A New Route To Hindered Tertiary Amines

Abstract

The Rh(2)(OAc)(4)-stabilized carbenoid derived from dimethyl diazomalonate has been found to insert into the N-H bond of sterically hindered secondary aliphatic amines to afford hindered tertiary aliphatic amines in quite satisfactory yields. For example dimethyl 2-(dicyclohexylamino)propanedioate was formed in 85% yield from dicyclohexylamine, and the severely hindered dimethyl 2-(2,2,6,6-tetramethyl-1-piperidinyl)propanedioate was formed in 38% yield from 2,2,6,6-tetramethylpiperidine. The Rh(2)(OAc)(4) - dimethyl diazomalonate reaction was found to work also for arylalkylamines and diarylamines. In these cases, small amounts of products resulting from formal insertion of the carbenoid into an aromatic C-H bond were detected. Substitution at ortho positions caused the yield of C-H insertion products to increase. Other diazo compounds, viz. ethyl diazoacetoacetate, 2-diazocyclohexane-1,3-dione, and 2-diazo-5,5-dimethylcyclohexane-1,3-dione, performed satisfactorily in Rh(2)(OAc)(4)-catalyzed reactions with arylalkylamines and diarylamines, but led to complicated reaction mixtures with dialkylamines.

Arylazanylpyrazolone Derivatives as Inhibitors of Mutant Superoxide Dismutase 1 Dependent Protein Aggregation for the Treatment of Amyotrophic Lateral Sclerosis

“…By employing ethyl diazoacetate, an NH insertion occurred to achieve the anilino esters in good yields, 20 which were used to generate the β-ketoester intermediates by attack of the enolate of ethyl acetate.…”

Bulk gold catalyzed oxidation reactions of amines and isocyanides and iron porphyrin catalyzed N-H and O-H bond insertion/cyclization reactions of diamines and aminoalcohols

“…N-H bond insertion reactions utilizing diazo compounds and amines provide a simple route for the formation of important products and synthetic intermediates, such as glycine ethyl ester derivatives, 55 tertiary amines, 56,57 and nitrogen heterocycles. 50 Several metal complexes are reported to catalyze N-H bond insertion reactions.…”

Bulk Gold-Catalyzed Reactions of Diazoalkanes with Amines and O2 to Give Enamines

“…But this reaction also gave a 66% yield of 15 even in the absence of the gold catalyst under the same conditions. Although this reaction has been reported to be catalyzed by complexes of Ru, Fe, and Cu [33][34][35][36][37][38][39][40][41][42][43][44][45], we are not aware of a previous report of the uncatalyzed reaction. …”

“…4) when catalyzed by a variety of homogeneous transition metal complexes. For reviews involving catalyzed diazo compound N-H insertion reactions, see: [33][34][35][36][37][38][39][40][41][42][43][44]. For examples of highly enantioselective metal-catalyzed intermolecular carbenoid N-H insertion reactions, see: [45].…”