Gold(I)‐Catalyzed Haloalkynylation of Aryl Alkynes: Two Pathways,One Goal

Haloalkynylation reactions provide an efficient method for the simultaneous introduction of a halogen atom and an acetylenic unit. For the first time, we report a gold(I)‐catalyzed haloalkynylation of aryl alkynes that delivers exclusively the cis addition product. This method enables the simple synthesis of conjugated and halogenated enynes in yields of up to 90 %. Notably, quantum chemical calculations reveal an exceptional interplay between the place of the attack at the chloroacetylene: No matter which C?C bond is formed, the same enyne product is always formed. This is only possible through rearrangement of the corresponding skeleton. Hereby, one reaction pathway proceeds via a chloronium ion with a subsequent aryl shift; in the second case the corresponding vinyl cation is stabilized by a 1,3‐chlorine shift. ¹³C‐labeling experiments confirmed that the reaction proceeds through both reaction pathways.     

Synthesis of 3,5‐Diarylcyclohex‐2‐enones by NH4Cl/HCl‐Catalyzed Cyclization and Deacetylation of 4‐Acetylhexane‐1,5‐diones

A new route for the synthesis of 3,5‐diarylcyclohex‐2‐enones is reported. The 4‐acetyl‐1,3‐diarylhexane‐1,5‐diones were obtained by the addition of pentane‐2,4‐dione to chalcones. The reaction of 4‐acetyl‐1,3‐diarylhexane‐1,5‐diones with NH₄Cl/HCl in EtOH under reflux conditions gave the 3,5‐diarylcyclohex‐2‐enones in good yields. All synthesized compounds were characterized by spectroscopic methods (¹H‐, ¹³C‐NMR, and IR), and elemental analyses.     

Reactions of α,β‐Enones with Diazo Compounds. Part 4

In this study, (E)‐ and (Z)‐enones carrying only a phenyl substituent at their C(β) atom were treaced with dimethyl diazomalonate in the presence of (acetylacetonato)copper(II). According to the configuration of the starting enones, the products were dioxole or dihydrofuran derivatives, significant heterocycles in natural products.     

Hydroalumination of a Chlorotrialkynylsilane: Spontaneous Stepwise 1,3‐Dyotropic Rearrangement via an Intermediate Silyl Cation

A new functionalised alkynylsilane, Cl‐Si(C?C‐CMe₃)₃ ( 3 ), was obtained by a facile multistep synthesis. Treatment of 3 with equimolar quantities of the hydrides H‐M(CMe₃)₂ (M=Al, Ga) gave the mixed alkenyl‐di(alkynyl)silanes, in which the chlorine atom adopts a bridging position between the aluminium and silicon atoms. Dual hydrogallation of 3 resulted in the formation of a di(alkenyl)‐alkynylsilane containing two gallium atoms, one of which is coordinated to the chlorine atom, and the second is bonded to the α‐carbon atom of the remaining alkynyl group. A tert‐butylsilane was unexpectedly formed by a unique 1,3‐dyotropic chlorine–tert‐butyl exchange for the corresponding dialuminium compound. One aluminium atom is bonded to a tert‐butyl group, a terminal chlorine atom and the α‐carbon atom of the ethynyl moiety; the second is coordinatively unsaturated, with two terminal tert‐butyl substituents. High‐level quantum‐chemical calculations favour a stepwise dyotropic rearrangement with an intermediate cationic silicon species over a simultaneous tert‐butyl–chlorine migration via a five‐coordinate silicon atom in the transition state.     

Metallation reactions. XXXIV. Synthesis of 2‐(1‐hydroxy‐1‐arylethyl)‐1,3‐benzoxathiol‐3‐oxide derivatives

The reaction of benzoxathiole‐3‐oxide with lithiumdiisopropylamide in tetrahydrofuran gave an anion, which was reacted with various aryl‐methyl‐ketones to give 2‐(1‐hydroxy‐1‐arylethyl)‐1,3‐benzoxathiol‐3‐oxide derivatives. The reaction was carried out in different temperature conditions: at ‐88 °C the trans addition stereoisomers to the sulfoxide oxygen atom were the main products.     

