Synthesis of Lactams via Isocyanide-Based Multicomponent Reactions

Abstract

Lactams are very important heterocycles as a result of their presence in a wide range of bioactive molecules, natural products and drugs, and also due their utility as versatile synthetic intermediates. Due to these reasons, numerous efforts have focused on the development of effective and efficient methods for their synthesis. Compared to conventional two-component reactions, multicomponent reactions (MCRs), particularly isocyanide-based MCRs, are widely used for the synthesis of a range of small heterocycles including lactam analogues. Despite their numerous applications in almost every field of chemistry, as yet there is no dedicated review on isocyanide-based multicomponent reactions (IMCRs) concerning the synthesis of lactams. Therefore, this review presents strategies towards the synthesis of α-, β-, γ-, δ- and ε-lactams using IMCRs or IMCRs/post-transformation reactions reported in the literature between 2000 and 2020.1 Introduction2 Developments in Lactam Synthesis2.1 α-Lactams2.2 β-Lactams2.3 γ-Lactams2.3.1 General γ-Lactams2.3.2 Benzo-Fused γ-Lactams2.3.3 Spiro γ-Lactams2.3.4 α,β-Unsaturated γ-Lactams2.3.5 Polycyclic Fused γ-Lactams2.4 δ-Lactams2.5 ε-Lactams3 Conclusions

Mechanochemical IMCR and IMCR-post transformation domino strategies: towards the sustainable DOS of dipeptide-like and heterocyclic peptidomimetics

“…The one-pot synthesis of PHPs like 7 via an IMCR-post transformation strategy under ecofriendly conditions has hardly been reported, accompanied by comparatively long reaction times and/or the use of excess reagents. 24 Concerning the IMCR to date, there is only one ecofriendly report available by Van der Eycken. 10 g Recently, El Kaim et al (Scheme 3b) reported the one-pot synthesis of PHPs like 7 via an Ugi-4CR-post transformation strategy under conventional heating.…”

Six‐Component Reactions and Beyond: The Nuts and Bolts

“…Indeed, it must be noted that handling low molecular isocyanides is relatively straightforward if one has a methanolic HCl solution on‐hand to re‐hydrate remnants of isocyanides on glassware, syringes or gloves. A wide range of reviews and book chapters in recent years on isocyanides articulate this peculiar transition new entrants to the field experience [88–96] …”

Amino-Functionalized Multiwall Carbon Nanotubes as Efficient Basic Catalysts for the Formation of γ-Lactams: Synthesis of N-1-Heptenyl-2-pyrrolidinone

“…Their synthesis is carried out through several organic reactions starting from acyclic or cyclic precursors [22] or through the transformation of pre-existing lactams by means of C-C or C-heteroatom bond formation [23]. The isocyanide-based multicomponent reactions are another widely reported route for the synthesis of lactams [24]. However, the synthesis usually consists of multiple reaction steps in the presence of organic solvents, sometimes under strict reaction conditions [25,26] or catalyzed by expensive transition metal compounds [27]; therefore, it is necessary to develop alternative synthetic approaches that are more efficient for the preparation of γ-lactam structures.…”