A New and Efficient Synthesis of 4-Functionalized Benzo[b]furans from 2,3-Dihalophenols

Abstract

Tandem Sonogashira coupling/5-endo-dig cyclization reactions on 2,3-dihalophenols suppose a straightforward entry to 4-halobenzo[b]furans, which can be easily transformed into 4-functionalized benzo[b]furans, that are difficult to synthesize by other procedures. On the other hand, the starting 2,3-dihalophenols are efficiently prepared from commercially available 3-halophenols, via their N,N-diethyl carbamates by selective lithiation at the 2-positions by treatment with s-BuLi/TMEDA or LDA at low temperature and reaction with halogen electrophilic reagents.

Transition metals in organic synthesis: Highlights for the year 2005

“…(10) A large variety of functionalized heterocyclic halides and sulfonates were employed in the palladiumcatalyzed Suzuki reaction. Heterocyclic ring-systems such as, bromo-oxabicyclo[3.2.1]octadienes [28], 6-bromoimidazo[1,2-a]pyridine [174], 3,5-dichloropyrimidine and 3,5-dichloropyridine [175], 4,7-dibromo-2,1,3-benzothiazole with a 3-indolylboronic acid [176], halo-amino-pyridines, pyrazines and pyrimidines [154], chloropyrazines in a synthesis of botryllazines [14], 4-chloroquinoline-2-one [177], 3-trifloxypyrazole [178], 8-bromo-2 -deoxyguanosine [179], 2-chloro-2 -deoxyinosine [180], 6-halopurines [30], 6-fluoro-, 6-(3-methylbutylsulfanyl)-, and 6-(3-methylsulfonyl)purine [181], 5-trifloxyindoles [29], 3-iodo-5-bromoindole [182], 4-bromobenzofuran [183], 5,7-dichloro-1,6-naphthyridin-2-(1H)-one [184], 7-bromo-pyrido [2,3-b]pyrazine [185], 5-iodo-1,2,3-triazoles [186], 3-bromo-2,5-dihydrofuran-2-one [187], 3-halo-indazoles [188,189], 3-chloro-2-pyrazolines and 3-chloro-1-phenyl-1,4,5,6-tetrahydropyridazine [190] and 3-iodo-4H-chromen-4-one [191] were used in Suzuki type cross-couplings. Regioselective coupling in the 4-position of 3-bromo-4-trifloxyquinolin-2(1H)-one [192], the 2-position of di-and tribrominated pyrroles [193] and the 3-position of 3,5-dichloropyrazin-2-ones [194] were reported.…”

“…(14) Heterocyclic ring systems were shown to readily participate in Sonogashira-type couplings [175,306]. Some more complex examples include reaction of 5-iodoarabinosyluridine [307], 3-iodofuran [308], 6-chloro-9H-purine [309], 8-bromoadenosine [310], 2,6-bis(4-iodopyrazol-1-yl)pyridine [311], 6-chloro-3H-pyrimidin-4-one [312], bromo-oxabicyclo[3.2.1]octadienes [28], a triazolopyrazinyl bromide [172], 5-trifloxyindoles [29], 5-bromobenzofuran [183], 3-iodo-5-bromoindole and 3-iodo-5-bromo-3-indazole [182], 7-bromo-pyrido [2,3-b]pyrazine [185], 5-iodo-1,2,3-triazoles [186,313], 4,5-diiodoimidazole [314] and 4-iodo-2-bromoquinoline [315] derivatives. Sonogashira coupling of 2-iodophenols followed by cyclization to give benzofurans was reported [183].…”

Activating tert-butyl hydroperoxide by chelated vanadates for stereoselectively preparing sidechain-functionalized tetrahydrofurans

“…For preparing substrates 1b-k we adhered to published procedures, which in selected instances were adapted for improving selectivity (Supplementary data) [84][85][86]. For synthesis of the rel-(1R,2R)-stereoisomer of diphenylhexenol 1e, also named 1,2-like-1e, we used diisobutyl aluminum hydride (DIBAL-H) [87] to control stereoselectivity in ketone reduction, leading to a 98/2-mixture of rel-(1R,2R)/(1S,2R)-diastereomers of 1e.…”

Convenient Access to meta‐Substituted Phenols by Palladium‐Catalyzed Suzuki–Miyaura Cross‐Coupling and Oxidation

“…Similarly,d irected ortho-metallation strategies have limited use in the generation of meta-substituted phenols. [5] Clearly,t he challenging preparation of these electrophilic partners severely limits the use of crosscoupling strategies to access meta-substituted phenols. Indeed, whilealarge number of Suzuki-Miyaura cross-couplingr eactions using meta-halophenols have been reported, [3] very few examples have ac arbon substituent at the ortho-position between the hydroxyl group and the meta-substituent, ando ft hese only four bear an alkyl group at that position (Scheme 1a).…”