Platinum‐Catalyzed Cascade Rearrangement Reaction of 1,5‐Diynyl Esters: Unusual Regioselective 1,5‐Hydride Migration

A highly regioselective sequential 1,3‐acyloxy migration/pentannulation/1,5‐hydride migration reaction is disclosed which provides an efficient access to (E)‐2‐vinyl‐3‐oxo‐1‐methyleneindenes under neutral and mild reaction conditions. The migrated hydrogen atom was derived from an unactivated alkyl group, and the long‐range 1,5‐H shift was confirmed through related deuterium experiments.     

A Copper‐Catalyzed Aerobic [1,3]‐Nitrogen Shift through Nitrogen‐Radical 4‐exo‐trig Cyclization

A novel radical [1,3]‐nitrogen shift catalyzed by copper diacetate under an oxygen atmosphere (1 atm) has been developed for the construction of a diverse range of indole derivatives from α,α‐disubstituted benzylamine. In this reaction, oxygen was used as a clean terminal oxidant, and water was produced as the only by‐product. Five inert bonds were cleaved, and two C−N bonds and one C−C double bond were constructed in one pot during this transformation. This unique method demonstrated broad application protential for the late‐stage modification of biologically active natural products and drugs. Mechanistic investigations indicate that a unique 4‐exo ‐trig cyclization of an aminyl radical onto a phenyl ring is involved in the catalytic cycle.     

Bridgehead Substitution via Putative Norborn‐1‐en‐3‐ones: Application in the Synthesis of Complex Molecules

The base‐mediated formation of a bridgehead double bond in a bicyclo[2.2.1]heptane system (anit‐Bredt molecules) is described. The synthesis of exocyclic norbornyl enones by Wittig reaction of α‐diketones is reported. These enones and their Michael adducts are used as substrates for the generation of transient bridgehead enones and their trapping with MeOH and H₂O. Bridgehead alcohols are easily synthesized from norbornyl enones and are exploited for the diversity oriented synthesis of frameworks of natural and unnatural products.     

Thermal Cyclization of Phenylallenes That Contain ortho‐1,3‐Dioxolan‐2‐yl Groups: New Cascade Reactions Initiated by 1,5‐Hydride Shifts of Acetalic H Atoms

A series of 2‐(1,3‐dioxolan‐2‐yl)phenylallenes that contained a range of substituents (alkyl, aryl, phosphinyl, alkoxycarbonyl, sulfonyl) at the cumulenic C3 position were prepared by using a diverse range of synthetic strategies and converted into their respective 1‐(2‐hydroxy)‐ethoxy‐2‐substituted naphthalenes by smooth thermal activation in toluene solution. Electron‐withdrawing groups at the C3 position accelerated these tandem processes, which consisted of 1) an initial hydride‐like [1,5]‐H shift of the acetalic H atom onto the central cumulene carbon atom; 2) a subsequent 6π‐electrocyclic ring‐closure of the resulting reactive ortho‐xylylenes; and 3) a final aromatization step with concomitant ring‐opening of the 1,3‐dioxolane fragment. If the 1,3‐dioxolane ring of the starting allenes was replaced by a dimethoxymethyl group, the reactions led to mixtures of two disubstituted naphthalenes, which were formed by the migration of either the acetalic H atom or the methoxy group, with the latter migration occurring to a lesser extent. Two of the final 1,2‐disubstituted naphthalenes were converted into their corresponding naphtho‐fused dioxaphosphepine or dioxepinone through an intramolecular transesterification reaction. A DFT computational study accounted for the beneficial influence of the 1,3‐dioxolane fragment on the carbon atom from which the H‐shift took place and also of the electron‐withdrawing substituents on the allene terminus. Remarkably, in the processes that contained a sulfonyl substituent, the conrotatory 6π‐electrocyclization step was of lower activation energy than the alternative disrotatory mode.     

