Iridium‐Catalyzed Carbonylative Synthesis of Chromenones from Simple Phenols and Internal Alkynes at Atmospheric Pressure

Abstract

Anovel procedure on the carbonylative synthesis of chromenones has been developed. With simple phenols and internal alkynes as the substrates,v arious chromenones were isolated in moderate to good yields with excellent regioselectivity and functional-group tolerance by using iridium as the catalyst and copper as the promotor at atmospheric pressure. Notably,t his is the first example on carbonylative annulation of simple phenols and alkynes.Coumarin was first isolated by Vogel in 1820 as an atural product from the Tonka bean, and then was synthesized for the first time by William Henry Perkin. [1] This ring system represents an important class of natural products present in aw ide variety of natural sources and has aw ide range of pharmacological properties,s uch as anti-HIV,a nti-TB,a nticancer, anti-inflammatory,a nticonvulsant and MAOi nhibitory properties. [2] Hence it continues to attract attention from synthetic chemists and medicinal chemists,a nd many synthetic methods have been developed for their preparation. [3] Among the known methodologies,p alladium-catalyzed carbonylative cyclization of 2-iodophenols with alkynes was established by Larock and Kadnikov in 2000. [3f,g] Through this type of transformation, CO,a sacheap and abundant C1 source,can be effectively introduced to coumarins.However, the main issue of this method is the use of 2-iodophenol as asubstrate as it requires tedious preactivation and has limited availability and low stability.T om eet the requests of atom efficiency and sustainable chemistry,anew methodology, which directly uses simple phenols as the reactant in carbonylative synthesis of coumarins is highly demanded.Tr ansition metal catalyzed carbonylative transformations and their applications in heterocycle synthesis are considered an important part of domino reactions. [4] However,t he catalysts applied are mainly focused on palladium-or rhodium-related catalysts.A lthough iridium-based catalysts have been successfully explored in CÀHa ctivation reactions. [5] Theapplication of an iridium catalyst in carbonylation is still limited to the Cativa process,w hich has been industrialized for the preparation of acetic acid from methanol, [6] and has recently been extended to hydroformylation of alkenes. [7] From both academic and practical points of view, it will be interesting to explore the applications of iridium catalysts in carbonylation chemistry.Additionally,acorporative catalyst system or catalyst relay is also attractive.Herein we report our new results on the carbonylative synthesis of coumarins from simple phenols and alkynes with CO gas at atmospheric pressure.Moderate to good yields of the desired products were isolated with excellent selectivity.Notably,this report is the first on carbonylative annulation of simple phenols and internal alkynes.Initially,p henol (1a)a nd 1,2-diphenylethyne (2a)w ere chosen as the model substrates in the presence of [{Ir-(COD)Cl} 2 ]a st he catalyst and p-xylene as the solvent to establish this carbonylation procedure (Table 1). To our...

Regioirregular and catalytic Mizoroki–Heck reactions

“…Figure 2 shows that cinnamates 1a-m cyclise in the presence of ligand-free Pd 3-4 catalysts to give the corresponding α coupled, exo-benzylenyl δ-lactones 2a-m in excellent yields and reasonable stereoselectivity, with the E isomer as the major product. These results strongly support that exo regioselectivity takes control and violate the long accepted β-directing electronic rules for the Mizoroki-Heck reaction in aryl iodide-substituted cinnamyl esters 1a(a)-m, with catalytic Pd 3-4 clusters, to intramolecularly couple the α carbon atom of the electron-poor alkene to the aryl iodide, and give otherwise difficult to prepare exobenzylidene lactones 2a(a)-m 17,18 .…”

“…Different representative Pd complex catalysts 15 (2 mol%) for the Mizoroki-Heck reaction gave low yields of product 2a, under optimal reaction conditions for their respective catalytic activity (entries 1-15), however, in-situ generated catalytic ligand-free ultrasmall Pd 3-4 clusters 16 gave significant amounts of the α product 2a (entries [16][17][18][19][20], up to a 69% yield by gas chromatography (GC, as a 4:1 mixture of E and Z isomers, see Supplementary Figure 1) and with an isolated yield after column chromatography of 52% for the α−E product 2a and <10% for the β coupling product 3a. The cinnamic ester 1aa, with an additional carbon atom in the alkyl chain, was also prepared and tested as a starting material for the coupling, and the result showed that the α coupling product, the unfavored seven-member ring ε-lactones 2aa and 2ab were formed in 55% isolated yield, without any trace of β coupling product 3aa (entry 21, see also Supplementary Figure 1).…”

The Chemistry of CO: Carbonylation

“…Recently, a novel carbonylative synthesis of chromenones from simple phenols and internal alkynes was developed by Wu and co-workers. 35 The reaction was performed at atmospheric pressure of CO; a number of chromenones were isolated in moderate to good yields with excellent regioselectivity and functional-group Besides arenes, alkenes have also been successfully carbonylatively activated. In 2016, Gaunt and co-workers developed a general carbonylation procedure for the preparation of b-lactams.…”

Selectivity Controlled Palladium-Catalyzed Carbonylative Synthesis of Propiolates and Chromenones from Phenols and Alkynes

“…More recently, we reported an iridium-catalyzed carbonylative cyclization of simple phenols with internal alkynes to produce chromenones. 9 The selectivity can be tuned by choosing the proper phosphine ligand. However, only disubstituted products can be obtained and we failed with terminal alkynes.…”