Controlling the Substitution Pattern of Hexasubstituted Naphthalenes by Aryne/Siloxyfuran Diels–Alder Additions: Regio‐ and Stereocontrolled Synthesis of Arizonin C1 Analogs

Abstract

3,4‐Dimethoxybenz‐1‐yne and 2‐siloxylated furans without or with a bromine atom at C‐3 undergo Diels–Alder reactions with orientational selectivity. Hydrolysis furnished a bromine‐free or a bromine‐containing naphthalene, respectively. Bromination of the former provided a regioisomer of the latter. Either of the two compounds was processed to give a variety of unnatural naphthoquinonopyrano‐γ‐lactones. This occurred by a succession of (1) Heck coupling, (2) asymmetric dihydroxylation, (3) oxa‐Pictet–Spengler cyclization, and (4) oxidation. The fifteen monomeric naphthoquinonopyrano‐γ‐lactone structures that we prepared resemble the natural product (–)‐arizonin C1 or its C‐5 epimer. Accordingly, they represent hexasubstituted naphthalenes likewise. The sixteenth naphthoquinonopyrano‐γ‐lactone that we synthesized is a kind of dimer. Its moieties are bridged differently than those in naturally occurring naphthoquinonopyrano‐γ‐lactone dimers.

Synthesis of Polysubstituted 3‐Methylisoquinolines through the 6π‐Electron Cyclization/Elimination of 1‐Azatrienes derived from 1,1‐Dimethylhydrazine

“…To that end, isovanillin ( 1a ) was subjected to a selective bromination with NBS (Scheme ) and the resulting bromophenol 9 was O ‐methylated to furnish 10 in 75 % overall yield. [19a] Next, the formyl moiety of 10 was exposed to propane‐1,3‐diol and Ce(OTf) 3 promotion, employing ( i PrO) 3 CH as carbonyl activator and water scavenger,[19b], [19c] to afford 96 % yield of the 1,3‐dioxane derivative 11 .…”

“…Then, the latter was subjected to a Heck reaction with methyl acrylate, which furnished the ortho ‐formyl cinnamate 12 in 82 % yield, after mild acid hydrolysis of the protecting group. [19d] One‐pot hydrazonation toward 13 and further exposure to thermal cyclization finally gave isoquinoline 14 , albeit in a rather poor 10 % yield, revealing a limitation in the scope of this reaction. This complements others previously found by the group of Hibino.…”

Design, synthesis, and evaluation of cytotoxic activities of arylnaphthalene lignans and aza‐analogs

“…Here too, the most significant obstacle in this scheme was the regioselective aromatic bromination as it has been strongly affected by the solvents and brominating agents used together with the substituents on the naphthalene core. [48][49][50][51][52][53][54][55][56][57][58][59][60][61] So, several parameters were examined and trials have been carried out to control the regioselectivity. The best conditions found were, on the one hand, reaction of 1 with pyridinium tribromide at 0°C in tetrahydrofuran (THF), [50] which gave the 3-bromo compound 15 in excellent yield without producing the 1-regioisomer (Scheme 6).…”

Stereoselective Total Synthesis of the Dimeric Naphthoquinonopyrano-γ-lactone (−)-Crisamicin A: Introducing the Dimerization Site by a Late-Stage Hartwig Borylation

“…The chemistry of Scheme ended with a “simple” oxa-Pictet–Spengler cyclization, incorporating acetaldehyde in the presence of BF 3 ·OEt 2 ( 7 → 6 ; 88% yield). In an “elaborate variant” of that cyclization, it concurred with tert -butyl ester cleavage and lactonization ( 13 → 6 ; 67% yield).…”

“…Disconcerted by the lack of precedence for such a pleasing outcome, , we tried many other oxa-Pictet–Spengler conditions before obtaining an inseparable mixture of naphthohydroquinonopyrano-γ-lactone diastereomers 6 , 5- epi - 6 , and 3a- epi - 6 . The newly formed compounds 5- epi - 6 and 3a- epi - 6 were the 3a,5 cis - and 3a,11b trans -isomer of the desired diastereomer 6 ( 3a,5 trans , 3a,11b cis ) according to 1 H NMR similarities to model compounds …”