TiCl3‐Mediated Synthesis of 2,3,3‐Trisubstituted Indolenines: Total Synthesis of (+)‐1,2‐Dehydroaspidospermidine, (+)‐Condyfoline,and (−)‐Tubifoline

2,3,3‐Trisubstituted indolenine constitutes an integral part of many biologically important monoterpene indole alkaloids. We report herein an unprecedented access to this skeleton by a TiCl₃‐mediated reductive cyclization of tetrasubstituted alkenes bearing a 2‐nitrophenyl substituent. The proof of concept is demonstrated firstly by accomplishing a concise total synthesis of (+)‐1,2‐dehydroaspidospermidine featuring a late‐stage application of this key transformation. A sequence of reduction of nitroarene to nitrosoarene followed by 6π‐electron‐5‐atom electrocyclization and a 1,2‐alkyl shift of the resulting nitrone intermediate was proposed to account for the reaction outcome. A subsequent total synthesis of (+)‐condyfoline not only illustrates the generality of the reaction, but also provides a mechanistic insight into the nature of the 1,2‐alkyl shift. The exclusive formation of (+)‐condyfoline indicates that the 1,2‐alkyl migration follows a concerted Wagner–Meerwein pathway, rather than a stepwise retro‐Mannich/Mannich reaction sequence. Conditions for almost quantitative conversion of (+)‐condyfoline to (?)‐tubifoline by way of a retro‐Mannich/1,3‐prototropy/transannular cyclization cascade are also documented.     

A Cinchona Alkaloid‐Functionalized Mesostructured Silica for Construction of Enriched Chiral β‐Trifluoromethyl‐β‐Hydroxy Ketones over An Epoxidation‐Relay Reduction Process

A cinchona alkaloid‐functionalized heterogeneous catalyst is prepared through a thiol‐ene click reaction of chiral N‐(3,5‐ditrifluoromethylbenzyl)quininium bromide and a mesostructured silica, which is obtained by co‐condensation of 1,2‐bis(triethoxysilyl)ethane and 3‐(triethoxysilyl)propane‐1‐thiol. Structural analyses and characterizations disclose its well‐defined chiral single‐site active center, and electron microscopy images reveal its monodisperse property. As a heterogenous catalyst, it enables an efficient asymmetric epoxidation of achiral β‐trifluoromethyl‐β,β‐disubstituted enones, the obtained chiral products can then be converted easily into enriched chiral β‐trifluoromethyl‐β‐hydroxy ketones through a sequential epoxidation‐relay reduction process. Furthermore, such a heterogeneous catalyst can be recovered conveniently and reused in asymmetric epoxidation of 4,4,4‐trifluoro‐1,3‐diphenylbut‐2‐enone, showing an attractive feature in a practical construction of enriched chiral β‐CF₃‐substituted molecules.     

Synthesis,structure and electrocatalytic properties of a water‐soluble copper complex supported by 2‐ethyl‐2‐(2‐hydroxybenzylideneamino)propane‐1,3‐diol ligand

The reaction of 2‐ethyl‐2‐(2‐hydroxybenzylideneamino)propane‐1,3‐diol (H₃L) with CuCl₂⋅2H₂O affords a new copper complex, [ClCu(H₂L)], which has been determined using X‐ray crystallography. In the solid, copper atom is four‐coordinated by two oxygen atoms and one nitrogen atom from the ligand and one chlorine atom. Electrochemical studies show that the complex can act as an electrocatalyst for hydrogen evolution from a dimethylformamide solution of acetic acid and a neutral buffer (pH = 7.0) with a turnover frequency of 46.2 and 482 moles of hydrogen per mole of catalyst per hour at an overpotential of 941.6 and 837.6 mV, respectively.     

