A novel stereoselective synthesis of cis-2-fluorocyclopropane-1-carboxylic acid

Stereoselective Synthesis of cis-2-Fluorocyclopropanecarboxylic Acid

“…13 Synthesis of dl-cis-2-Fluorocyclopropanecarboxylic Acid (dl-1). 8,11 To a solution of trans-6b (660 mg, 2.20 mmol) in ethanol (11 mL) were added magnesium powder (160 mg, 6.59 mmol) and HgCl 2 (25.8 mg, 9.50 μmol); the mixture was stirred at room temperature for 16 h. The mixture was poured into a mixture of water (10 mL) and 0.5 mol/L aqueous HCl solution (1 mL), the resulting mixture was extracted with pentane. The organic extracts were dried over anhydrous sodium sulfate, filtered, and then concentrated in vacuo (45 °C, 756 mmHg) to give crude tert-butyl cis-2-fluorocyclopropanecarboxylate (418 mg).…”

“…6,7 The second approach (ii) involves the synthesis of precursors of 1 by way of cyclopropanation of butadiene with fluorocarbenoid species, 8,9 and the last approach (iii) includes a fluorination step of suitable intermediates using an F 2 gas. 10,11 The synthesis of optically active (S,S)-1 was achieved via enantioselective hydrolysis of the racemic esters of 1 by microorganisms or diastereomeric separation of the racemate 1 by recrystallization with chiral amine. 12,13 On the other site, asymmetric synthesis of N-protected 2 (iv) was accomplished with cyclopropanation of optically active N-vinyl oxazolidinone or N-vinyl lactam with fluorocarbenoid species.…”

“…46−48 As shown in Scheme 2, the relative stereochemistry of trans-6b was elucidated by conversion to dl-1 according to the reported procedure. 11 Similarly, the l-menthyl ester 6c was converted to the enantiomeric pair of 1 after diastereomeric HPLC separation (Scheme 3). The dephenylsulfonylation of (S,R)-6c was carried out successfully using magnesium powder in methanol, 49 and removal of the l-menthyl group with aqueous lithium hydroxide solution in tetrahydrofuran and methanol gave (S,S)-1 as a colorless solid.…”

“…The fluorine atom in both ( S , S )- 1 and ( R , S )- 2 is arranged in a cis configuration next to the carboxyl and amine groups, and complicates their stereoselective synthesis. Accordingly, numerous synthetic approaches to control the stereochemistry of the two adjacent stereogenic centers of these fluorine-containing cyclopropanes have been investigated. − …”

“…Representative approaches toward 1 can be categorized into three types (Figure ). The first type (i) consists of cyclopropanations of bromofluoroethene with diazoacetates. , The second approach (ii) involves the synthesis of precursors of 1 by way of cyclopropanation of butadiene with fluorocarbenoid species, , and the last approach (iii) includes a fluorination step of suitable intermediates using an F 2 gas. , The synthesis of optically active ( S , S )- 1 was achieved via enantioselective hydrolysis of the racemic esters of 1 by microorganisms or diastereomeric separation of the racemate 1 by recrystallization with chiral amine. , On the other site, asymmetric synthesis of N -protected 2 (iv) was accomplished with cyclopropanation of optically active N -vinyl oxazolidinone or N -vinyl lactam with fluorocarbenoid species. − Though many of the efforts have focused on the stereoselective synthesis of racemic or optically active 1 and 2 , there is room to improve the stereoselectivity. We herein report an efficient synthesis of dl - and ( S , S )- 1 via the stereoselective cyclopropanation of sulfonylalkene and diazoacetates.…”