Diels−Alder Reactions of Hexafluoro-2-butyne with 2-Heterosubstituted Furans:  A Facile and General Synthesis of 1,4-Disubstituted 2,3-Di(trifluoromethyl)benzenes

Abstract

An electron-donating heteroatom substituent at position-2 of a furan promotes regiospecific opening of the 7-oxa bridge of the Diels-Alder cycloadduct with hexafluoro-2-butyne, producing a 4-heterosubstituted 2,3-di(trifluoromethyl)phenol building block in a single step. The phenol and heteroatom substituent are easily transformed to the corresponding iodide or triflate that readily undergoes Heck, Suzuki, and Stille reactions to install a variety of substituents in high yields. This methodology provides a facile and general synthesis of 1,4-disubsituted 2, 3-di(trifluoromethyl)benzenes.

Synergy between Heterogeneous Catalysis and Microwave Irradiation in an Efficient One-Pot Synthesis of Benzene Derivatives via Ring-Opening of Diels-Alder Cycloadducts of Substituted Furans

“…1 The resultant 7-oxabicyclo[2.2.1]heptenes are valuable synthetic intermediates that have been further elaborated to substituted arenes. 2 Although these oxabicycles are easily prepared through cycloaddition reactions of furans, and the oxygen bridge can be removed by a variety of methods, 3 only in a few cases it is possible to obtain benzene derivatives in a single step 4,5 and usually a mixture of compounds is obtained. 6,3d Microwave radiation is an unconventional energy source whose usefulness in synthetic organic chemistry has been increasingly recognised in recent years.…”

Convergent Synthesis of Dronedarone, an Antiarrhythmic Agent

“…Aryldiazonium salt formation of 10 and subsequent iodination using potassium iodide afforded iodoarene 11. 18,19) The conversion of nitrophenol 11 to 9 was accomplished by a three-step sequence of reduction, N-mesylation, and bis-acetal formation in good yield. Sonogashira cross-coupling of 9 with the terminal alkyne provided 8, a precursor of electrophilic cyclization.…”

“…2-Iodo-4-nitrophenol (11) According to the modified procedures by Dai and Lai 18) and Zhu et al, 19) to a solution of 2-amino-4-nitrophenol (10) (14.8 g, 96.0 mmol) in 30% H 2 SO 4 (500 mL) and dimethyl sulfoxide (DMSO) (500 mL) was added a solution of NaNO 2 (9.94 g, 144 mmol) in water (50 mL) at 0°C. The reaction mixture was stirred at the same temperature for 1 h, after which a solution of KI (47.8 g, 288 mmol) in water (50 mL) was added.…”

Olefin‐Metathesis‐Based Synthesis of Furans by an RCM/Deprotonation/Phosphorylation Sequence and Their Diels–Alder Reactions

“…For example, as shown in Scheme 4, 2-methoxyfuran (9) was found to undergo a cycloaddition reaction with hexafluorobutyne (10) to give 11, which rearranges thermally, even in the absence of acid, to phenol 12. [40] In this particular case, the rearrangement is facilitated by the electron-donating character of the 2-methoxy substituent. The electron-withdrawing nature of the phosphate group will most likely contribute to the stability of the cycloaddition products 7 described in this work.…”

“…Diels-Alder reaction of 2-methoxyfuran and thermal rearrangement to a phenol. [40] absence of a proton at C-5 of the furan precursor. It has, for instance, been shown that Diels-Alder adducts 13 of 2-(aryloxy)furans with a hydroxymethyl substituent at C-5 are stable, but that in the presence of an acid the side-chain is cleaved to formaldehyde with concomitant rearrangement to phenol 14 (Scheme 5).…”