Synthesis of Functionalized Indoles with a Trifluoromethyl‐Substituted Stereogenic Tertiary Carbon Atom Through an Enantioselective Friedel–Crafts Alkylation with β‐Trifluoromethyl‐α,β‐enones

Chiral complexes of BINOL‐based ligands with zirconium tert‐butoxide catalyze the Friedel–Crafts alkylation reaction of indoles with β‐trifluoromethyl‐α,β‐unsaturated ketones to give functionalized indoles with an asymmetric tertiary carbon center attached to a trifluoromethyl group. The reaction can be applied to a large number of substituted α‐trifluoromethyl enones and substituted indoles. The expected products were obtained with good yields and ees of up to 99 %.     

Reactions of Acid Chlorides/Ketenes with 2‐Substituted 4,5‐Dihydro‐4,4‐dimethyl‐1,3‐thiazoles: Formation of Penam Derivatives

Addition reactions of acid chlorides with various 2‐substituted 4,5‐dihydro‐4,4‐dimethyl‐5‐(methylsulfanyl)‐1,3‐thiazoles under basic conditions were studied. Two kinds of products were obtained from these additions, β‐lactams and non‐β‐lactam adducts. When the reaction was carried out with 4,5‐dihydro‐1,3‐thiazoles with a Ph substituent at C(2), the reaction proceeded via formal [2+2] cycloaddition and led to the correspoding β‐lactam. On the other hand, acid chlorides and 4,5‐dihydro‐1,3‐thiazoles bearing an α‐H‐atom at the C(2)‐substituent underwent C(α)‐ and/or N‐addition reactions and furnished non‐β‐lactam adducts, i.e., C(α)‐ and/or N‐acylated 1,3‐thiazolidines. The attempted transformations of sulfonyl esters of exo‐6‐hydroxy penams to endo‐6‐azido penams failed, although they were successful with mono‐β‐lactams under the same conditions.     

Photochemical Reactions of Regioisomeric 2,2‐Dimethyl‐5,5‐diphenyl‐ and 5,5‐Dimethyl‐2,2‐diphenyl‐Substituted Diazo Ketones of a Tetrahydrofuran Series

The principal direction of conventional photolysis of the regioisomeric 2,2‐dimethyl‐5,5‐diphenyl‐ and 5,5‐dimethyl‐2,2‐diphenyl‐substituted 4‐diazodihydrofuran‐3(2H)‐ones 1a and 1b , respectively, is the Wolff rearrangement, while other photochemical processes, which are giving rise to the formation of C? H‐insertion, 1,2‐alkyl‐ or ‐aryl‐shifts, as well as H‐atom‐abstraction products occur to a much lower degree (Schemes 2 and 3). The ratio of similar reaction products from both regioisomers 1a and 1b is essentially independent of their structure, and a substantial effect of the relative position of the Ph and diazo group to each other on the yield of C? H‐insertion products does not occur. Based on stereochemical considerations, the Wolff rearrangement of diazodihydrofuran‐3(2H)‐ones apparently proceeds in a concerted manner, whereas the appearance in the reaction mixture of 1,2‐shift and H‐atom‐abstraction products points to the parallel generation during photolysis of singlet and triplet carbenes (Schemes 4 and 5).     

Synthesis of 5‐(functionalized acyl)‐1,3‐dialkyl‐substituted barbituric and 2‐thiobarbituric acids

A sodium derivative of 1,3‐dimefhylbarbituric acid or 1,3‐diethyl‐2‐thiobarbituric acid undergoes an efficient monoacylation at C5 by the reaction with ω‐chloroalkanoyl chloride or diacid dichloride in the presence of pyridine in tetrahydrofuran. A nucleophilic displacement of the chlorine in a 5‐chloroacetyl‐bartiburate can be accomplished by using a one‐pot procedure. By contrast, a similar transformation of a 5‐(chlorobutanoyl)barbituric acid requires intramolecular cyclization in the presence of a nonnucleophilic base followed by treatment with a nucleophile of the resultant 5‐[4,5‐dihydro(3H)‐2‐furylidene]barbiturate.     

