Diastereoselective Manipulations of Bicyclo[m.1.0]alkane Derivatives. 2. Nucleophilic Additions to the Carbonyl Carbons of Bicyclo[m.1.0]alkan-2-ones(1)

Enantiomerically enriched bicyclo[m.1.0]alkan-2-ones having larger ring sizes between five and 16 members were prepared and subjected to additions of nucleophiles to the carbonyl carbon. Such additions were efficient and highly diastereoselective for all nucleophiles for bicycles with ring sizes greater than seven. Diastereoselectivity for these additions is rationalized by assuming early transition states and exposure of the same carbonyl face to the ring exterior in the vast majority of populated conformers for each bicyclic ketone.     

Regiochemistry of addition of aminoheterocycles to α-cyanocinnamonitriles: formation of aza-bridged bi- and tricycles

The additions of various five-membered ring aminoheterocycles to α-cyanocinnamonitriles were studied. Regiochemistry of product formation can in most cases be controlled by choosing the appropriate electrophile. An α-cyanocinnamonitrile with an additional β-leaving group normally provides products arising from initial attack of the ring amino group, while exo attack predominates in the case of the parent α-cyanocinnamonitrile. Aminopyrazole and aminoindazole provide only exo products with either electrophile. Product assignments were made via X-ray and 2D NMR methods; these assignments serve as a benchmark to several literature references and to future investigations of conjugate additions of these nucleophiles.     

Dynamic mechanical properties of poly-α-olefins containing ring structures in side chains

Dynamic loss modulus curves have been determined over a temperature range beginning at liquid nitrogen temperature for poly-α-olefin polymers containing various ring structures, i.e., phenyl, cyclohexyl, cyclopentyl, and naphthyl, in the side chain. Glass transition and appropriate secondary relaxation temperatures were observed for each polymer. Separation of each pendant ring structure from the main backbone chain by successive additions of methylene units results in lower glass-transition temperatures. Comparison of polymers with similar side chains and different ring structures shows that the respective glass-transition temperatures decrease in the order naphthyl > cyclohexyl > phenyl > cyclopentyl. Secondary relaxation peaks were obtained at about ?150°C for polymers containing the cyclohexyl and cyclopentyl rings. A similar peak was observed for the polymer possessing a phenyl ring separated from the main chain backbone by two methylene units. The comparable polymer containing the naphthyl ring structure exhibited a broad secondary relaxation peak centered at ?20°C. The polymers possessing cyclohexyl rings separated from the main chain backbone by one or two methylene units had an additional low temperature peak at ?80°C. The molecular mechanism associated with this relaxation may be related to intramolecular transformations of the cyclohexyl ring between its “chair–chair” conformations.     

Open versus closed 1,3-dipolar additions of C60: a theoretical investigation on their mechanism and regioselectivity

[reactions: see text] 1,3-Dipolar additions of C60 with dipoles, diazomethane, nitrile oxide, and nitrone have been modeled at the B3LYP/6-31G(d,p)//AM1 level, and their mechanism, regiochemistry, and nature of addition are investigated. All of these reactions lead to the formation of fullerene fused heterocycles; theoretically, these reactions can take up four types of additions, viz., closed [6,6], open [5,6], closed [5,6], and open [6,6] additions, and all of them have been examined. Energetics and thermodynamic analysis of these reactions show that closed [5,6] and open [6,6] additions are not probable and that closed [6,6] additions are the most favored ones and follow a concerted mechanism. Experimental evidence that C60-diazomethane reactions yielded closed [6,6] fullerenopyrazoline provides good support to the theoretical predictions. The observed order of reactivity has been explained based on the double bond character, forcing double bonds in the pentagons of C60, and strain. During the addition, dipoles distort more than C60 and concerted closed [6,6] TSs are found to be more reactant-like or early TS. Inclusion of toluene as solvent through the PCM model increases the reaction rate and exothermicity. NICS values computed at the centers of the reacting benzenoid ring of fullerene clearly reveal, in both open and closed additions, the loss in them of aromaticity during the reaction.     

Stéréosélectivité de l'addition de réactifs nucléophiles sur des cétones polycycliques à jonction trans

The nucleophilic additions of hindered organometallic compounds to polycyclic ketones with trans ring junctions involve predominant axial attack when flattening of the ring containing the carbonyl group occurs. The influence of nucleophile structure (O-Por C-metallated character) on equatorial or axial attack is discussed.     

