Mono- and Biscouplings Using Triarylbismuths for the Atom-Efficient Arylations of Functionalized Furans under Palladium Catalysis

Abstract

Palladium-catalyzed cross-coupling reactions of functionalized bromofurans with triarylbismuths have been described for the atom-economic synthesis of functionalized arylfuran systems. The coupling reactions using triarylbismuths with various 2-bromofurans and 2,5-dibromofuran underwent smoothly to afford the corresponding 2-arylfurans and 2,5-diarylfurans in high yields in a short reaction time (one hour).Heteroaromatic ring systems are important building blocks for various applications in organic synthesis. 1 Furan systems serve as useful synthons in various synthetic transformations to generate molecular complexity. 2 Substituted furans are also key intermediates in the synthesis of various pharmacologically important compounds for medicinal applications. 3 Furan skeletons in particular are also useful for molecular electronic applications. 4 Hence, the development of new synthetic methodologies for furan skeletons is of important concern. Cross-coupling methodology is widely applied to enhance the molecular complexity in synthetic organic chemistry and this led to the development of various viable protocols to access challenging target structures. 5 Furthermore, arylfuran skeletons have been known for various medicinal applications. In this context, generation of arylfuran skeletons is synthetically important and can be accomplished through a cross-coupling methodology involving halofurans and organometallic reagents under metal-catalyzed conditions 6,7 in addition to other methods. 8 An alternative strategy also involves metal-catalyzed couplings of furanyl organometallics with aryl halides. 9-12 For example, the cross-couplings of 2-furanyl-boronic acids, 9 zinc, 10 or tin 11 reagents with aryl halides are reported for the synthesis of 2-arylfurans. The couplings of 2-furanyltellurides with aryltrifluroborates are also reported. 12 The corresponding biscouplings 13 with 2,5-bis(butyltellanyl)furan 13a or 2,5-bis(tri-n-butylstannyl)furan 13b with aryl halides is an extended strategy for an easy synthesis of 2,5-diarylfurans. Recently, the regioselective couplings involving furan systems have also been realized under metal-catalyzed conditions. 14 We have demonstrated the couplings of aryl halides and triflates with triarylbismuths under palladium-catalyzed conditions. 15 The novel coupling ability of triarylbismuths with 2-bromothiophenes under palladium catalysis was also realized very recently. 16 These investigations revealed the high cross-coupling ability of triarylbismuths with three aryl groups in short reaction times with excellent product yields. This prompted us to expand the scope of triarylbismuths in couplings with halofurans under palladium-catalyzed conditions and herein we report this study as follows.5-Bromofurfural is an important substrate for a variety of coupling reactions. 17 So, it was of interest to carry out the Table 1 Screening Conditions a-c Entry Catalyst/ligand Base (equiv) Solvent Time (h) Yield (%)

Rapid pseudo five-component synthesis of intensively blue luminescent 2,5-di(hetero)arylfurans via a Sonogashira–Glaser cyclization sequence

“…In addition, some starting materials are either not readily available or quite expensive. 2,5-dihalogenated furans can be in principle employed in cross-coupling reactions, however, the poor stability of these dihalogenated precursors renders this approach very tedious [ 29 ]. Recent publications report gold-catalyzed syntheses of di(hetero)arylfurans starting from arylbutadiynes [ 30 – 31 ].…”

5-Phenyl-2-furaldehyde: Synthesis, Reactions and Biological Activities

“…The coupling reaction of 5 with Ph 3 Bi furnished 5-phenyl-2-furaldehyde (3) in high yield (89%) with using Pd(OAc) 2 as a catalyst and Cs 2 CO 3 base in Nmethylpyrrolidone (NMP) solvent (Scheme 15) (34) .…”

An efficient continuous flow approach to furnish furan-based biaryls

“…Given the abundance of furanyl-biaryl analogues in the literature it is unsurprising that synthetic methodologies to access the scaffold have been extensively reported. Typical approaches involve the use of a furanylboronic acid or furanylbromide in Suzuki cross-coupling conditions with a range of Pd-based catalysts including Pd(OAc) 2 , 2,[11][12][13][14][15][16][17] PdCl 2 (PPh 3 ) 2 , [18][19][20] Pd(PPh 3 ) 4 , [18][19][20][21][22][23][24][25][26] Pd 2 (dba) 3 , 27 and Pd(OH) 2 . 28 Whilst these methodologies typically afford the furanylbiaryl scaffold in good to excellent yields a common problem faced, particularly by the pharmaceutical industry, in using Fig.…”