Umpolung Reactivity of Ynamides: An Unconventional [1,3]‐Sulfonyl and [1,5]‐Sulfinyl Migration Cascade

A regioselective sulfonyl/sulfinyl migration cycloisomerization cascade of alkyne‐tethered ynamides is developed in the presence of XPhosgold catalyst. This reaction is the first example of a general [1,3]‐sulfonyl migration from the nitrogen center to the β‐carbon atom of ynamides, followed by umpolung 5‐endo‐dig cyclization of the ynamide α‐carbon atom to the gold‐activated alkyne, and final deaurative [1,5]‐sulfinylation. This process allows the synthesis of peripherally decorated unconventional 4‐sulfinylated pyrroles with broad scope from N‐propargyl‐tethered ynamides. In contrast, N‐homopropargyl‐tethered ynamides undergo intramolecular tetradehydro Diels–Alder reaction to provide 2,3‐dihydro‐benzo[f]indole derivatives. Control experiments and density‐functional theory studies were used to study the reaction pathways.     

One‐pot Regioselective Synthesis of Novel 1‐N‐Methyl‐spiro[2,3′]oxindole‐spiro[3,3″]‐1″‐N‐arylpyrrolidine‐2″,5″‐dione‐4‐arylpyrrolidines through Multicomponent 1,3‐Dipolar Cycloaddition Reaction of Azomethine Ylide

An atom economic and facile synthesis of novel dispiro–oxindole–pyrrolidines has been achieved via a three‐component tandem cycloaddition of azomethine ylide generated in situ from isatin and sarcosine by decarboxylative condensation with N‐aryl‐3‐benzylidene‐pyrrolidine‐2,5‐dione derivatives as dipolarophiles. The salient features of synthetic procedure are characterized by the mild reaction conditions, high yields, high regioselectivity and stereoselectivity, one‐pot procedure, and operational simplicity. This regioselectivity was assumed to be under the influence of π–π stacking interactions between the aromatic rings of azomethine ylide and N‐aryl‐3‐benzylidene‐pyrrolidine‐2,5‐diones that further control the exo–endo selectivity of the reaction 1,3‐dipolar cycloaddition. The regiochemistry and structures of the cycloadducts were determined with spectroscopic data.     

BIMP‐Catalyzed 1,3‐Prototropic Shift for the Highly Enantioselective Synthesis of Conjugated Cyclohexenones

A bifunctional iminophosphorane (BIMP)‐catalysed enantioselective synthesis of α,β‐unsaturated cyclohexenones through a facially selective 1,3‐prototropic shift of β,γ‐unsaturated prochiral isomers, under mild reaction conditions and in short reaction times, on a range of structurally diverse substrates, is reported. α,β‐Unsaturated cyclohexenone products primed for downstream derivatisation were obtained in high yields (up to 99 %) and consistently high enantioselectivity (up to 99 % ee). Computational studies into the reaction mechanism and origins of enantioselectivity, including multivariate linear regression of TS energy, were carried out and the obtained data were found to be in good agreement with experimental findings.     

Quantum study on the electrocyclic reactions of CH2CHCHCHX (XH,F, Cl)

The microscopic mechanisms of the electrocyclic reactions for cis‐1,3‐butadiene and its monofluoro‐, monochloroderivatives have been studied by density functional theory (DFT), using the B3LYP method and 6‐311++G** basis sets. We optimized the geometric configurations of reactants, transition states, and products; verified all the probable transition states through vibrational analysis; and calculated the relative single‐point energies at the QCISD(T)/6‐311++G**//B3LYP/6‐311++G**. The results show that the monofluoro‐, monochloroderivatives of cis‐1,3‐butadiene both have two conformers; the reactant favors the electrocyclic reaction when one outboard hydrogen atom of the CH₂ groups is substituted by the fluorine or chlorine atom. © 2004 Wiley Periodicals, Inc. Int J Quantum Chem, 2004