a refluxing mixture of acetone and hydrochloric acid.…”