[4 + 2] Cyclization of para-Quinone Methide Derivatives with Alkynes

Abstract

The first cyclization of para-quinone methide derivatives with alkynes was established by utilizing the [4 + 2] reaction of ortho-hydroxyphenyl-substituted para-quinone methides with ynones or benzyne, which efficiently constructed the scaffolds of chromene and xanthene in high yields (up to 88%). This protocol has not only fulfilled the task of developing cyclization reactions of para-quinone methide derivatives but also provided an efficient method for constructing chromene and xanthene scaffolds.

Enantioselective Catalytic [4+1]‐Cyclization of ortho‐Hydroxy‐para‐Quinone Methides with Allenoates

“…It has been described by others that the tert ‐butyl groups of the phenol derivatives obtained by addition of nucleophiles to QMs can be cleaved off under (Lewis) acidic conditions . We thus carried out a few (unoptimized) test reactions to see if a similar debutylation is also possible on the highly functionalized diester‐containing dihydrobenzofuranes 5 (Scheme ).…”

In the Mists of a Fungal Metabolite: An Unexpected Reaction of 2,4,5-Trimethoxyphenylglyoxylic Acid

“…Their high reactivity and potential has also been exploited in the total synthesis of some natural products such as the flavonoids rugaurone A-C [14] cherylline [15] and 20-deoxy-elansolid B1 [16]. Furthermore, the reactions of p-QMs have extensively been studied to generate compounds of pharmaceutical interest [17][18][19][20] and quite recently they were used as starting materials for an organo-catalytic asymmetric α-alkylation of aldehydes [21].During our research on metabolites from fungi and lichens we came across the chemical properties and reactions of phenylglyoxylic acids [22]. Thereby, we encountered several unexpected and unprecedented reactions yielding 3,3-diaryl substituted benzofuranones which undergo retro-Friedel-Crafts alkylation in hydrochloric acid forming the p-QM structure.…”

“…Their high reactivity and potential has also been exploited in the total synthesis of some natural products such as the flavonoids rugaurone A-C [14] cherylline [15] and 20-deoxy-elansolid B1 [16]. Furthermore, the reactions of p-QMs have extensively been studied to generate compounds of pharmaceutical interest [17][18][19][20] and quite recently they were used as starting materials for an organo-catalytic asymmetric α-alkylation of aldehydes [21].…”

“…Hydroxy-5-methoxy-3-(2,4,5-trimethoxyphenyl)benzofuran-2(3H)-one(17) Compound 6 (250 mg, 0.73 mmol) was suspended in hydrochloric acid (25 mL) and zinc (250 mg, 3.82 mmol) was added at 0 • C. The reaction was stirred for 4 h at room temperature, diluted with water (20 mL) and extracted with EtOAc(3 × 50mL). The combined organic extracts were washed with brine and dried (MgSO 4 ).…”

DataSheet1.PDF

“…Inspired by the seminal works of Fan and Jorgensen (Chu et al, 2013;Caruana et al, 2014), numerous of methods utilizing p-QMs as vinylogous Michael acceptors have been successfully developed through 1,6-conjugate addition and annulation reactions (Lou et al, 2015;Wang et al, 2015;Deng et al, 2016;Dong et al, 2016;He et al, 2016;Li et al, 2016;Ma et al, 2016;Zhang et al, 2016;Roiser and Waser, 2017;Zhang et al, 2017). Recently, Enders and co-workers first demonstrated the potential of ortho-hydroxyphenyl-substituted p-QMs in [4 + 2] cyclization reaction (Zhao et al, 2016), which subsequently enables the extensively investigation of [4 + 1] ( Chen et al, 2018;Liu L. et al, 2018;Xiong et al, 2018;Zhi et al, 2018;Zhou et al, 2018;Lu et al, 2019;Tan et al, 2019) [4 + 2] (Jiang X. L. et al, 2018;Mei et al, 2018;Zhang et al, 2018;Yang et al, 2019;Zhang et al, 2019;Huang et al, 2020;Roy et al, 2020;Tan et al, 2020;You et al, 2020) and [4 + 3] (Jiang F. et al, 2018;Li et al, 2018 Q Chen et al, 2019) annulations by various research groups. Although great progress has been witnessed in this field, the employment of p-QMs substrates in the construction of heterocyclic frameworks, especially nitrogen-containing heterocyclic frameworks, still remains underdeveloped (Scheme 1A).…”