Iridium‐Catalyzed C(sp³)−H Addition of Methyl Ethers across Intramolecular Carbon–Carbon Double Bonds Giving 2,3‐Dihydrobenzofurans

Abstract

Intramolecular addition of an O-methyl C(sp 3 )À H bond across a carbon-carbon double bond occurs in the iridium-catalyzed reaction of methyl 2-(propen-2-yl)phenyl ethers. The Ir/(S)-DTBM-SEGPHOS catalyst promotes the reaction efficiently in toluene at 110-135°C to afford 3,3-dimethyl-2,3dihydrobenzofurans. Enantioselective C(sp 3 )À H addition is achieved in the reaction of methyl 2-(1siloxyethenyl)phenyl ethers, affording enantioenriched 3-hydroxy-2,3-dihydrobenzofuran derivatives with up to 96% ee.

Synthesis of (±)‐epi‐Jungianol by the Gold(I)‐Catalyzed Propargyl Claisen Rearrangement/Hydroarylation Cascade Reaction of Propargyl Vinyl Ethers

“…The synthesis of epi-jungianol is reported in Schemes 6-8. Starting from known 2-bromo-6-methylanisole 17, [19] we prepared propargyl alcohol 18 (74 %) by Sonogashira coupling (Scheme 6) and this was acetylated to quantitatively give 19.…”

“…The synthesis of epi ‐jungianol is reported in Schemes 678. Starting from known 2‐bromo‐6‐methylanisole 17 , [19] we prepared propargyl alcohol 18 (74 %) by Sonogashira coupling (Scheme 6) and this was acetylated to quantitatively give 19 . Coupling with 1‐bromo‐2‐propanol 8 c under the optimized conditions provided ether 20 in 62 % yield and elimination with t ‐BuOK gave propargyl vinyl ether 21 in 49 %.…”

“…Microanalyses were carried out with a CHN Thermo FlashEA 1112 Series elemental analyzer. Compounds 10, [5] 17, [19] 5 [8] and 29, [8] are known. Acetate 10 [5] and bromohydrines 8 a-c, [13,14] were prepared as reported.…”

Recent Advances in Synthetic Strategies to 2,3-Dihydrobenzofurans

“…Ohmura, Suginome, and co-workers reported, in 2019, that methyl 2-(propen-2-yl)phenyl ethers underwent intramolecular iridium-catalyzed addition of an O-methyl C(sp 3 )-H bond across a C=C bond to afford 3,3-disubstituted DHBs. 102 For example, for substituted methyl 2-(1-TBSOvinyl)phenyl ethers, the Ir/(S)-DTBM-SEGPHOS catalyst promoted the enantioselective C(sp 3 )-H addition reaction efficiently in toluene at high temperatures to give enantioenriched 3-substituted 3-(TBSO)-DHBs with up to 96% ee (Scheme 36). T. Laurita et al…”

Oxyselenocyclization of 2‐Allylphenols for the Synthesis of 2,3‐Dihydrobenzofuran Selenides

“…As a consequence of the diverse panel of biological activity displayed by these compounds, several synthetic procedures have been developed to access the 2,3‐DHB core. Some of the most efficient methods reported in the literature involve radicalar [18–24] or anionic cyclizations, [25–28] biomimetic couplings, [29–34] cycloaddition processes, [35–40] reactions mediated by Lewis acids [41–45] or transition‐metals [46–50] among other strategies [51–56] …”