Borohydride and cyanoborohydride reduction of thioimonium salts. A convenient route for transformation of amides to amines

Abstract

In the synthesis of deethylcatharanthine via the chloroacetamide photopyclization route recently reported from our laboratory,1 the final stage of the synthesis required

Randomized comparison of self-fixating and sutured mesh in open inguinal hernia repair

“…The reaction was found to be efficient when operating on a small scale (200 mg), but on a multigram scale (10 g) the yields were not reproducible. For this reason, we shifted toward the preparation of methyl isothiouronium salt 6 , obtained by reaction of 4 with MeI in THF,22 which was not isolated but directly reduced with NaBH 3 CN in MeOH/AcOH (pH 5) to afford pure amine 5 (64 %) (Scheme ).…”

1H‐Azepine‐4‐amino‐4‐carboxylic Acid: A New α,α‐Disubstituted Ornithine Analogue Capable of Inducing Helix Conformations in Short Ala‐Aib Pentapeptides

“…The reaction was found to be efficient when operating on a small scale (200 mg), but on a multigram scale (10 g) the yields were not reproducible. For this reason, we shifted toward the preparation of methyl isothiouronium salt 6, obtained by reaction of 4 with MeI in THF, [22] which was not isolated but directly reduced with NaBH 3 CN in MeOH/AcOH (pH 5) to afford pure amine 5 (64 %) (Scheme 3).…”

Synthesis by Reduction

“…[251] In a second example, the thioamide 171 is activated by S-alkylation with iodomethane to give the iminium salt 172, which is reduced with the very mild reducing agent sodium cyanoborohydride at pH 4 to form the b-aminopropanoate 173 in 53% yield (Scheme 41). [253] This example demonstrates the compatibility of the ester group with this reduction method. [253] Scheme 41 Reduction of S-Alkylthioimidates with Hydrides [251,253] 164 Lawesson 3a-(1,3-Benzodioxol-5-yl)-2,3,3a,4,7,7a-hexahydro-1H-indol-3-yl Acetate (155): [245] SnCl 4 •2Et 2 O (400 mg, 1.05 mmol) and NaBH 4 (180 mg, 4.76 mmol) were added quickly in three portions to a cooled soln of imidate 154 (470 mg, 1.37 mmol) in DME (15 mL), and the mixture was stirred at 0 8C for 40 min.…”

“…[253] This example demonstrates the compatibility of the ester group with this reduction method. [253] Scheme 41 Reduction of S-Alkylthioimidates with Hydrides [251,253] 164 Lawesson 3a-(1,3-Benzodioxol-5-yl)-2,3,3a,4,7,7a-hexahydro-1H-indol-3-yl Acetate (155): [245] SnCl 4 •2Et 2 O (400 mg, 1.05 mmol) and NaBH 4 (180 mg, 4.76 mmol) were added quickly in three portions to a cooled soln of imidate 154 (470 mg, 1.37 mmol) in DME (15 mL), and the mixture was stirred at 0 8C for 40 min. Excess hydride was carefully decomposed by addition of H 2 O and the mixture was extracted with CH 2 Cl 2 .…”

“…The S-alkylation of thioamides can be performed using iodomethane instead of triethyloxonium tetrafluoroborate, demonstrating the high reactivity of the thioamide group in comparison with the amide group. [252,253] Moreover, sodium cyanoborohydride, a very mild reducing agent, can reduce the S-alkylthioiminium salts; [252][253][254] the reaction times are also markedly reduced.…”