Iodine(III)-Mediated Generation of Nitrogen-Tethered Orthoquinol Acetates for the Construction of Oxygenated Indole, Quinoline, and Phenanthridine Alkaloid Motifs

Abstract

Functionalized indole and quinoline derivatives are conveniently prepared from nitrogen-tethered 2-methoxyphenols via phenyliodine(III) diacetate mediated oxidative acetoxylation, followed by a fluoride- or base-induced intramolecular nucleophilic addition reaction. This regioselective Michael-type addition step is further discussed in view of the rearrangement of orthoquinol acetate intermediates into paraquinol acetates that is sometimes observed in situ. Application of this methodology to the synthesis of a functionalized phenanthridine, and its potential for the construction of polyoxygenated lycorine-type alkaloid skeleta are here described.

Understanding the Cardioprotective Effects of Flavonols: Discovery of Relaxant Flavonols without Antioxidant Activity

“…Hz, H5), 7.31-7.43 (m, 7H, Ph,H2,6),9.81 (s, 1H, COH). The 1 H NMR spectrum was in agreement with that previously reported 28. 4-Benzyloxy-3-bromobenzaldehyde.…”

Iodane-mediated and electrochemical oxidative transformations of 2-methoxy- and 2-methylphenols

“…We have already reported several examples of this alternative to the lead tetraacetate-mediated Wessely oxidation. 17,18,[25][26][27] Of particular significance is the fact that the orthoquinol acetates do not succumb to Diels-Alder dimerization processes as easily as their 6,6-dimethoxy analogues (R = Nu = OMe), and hence can be exploited in various synthetic schemes. 15 The 6,6-dimethoxycyclohexa-2,4-dienone derivatives, or orthoquinone monoketals, are most conveniently prepared by oxidative methoxylation using DIB in MeOH and can be trapped in situ by either dienophiles or, in some instances, dienes to construct rapidly complex carbocyclic systems.…”

Oxidative Dearomatization of Phenols: Why, How and What For?

“…All of these phenols were then efficiently dearomatized using PIDA to afford, in excellent yields, the expected ortho-quinol acetates 34i-m. 46,47 Of particular note is the fact that similar PIDA oxidations of freeamino-tethered phenols gave rise to intractable mixtures. Protection of the appended amino groups was thus proved to be crucial to the success of our operations.…”

“…The 2-oxoindole 35l and the 3,4-dihydro-2-oxoquinoline 35m were obtained after refluxing overnight in tetrahydrofuran in unoptimized yields of 17 and 38%, respectively (Scheme 11). 24,46,47 The regiochemistry of all these cyclized products was determined in the same manner as that followed for the oxocyclization cases (see Scheme 4). Here, the cyclic connectivity at the nitrogen atom was confirmed by the detection of a diagnostic NMR threebond response in long-range C-H bond correlation maps (e.g., see 35m in Scheme 11).…”