Synthesis and Reactivity of 5,10,15‐Triaryl Doubly N‐Confused Bilanes

A series of 5,10,15‐tris(pentafluorophenyl) doubly N‐confused bilanes were synthesized in a stepwise manner with the aid of sterically demanding N‐protecting groups, in which the difference in reactivity between regular pyrrole and N‐confused pyrrole plays a crucial role in the synthetic strategy. Some doubly N‐confused bilanes were converted into porphyrinoids or a unique 2:2 copper(II) complex with a helical structure. In addition, the conformations and electronic states of the doubly N‐confused bilanes were investigated theoretically, giving fruitful information about the effect of confusion on the bilane skeleton.     

Studies on the Mass Spectra of N‐Aryl α,β‐Unsaturated γ‐Lactams

The mass spectra of a series of N‐aryl α,β‐unsaturated γ‐lactams were studied. Besides the molecular ion, the three characteristic fragments such as [M⁺‐29], [M⁺‐55], and [M⁺‐82] were commonly found in a series of N‐Aryl α,β‐unsaturated γ‐lactams in EI/MS. Further more the mechanism for the interpretation of these fragments is also de scribed.     

A New Route to N‐Aryl 2‐Alkenamides,N‐Allyl N‐Aryl 2‐Alkenamides,and N‐Aryl α,β‐Unsaturated γ‐Lactams from N‐Aryl 3‐(Phenylsulfonyl)propanamides

A series of N‐aryl 2‐alkenamides were produced efficiently by treating N‐aryl 3‐(phenylsulfonyl)‐propanamides with potassium tert‐butoxide in THF at 0°C. With out isolation, it was further treated with an additional equivalent of potassium tert‐butoxide and allyl bromide to give N‐allyl N‐aryl 2‐alkenamides in one pot in good yields. Followed by a ring‐closing metathesis reaction, these N‐allyl N‐aryl 2‐alkenamides were respectively converted into corresponding N‐aryl α,β‐unsaturated γ‐lactams in moderate yields.     

Oxaphospholes and Bisphospholes from Phosphinophosphonates and α,β‐Unsaturated Ketones

The reaction of a {W(CO)₅}‐stabilized phosphinophosphonate 1 , (CO)₅WPH(Ph)? P(O)(OEt)₂, with ethynyl‐ ( 2 a – f ) and diethynylketones ( 7 – 11 , 18 , and 19 ) in the presence of lithium diisopropylamide (LDA) is examined. Lithiated 1 undergoes nucleophilic attack in the Michael position of the acetylenic ketones, as long as this position is not sterically encumbered by bulky (iPr)₃Si substituents. Reaction of all other monoacetylenic ketones with lithiated 1 results in the formation of 2,5‐dihydro‐1,2‐oxaphospholes 3 and 4 . When diacetylenic ketones are employed in the reaction, two very different product types can be isolated. If at least one (Me)₃Si or (Et)₃Si acetylene terminus is present, as in 7 , 8 , and 19 , an anionic oxaphosphole intermediate can react further with a second equivalent of ketone to give cumulene‐decorated oxaphospholes 14 , 15 , 24 , and 25 . Diacetylenic ketones 10 and 11 , with two aromatic acetylene substituents, react with lithitated 1 to form exclusively ethenyl‐bridged bisphospholes 16 and 17 . Mechanisms that rationalize the formation of all heterocycles are presented and are supported by DFT calculations. Computational studies suggest that thermodynamic, as well as kinetic, considerations dictate the observed reactivity. The calculated reaction pathways reveal a number of almost isoenergetic intermediates that follow after ring opening of the initially formed oxadiphosphetane. Bisphosphole formation through a carbene intermediate G is greatly favored in the presence of phenyl substituents, whereas the formation of cumulene‐decorated oxaphospholes is more exothermic for the trimethylsilyl‐containing substrates. The pathway to the latter compounds contains a 1,3‐shift of the group that stems from the acetylene terminus of the ketone substrates. For silyl substituents, the 1,3‐shift proceeds along a smooth potential energy surface through a transition state that is characterized by a pentacoordinated silicon center. In contrast, a high‐lying transition state TS(E′–F′)_R=Ph of 37 kcal mol^?1 is found when the substituent is a phenyl group, thus explaining the experimental observation that aryl‐terminated diethynylketones 10 and 11 exclusively form bisphospholes 16 and 17 .     

