Macrocycle ring expansion by double Stevens rearrangement

New benzimidazolidinone cyclophanes were synthesized through a double Stevens rearrangement employed as a ring expansion technique. Para-substituted heterophanes underwent efficient rearrangement. Meta-substituted heterophanes were also prepared. Structure analyses of the new cyclophanes are also provided. [reaction: see text]     

Design of new synthetic strategies to cyclophanes via ring-closing metathesis

A simple synthetic methodology to cyclophanes containing hydroxyl groups has been reported. The key steps involved here are: Grignard reaction, double Claisen rearrangement, and ring-closing metathesis. The strategy reported here is protecting group-free synthesis.     

Diversity-oriented approach to cyclophanes via Claisen rearrangement and ring-closing metathesis as key steps

Among numerous reactions to prepare cyclophane derivatives, Claisen rearrangement reaction is very useful. We have prepared cyclophanes containing ethylene oxy bridge by double Claisen rearrangement reaction and ring-closing metathesis reaction as key steps.     

Synthesis of [m.n]Cyclophanes: Regiochemistry Transfer from Vinyl Halides to Cyclophanes via Fischer Carbene Complexes

The double benzannulation of bis‐carbene complexes of chromium with α,ω‐diynes generates [m.n]cyclophanes in which all three rings are generated in a single reaction. This triple annulation process is very flexible allowing for the construction of symmetrical [n.n]cyclophanes and unsymmetrical [m.n]cyclophanes as well as isomers in which the two benzene rings are both meta bridged or both para bridged, and isomers that contain both meta and para bridges. The connectivity patterns of the bridges in the cyclophanes can be controlled by regioselectivity transfer from the bis‐vinyl carbene complexes in which the substitution pattern of the vinyl groups in the carbene complexes dictate the connectivity pattern in the [m.n]cyclophanes. This synthesis of [n.n]cyclophanes is quite flexible with regard to ring size and can be used with tether lengths ranging from n=2 to n=16 and thus to ring sizes with up to 40 member rings. The only limitation to regioselectivity transfer from the carbene complexes to the [m.n]cyclophanes was found in the synthesis of para,para‐cyclophanes with four carbon tethers for which the loss of fidelity occurred with the unexpected formation of meta,para‐cyclophanes.     

双消除法一锅简便合成1－丙炔基芳香化合物

报道了一种便捷合成1-丙炔基芳香化合物的新方法. 在充分探讨反应条件的基础上, 利用硫试剂乙基苯基砜与芳香醛组合, 采用双消除反应成功地一锅合成了一系列1-丙炔基芳香化合物1a～1s. 运用此法不仅合成出一些含有醚键、萘环、杂环以及含有两个1-丙炔基的化合物, 重要的是芳环上含有卤原子(Br和I)的化合物也能顺利地合成出来. 该方法原料易得, 操作简单, 产物容易分离纯化并且产率理想.     

Palladium-catalyzed homocoupling reactions between two Csp(3)-Csp(3) centers

[reaction: see text] A novel palladium-catalyzed coupling reaction between two Csp(3)-Csp(3) centers has been investigated. This protocol is initiated by the oxidative addition of an alpha-halo carbonyl compound to a palladium(0) species, followed by the double transmetalation. The key dialkyl palladium intermediate undergoes reductive elimination to form the desired coupling product.     

Synthesis of a new class of electron rich chiral cyclophanes with large cavities

BINOL based electron rich chiral cyclophanes possessing large cavities have been synthesized starting from m-terphenyl dibromide and methyl m-/p-cinnamate. The presence of double bonds in the chiral cyclophanes makes them electron rich as revealed by C-T complexation studies of such cyclophanes donors with guests like TCNE, TCNQ and DDQ.     

Out-of-plane deformations of cyclic polyenes : A force-field interpretation of structural data

Spectroscopic force fields of benzene are shown to be compatible with the observed non-coplanarity of benzene rings with their H- or C- substituents in strained compounds, e.g. cyclophanes. A simplified force field for annulenes and cyclophanes is discussed, and ratios of the twist and out-of-plane bending force constants involved are derived from structural data. The resistance to twisting of partial double bonds is found to increase with decreasing bond length. Various formulae to calculate out-of-plane deformation coordinates are collected in an appendix.     

新型丁二炔-二酰胺大环化合物的合成及与TTF和DNP在溶液中的络合行为

由三甘醇和四甘醇出发,经炔丙基烷基化、Mitsunobu反应和Eglinton偶联反应3步合成了2个含均苯四甲酸二酰亚胺结构单元以及丁二炔结构单元的大环化合物,关环产率分别为81%和85%.大环化合物及中间体的化学结构经核磁共振氢谱、碳谱、低分辨质谱、高分辨质谱或元素分析等确认.通过氘代丙酮中1HNMR实验以及氯仿中紫外滴定实验研究了这类大环化合物与客体分子四硫富瓦烯(TTF)和1,5-二甲氧基萘(DNP)在溶液中的相互作用,结果发现,大环化合物的核磁化学位移及紫外光谱均发生变化.通过得到的主-客体间的络合常数可知,此类新型大环化合物与TTF和DNP之间有一定的络合作用.     