Synthesis of some unsymmetrical bridged terpyridines

Novel unsymmetrical terpyridines 1 and 2 are synthesized using intra- and intermolecular Michael additions as the key reactions, followed by the construction of the central pyridine ring. Terpyridine 1 represents a heretofore unknown hexacyclic ring system.     

Synthesis of polyfunctional,linearly condensed six-membered ring systems by regioselective tandem Diels-Alder additions. Synthesis and reactivity of 6,7-bis(chloromethyl)-8,9-bis(methylene)-2-oxabicyclo[3.2.1]nonan-3-one

The title compound is a useful starting material for the preparation of complex linearly condensed six-membered ring sytems via tandem Diels-Alder additions.     

Palladium-catalyzed addition of nitrogen pronucleophiles to alkylidenecyclopropanes

The inter- and intramolecular additions of cyclic amides (nitrogen pronucleophiles) to methylenecyclopropanes proceeded smoothly in the presence of catalytic amounts of Pd(PPh(3))(4), affording the corresponding hydroamination products in good to high yields with high regioselectivities. The ring opening of methylenecyclopropanes occurred at the distal position of the cyclopropane ring.     

Titanocene‐Catalyzed Radical Opening of N‐Acylated Aziridines

Aziridines activated by N‐acylation are opened to the higher substituted radical through electron transfer from titanocene(III) complexes in a novel catalytic reaction. This reaction is applicable in conjugate additions, reductions, and cyclizations and suited for the construction of quaternary carbon centers. The concerted mechanism of the ring opening is indicated by DFT calculations.     

环氧乙烷亲核开环的区域选择性规则在有机化学教学中的应用

环氧乙烷亲核开环的区域选择性规则是有机化学中典型脂肪三元杂环亲核性开环的选择性规则,具有普遍性。本文以非对称环氧乙烷的亲核性开环为核心,从开环反应过渡态稳定性的角度讨论了决定环氧乙烷亲核开环区域选择性的原因。介绍了该区域选择性规则在经过三元杂环正离子中间体的非对称烯烃亲电加成反应区域选择性教学中的应用。加强学生对不同反应的机理和选择性的联系,起到教学中融会贯通的作用,可以提高教学效率和效果。     

Cinchona alkaloids in the asymmetric synthesis of 2-(phenylsulfanyl)aziridines

Enantioselective aza-Michael initiated ring closure (MIRC) additions of ethyl nosyloxycarbamate to 2-(phenylsulfanyl)-2-cycloalkenones catalysed by Cinchona alkaloids were studied. The results suggest that the enantioselectivity obtained is influenced by the structure of the catalyst and the different amination conditions. Substrate ring size also plays an important role.     

Regiocontrol switching in CC bond formation during decomplexation of a tricarbonyl(η4-cyclohexadiene)iron complex

A study has been made of additions of nucleophiles to the tricarbonyl(η⁴-cyclohexadiene)iron complex 1 and subsequently reaction of the resulting anions with several electrophiles in the presence of added ligands. Carbonyl insertion to form a functionalised cyclohexene ring is assisted by the addition of phosphines. Depending on the electrophilic reagent, an unusual phosphine-controlled switch in regiochemistry (PhCH₂Br), and interruption of the process prior to loss of the metal (CH₂=CHCH₂Br), have been observed.     

Using stereoelectronic effects to explain selective reactions of 4-substituted five-membered ring oxocarbenium ions

[reaction: see text] The utility of the inside attack model to predict and analyze the stereoselectivities of nucleophilic additions to complex five-membered ring oxocarbenium ions is demonstrated in a systematic study of C-4-substituted acetals.     

Diazapolycyclic compounds. XX. Stereochemistry of some addition reactions to the double bond at the terminal tetrahydropyridazine ring of methyl substituted 4a,12a-diaza-1,4,4a,5,12,12a- and 4a,12a-diaza-3,4,4a,5,12,12a-hexahydronaphthacene-5,12-diones,and the corresponding epoxides

The stereochemistry of N-bromosuccinimide electrophilic additions to the double bond at the terminal tetrahydropyridazine ring moiety of the 4a,12a-diazatetracyclic compounds 1-4 has been studied. These reactions appear as very regio- and stereoselective. Most the of the results obtained support the hypothesis that the N-bromoamide additions to cyclohexenes and heterocyclic analogous do not occur via the usual Ad_E2 mechanism, because the nucleophilic step is the rate-limiting one and the main product-determining factor. On the other hand, epoxidation of the double bond in 1-4 and further opening of the oxirane ring take place in accordance with the normal stereochemical rules.     

