1,3-Butadiynamides the Ethynylogous Ynamides: Synthesis, Properties and Applications in Heterocyclic Chemistry.

1,3-butadiynamides-the ethynylogous variants of ynamides-receive considerable attention as precursors of complex molecular scaffolds for organic and heterocyclic chemistry. The synthetic potential of these C4-building blocks reveals itself in sophisticated transition-metal catalyzed annulation reactions and in metal-free or silver-mediated HDDA (Hexa-dehydro-Diels-Alder) cycloadditions. 1,3-Butadiynamides also gain significance as optoelectronic materials and in less explored views on their unique helical twisted frontier molecular orbitals (Hel-FMOs). The present account summarizes different methodologies for the synthesis of 1,3-butadiynamides followed by the description of their molecular structure and electronic properties. Finally, the surprisingly rich chemistry of 1,3-butadiynamides as versatile C4-building blocks in heterocyclic chemistry is reviewed by compiling their exciting reactivity, specificity and opportunities for organic synthesis. Besides chemical transformations and use in synthesis, a focus is set on the mechanistic understanding of the chemistry of 1,3-butadiynamides-suggesting that 1,3-butadiynamides are not just simple alkynes. These ethynylogous variants of ynamides have their own molecular character and chemical reactivity and reflect a new class of remarkably useful compounds.

Media-Driven Pd-Catalyzed Reaction Cascades with 1,3-Diynamides Leading Selectively to Either Indoles or Quinolines.

Divergent Pd-catalyzed reaction cascades with various 1,3-diynamides yielding either 2-amino-3-alkynylindoles or 2-amino-4-alkenylquinolines were established. Omitting or adding TBAF (tetrabutylammonium fluoride) to the reaction of N,N-(2-iodophenyl)(4-toluenesulfonyl)-1,3-diynamides with secondary or primary amines in the presence of KOH in THF and catalytic amounts of Pd(PPh3 )4 completely changed the outcome of the reaction. In the absence of TBAF, 2-amino-3-alkynylindoles were the sole products, while the presence of TBAF switched the product formation to 2-amino-4-alkenylquinolines. Deuterium labeling proceeded selectively at the C3 and C11 positions of the 2-amino-4-alkenylquinoline products and this suggests the unprecedented formation of [4]cumulenimines from 1,3-diynamides as reactive key intermediates.

Synthesis and Structure-Photophysics Evaluation of 2-N-Amino-quinazolines: Small Molecule Fluorophores for Solution and Solid State.

2-N-aminoquinazolines were prepared by consecutive SN Ar functionalization. X-ray structures display the nitrogen lone pair of the 2-N-morpholino group in conjugation with the electron deficient quinazoline core and thus representing electronic push-pull systems. 2-N-aminoquinazolines show a positive solvatochromism and are fluorescent in solution and in solid state with quantum yields up to 0.73. Increase in electron donor strength of the 2-amino substituent causes a red-shift of the intramolecular charge transfer (ICT) band (300-400 nm); whereas the photoluminescence emission maxima (350-450 nm) is also red-shifted significantly along with an enhancement in photoluminescence efficiency. HOMO-LUMO energies were estimated by a combination of electrochemical and photophysical methods and correlate well to those obtained by computational methods. ICT properties are theoretically attributed to an excitation to Rydberg-MO in SAC-CI method, which can be interpreted as n-π* excitation. 7-Amino-2-N-morpholino-4-methoxyquinazoline responds to acidic conditions with significant increases in photoluminescence intensity revealing a new turn-on/off fluorescence probe.

Taming the Reactivity of Phosphiranium Salts: Site-Selective C-Centered Ring Opening for Direct Synthesis of Phosphinoethylamines.

Advances in the field of phosphorus chemistry are documented, by revealing the synthetic utility of previously underutilized quaternary phosphiranium salts (QPrS) as three-chain-atom electrophilic building blocks. Notably, control of their challenging C-centered electrophilicity is disclosed with an expedient synthesis of tertiary ß-anilino phosphines as a proof-of-concept.

