Metal-Free Synthesis of 4-Chloroisocoumarins by TMSCl-Catalyzed NCS-Induced Chlorinative Annulation of 2-Alkynylaryloate Esters

Abstract

4-Chloroisocoumarins can be conveniently prepared from 2-alkynylaryloate esters via the activation of alkynes by electrophilic chlorine, generated in situ from N-chlorosuccinimide (NCS) in the presence of 10 mol % trimethylsilyl chloride (TMSCl), which leads to 6-endo-dig-selective chlorinative annulation to give the desired products in moderate to quantitative yields. The procedure employs readily available reagents and can be conveniently carried out on a wide scope of substrates under mild conditions (0 °C to rt). Furthermore, the reaction is scalable for gram-scale preparation of 4-chloroisocoumarins. Additionally, 4-bromo- and 4-iodoisocoumarins can be prepared in moderate to good yields by replacing NCS with N-bromosuccinimide (NBS) and N-iodosuccinimide (NIS), respectively.

Dihalooxygenation of Alkynes and Alkynols: Preparation of 2,2-Dihaloketones and gem-Dihalolactols

“…Due to the limitations mentioned above, and relying on our previously reported work on the in situ generation of halogen and interhalogen species (X–Cl) 10a and their utility in halogenation reactions, 10` c d e we envisioned that our halogenation methods might be used for the development of a mild and operationally simple dichloro- or dibromooxygenation of internal alkynes 1 to synthesize 2,2-dihaloketones 2 (Scheme 1 C; Pathway A, n = 1) or gem -dihalogenated lactol derivatives 3 (Scheme 1 C; Pathway B, n ≥ 2).…”

Enantioselective Synthesis of Fused Isocoumarins via Palladium-Catalyzed Annulation of Alkyne-Tethered Malononitriles

“…These data were consistent with the reported literature. 25 A mixture of PPh 3 (16.40 g, 62.6 mmol, 1.3 equiv), imidazole (4.26 g, 62.6 mmol, 1.3 equiv), and methyl 2-(4-hydroxybut-1-yn-1yl)benzoate S1 (9.83 g, 48.2 mmol, 1.0 equiv) in DCM (30 mL) were added to a 100 mL round-bottom flask. The mixture was stirred at room temperature until the solid was dissolved completely.…”

“…1 H NMR (400 MHz, CDCl 3 ): δ 7.98–7.96 (m, 1H), 7.56–7.42 (m, 2H), 7.39–7.30 (m, 1H), 3.91 (s, 3H), 3.85 (t, J = 5.6 Hz, 2H), 2.71 (t, J = 5.6 Hz, 2H). These data were consistent with the reported literature …”

Ready Access to Benzannulated [5,5]-Oxaspirolactones Using Au(III)-Catalyzed Cascade Cyclizations

“…Hence, initially, model substrate 5a ((2-(4hydroxyalkynyl)benzoate)) was prepared using the synthetic sequence of propargyl magnesium bromide addition (prepared from propargyl bromide (1a) using Mg, HgCl 2 (cat. ), Et 2 O) on to cyclohexanone (2a) to give homopropargylic alcohol 18 3a followed by subsequent Sonogashira coupling 19 (Pd-(PPh 3 ) 2 Cl 2 , CuI, TEA, DMF) with methyl 2-iodobenzoate (4a) (entry b, Scheme 1). 20 Then, 5a was treated with 10 mol % of HAuCl 4 •xH 2 O (Gold(III) chloride hydrate, ∼50% Au basis; CAS No.…”