Highly Efficient Synthesis of New α‐Arylamino‐α′‐chloropropan‐2‐ones via Oxidative Hydrolysis of Vinyl Chlorides Promoted by Calcium Hypochlorite

Abstract

Abstract:The oxidative hydrolysis of different trifluoroacetyl-protected N-(2-chloroallyl)anilines, promoted by calcium hypochlorite, is able to yield several not previously described a-arylamino-a'-chloropropan-2-ones, very valuable building blocks that are useful as precursors of several drugs, in excellent yields and short reaction times. The main requirement of the reaction for avoiding the undesired aromatic chlorination (N-protection) is effectively solved by the use of the easily formed and removed N-trifluoroacetyl group. Thus, it is possible to perform the oxidative hydrolysis-deprotection step using a one-pot strategy, obtaining quantitative yields in very short reaction times.

Ring-Closing Synthesis of Dibenzothiophene Sulfonium Salts and Their Use as Leaving Groups for Aromatic 18F-Fluorination

“…Several hypochlorite salts mediated ring-closing of the thioether 10a ; however, yields varied considerably, and chlorination of the dimethoxy-substituted aromatic group became a prominent side reaction (results not shown). Eventually, we found that calcium hypochlorite, in an acetate-buffered (pH 4) water–acetone solvent system, 31 reacted cleanly with 10a to give the target sulfonium salt 11a in 43% yield within 15 min at room temperature ( Table 2 , entry 9) (Method B). The latter system is appealing, as it is exceptionally mild and relies exclusively on low-toxicity, biocompatible components.…”

Novel Enantiopure Sigma Receptor Modulators: Quick (Semi-)Preparative Chiral Resolution via HPLC and Absolute Configuration Assignment

“…The appropriate aryl-bromine was lithiated with an excess of tert -butyllithium ( t -BuLi) in anhydrous diethyl ether (Et 2 O) at −78 °C, followed by the addition of A : the desired tertiary alcohols 1 and 3 were obtained in practical yields. Subsequently, the so-obtained alcohols were subjected to dehydration with trifluoroacetic anhydride under copper(I) triflate catalytic conditions [20]. Purification on alumina column chromatography provided the olefins 2a and 4a , which were hydrogenated (Pd (0)/C 10% ( p / p )) to give the corresponding reduced amines 2 and 4 .…”

Chemoselective Synthesis of N‐Substituted α‐Amino‐α′‐chloro Ketones via Chloromethylation of Glycine‐Derived Weinreb Amides

“…Regardless of the nature of the halogen atom in the general structure of α‐amino‐α′‐halo ketones, it is clear that the substituents at the nitrogen atom have significant influence on the chemical reactivity and stability of these substrates 13. Only recently, some of us described a successful preparation of a series of α‐arylamino‐α′‐chloro ketones bearing different substituents at the nitrogen atom via a hypochlorite‐induced oxidative hydrolysis of N‐ trifluoroacetyl‐protected 2‐haloallylanilines 14,15. However, these studies revealed a huge effect of the N‐ protecting group on the oxidation reaction.…”

“…[12] Regardless of the nature of the halogen atom in the general structure of a-amino-a'-halo ketones, it is clear that the substituents at the nitrogen atom have significant influence on the chemical reactivity and stability of these substrates. [14,15] However, these studies revealed a huge effect of the N-protecting group on the oxidation reaction. [14,15] However, these studies revealed a huge effect of the N-protecting group on the oxidation reaction.…”