The development of a mild and general method for the alkylation of amides with relatively unreactive alkyl halides (i.e., poor substrates for S N 2 reactions) is an ongoing challenge in organic synthesis. We describe herein a versatile transition-metal-catalyzed approach: in particular, a photoinduced, copper-catalyzed monoalkylation of primary amides. A broad array of alkyl and aryl amides (as well as a lactam and a 2-oxazolidinone) couple with unactivated secondary (and hindered primary) alkyl bromides and iodides using a single set of comparatively simple and mild conditions: inexpensive CuI as the catalyst, no separate added ligand, and C–N bond formation at room temperature. The method is compatible with a variety of functional groups, such as an olefin, a carbamate, a thiophene, and a pyridine, and it has been applied to the synthesis of an opioid receptor antagonist. A range of mechanistic observations, including reactivity and stereochemical studies, are consistent with a coupling pathway that includes photoexcitation of a copper–amidate complex, followed by electron transfer to form an alkyl radical.
1) Reaction of Standard Condition
Using photo-induced (hn 254), copper- catalyzed (10% CuI), two ratio base(LiOt-Bu), CH3CN/DMF as solvents and
stirring for 24 hrs at room temperature, Amides react with inactivated second alkyl...
Coupling N-alkylation of Amides with Secondary Alkyl Halides
Yapin Wang
Emaill: ywang2@lsuhsc.edu
1) Reaction of Standard Condition
Using photo-induced (hn 254), copper- catalyzed (10% CuI), two ratio base(LiOt-Bu), CH3CN/DMF as solvents and
stirring for 24 hrs at room temperature, Amides react with inactivated second alkyl...