Iodoarene-Catalyzed Cyclizations of Unsaturated Amides

Abstract

ABSTRACT:The cyclization of N-alkenylamides catalyzed by iodoarenes under oxidative conditions is presented. Five-, six-and seven-membered rings with a range of substitutions can be prepared by this route. Preliminary data from the use of chiral iodoarenes as precatalysts show that enantiocontrol is feasible.Research in hypervalent iodine chemistry has gained considerable momentum in recent years.1 In particular, the emergence of catalytic and enantioselective processes with iodine(III) species is starting to make these competitive with metal-catalysis. 2Recent examples include the catalytic enantioselective spirolactonization of phenols, 3 dioxygenation of styrenes, 4 and intramolecular C-H/C-H cross-coupling.5 This ability to effect "metallike" synthetic transformations without the toxicity, supply or cost issues of transition metal salts is attractive.We have previously developed catalytic methods using insitu generated hypervalent iodine species and have reported the oxidative cyclization of δ-alkynyl β-ketoesters 6 and the enantioselective oxidative cyclization of δ-ketoacids. 7 We wished to extend this catalytic concept to the formation of useful heterocycles such as oxazolines and dihydrooxazines. Oxazolines are common structural motifs found in natural products with notable biological activities, e.g. the leupyrrins, active against fungi and eukaryotic cells, 8 and the bistratamides, which possess anticancer properties (Figure 1). 9 Dihydrooxazines are useful synthetic intermediates in organic synthesis 10 and derivatives possessing fungicidal activity have also been reported. 11In this Communication, we disclose our results on the catalytic cyclization of unsaturated amides to give oxazolines, dihydrooxazines and larger ring analogs. At the beginning of our study, Moon and Harned published the stoichiometric hypervalent iodine mediated cyclization of N-allylamides (Scheme 1). 12Their report was limited to five membered ring formation, the use of terminal alkenes and the products described were all racemic. Herein, we reveal catalytic conditions for the cyclization and expand the scope of the process to include other ring sizes and more substituted alkenes. In addition, we have achieved enantiocontrol in this cyclization using chiral iodoarenes. There are few examples in the literature of iodoarene-catalyzed reactions involving alkenes. 4,13 One issue with these processes is the potential for undesired oxidation of the olefin in preference to the iodoarene especially as common oxidants for the conversion of iodoarenes into the active iodine(III) species include peracids.

Iodoarene-catalyzed cyclizations of N-propargylamides and β-amidoketones: synthesis of 2-oxazolines

“…By using 2-iodoanisole as precatalyst in the presence of p -toluenesulfonic acid and m -chloroperbenzoic acid in acetonitrile, 4a cyclized to 6a in 92% yield as determined by 1 H NMR analysis of the crude reaction mixture (Table 1, entry 1). In line with our previous findings with N -alkenylamides, the use of iodobenzene in place of 2-iodoanisole provided a diminished yield of 6a (Table 1, entry 2) [12]. The iodoarene was found to be essential for the conversion of the starting material, as its absence led to complete return of 4a (Table 1, entry 3).…”

“…In this regard, we have reported the use of iodoarenes as precatalysts in the cyclizations of N -alkenylamides 1 [12], δ-alkynyl β-ketoesters 2 [13] and 5-oxo-5-phenylpentanoic acid ( 3 , Scheme 1–c) [14]. These three cyclizations exemplify three different proposed reaction pathways, i.e., iodine(III) activation of alkenes, alkynes and ketones.…”

Iodophenylsulfonates and Iodobenzoates as Redox‐Active Supporting Electrolytes for Electrosynthesis

“…This point is further illustrated by the oxidative cyclization of allylamide 10 to the corresponding 2‐oxazolines 11a and 11b (see Scheme ). The synthesis of 11b was previously reported by Moran and coworkers to efficiently proceed by treatment of 10 with Selectfluor in presence of 4‐methoxyiodobenzene and TFA . The authors proposed that the olefinic double bond on 10 is activated by an in situ formed iodine(III) species, thus inducing cyclization via intramolecular nucleophilic attack of the amide oxygen and formation of the λ 3 ‐iodane intermediate 12 (Scheme , L=F or CF 3 CO 2 ).…”

Catalytic Cycloisomerization–Fluorination Sequence of N‐Propargyl Amides by Iodoarene/HF⋅Pyridine/Selectfluor Systems

“…[19] In these reports, including the aminofluorination of 4-or 5-alkenamines, [7] ArIF 2 catalysts derived from ArI, mCPBA, and HF·Py (or aq. [21] Therefore, we next examined the catalytic cycloisomerization-fluorination reactions of 1a using iodine(III) species in situ generated from various ArI precatalysts (20 mol %) and Selectfluor (1.5 equiv)i nt he presenceo fH F·Py (10 equiv)i nD CE at 80 8Cf or 24 h( Ta ble1,e ntries 2-10). However,i ti saconcern that the use of mCPBA as at erminal oxidantw ould bring about the introduction of the oxygen functional group to the side chain of oxazoles.…”