Methodologies in Amine Synthesis

Challenges and Applications

Alfredo Ricci, Luca Bernardi, Alfredo Ricci, Luca Bernardi

• Verlag: Wiley-VCH
• Jahr: 2021
• ISBN:
  9783527826193
• Auflage: 1
• Thema: Ciencias físicas
• Thema: Química orgánica

Discover a comprehensive overview of efficient synthetic routes to an important compound class in organic and pharmaceutical chemistry

Methodologies in Amine Synthesis: Challenges and Applications deliverspowerful and state-of-the-art methods for the efficient preparation of amines. The text summarizes recent advances in the electrophilic amination reaction, hydroamination, C-H amination and newly developed photocatalytic approaches. The distinguished editor has included resources that discuss organocatalytic and enzymatic routes to the generation of amines under mild and environmentally friendly conditions.

The book also highlights the relevance of the amino function in bioactive molecules, drugs, and smart materials, as well as the palladium-catalyzed aromatic amination reaction. It presents efficient and practical synthetic methods, highlights the opportunities and challenges associated with each, and discusses their possible applications in pharmaceutical chemistry and materials science.

Edited by the expert who wrote Modern Amination MethodsandAmino Group Chemistry, the book includes a breadth and depth of material essential to the practice of academic and industrial chemists working in organic synthesis and catalysis.Readers will also benefit from the inclusion of:

• A thorough introduction to new openings and perspectives in the electrophilic amination
• Discussions of asymmetric catalysed hydroaminomethylation and amino organocatalysis
• A treatment of the synthetic application of transaminase or MAO biocatalysis to the synthesis of amines
• An exploration of recent developments in C-H amination, as well as photocatalyticapproaches to the synthesis of amines
• An examination of primary amines from renewable bio-based resources

Perfect for organic, natural product, catalytic, medicinal, and polymer chemists, Methodologies in Amine Synthesis: Challenges and Applications will also earn a place in the libraries of materials scientists and chemists working with organometallics who desire a one-stop reference edited by a well-known expert in the field.

1
Substitution‐type Electrophilic Amination Using Hydroxylamine‐Derived Reagents

Zhe Zhouand László Kürti

Rice University, Department of Chemistry, 6500 Main Street, Houston, TX, 77030, USA

1.1 Introduction

Electrophilic amination is a class of organic reactions where C—N bonds are formed via the use of electrophilic aminating reagents [1–4]. Depending on the specific reaction pathway, electrophilic amination reactions can be classified either as substitution or addition. This chapter focuses on substitution reactions. Aminating reagents for the substitution‐type electrophilic aminations are essentially NR₂⁺ synthons, and the electrophilicity on the nitrogen atom is generally achieved by attaching a more electronegative functionality (X) to the nitrogen atom that can serve as a leaving group. Common structural motifs for this class of reagents include chloramines, hydroxylamines, and oxaziridines (i.e. cyclic hydroxylamine derivatives). Because of the safety hazards associated with the use of chloramines, recent developments in this area have been focused on the use of more stable hydroxylamine‐type reagents (Scheme 1.1).

Substitution‐type electrophilic amination reactions can operate under either uncatalyzed or catalyzed conditions. The majority of catalytic substitution‐type electrophilic amination reactions are catalyzed by complexes of transition metals (TMs). In the uncatalyzed reactions, the carbon nucleophile directly attacks the electrophilic nitrogen atom and a new C—N bond is formed. In the TM‐catalyzed reactions, the transition metal first enters into the N—X bond via an oxidative addition, and the new C—N bond is formed after sequential ligand exchange and reductive elimination (Scheme 1.2). The major difference between TM‐catalyzed substitution‐type electrophilic amination reactions and TM‐catalyzed C–N cross‐coupling reactions (i.e. Buchwald–Hartwig coupling) is the role of the nitrogen source: it acts as an electrophile in the former while as a nucleophile in the latter.

The majority of the literature in this area concerns the TM‐catalyzed versions of substitution‐type electrophilic amination. Therefore, they will be discussed first in this chapter.

Scheme 1.1 General structure of electrophilic aminating reagent.

Scheme 1.2 Mechanisms of two main types of electrophilic amination.

1.2 Cu‐Catalyzed Reactions

Narasaka and coworkers reported an early iteration of Cu‐catalyzed substitution‐type electrophilic amination of Grignard reagents utilizing O‐sulfonyloximes as aminating reagents. The reactions can also give products without copper catalysis, albeit with much lower yields. Because of the nature of the aminating reagents, subsequent acidic hydrolysis is needed to convert the imine products to the desired amines [5, 6]. A similar amination process of organozinc reagents was reported by the Erdik group around the same time. In this case, in addition to the O‐sulfonyloximes, the authors showed that the reaction can also proceed with methoxyamine when excess of the organometallic reagent was used (Scheme 1.3) [7, 8]. These early reactions have several drawbacks that affect their utilizations, including a very limited substrate scope, low conversion rate due to many side reactions, and, most importantly, the need to use a strong acid to hydrolyze the initial imine products. The use of strong acidic conditions in the hydrolysis makes these procedures unsuitable for substrates containing acid‐labile functionalities.

Scheme 1.3 Early examples of Cu‐catalyzed electrophilic amination.

Source: Erdik a...