Synthesis of α-Halo-γ-hydroxyenamides by Titanium Tetrahalide Mediated Addition of Aldehydes or Ketones to Ynamides

Abstract

α-Chloro- or α-bromo-γ-hydroxyenamides were synthesized by the reaction of an ynamide, titanium tetrahalide, and an aldehyde or a ketone. A γ-hydroxy trisubstituted enamide was prepared stereoselectively by Suzuki coupling of an obtained α-chloro-γ-hydroxyenamide with phenyl boronic acid. Intramolecular cyclization of α-chloro-γ-hydroxyenamide took place to provide a 2,3-dihydrobenzoisothiazole 1,1-dioxide derivative by palladium-catalyzed C-H activation of the tosyl group. Hydrochlorination of ynamides proceeded to give α-chloroenamides by treatment with titanium tetrachloride followed by addition of water.

Keteniminium Ions: Unique and Versatile Reactive Intermediates for Chemical Synthesis

“…In sharp contrast, the use of carbon-based electrophiles for the generation of keteniminium ions is much less documented, despite its clear synthetic potential. Indeed, besides benzhydryl halides 82 and aldehydes/ketones 83 activated with a strong Lewis acid highlighted in Scheme 28 (intramolecular versions using such electrophiles will be described in Section 3.2.4), the use of other C-electrophiles is rarely discussed. 81 While many of such electrophiles are sufficiently electrophilic to react with ynamides, as evi-…”

Approach to Tertiary-Type β-Hydroxyl Carboxamides Through Sc(OTf)3-Catalyzed Addition of Ynamides and Ketones

“…Our investigation started with the addition reaction of ynamide 1a and ketone 2a. First, similar conditions (TiCl 4 and BF 3 • Et 2 O) used by Matsuo 17 and Xu 15 failed to promote this addition process (Table 1, entries 1−2). Initial trials with Sc(OTf) 3 in several solvents also turned out to be fruitless (Table 1, entries 3−5).…”

“…Recent years, ynamide has undoubtedly become one of the most fascinating building blocks in synthetic chemistry, and many important chemical conversions of ynamides have been successfully achieved . Among them, reactions of ynamides with ketones were reported to afford different products including acrylic amides, γ-hydroxyenamides, and α-halo-γ-hydroxyenamides under the promotion of different Lewis acids (Figure ). As a continuation of our interest in synthetic application of ynamides, we have reported an effective approach to access functionalized pyrido and pyrrolo­[1,2- c ]­[1,3]­oxazin-1-ones through nucleophilic addition–cyclization process of N,O -acetal with ynamides .…”

Regio‐ und stereoselektive Synthese α,β‐disubstituierter Enamide durch Voraktivierung von Inamiden

“…So sind diverse Methoden entwickelt worden, die Heteroatom-funktionalisierte Enamide aus Inamiden erzeugen. [8,9] C-C-Bindungen kçnnen auch durch Carbometallierung von Inamiden gebildet werden, wonach b,b-disubstituierte Enamide mit hoher Regioselektivitäte rhalten werden (Schema 1B). [10,11] Es ist auffallend, dass Methoden zur Bildung a,b-disubstituierter Enamide deutlich seltener sind (Schema 1C).…”

“…Hier konnte gezeigt werden, dass Dichlormethan die besten Ausbeuten liefert (Nr. [6][7][8][9]. Um die Ausbeute der Reaktion weiter zu ver-bessern, wurden die Dauer der Voraktivierung und die Reaktionsdauer sowie -temperatur untersucht (Nr.…”