Rh₂(esp)₂‐Catalyzed Coupling of α‐Diazo‐γ‐butyrolactams with Aromatic Amines

Abstract

Decomposition of α‐diazo‐γ‐butyrolactams in the presence of aromatic and heteroaromatic amines, under Rh2(esp)2 catalysis, led to corresponding α‐arylamino‐γ‐butyrolactams, which are of significant value for medicinal chemistry. The reaction scope encompasses primary as well as secondary, diversely substituted anilines and heteroaromatic amines. Insertion into the anilinic amino group was shown to be selective over amide and sulfonamide N–H insertion.

Preparation and in situ use of unstable N-alkyl α-diazo-γ-butyrolactams in RhII-catalyzed X–H insertion reactions

“…For aromatic amines, this catalyst proved inefficient and was replaced by 0.5 mol % of Rh 2 (esp) 2 . The attempted change of the catalyst to Rh 2 (esp) 2 in the reac- tions with alcohols and thiols (which earlier gave a remarkable improvement of the product yields of NH-insertion reactions [2]) resulted in no notable improvement in this case.…”

“…The viability of either (or both) of these possibilities is currently investigated. It should be noted that a similar Rh 2 (esp) 2 -catalyzed reaction of one of the N-aryl-α-diazo-γ-butyrolactams 1 with 2,6-dimethylaniline previously gave an excellent yield of the N-H insertion product [2].…”

“…The only attempt to employ an aliphatic amine, cyclopropylamine (which would presumably be less reactive in the Rh IIcatalyzed insertion reaction [2]) resulted in the formation of a sole identifiable product -enamine 8a, isolated chromatographically from a complex mixture of unidentified byproducts. The formation of 8a (that was also observed previously, along with the expected, saturated coupling product of the Rh II -catalyzed reaction of cyclopropylamine with N-phenyl-α-diazo-2-pyrrolidone [2]) can be rationalized, as proposed previously [2], either by the oxidation of diazolactam 6c to a respective ketone (a process described in the literature for other α-diazocarbonyl compounds [6]), followed by a nucleophilic attack of cyclopropylamine. Alternatively, the formation of the enamine product could be envisaged via the reaction of the amine with bishydrazone 5, which would have formed, if the N-H insertion pathway was not sufficiently rapid.…”

“…Faced with this serious limitation of the reactivity scope, we set off to investigate the possibility of using unstable compounds 4 in situ, promptly after their formation, in various Rh II -catalyzed X-H insertion reactions, particularly the recently described rhodium carbene insertion into O-H [1], N-H [2] and S-H [3] bonds of alcohols, aromatic amines, and thiols, respectively. Herein, we report the results of these studies.…”

tert‐Butyl 3‐Diazo‐2‐oxopyrrolidine‐1‐carboxylate – A New Reagent for Introduction of the 2‐Oxopyrrolidin‐3‐yl Motif via RhII‐Catalyzed X–H Insertion Reactions

“…The primary means of introducing the NH ‐2‐pyrrolidone moiety is via the use of either 3‐amino‐2‐pyrrolidone or 3‐bromo‐2‐pyrrolidone. Recently, we have been investigating synthesis and Rh II ‐catalyzed X–H insertion reactions of a novel type of α‐diazocarbonyl compounds – α‐diazo‐γ‐lactams 1 . The primary limitation of this chemistry was identified with respect to the substituents on the lactam nitrogen atom: the diazo compounds were stable to isolation and use in subsequent transformation only for N ‐aryl lactams, i.e.…”