Enantioselective Multicomponent Synthesis of Fused 6–5 Bicyclic 2‐Butenolides by a Cascade Heterobicyclisation Process

Abstract

The successive coupling of an alkoxy(aryl/heteroaryl)carbene complex of chromium with either a ketone or an imide lithium enolate and then a 3-substituted (H, TMS, PhCH(2), PhCH(2)CH(2), Me) propargylic organomagnesium reagent has afforded novel hydroxy-substituted bicyclic [4.3.0]-γ-alkylidene-2-butenolides with three modular points that has allowed the efficient introduction of molecular complexity, including a homopropargylic alcohol core. The selective formation of these five- or six-component heterobicyclisation products is the result of the regioselective integration of the Grignard reagent as a propargyl fragment followed by a cascade CO/alkyne/CO insertion, ketene trapping and elimination sequence. By using lithium enolates of chiral N-acetyl-2-oxazolidinones and the corresponding propargylic organocerium reagents, both enantiomers of these bicyclic heterocycles were efficiently prepared with very high enantiomeric purity. Architecturally, these fused bicyclic butenolides are characterised by a highly unsaturated and oxygenated core and they exhibit strong blue fluorescence in solution.

Para-selective borylation of monosubstituted benzenes using a transient mediator

“…The crude product was purified by column chromatography on silica gel (EtOAc/hexane = 1/4) to afford 1w as a white solid (618 mg, 60% yield). 7 Procedure C: 11 To a solution of sulfide (1.0 equiv.) in EtOH (0.625 M) was added oxone (0.6 equiv.).…”

“…Typically, para-selectivity control often dominated by steric and electronic factors of substrates, and high selectivity was observed mainly for electron-rich arenes, which have been represented in electrophilic aromatic substitution reaction of aromatics. 3 Recently, major progress to face this challenging para-C-H functionalization has been achieved through electronic recognition, 4 steric control, 5 template assistance, 6 and radical involved processes 7 (Scheme 1A). Despite undisputable advances, those methods are still lack of generality with insufficient regioselectivity, either requiring large excess of arenes or working with the assistance of directing group (template), and normally resulting in a mixture of para-substituted product with other isomers.…”

Para-Selective Borylation of Monosubstituted Benzenes Using a Transient Mediator

“…The crude product was purified by column chromatography on silica gel (EtOAc/hexane = 1/4) to afford 1w as a white solid (618 mg, 60% yield). 7 NaH (60% in oil, 1.50 g, 37.5 mmol) was added slowly to a stirred solution of carbazole (4.17 g, 25.0 mmol) in dry THF (50 mL) under a nitrogen atmosphere at room temperature. After 30 min, tetrafluoroisophthalonitrile (1.0 g, 5.0 mmol) was added.…”

Para-Selective Borylation of Monosubstituted Arenes Using a Transient Mediator

“…The crude product was purified by column chromatography on silica gel (EtOAc/hexane = 1/4) to afford 1w as a white solid (618 mg, 60% yield). 7 To a solution of the crude product (0.76 g, 5.0 mmol) in EtOH (10.0 mL) was added 30% H2O2 aqueous solution (1.35 mL, 15.0 mmol) under an ice-water bath. The mixture was then stirred at the room temperature for 24 hours.…”