Synthesis of a Furoindoline Scaffold via an Interrupted Fischer Indolization

Abstract

A. 3-Methyltetrahydrofuran-2-ol (2). A single-necked (24/40 joint) 1000-mL round-bottomed flask, charged with a Teflon-coated magnetic stir bar (5 x 1 cm, football-shaped), and a 125 mL pressure-equalizing addition funnel (24/40 joint) are dried in an oven overnight (160 °C). The glassware is assembled while hot, and the addition funnel is sealed with a 24/40 rubber septum with an argon inlet and an outlet connected to a bubbler. The apparatus is allowed to cool to 23 °C under a stream of dry argon. The joint between the addition funnel and round-bottomed flask is wrapped tightly with Teflon tape and clamped with a Keck clip (24/40) (Note 2). 3-Methyldihydrofuran-2(3H)-one (1) (3.3 mL, 3.52 g, 35.2 mmol, 1.0 equiv) (Note 3) is added to the addition funnel through the septum using a plastic i-Bu2AlH CH2Cl2, –78 °C