Evidence of Phosphonium-Carbenium Dication Formation in a Superacid: Precursor to Fluorinated Phosphine Oxides.

Unambiguously confirmed by low-temperature in situ NMR experiments, X-ray diffraction and vibrational spectroscopy, phosphonium-carbenium superelectrophiles are shown to be generated in strong acidic conditions. Representing crucial intermediates, their exploitation allows for the synthesis of unprecedented fluorinated (cyclic) phosphine oxides.

Application of Ynamides in the Synthesis of 2-(Tosylamido)- and 2,5-Bis(tosylamido)thiophenes.

A step-economic and metal-catalyst-free synthesis of 2-(tosylamido)- and 2,5-bis(tosylamido)-thiophenes from nonsymmetrical 1,3-butadiynamides and symmetrical 1,3-butadiyne-1,4-diamides is reported. The reaction proceeds in the presence of Na2S·9H2O (2-3 equiv) under mild reaction conditions (50 °C) and is facilitated by polarized carbon-carbon triple bonds in ynamides. This new approach to thiophenes based on the chemistry of ynamides was applied to the synthesis of a bis(tosylamido)-capped terthiophene having a string of N,S-heteroatoms embedded in a highly π-conjugated molecular frame.

Recent advances in synthesis of P-BH3 compounds.

This chapter is dedicated to the main achievements since 2007 regarding the synthesis of BH3-phosphorus complexes. Among this class of compounds, phosphine-boranes are the most studied derivatives, mainly as valuable surrogates of phosphines, enabling easy handling and purification. In contrast, metal phosphido-boranes have so far only been considered as in situ intermediates in the P-functionalization of secondary phosphine-boranes. Thorough investigations of their structures as well as their chemical properties have recently been reported. Besides phosphine-boranes and their phosphides, new families of phosphorus-BH3 complexes, have emerged as useful precursors of new structures in the asymmetric series. New routes toward optically active phosphinous-acid boranes and their esters were developed and applied to the synthesis of enantiopure P-stereogenic secondary and tertiary phosphine-boranes. The stereoselective synthesis of P-stereogenic aminophosphine-boranes, precursors of a new class of chiral ligands, has been reported. Studies dealing with the synthesis and reactivity of phosphonite-boranes were successfully applied to the development of efficient syntheses of functionalized H-phosphinates, compounds difficult to access by other routes.

Silyl alkynylphosphine-boranes: key precursors of triazolylphosphines via tandem desilylation-click chemistry.

A versatile synthesis of 1,2,3-triazolyl-4-phosphines from the borane complexes of phosphino-alkynes is reported. The efficiency of the procedure relies on the use of readily available silyl-protected alkynylphosphine-boranes, which were subjected to desilylation with TBAF followed by copper-catalyzed azide-alkyne-cycloaddition in one pot. Subsequent treatment with DABCO afforded the targeted triazolylphosphines in high yields. The reported method was applied to the synthesis of the first example of an enantioenriched P-stereogenic triazolylphosphine (98.8% ee).

Unprecedented synthesis of alkynylphosphine-boranes through room-temperature oxidative alkynylation.

An original and user-friendly synthesis of alkynylphosphine-boranes, useful building blocks in organic synthesis, based on an oxidative P-alkynylation reaction with readily available copper acetylides is reported. The ability of a secondary phosphine protected with a borane to undergo oxidative coupling without oxidation of the P-moiety is demonstrated for the first time. The reaction, which proceeds at room temperature, is applicable to the preparation of enantioenriched and structurally complex alkynylphosphine-boranes.

Stoichiometric and catalytic synthesis of alkynylphosphines.

