Mechanism of Electrophilic Chlorination:  Experimental Determination of a Geometrical Requirement for Chlorine Transfer by the Endocyclic Restriction Test

Abstract

An endocyclic restriction test for acid-catalyzed transfer of chlorine from a protonated chloroamine to an aromatic ring provides data that are consistent with a transition structure with a large bond angle between the entering and leaving groups around chlorine. These results rule out a dissociative mechanism or a mechanism that has an oblique angle between the entering and leaving groups.

Benzannulation via the Reaction of Ynamides and Vinylketenes. Application to the Synthesis of Highly Substituted Indoles

“…Reaction of a solution of carbamate 10 44 (0.683 g, 5.21 mmol, 1.0 equiv) in 21 mL of THF with KHMDS (5.8 mL, 0.91 M in THF, 5.3 mmol, 1.0 equiv), pyridine (10.0 mL, 9.78 g, 124 mmol, 23.8 equiv), CuI (0.992 g, 5.21 mmol, 1.0 equiv), and bromo alkyne 15 5 (13 mL, 0.60 M in benzene, 7.8 mmol, 1.5 equiv) according to the general procedure afforded 2.235 g of a brown oil. Column chromatography on 110 g of silica gel (gradient elution 0–5% EtOAc-hexanes) gave 0.517 g of a yellow oil.…”

Synthesis of versatile TIPNO-based alkoxyamines

“…Here, starting with 4, we have prepared in two steps alkoxyamines with different amino substituents. Methylcarbamic acid tert-butyl ester 5 [57] was deprotonated by sodium hydride in DMF and condensed with 4 to afford the carbamate alkoxyamine 6 (Scheme 3) with a yield of 89%. Under the same conditions, methylcarbamic acid tert-butyl ester 5 was also coupled with vinyl benzyl chloride to give the vinylcarbamate 7 (Scheme 4) with a yield of 47%.…”

“…The following derivatives, 2,2,5-trimethyl-4-phenyl-3-azahexane-3-oxyl (TIPNO) 2 [3], 2,2,5-trimethyl-3-(1-(4 0 -chloromethyl)phenylethoxy)-4-phenyl-3-azahexane 4 [49], O-[1-(4-azidomethyl-phenyl)-ethyl]-N-tert-butyl-N-(2-methyl-1-phenylpropyl)-alkoxyamine 11 [55], Mn(Salen)Cl 3 [49], methylcarbamic acid tert-butyl ester 5 [57] were synthesized according to literature procedures. [48] (1)…”

Chloramphenicol Biosynthesis: The Structure of CmlS, a Flavin-Dependent Halogenase Showing a Covalent Flavin–Aspartate Bond

“…It is well known that chloramines require either specific or general acid catalysis to react with nucleophiles, the type of catalysis dictated by the strength of the nucleophile. 40,41 A proton relay, initiated by E44, could deliver the required proton during the chlorination transition state. It is also possible that E44 could act remotely as a general base to assist the generation of the enolate for subsequent chlorination.…”