Formal Radical Cyclization onto Benzene Rings:  A General Method and Its Use in the Synthesis of ent-Nocardione A

Abstract

An indirect method is described for effecting radical cyclization onto a benzene ring. Cross-conjugated dienones 6, which are readily prepared from phenols, undergo radical cyclization (6 --> 7 --> 8), and the products (8) are easily aromatized. The method has been applied to the synthesis of ent-nocardione A (21).

Development of an Automated Microfluidic Reaction Platform for Multidimensional Screening: Reaction Discovery Employing Bicyclo[3.2.1]octanoid Scaffolds

“…During reaction optimization, we observed that when rigorously water-free conditions were utilized for [5+2] cycloaddition of monoketal 1 31 and styrene (Scheme 1), the major product was diene 12 rather than the desired bicyclo[3.2.1]octanoid 7 . Ring-opened product 12 appears to arise from a retro-Dieckmann-type process with oxonium intermediate 13 and the methanol liberated during formation of oxonium intermediate 14 32.…”

Stereoselective Synthesis of [4.3.1]Propellane Fragment of Phainanoids A–F

“…Reduction by LiEt 3 BH or LiAlH(O t ‐Bu) 3 did not proceed at all. Use of DIBAL‐H, 9‐BBN, NaBH 4 /CeCl 3 , or K‐selectride provided 10a and 10b along with unexpected rearomatized phenol 10c . Although L‐selectride afforded the desired alcohol 10a with excellent selectivity in the crude mixture, rearomatization of 10a into 10c occurred significantly during work‐up procedure.…”

“…Use of DIBAL-H, 9-BBN, NaBH 4 /CeCl 3 , or K-selectride provided 10a and 10b along with unexpected rearomatized phenol 10c. 6 Although L-selectride afforded the desired alcohol 10a with excellent selectivity in the crude mixture, rearomatization of 10a into 10c occurred significantly during work-up procedure. Red-Al reagent proved to be the best choice so far in terms of both yield and selectivity.…”

“…In summary, stereoselective synthesis of [4.3.1]propellane model compound 2, a common structural motif in phainanoids A-F (1a-1f), was achieved in 13 steps from 2,5-dimethoxycinnamic acid (6). The key steps are regioselective demethylation of C 7 -methoxy group, PIFA-mediated oxidation of phenol moiety, syn-selective 1,2-reduction of dienone functional group, and hydroxyl group-directed cyclopropanation reaction.…”

Enantioselective nickel-catalyzed arylative intramolecular 1,4-allylations

“…Proton loss from 10 then gives 8. 14 The fact that phenols 8 are observed in appreciable quantities only when certain arylboronic acids are used may indicate that the boronic acid serves as a hydrogen bond donor to promote ring-opening. 15 Confirmation of the ability of acid to promote the formation of phenols 8 was provided by heating 6l with TsOH•H2O (0.5 equiv) at 80 °C, which gave 8l in 65% yield (eqn (1)).…”