Palladium-catalyzed highly regioselective mono and double Sonogashira cross-coupling reactions of 5-substituted-1,2,3-triiodobenzene under ambient conditions
Abstract:Efficient and highly regioselective synthesis of 2,3-diiodinated diphenylacetylene and iodinated meta-terphenylacetylene derivatives via mono and double Sonogashira cross-coupling reactions.
“…Li et al have cyclised methyl 2-(phenylethynyl)benzoate using copper(II) chloride in 1,2-dichloroethane, [36] so we decided to examine the analogous ferrocene-based structure with phenyl groups in the terminal alkyne positions. This was synthesised by a double Sonogashira approach (Scheme 3), [37,38] to investigate the hypothesis that the asymmetric copper reaction conditions could also cyclise this structure. This simple two-step sequence allows a wide variety of structures to be generated from the 2,5-diiodomethyl ester 3 and the extension of our previous preparation of 1 afforded 6 in excellent yield.…”
A new copper catalysed desymmetrisation reaction of bisalkynyl ferrocenecarboxylic acids using (R,R)-Ph-Pybox results in the first asymmetric synthesis of planar chiral pseudo-isocoumarins in up to 64 % enantiomeric excess and up to 99 % yield with complete regioselectivity. Tri-functionalised planar chiral ferrocenes are synthesised in five steps from commercially available materials, without the need for traditional directing group chemistry via an easily diversified route exploiting the double Sonogashira coupling reaction. The absolute configuration of the chiral heterocycles is proven by chemical correlation and circular dichroism spectroscopy giving the asymmetric reaction synthetic utility and opening the way for the rational extension of this method to produce bioactive isocoumarin-fused ferrocene derivatives.
“…Li et al have cyclised methyl 2-(phenylethynyl)benzoate using copper(II) chloride in 1,2-dichloroethane, [36] so we decided to examine the analogous ferrocene-based structure with phenyl groups in the terminal alkyne positions. This was synthesised by a double Sonogashira approach (Scheme 3), [37,38] to investigate the hypothesis that the asymmetric copper reaction conditions could also cyclise this structure. This simple two-step sequence allows a wide variety of structures to be generated from the 2,5-diiodomethyl ester 3 and the extension of our previous preparation of 1 afforded 6 in excellent yield.…”
A new copper catalysed desymmetrisation reaction of bisalkynyl ferrocenecarboxylic acids using (R,R)-Ph-Pybox results in the first asymmetric synthesis of planar chiral pseudo-isocoumarins in up to 64 % enantiomeric excess and up to 99 % yield with complete regioselectivity. Tri-functionalised planar chiral ferrocenes are synthesised in five steps from commercially available materials, without the need for traditional directing group chemistry via an easily diversified route exploiting the double Sonogashira coupling reaction. The absolute configuration of the chiral heterocycles is proven by chemical correlation and circular dichroism spectroscopy giving the asymmetric reaction synthetic utility and opening the way for the rational extension of this method to produce bioactive isocoumarin-fused ferrocene derivatives.
“…1 ) and exemplified its performance and utility in the Sonogashira cross coupling as the target reaction, because diphenylacetylene derivatives are the precursors of drugs and biological substances and found in a wide variety of natural products and pharmaceutical agents (Fig. 2 ) 25 . Figure 1 The proposed structure of γ-Fe 2 O 3 @PEG@PAMAM G 0 -Cu.…”
Section: Introductionmentioning
confidence: 99%
“…The formation of carbon–carbon bonds in cross-coupling reactions is considered as one of the most important organic chemistry reactions, which have been extremely practical and useful tools for the formation of complex molecules from simple molecules 21 – 24 . Asymmetric carbon–carbon coupling reactions are equally important and valuable in the synthesis of natural and medicinal compounds 25 . The most prominent and well-recognized transverse couplings are Heck, Negishi, Suzuki and Sonogashira reactions 26 .…”
A nanomagnetic hydrophilic heterogeneous copper catalyst, termed γ-Fe2O3@PEG@PAMAM G0-Cu, has been successfully prepared and characterized using FT–IR, XRD, FE-SEM, TEM, EDX, mapping, TGA/DTG, VSM and ICP analyses. The catalyst displayed excellent activity for the palladium-free Sonogashira cross coupling reaction of various aryl iodides and bromides with phenylacetylene derivatives in pure water. The presence of polyethylene glycol coupled with hydrophilic character of the Cu-catalyst adorned on γ-Fe2O3 MNPs provides the ready dispersion of the catalyst particles in water, leading to higher catalytic performance as well as facile catalyst recovery via simple magnetic decantation. The recovered catalyst was reused for at least six successive runs with little reduction in its catalytic activity and any noticeable changes in its structure. The use of water as a green solvent, without requiring any additive or organic solvent, as well as the exploitation of abundant and low-cost copper catalyst instead of expensive Pd catalyst along with the catalyst recovery and scalability, make this method favorable from environmental and economic points of view for the Sonogashira coupling reaction.
“…1) and exempli ed its performance and utility in the Sonogashira cross coupling as the target reaction, because diphenylacetylene derivatives are the precursors of drugs and biological substances and found in a wide variety of natural products and pharmaceutical agents (Fig. 2) 21 .…”
A nanomagnetic hydrophilic heterogeneous copper catalyst, termed γ-Fe2O3@PEG@PAMAM G0-Cu, has been successfully prepared and characterized using FT–IR, XRD, FE-SEM, TEM, EDX, mapping, TGA/DTG, VSM and ICP analyses. The catalyst displayed excellent activity for the palladium-free Sonogashira cross coupling reaction of various aryl iodides and bromides with phenylacetylene derivatives in pure water. The presence of polyethylene glycol coupled with hydrophilic character of the Cu-catalyst adorned on γ-Fe2O3 MNPs provides the ready dispersion of the catalyst particles in water, leading to higher catalytic performance as well as facile catalyst recovery via simple magnetic decantation. The recovered catalyst was reused for at least six successive runs with little reduction in its catalytic activity and any noticeable changes in its structure. The use of water as a green solvent, without requiring any additive or organic solvent, as well as the exploitation of abundant and low-cost copper catalyst instead of expensive Pd catalyst along with the catalyst recovery and scalability, make this method favorable from environmental and economic points of view for the Sonogashira coupling reaction.
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