Carboxylate‐Directed Tandem Functionalisations of α,β‐Dihaloalkenoic Acids with 1‐Alkynes: A Straightforward Access to (Z)‐Configured, α,β‐Substituted γ‐Alkylidenebutenolides

Abstract

An easy and mild copper(I)‐catalysed lactonisation of readily available (E)‐2,3‐dihalopropenoic acid derivatives regio‐ and stereoselectively leads to rarely described (Z)‐3‐halo‐5‐ylidene‐5H‐furan‐2‐ones. These compounds are subsequently able to undergo classical Pd‐catalysed cross‐coupling reactions, providing 3‐substituted and 3,4‐disubstituted 5‐ylidene‐5H‐furan‐2‐ones (see scheme).

First studies directed towards the diastereoselective synthesis of the BCD tricyclic core of brownin F

“…17 One major advantage of our Pd-free Sonogashira coupling reaction is that no further side reaction (including oxidative addition on the remaining α-halogen or β-elimination) is observed when an αβ-dihaloalkenoic acid such as 7b is used in the process. 18 Once again the base promoted cyclisation proceeded smoothly with total conversion, regio-, chemo-and diastereoselectivity, and cycloadduct 2b now proved somewhat more stable as it could be purified by flash chromatography on silica gel and isolated in 55% yield. The relative stereochemistry was assigned by analogy with previous results and associated DFT calculations.…”

“…Fractions that contained the desired product were gathered and concentrated under reduced pressure to give the γ-alkylidenebutenolide (0.11 g) in 58% yield. R f (PE-EtOAc: 6/4) = 0.29; HRMS (ESI): m/z calcd for C 18 Compound 6. To a cooled (0°C) solution of the γ-alkylidenebutenolide 9 (1 equiv.…”

Emergence of Copper‐Mediated Formation of C–C Bonds

“…In this way, different natural product moieties were also prepared through a copper‐based coupling strategy. γ‐Alkylidenebutenolides were easily functionalized to afford α,β‐substituted γ‐alkylidenebutenolides (Scheme ) with good yields . Moreover, regioselective copper‐mediated syntheses of pyranones were also reported (Scheme ) .…”

Straightforward Access to a Great Diversity of Complex Biorelevant γ-Lactams Thanks to a Tunable Cascade Multicomponent Process

“…14 In addition, it was reported in 2009 that the palladium-free Sonogashira coupling between (Z)-3-iodoacrylic acids 8 and terminal alkynes 9, followed by a 5-exo-dig oxa-cyclization, offered a convenient access to γ-alkylidenebutenolides 10 (Scheme 1a). 15,16 It is also generally known that treatment of γ-alkylidenebutenolides 10 with primary amines 11 leads to the formation of γ-hydroxy-γ-butyrolactams 7 (Scheme 1a), and this approach is commonly used. 17,18 Moreover, treatment of γhydroxybutyrolactams 7 with acid sources results in the formation of the corresponding N-acyliminium ions 12, which can evolve either to γ-alkylidene-γ-butyrolactams 13 19 or γfunctionalized lactams 14 20 (Scheme 1a).…”

“…In addition, it was reported in 2009 that the palladium-free Sonogashira coupling between ( Z )-3-iodoacrylic acids 8 and terminal alkynes 9 , followed by a 5- exo -dig oxa-cyclization, offered a convenient access to γ-alkylidenebutenolides 10 (Scheme a). , It is also generally known that treatment of γ-alkylidenebutenolides 10 with primary amines 11 leads to the formation of γ-hydroxy-γ-butyrolactams 7 (Scheme a), and this approach is commonly used. , Moreover, treatment of γ-hydroxybutyrolactams 7 with acid sources results in the formation of the corresponding N -acyliminium ions 12 , which can evolve either to γ-alkylidene-γ-butyrolactams 13 or γ-functionalized lactams 14 (Scheme a). By taking advantage of these transformations, Commeiras and co-workers proposed new multicomponent synthetic strategies using readily or commercially available ( Z )-3-iodoacrylic acids as well as ( E )-2,3-dihalogenoacrylic acids 8 , terminal alkynes 9 , and primary amines 11 in the presence of a copper­(I) catalyst to provide either γ-hydroxy-γ-butyrolactams 7 or various γ-lactam motifs 13 – 16 . , In this review, we provide a comprehensive survey of this copper­(I)-mediated multicomponent process, which could be compared to a (3 + 1 + 1) ring construction cyclization approach, that enables the preparation, in a simple and atom-economical transformation, of a great diversity of complex biorelevant γ-hydroxy-γ-butyrolactams 7 and their one-pot postfunctionalization (Scheme b).…”