Chlorination of bicyclo[1.1.1]pentane derivatives

Synthesis and Preliminary Biological Evaluation of 2′‐Substituted 2‐(3′‐Carboxybicyclo[1.1.1]pentyl)glycine Derivatives as Group I Selective Metabotropic Glutamate Receptor Ligands

“…Partial alkaline hydrolysis of the diester 13 provided the monoester 14 [17] (63 %) that was converted into the corresponding alcohol 15 by sodium borohydride reduction of the corresponding oxyanhydride (52 %). A Swern oxidation [19] of alcohol 15 led to the corresponding aldehyde 16 in 85 % yield which was submitted to condensation with (R)-a-phenylglycinol.…”

“…[16,17] Although the conversion of the dichloro derivative 13 into the monochloro form by the use of tributyltin hydride was previously reported (23 % yield), [17] we investigated the possibility to partially reduce the dichloro function by an alternative reducing agent. In our hands, tris(trimethylsilyl)silane, reported to be an efficient substitute for tributyltin hydride in radical-based reductions, [22] was able to convert 13 into 19 in good yield (63 %).…”

“…The synthesis and preliminary biological properties of the first representatives of this new class, namely (2R)-and (2S)-(2',2'-dichloro-3'-carboxybicyclo[1.1.1]pentyl)glycines ((R)-DCCBPG, 10) and ((S)-DCCBPG, 11) (Scheme 1), and 2-(2'-chloro-3'-carboxybicyclo[1.1.1]pentyl)glycine (MCCBPG, 12) (Scheme 2), are reported herein. [16][17][18] was used as the starting material for the preparation of our title compounds (Scheme 1).…”

“…2,2-Dichloro-3-(methoxycarbonyl)bicyclo[1.1.1]pentane-1-carboxylic acid (14): A solution of NaOH in methanol (2.5 m, 2.95 mL) was added dropwise to a magnetically stirred solution of dimethyl 2',2'-dichlorobicyclo[1.1.1]pentyl-1,3-dicarboxylate (13) [16,17] (0.190 g, 7.38 mmol) in dry THF (57 mL), and the resulting mixture was stirred at room temperature for 30 min. The solvent was partially removed, the residue was diluted with water (50 mL), and the aqueous phase was extracted with CH 2 Cl 2 (3 30 mL).…”

Coupling between Substituents as a Function of Cage Structure: Synthesis and Valence Ionized States of Bridgehead Disubstituted Parent and Hexafluorinated Bicyclo[1.1.1]pentane Derivatives C5X6Y2

“…Commercially available tris(trimethylsilyl)silane (Aldrich), tert ‐butyl peroxide (Aldrich), chlorine (Aldrich), aqueous ammonia (Fisher Scientific), and phosphorus pentoxide (Fisher Scientific) were used without purification. The syntheses of 1 ,40 1,3‐Cl 2 ‐ 1 ,41 1,3‐Br 2 ‐ 1 ,42 1,3‐I 2 ‐ 1 ,43 1,3‐(CN) 2 ‐ 1 ,44 1,3‐Br 2 ‐2,2‐Cl 2 ‐ 1 ,45 1,3‐Br 2 ‐ 2 ,30 and 1,3‐I 2 ‐ 2 30 were reported previously.…”