Use of β‐Amido Allylboronate as a Nucleophilic Reagent in Catalytic Amide Allylation of N‐Carbonyl Imides

Abstract

This communication describes the utility of β‐amido allylboronate as a nucleophile in the catalytic amide allylation of N‐carbonyl imides. The reaction of the imide substrates with the boronates has been accomplished by using catalytic zinc bromide and basic additives (ethanol, potassium carbonate and 18‐crown 6‐ether), affording azaspiro‐γ‐lactones through a ring opening‐reclosure process with yields up to 100 %. The cost‐effective and easy‐to‐handle method established here tolerated for gram‐scale synthesis without significant loss of reaction efficiency.

Zinc Hydroxide‐Catalyzed Asymmetric Allylation of Acetophenones with Amido‐Functionalized Allylboronate in Water

“…We chose 2‐butanone as a substrate because of its water‐soluble property. Similar to the results obtained in the previous experiment performed in toluene, 1 a did not show sufficient reactivity without additives (Entry 1 in the Table S1 in the Supporting Information). Variety of alkali or alkaline‐earth metal salts were first examined as a water‐soluble additive, but no or only a trace amount of the desired product was observed (Entries 2–5).…”

“…In addition to the reaction using nonsubstituted allylmetal reagents, allylation with functionalized ones is of great importance due to the broad utility in complex molecule synthesis . In this context, we demonstrated the utility of allylboronate ( 1 ) bearing amide functionality at the β position for the construction of spiroheterocycles and have succeeded the syntheses of four types of bisheterocyclic spiro compounds . Moreover, we recently discovered the remarkable air‐ and water‐stability of 1 , which remained intact even after exposure to air and water for more than one week .…”

“…[13][14][15][16][17][18][19] In this context, we demonstrated the utility of allylboronate (1) bearing amide functionality at the β position for the construction of spiroheterocycles and have succeeded the syntheses of four types of bisheterocyclic spiro compounds. [17,20,21] Moreover, we recently discovered the remarkable air-and water-stability of 1, which remained intact even after exposure to air and water for more than one week. [17] These synthetic utility and chemical stability of 1 motivated us to explore a new catalytic enantioselective amido-functionalized allylation in water (Scheme 1c).…”

Bifurcated synthesis of methylene-lactone- and methylene-lactam-fused spirolactams via electrophilic amide allylation of γ-phenylthio-functionalized γ-lactams

“…Our research group succeeded the enantiopure synthesis of these compounds, in which enantioselective allylation of an isatin derivative with an amido-functionalized allylstannane was employed as a key reaction (Scheme 1b) [10,11]. More recently, an amide-functionalized allyl boronate was developed as an alternative reagent for the allylstannane [12][13][14][15][16], which led to the syntheses of not only cytotoxic methylene-lactones spiro-fused to a lactam Scheme 1: Examples of (a) bioactive compounds bearing an α-methylene-γ-butyrolactone structure, (b) syntheses of spirocyclic compounds through nucleophilic amide allylation, and (c) syntheses of spirocyclic compounds through electrophilic amide allylation.…”

“…ring (B) but also their analogous methylene-lactams (C) through zinc-catalyzed addition to N-carbonyl imides [13,14,16].…”