Alkynylphosphines or their borane complexes are available either through C-P bond forming reactions or through modification of the phosphorus or the alkynyl function of various alkynyl phosphorus derivatives. The latter strategy, and in particular the one involving phosphoryl reduction by alanes or silanes, is the method of choice for preparing primary and secondary alkynylphosphines, while the former strategy is usually employed for the synthesis of tertiary alkynylphosphines or their borane complexes. The classical C-P bond forming methods rely on the reaction between halophosphines or their borane complexes with terminal acetylenes in the presence of a stoichiometric amount of organometallic bases, which precludes the access to alkynylphosphines bearing sensitive functional groups. In less than a decade, efficient catalytic procedures, mostly involving copper complexes and either an electrophilic or a nucleophilic phosphorus reagent, have emerged. By proceeding under mild conditions, these new methods have allowed a significant broadening of the substituent scope and structure complexity.

Neutral copper-phosphido-borane complexes: synthesis, characterization, and use as precatalysts in C(sp)-P bond formation.

Copper-phosphido-borane complexes were synthesized and isolated for the first time. Their structures were experimentally and computationally investigated. They were shown to display catalytic activity in C(sp)-P bond formation.

Synthesis of ß- and γ-carbolines via ruthenium and rhodium catalysed [2+2+2] cycloadditions of yne-ynamides with methylcyanoformate.

A flexible approach towards substituted ß- and γ-carbolines based on transition metal catalysed [2+2+2] cycloaddition reactions between functionalised yne-ynamides and methylcyanoformate is described. The versatility of this new reaction sequence is demonstrated by its application in the total synthesis of the marine natural product eudistomin U.

Copper-catalyzed synthesis of alkynylphosphine derivatives: unprecedented use of nucleophilic phosphorus compounds.

A new and smooth approach towards alkynylphosphine derivatives is described. It relies on the unprecedented catalytic coupling of secondary phosphine boranes with alkynyl bromides using the CuI/1,10-phenanthroline couple.

Structure determination of bisacetylenic oxylipins in carrots (Daucus carota L.) and enantioselective synthesis of falcarindiol.

Although bisacetylenic oxylipins have been demonstrated to exhibit diverse biological activities, the chemical structures of many representatives of this class of phytochemicals still remain elusive. As carrots play an important role in our daily diet and are known as a source of bisacetylenes, an extract made from Daucus carota L. was screened for bisacetylenic oxylipins, and, after isolation, their structures were determined by means of LC-MS and 1D/2D NMR spectroscopy. Besides the previously reported falcarinol, falcarindiol, and falcarindiol 3-acetate, nine additional bisacetylenes were identified, among which six derivatives are reported for the first time in literature and three compounds were previously not identified in carrots. To determine the absolute stereochemistry of falcarindiol in carrots, the (3R,8R)-, (3R,8S)-, (3S,8R)-, and (3S,8S)-stereoisomers of falcarindiol were synthesized according to a novel 10-step total synthesis involving a Cadiot-Chodkiewicz cross-coupling reaction of (S)- and (R)-trimethylsilanyl-4-dodecen-1-yn-3-ol and (R)- and (S)-5-bromo-1-penten-4-yn-3-ol, respectively. Comparative chiral HPLC analysis of the synthetic stereoisomers with the isolated phytochemical led to the unequivocal assignment of the (Z)-(3R,8S)-configuration for falcarindiol in carrot extracts from Daucus carota L.

First total synthesis of antiostatin A1, a potent carbazole-based naturally occurring antioxidant.

The first total synthesis of the potent antioxidant antiostatin A1 is reported, where its key features rely on a chemo- and regioselective rhodium-catalysed crossed alkyne cyclotrimerisation reaction applying functionalised ynamides and a palladium-catalysed arylamidation reaction.

Highly stereoselective C-allylation of an enantiopure alpha-sulfinyl thioacetamide.

The alkylation of the lithium enolate of enantiopure alpha-cyclohexylsulfinyl thioacetamide 1 with allyl bromides 5 possessing an electron-withdrawing group at the vinylic position does not occur at the sulfur center - as expected in the sulfur series - but at the carbon center through conjugate addition followed by bromide elimination. The modest to excellent 1,2-asymmetric induction achieved by the alkylsulfinyl group (dr up to 100:0) is explained by an electronic model.