Intramolecular hetero-Michael addition of beta-hydroxyenones for the preparation of highly substituted tetrahydropyranones

Structurally diverse beta-hydroxyenones are shown to undergo nonoxidative 6-endo-trig ring closure to form highly substituted tetrahydropyranones. Amberlyst-15, Al(ClO(4))(3) x 9 H(2)O and [Pd(MeCN)(4)](BF(4))(2) were found to be suitable catalysts for these intramolecular conjugate additions, preventing side reactions, such as dehydration or retroaldolisation. The use of [Pd(MeCN)(4)](BF(4))(2) is particularly effective, as this palladium-mediated reaction is under kinetic control and generates tri- and tetrasubstituted tetrahydropyranones with high levels of diastereocontrol. In the presence of the Lewis acid Al(ClO(4))(3) x 9 H(2)O, the reaction proceeded with a similar level of diastereocontrol; however, in contrast to [Pd(MeCN)(4)](BF(4))(2), this catalyst can promote enolisation. The palladium-mediated reaction was also found to be compatible with an enantioenriched beta-hydroxyenone substrate, giving no loss of enantiopurity upon ring closure. The most distinctive synthetic development to emerge from this new chemistry is the possibility to access tri- and tetrasubstituted 2,6-anti-tetrahydropyranones from anti-aldol precursors. These compounds are particularly difficult to access by using alternative methodologies. Two modes of activation were envisaged for the ring closure, involving metal coordination to either the C=C or C=O functional groups. Experimental results suggest that C=O coordination was the preferred mode of activation for reactions performed in the presence of Al(ClO(4))(3) x 9 H(2)O or [Pd(MeCN)(4)](BF(4))(2).     

Equilibration in bicyclic pyroglutamates by ring opening-reclosure

Enantiopure bicyclic tetramates, readily obtained by Dieckmann ring closure on oxazolidine-derived templates, can be further converted to hydroxypyroglutamates by kinetically controlled nucleophilic additions, and some of these products are capable of equilibration via a facile retro-aldol/aldol reclosure.     

Grignard reactions of 4-substituted-2-keto-1,3-dioxanes: highly diastereoselective additions controlled by a remote alkyl group

[see reaction]. The reactions of Grignard reagents with a representative series of simple cis-2-keto-4-substituted-1,3-dioxanes have been investigated. The stereochemical outcome of these highly diastereoselective additions (dr > 90:10) is consonant with Cram's chelate model on the assumption that RMgX coordinates preferentially with the ring oxygen remote from the C(4) substituent.     

Efficient stereoselective syntheses of cyclic amino acids via Michael-induced ring-closing reactions

[reaction: see text] Zn-chelated glycine ester enolates are highly efficient nucleophiles for the synthesis of trans-methoxycarbonylcyclopropyl- and cyclobutylglycines by domino sequences of Michael additions and subsequent ring closures. They react to give the anti isomers with high yields and excellent diastereoselectivities.     

Orbital Unsymmetrization Affects Facial Selectivities of Diels-Alder Dienophiles

We investigated the Diels-Alder reactions of maleic anhydrides embedded in a dibenzobicyclo[2.2.2]octatriene motif as a nonsterically biased dienophile. Substituents on a benzene ring in these dienophiles are far from the reaction center, providing a sterically equivalent pi-face. Instead substituents can unsymmetrize the dienophilic pi face through pi (anhydride)-pi (aromatic) orbital interactions. Electron-withdrawing substituents affect the facial bias and relative rates of these cycloadditions. The preference of the cycloadditions is opposite in direction to those observed in nucleophilic additions of 2-substituted-9,10-dihydro-9,10-ethanoanthracen-11-ones (dibenzobicyclo[2.2.2]octadienones) and in electrophilic additions of 2-substituted 9,10-dihydro-9,10-ethenoanthracenes (dibenzobicyclo[2.2.2]octatrienes), though all of them have related dibenzobicyclic systems.     

PhI(OAc)2-mediated additions of 2,4-dinitrophenylsulfenamide with methylenecyclopropanes (MCPs) and a methylenecyclobutane (MCB)

We report herein stereoselective additions of a nitrene derived from PhI(OAc)₂ and 2,4-dinitrophenylsulfenamide with methylenecyclopropanes (MCPs) and a methylenecyclobutane (MCB) to give the corresponding ring enlargement products, (cyclobutylidene)amide or (cyclopentylidene)amide derivatives, in moderate to excellent yields. The reaction mechanism has been discussed on the basis of control experiments and previous investigation.