Halide‐Anion Binding by Singly and Doubly N‐Confused Porphyrins

The halide‐binding properties of N‐confused porphyrin (NCP, 1 ) and doubly N‐confused porphyrins (trans‐N₂CP ( 2 ), cis‐N₂CP ( 3 )) were examined in CH₂Cl₂. In the free‐base forms, cis‐N₂CP ( 3 ) showed the highest affinity to each anion (Cl^?, Br^?, I^?) with association constants K_a=7.8×10³, 1.9×10³, and 5.8×10² M ^?1, respectively. As metal complexes, on the other hand, trans‐N₂CP 2–Cu exhibited the highest affinity to Cl^?, Br^?, and I^? with K_a=9.0×10⁴, 2.7×10⁴, and 1.9×10³ M ^?1, respectively. The corresponding K_a values for cis‐N₂CP 3–Cu and NCP 1–Cu were about 1/10 and 1/2, respectively, of those of 2–Cu . With the help of density functional theory (DFT) calculations and complementary affinity measurements of a series of trisubstituted N‐confused porphyrins, the efficient anion binding of NCPs was attributed to strong hydrogen bonding at the highly polarized NH moieties owing to the electron‐deficient C₆F₅ groups at meso positions as well as the ideally oriented dipole moments and large molecular polarizability. The orientation and magnitude of the dipole moments in NCPs were suggested to be important factors in the differentiation of the affinity for anions.     

Intermediates Formed in the Reactions of Organocuprates with α,β‐Unsaturated Nitriles

Conjugate additions of organocuprates are of outstanding importance for organic synthesis. To improve our mechanistic understanding of these reactions, we have used electrospray ionization mass spectrometry for the identification of the ionic intermediates formed upon the treatment of LiCuR₂ ? LiCN (R=Me, Bu, Ph) with a series of α,β‐unsaturated nitriles. Acrylonitrile, the weakest Michael acceptor included, did not afford any detectable intermediates. Fumaronitrile (FN) yielded adducts of the type Li_n?1Cu_nR_2n(FN)_n^?, n=1–3. When subjected to fragmentation in the gas phase, these adducts were not converted into the conjugate addition products, but re‐dissociated into the reactants. In contrast, the reaction with 1,1‐dicyanoethylene furnished the products of the conjugate addition without any observable intermediates. Tri‐ and tetracyanoethylene proved to be quite reactive as well. The presence of several cyano groups in these substrates opened up reaction pathways different from simple conjugate additions, however, and led to dimerization and substitution reactions. Moreover, the gas‐phase fragmentation behavior of the species formed from these substrates indicated the occurrence of single‐electron transfer processes. Additional quantum‐chemical calculations provided insight into the structures and stabilities of the observed intermediates and their consecutive reactions.     

Modular Synthesis of Novel Macrocycles Bearing α,β‐Unsaturated Chemotypes through a Series of One‐Pot,Sequential Protocols

A series of one‐pot, sequential protocols was developed for the synthesis of novel macrocycles bearing α,β‐unsaturated chemotypes. The method highlights a phosphate tether‐mediated approach to establish asymmetry, and consecutive one‐pot, sequential processes to access the macrocycles with minimal purification procedures. This library amenable strategy provided diverse macrocycles containing α,β‐unsaturated carbon‐, sulfur‐, or phosphorus‐based warheads.     

Interplay of α,α‐ versus α,β‐Conjugation in the Excited States and Charged Defects of Branched Oligothiophenes as Models for Dendrimeric Materials

This article investigates the excited and charged states of three branched oligothiophenes with methyl–thienyl side groups as models to promote 3D arrangements. A comparison with the properties of the parent systems, linear all‐α,α‐oligothiophenes, is proposed. A wide variety of spectroscopic methods (i.e., absorption, emission, triplet–triplet transient absorption, and spectroelectrochemistry) in combination with DFT calculations have been used for this purpose. Whereas the absorption spectra are slightly blueshifted upon branching, both the emission spectra and triplet–triplet absorption spectra are moderately redshifted; this indicates a larger contribution of the β‐linked thienyl groups in the delocalization of the S₁ and T₁ states rather than into the S₀ state. The delocalization through the α,β‐conjugated path was found to be crucial for the stabilization of the trication species in the larger branched systems, whereas the linear sexithiophene homologue can only be stabilized up to the dication species.     

N‐Heterocyclic Carbene Catalyzed Synthesis of δ‐Sultones via α,β‐Unsaturated Sulfonyl Azolium Intermediates

A limited array of reactive intermediates have enabled a wealth of discoveries in N‐heterocyclic carbene organocatalysis. In this study, the viability of α,β‐unsaturated sulfonyl azoliums as double electrophiles in new reactions is examined. Specifically, the (3+3) annulation of such species with the trimethylsilyl enol ethers of various 1,3‐dicarbonyl compounds has been developed. This reaction provides access to a range of novel unsaturated δ‐sultones (18 examples) in good yields (40–88 %) under mild reaction conditions. Mechanistic studies and the development of an enantioselective variant (55 % yield, 73:27 e.r.) support the intermediacy of an α,β‐unsaturated sulfonyl azolium species.     

