Stereospecific Construction of Contiguous Quaternary All‐Carbon Centers by Oxidative Ring Contraction

Oxidative ring contraction of cyclic α‐formyl ketones was facilitated by the action of H₂O₂ under operationally simple and environmentally benign reaction conditions. The process was highly regioselective and enables stereospecific construction of contiguous quaternary all‐carbon centers from stereodefined all‐substituted all‐cyclic ketones. The asymmetric syntheses of (+)‐cuparene and (+)‐tochuinyl acetate were also successively achieved by taking advantage of this novel protocol.     

4,5‐Dimethyl‐2‐Iodoxybenzenesulfonic Acid Catalyzed Site‐Selective Oxidation of 2‐Substituted Phenols to 1,2‐Quinols

A site‐selective hydroxylative dearomatization of 2‐substituted phenols to either 1,2‐benzoquinols or their cyclodimers, catalyzed by 4,5‐dimethyl‐2‐iodoxybenzenesulfonic acid with Oxone, has been developed. Natural products such as biscarvacrol and lacinilene C methyl ether could be synthesized efficiently under mild reaction conditions. Furthermore, both the reaction rate and site selectivity could be further improved by the introduction of a trialkylsilylmethyl substituent at the 2‐position of phenols. The corresponding 1,2‐quinols could be transformed into various useful structural motifs by [4+2] cycloaddition cascade reactions.     

Non‐Enzymatic Oxidation of a Pentagalloylglucose Analogue into Members of the Ellagitannin Family

The occurrence of more than 1000 structurally diverse ellagitannins has been hypothesized to begin with the oxidation of penta‐O ‐galloyl‐β‐d ‐glucose (β‐PGG) for the coupling of the galloyl groups. However, the non‐enzymatic behavior of β‐PGG in the oxidation is unknown. Disclosed herein is which galloyl groups tended to couple and which axial chirality was predominant in the derived hexahydroxydiphenoyl groups when an analogue of β‐PGG was subjected to oxidation. The galloyl groups coupled in the following order: at the 4,6‐, 1,6‐, 1,2‐, 2,3‐, and 3,6‐positions with respective S ‐, S ‐, R ‐, S ‐, and R ‐axial chirality. Among them, the most preferred 4,6‐coupling reflected the what was observed for natural ellagitannins. A new finding was that the second best coupling occured at the 1,6‐positions. With the detection of a 3,6‐coupled product, this work demonstrated that even ellagitannin skeletons with an axial‐rich glucose core may be generated non‐enzymatically.     

Enantiospecific sp2–sp3 Coupling of ortho‐ and para‐Phenols with Secondary and Tertiary Boronic Esters

The coupling of ortho ‐ and para ‐phenols with secondary and tertiary boronic esters has been explored. In the case of para ‐substituted phenols, after reaction of a dilithio phenolate species with a boronic ester, treatment with Ph₃BiF₂ or Martin's sulfurane gave the coupled product with complete enantiospecificity. The methodology was applied to the synthesis of the broad spectrum antibacterial natural product (−)‐4‐(1,5‐dimethylhex‐4‐enyl)‐2‐methyl phenol. For ortho ‐substituted phenols, initial incorporation of a benzotriazole on the phenol oxygen atom was required. Subsequent ortho ‐lithiation and borylation gave the coupled product, again with complete stereospecificity.