Oxazole Synthesis by Sequential Asmic-Ester Condensations and Sulfanyl–Lithium Exchange–Trapping

Abstract

Oxazoles are rapidly assembled through a sequential deprotonation−condensation of Asmic, anisylsulfanylmethylisocyanide, with esters followed by sulfanyl−lithium exchange−trapping. Deprotonating Asmic affords a metalated isocyanide that efficiently traps esters to afford oxazoles bearing a versatile C-4 anisylsulfanyl substituent. Interchange of the anisylsulfanyl substituent is readily achieved through a first-in-class sulfur−lithium exchange−electrophilic trapping sequence whose versatility is illustrated in the three-step synthesis of the bioactive natural product streptochlorin.

Dibenzothiazepine Based MCR Chemistry

“…[48] Satisfyingly, under mild conditions, we were able to get the desired polycyclic thiazepines 4 a-g in good yields (Scheme 3, 22-91 %). We employed not only TosMIC and its substituted derivatives (4 b-c, 4 e-f) but also other acidic isocyanides such as the phenylsulfane (related to AsMIC) [49] and the fluorene isocyanide. Interestingly, the phenylsulfane isocyanide behaves similarly to TosMIC by which the thiophenolate acts as the leaving group (4 a).…”

One-step synthesis of imidazoles from Asmic (anisylsulfanylmethyl isocyanide)

“…Raney nickel hydrogenolysis was effective in interchanging the C4 anisylsulfanyl group for hydrogen ( Scheme 3 ); attempted lithium–anisylsulfanyl exchange [ 19 ] or palladium- [ 22 ] or nickel- [ 23 ] anisylsulfanyl cross coupling was not successful. Raney nickel reduction of 7f and 7m afforded the monosubsituted imidazoles 8f and 8m , respectively.…”

“…Installation of an electron withdrawing group adjacent to an isocyanide facilitates the deprotonation but creates weak nucleophiles 2 that are insufficiently nucleophilic to react with nitriles [ 14 ]. Described below is the use of Asmic, anisylsulfanylmethylisocyanide ( 5 ) [ 15 ], whose deprotonation affords a potent nucleophile that reacts directly with nitriles to provide an efficient, general approach to an array of imidazoles; Asmic is a crystalline, virtually odorless isocyanide with the advantage over related methods [ 16 – 17 ] in being readily prepared in fewer steps on at least 20 g scale [ 18 ], applicable for the synthesis of several heterocycles [ 19 – 20 ], and able to generate imidazoles from a broad array of nitrile and imidate electrophiles.…”

An Overview of Bioactive 1,3-Oxazole-Containing Alkaloids from Marine Organisms

“…In addition to potent fungicidal activity against Pythium, Botrytis cinerea, Septoria tritici, Pyricularia Oryzae, Fusarium culmorum and Rhizoctonia solani, compound 5 displayed a strong inhibitory effect on angiogenesis by blocking NF-κB signaling, as well as human leukemia and normal liver cell lines with IC 50 values of 1.05 and 10.9 µg/mL, respectively [11,13,14]. It is noteworthy that one three-step synthesis of compound 5 had been readily achieved by sequential asmicester condensations and sulfanyl-Lithium exchange-trapping [15]. As a promising inhibitor of lipid peroxidation, compound 6 was firstly synthesized by Nishida and coworkers in 1998, and its absolute configuration was unambiguously determined as S, S [16].…”