Regioselective Reactions of Highly Substituted Arynes

Abstract

The fully regioselective reactivity of four new highly substituted silyl aryl triflate aryne precursors in aryne acyl-alkylation, acyl-alkylation/ condensation, and heteroannulation reactions is reported. The application of these more complex arynes provides access to diverse natural product scaffolds and obviates late-stage functionalization of aromatic rings.It has been well established that substituted arynes undergo nucleophilic attack with levels of regioselectivity dependent on the identity of substituents and their locations relative to the reactive aryne triple bond. 1 In our own investigations, we have observed fully regioselective acyl-alkylation 2 and aryne heteroannulation 3 reactions with the aryne (2) generated in situ from a 3-methoxy-substituted silyl aryl triflate (1) (Scheme 1). Each of these products (3-6) stems presumably from initial attack at C(1) of the aryne (2), which suggests that the o-methoxy substituent electronically polarizes the triple bond and sterically shields the adjacent atom to favor this reactivity. More recently, we have been able to exploit this selectivity in aryne acyl-alkylation/condensation sequences to produce either substituted hydroxynaphthoquinones (6) or hydroxyisoquinolines (5). 4 These observations led us to investigate whether more highly functionalized silyl aryl triflates would also exhibit the predictable regioselectivity seen for precursor 1.Specifically, we chose to examine whether unsymmetrically substituted polyalkyoxy silyl aryl triflates would react

Synthesis of toxyloxanthone B

“…The substituted benzyne derived from precursor 5 is unsymmetrical and therefore could lead to two nucleophilic addition products. However, Stoltz and coworkers have previously shown that the aryne derived from 5 undergoes regioselective attack as indicated in Scheme 1, 24 and therefore we were confident that the correct xanthone would result from our projected coupling reaction.…”

“…Selective protection of the non-hydrogen bonded phenol as its MOM-ether gave the required methyl salicylate 4 (Scheme 2). The aryne precursor 5 was prepared from phloroglucinol as described by Stoltz and co-workers, 24 setting the stage for the key step.…”

Synthesis ofo-(Dimethylamino)aryl Ketones, Acridones, Acridinium Salts, and 1H-Indazoles by the Reaction of Hydrazones and Arynes

“…The use of the unsymmetrical 3,5-dimethoxy-2-(trimethylsilyl)phenyl triflate 122 41 in a reaction with o -fluorobenzaldehyde dimethylhydrazone resulted in the formation of compound 123 in a 78% yield as a single regioisomer (Scheme 10). Compound 123 is found in nature, 42 as well as its 1-demethylated 33 and 1,3-bisdemethylated 43 derivatives.…”

Hyperbranched Polyfluorinated benzyl ether polymers: Mechanism, kinetics, and optimization

“…The disubstituted phloroglucinol was obtained in relatively good yields (16.6%) compared with similar phloroglucinol etherifications that additionally required tedious protection/deprotection steps (19%). 31 The phenol-bearing AB 2 system, missing a methylene spacer when compared with the benzyl ether polymer, was expected to be less susceptible to cyclization. By exposing the phenolbased AB 2 monomer to the optimum potassium carbonate/ 18-crown-6 stoichiometry in a concentrated solution (0.8 M) of toluene and dilute solution of acetonitrile (0.1 M), the cyclization probability during a polymerization was assessed.…”