Direct Synthesis of 3-Morpholino-2,3-dihydroindoles from Enamines and Aryl Azides

Convergent synthesis of thiodiazole dioxides from simple ketones and amines through an unusual nitrogen-migration mechanism

“…2A). Each of these species can further transform in several ways, including through C–C bond cleavage (Type I) 13 and migration of a carbon (Type II), 13 a – d ,14 nitrogen (Type III), 13 e ,14 b , c ,15 b or hydride (Type IV) 10,13 e ,14 a ,15 substituent (Fig. 2A).…”

Metal-Free Multicomponent Strategy for Amidine Synthesis

“…According to the proposed reaction mechanism (see Figure a), imine ( IM1 ) is first formed by a nucleophilic addition of an amine to the carbonyl group of a ketone . The newly formed imine can then undergo an imine–enamine tautomerization to form an enamine intermediate ( IM2 ). , Sulfonyl azide reacts with the enamine via a 1,3-dipolar cycloaddition to form a triazoline intermediate ( IM3 ). ,, Finally, the product is formed in a ring-opening reaction together with the release of diazomethane gas. We first set out to verify the likelihood of the ring closing and opening steps by identifying the release of diazomethane.…”

“…36,37 Sulfonyl azide reacts with the enamine via a 1,3-dipolar cycloaddition to form a triazoline intermediate (IM3). 14,38,39 Finally, the product is formed in a ring-opening reaction together with the release of diazomethane gas. We first set out to verify the likelihood of the ring closing and opening steps by identifying the release of diazomethane.…”

“…The early studies described above seemingly provided a metal-free approach for the formation of sulfonyl amidines (Scheme b, top left); − however, they relied on the preparation and isolation of stable enamines by a reaction with 50 mol % loading of titanium tetrachloride . Inspired by this pioneering work, we envisioned a strategy that would leverage the in situ metal-free formation of structurally diverse enamines by the addition of amines to ketones.…”

“…In light of the above-mentioned considerations, it is not surprising that amidine synthesis has received attention in recent years. Early studies were based on reacting enamines and sulfonyl azides; however, this methodology depended on the isolation of stable enamine substrates, significantly limiting the scope (Scheme b, top left). − …”