Highly Diastereo‐ and Enantioselective Silver‐Catalyzed Double [3+2] Cyclization of α‐Imino Esters with Isocyanoacetate

Abstract

Presented herein is a new complexity-generating method in which both functionalities of α-imino esters undergo stereoselective cyclization with isocyanoacetates to produce directly linked oxazole-imidazolines, which can be transformed into highly functionalized α,β-diamino esters and imidazolinium salts in high diastereo- and enantiopurity.

Recent Advances in the Synthesis of Imidazolines (2009–2020)

“…In that same year, Zhao and co-workers reported a new method to synthesize a linked oxazole-imidazoline by utilizing the bifunctional α-imino ester (117) (Scheme 35). [50] The reaction was advanced by stereoselective cyclization of the α-imino ester (117) with isocyanoacetate (118) in the presence of silver oxide Ag 2 CO 3 generate 99% of the racemic product. Chloride salts of Cu, Zn, and Au, along with strong Lewis acids such as BF 3 • OEt 2 and Sc(OTf) 3 , provided less than 2% product.…”

Copper-catalyzed direct coupling of benzoxazin-2-ones with indoles for the synthesis of diverse 3-indolylbenzoxazin-2-ones: access to natural cephalandole A

“…Imino cyclic esters were synthesized in the laboratory according to known procedure. 25 All indoles were prepared by either N-alkylation or N-arylation according to known method. 26 Solvents were used without further purication.…”

Direct Catalytic Enantio‐ and Diastereoselective Ketone Aldol Reactions of Isocyanoacetates

“…), 4a was formed with enhanced diastereocontrol and yield when silver(I) oxide was employed (see entry 2). In terms of diastereoselectivity,E tOAc was found to be the best solvent compared with TBME, CH 2 Cl 2 ,o riPrOAc (entries 2a nd [6][7][8]. Changing the temperature of the reaction to À30 8 8Corto 0 8 8Cfrom À20 8 8Cmade no improvement to the enantioselectivity (entries 9a nd 10).…”

“…Isocyanoacetate ester addition reactions to carbonyl [7] or imine electrophiles [8,9] directly afford the respective oxazoline or imidazoline heterocycles,which can be ring-opened under mild hydrolytic conditions to yield b-substituted a-amino acids.A lthough the catalytic asymmetric version of this reaction has been widely studied using aldehydes, [7] to date, no enantioselective example using unactivated ketones has been reported despite its potential to provide an elegant asymmetric route to a-amino acid derivatives possessing ac hiral tertiary alcohol in the b-position (Scheme 1). [10] In ar elated study,t he asymmetric aldol addition reaction of isothiocyanato esters and unactivated ketones,w hich afforded oxazolidinethione products with af ully substituted b-stereocenter,w as described.…”