Origin of the Enantioselectivity in Organocatalytic Michael Additions of β‐Ketoamides to α,β‐Unsaturated Carbonyls: A Combined Experimental,Spectroscopic and Theoretical Study

The organocatalytic enantioselective conjugate addition of secondary β‐ketoamides to α,β‐unsaturated carbonyl compounds is reported. Use of bifunctional Takemoto’s thiourea catalyst allows enantiocontrol of the reaction leading either to simple Michael adducts or spirocyclic aminals in up to 99 % ee. The origin of the enantioselectivity has been rationalised based on combined DFT calculations and kinetic analysis. This study provides a deeper understanding of the reaction mechanism, which involves a predominant role of the secondary amide proton, and clarifies the complex interactions occurring between substrates and the catalyst.     

Ligand‐Controlled α‐ and β‐Arylation of Acyclic N‐Boc Amines

The palladium‐catalyzed ligand‐controlled arylation of α‐zincated acyclic amines, obtained by directed α‐lithiation and transmetalation, is described. Whereas PtBu₃ gave rise to α‐arylated Boc‐protected amines, more flexible N‐phenylazole‐based phosphine ligands induced major β‐arylation through migrative cross‐coupling.     

Experimental and Theoretical Studies on the Rearrangement of 2‐Oxoazepane α,α‐Amino Acids into 2′‐Oxopiperidine β2,3,3‐Amino Acids: An Example of Intramolecular Catalysis

Enantiopure β‐amino acids represent interesting scaffolds for peptidomimetics, foldamers and bioactive compounds. However, the synthesis of highly substituted analogues is still a major challenge. Herein, we describe the spontaneous rearrangement of 4‐carboxy‐2‐oxoazepane α,α‐amino acids to lead to 2′‐oxopiperidine‐containing β^2,3,3‐amino acids, upon basic or acid hydrolysis of the 2‐oxoazepane α,α‐amino acid ester. Under acidic conditions, a totally stereoselective synthetic route has been developed. The reordering process involved the spontaneous breakdown of an amide bond, which typically requires strong conditions, and the formation of a new bond leading to the six‐membered heterocycle. A quantum mechanical study was carried out to obtain insight into the remarkable ease of this rearrangement, which occurs at room temperature, either in solution or upon storage of the 4‐carboxylic acid substituted 2‐oxoazepane derivatives. This theoretical study suggests that the rearrangement process occurs through a concerted mechanism, in which the energy of the transition states can be lowered by the participation of a catalytic water molecule. Interestingly, it also suggested a role for the carboxylic acid at position 4 of the 2‐oxoazepane ring, which facilitates this rearrangement, participating directly in the intramolecular catalysis.     

carbo‐Naphthalene: A Polycyclic carbo‐Benzenoid Fragment of α‐Graphyne

A ring carbo‐mer of naphthalene, C₃₂Ar₈ (Ar=p‐n‐pentylphenyl), has been obtained as a stable blue chromophore, after a 19‐step synthetic route involving methods inspired from those used in the synthesis of carbo‐benzenes, or specifically devised for the present target, like a double Sonogashira‐type coupling reaction. The last step is a SnCl₂/HCl‐mediated reduction of a decaoxy‐carbo‐decalin, which is prepared through successive [8+10] macrocyclization steps. Two carbo‐benzene references are also described, C₁₈Ar₆ and o‐C₁₈Ar₄(C≡C‐SiiPr₃)₂. The carbo‐naphthalene bicycle is locally aromatic according to structural and magnetic criteria, as revealed by strong diatropic ring current effects on the deshielding of ¹H nuclei of the Ar groups and on the negative value of the DFT‐calculated NICS at the center of the C₁₈ rings (?12.8 ppm). The stability and aromaticity of this smallest fused molecular fragment of α‐graphyne allows prediction of the same properties for the carbon allotrope itself.     

1,4‐Addition of Bis(iodozincio)methane to α,β‐Unsaturated Ketones: Chemical and Theoretical/Computational Studies

1,4‐Addition of bis(iodozincio)methane to simple α,β‐unsaturated ketones does not proceed well; the reaction is slightly endothermic according to DFT calculations. In the presence of chlorotrimethylsilane, the reaction proceeded efficiently to afford a silyl enol ether of β‐zinciomethyl ketone. The C? Zn bond of the silyl enol ether could be used in a cross‐coupling reaction to form another C? C bond in a one‐pot reaction. In contrast, 1,4‐addition of the dizinc reagent to enones carrying an acyloxy group proceeded very efficiently without any additive. In this case, the product was a 1,3‐diketone, which was generated in a novel tandem reaction. A theoretical/computational study indicates that the whole reaction pathway is exothermic, and that two zinc atoms of bis(iodozincio)methane accelerate each step cooperatively as effective Lewis acids.