A Multimetallic Piano-Stool Ir–Sn₃ Catalyst for Nucleophilic Substitution Reaction of γ-Hydroxy Lactams through N-Acyliminium Ions

Abstract

A multimetallic piano-stool complex [Cp*Ir(SnCl(3))(2){SnCl(2)(H(2)O)(2)}] (1) having Ir-Sn(3) motif has been synthesized from [Cp*IrCl(2)](2) and SnCl(2). The multimetallic complex catalytically promotes the nucleophilic substitution reaction (here after α-amidoalkylation reaction) of γ-hydroxylactams generated from phthalimidals to obtain decorated isoindolinones in excellent yields. Succinamidals, however, lead to the substituted pyrrolidinones (thermodynamic control product) via S(N)1-type path as well as eliminated pyrrolinones (kinetic control product) via an E1-type path, depending on the reaction parameters. A straightforward application of this methodology is to synthesize benzo-fused indolizidine alkaloid mimics.

Multimetallic Iridium‐Tin (Ir‐Sn3) Catalyst in N‐Acyliminium Ion Chemistry: Synthesis of 3‐Substituted Isoindolinones via Intra‐ and Intermolecular Amidoalkylation Reaction

“…Phthalic anhydride‐derived γ‐hydroxylactams containing the aromatic nucleophiles reacted in the presence of only 1 mol% of 1 under mild reaction conditions to provide the cyclized products 4a and 4b in excellent yields. Compared to the intermolecular version where less electron‐rich arenes like toluene remained unreactive,20a here the reaction took a much longer time (12 h) to afford 95% of cyclized product 4b . Electron‐poor arenes remained unreactive towards the cyclization reaction.…”

“…In our previous report on 1 ‐catalyzed intermolecular α‐amidoalkylation reactions with a variety of carbon nucleophiles we found that, along with electron rich‐arenes and heteroarenes, 4‐hydroxycoumarin could also be employed for the successful formation of isoindolinone derivatives in excellent yields 20a. So here we thought to extend the scope of the alkylation reaction with other β‐dicarbonyl compounds.…”

“…The multimetallic complex 1 was synthesized via insertion of SnCl 2 across the iridium‐chlorine bonds of [Cp*IrCl 2 ] 2 in dichloroethane at 80 °C 20a. As shown in Figure 2, 1 adopts a three‐legged piano‐stool geometry, as is common to the Cp*Ir(III) complexes.…”

“…Encouraged by the initial success on 1 ‐catalyzed intermolecular α‐amidoalkylation reaction with heteroatom nucleophiles,20a we thought to broaden the scope with different types of nitrogen (sulfonamides and amides), oxygen (alcohols) and sulfur (thiols) nucleophiles. Very good yields of the products 9a–d were isolated with nitrogen nucleophiles like toluenesulfonamide, benzenesulfonamide, benzamide and acetamide (Table 6).…”

“…Also, 4‐aminothiophenol reacted with a succinimide‐derived lactam leading to 9q (from S ‐attack) as the sole product. For succinimide‐derived hydroxylactams it is noteworthy to mention that, unlike with oxygen and nitrogen nucleophiles where the dehydrated products were predominately formed, substituted products were isolated only with sulfur nucleophiles 20a. Curiously, for the lactam substrates 3c and 3r it was observed that the intermolecular reaction with thiophenols prevented the π‐cyclization via the aromatic ring, and thus led to N , S ‐acetals ( 9l , 9r and 9s ) as the sole products.…”