1,x-elimination reactions: extending the limits of a classical organic reaction

Alpha,omega-dibromo derivatives in which the two terminal carbon atom are separated by an unsaturated spacer unit ("pi spacer") undergo 1,x-elimination reactions (with x=6, 8, 10, and 14), using Mori's reagent (nBu3SnSiMe3/CsF). The resulting cumulenic intermediates cyclodimerize in a subsequent step yielding novel macrocyclic acetylenic and bridged aromatic compounds (cyclophanes). Thus 1,6-eliminations were carried out with dibromide 17 to yield 1,3,7,9-cyclododecatetrayne (20) and with benzylbromide 24 to provide cyclophanes 26 and 27. By 1,8-eliminations the 16-membered macrocycle 33 could be prepared from enediyne 31, the benzannelated 1,5-cyclooctadiyne 41 from dibromide 38, and a mixture of cyclophanes 45 and 46 from the precursor 43. 1,10-Eliminations were carried out successfully with dibromides 47, 50, and 53 yielding the corresponding unsaturated cyclophanes ("cyclophynes") 49, 52, and 55. The influence of the solvent on the cyclodimerization 47-->49 was investigated, with acetonitrile providing the highest yields. The heterophanes 59 a and b were obtained by 1,10-elimination of the precursor dibromides 57 a and b, and in an elimination experiment involving a 1:1 mixture of the dibromides 50 and 57 b the "mixed dimer" 60 was isolated, besides the homodimers 52 and 59 b. The method reached its limits with the 1,14-elimination of 68, 70, and 74 providing the cyclophanes 69, 71, and 75 in varying amounts. Two final debrominations with 76 and 77, which in principle could undergo 1,16- and 1,20-eliminations reactions, respectively, failed. The structures of the new cyclophanes 49, 50, 59 a, and 59 b were established by X-ray structural analysis; all other structure assignments rest on the usual spectroscopic and analytical data.     

Migration of Double Bond of Alkene in the Reaction of Iron-Catalyzed Olefination from Sulfonylcarbanion

Sulfonylcarbanion can be converted into alkene by elimination⁽¹⁾(eq 1),mix-coupling⁽²⁾ (eq 2) or homocoupling⁽³⁾ (eq 3) under iron catalysis. Besides desired alkenes, isomerized alkenes were detected in the reaction of elimination or mix-coupling. However, no migration of double bond in alkene was found in homocoupling reaction. Some experimental results were obtained to discuss the alkene isomerism in the iron-catalyzed sulfonylcarbanion olefination and some evidences were given to support the proposed mechanism of iron-catalyzed sulfonylcarbanion olefination.     

Synthesis of [n]- and [n.n]cyclophanes by using Suzuki-Miyaura coupling

Reaction of the bis-9-BBN adduct of several dienes with 1,3-dibromobenzene via Suzuki coupling leads to a series of [n]metacyclophanes ranging in size from 10 to 17 atom members. In each case, two carbon-carbon bonds are formed in one reaction vessel. However, when the bis-9-BBN adduct of 1,5-hexadiene is coupled with a variety of aryl dihalides, larger [n.n]cyclophanes were formed in preference to the [n]cyclophanes. Four carbon-carbon bonds are formed in this instance. Single-crystal X-ray analyses of these [n.n]cyclophanes reveal interestingly shaped molecules with large cavities.     

Benzidine/Quinoidal‐Benzidine‐Linked,Superbenzene‐Based π‐Conjugated Chiral Macrocycles and Cyclophanes

Synthesis of fully conjugated cyclophanes containing large‐size polycyclic aromatics is challenging. Now, three benzidine‐linked, hexa‐peri‐hexabenzocoronene (superbenzene)‐based ortho‐, para‐, and meta‐cyclophanes are synthesized through intermolecular Yamamoto coupling reaction of structurally pre‐organized precursors. Subsequent oxidative dehydrogenation gave the corresponding quinoidal benzidine‐linked cyclophanes. Their geometries were confirmed by X‐ray crystallographic analysis and their electronic properties were investigated by electronic absorption, cyclic voltammetry, and DFT calculations. The quinoidal benzidine‐linked cyclophanes show thermally populated paramagnetic activity with a relatively large singlet‐triplet energy gap. Two enantiomers for the ortho‐cyclophanes ( 1‐NH and 1‐N ) were isolated and their chiral figure‐of‐eight macrocyclic structures were identified. The cage‐like cyclophanes 2‐NH and 3‐NH with concave surface can selectively encapsulate fullerene C₇₀.     

Palladium-Catalyzed Enantioselective C−H Olefination to Access Planar-Chiral Cyclophanes by Dynamic Kinetic Resolution

Planar-chiral cyclophanes have received increasing attention for drug discovery and catalyst design. However, the catalytically asymmetric synthesis of planar-chiral cyclophanes has been a longstanding challenge. We describe the first Pd(II)-catalyzed enantioselective C−H olefination of prochiral cyclophanes. The low rotational barrier of less hindered benzene ring in the substrates allows the reaction to proceed through a dynamic kinetic resolution. This approach exhibits broad substrate scope, providing the planar-chiral cyclophanes in high yields (up to 99 %) with excellent enantioselectivities (up to >99 % ee). The ansa chain length scope studies reveal that the chirality of the cyclophanes arises from the bond rotation constraint of the benzene ring around the macrocycle plane, rather than the C−N axis. The C−H activation approach is also applicable to the late-stage modification of bioactive molecules and pharmaceuticals.     

Benzidine/Quinoidal-Benzidine-Linked,Superbenzene-Based π-Conjugated Chiral Macrocycles and Cyclophanes

Synthesis of fully conjugated cyclophanes containing large-size polycyclic aromatics is challenging. Now, three benzidine-linked, hexa-peri-hexabenzocoronene (superbenzene)-based ortho-, para-, and meta-cyclophanes are synthesized through intermolecular Yamamoto coupling reaction of structurally pre-organized precursors. Subsequent oxidative dehydrogenation gave the corresponding quinoidal benzidine-linked cyclophanes. Their geometries were confirmed by X-ray crystallographic analysis and their electronic properties were investigated by electronic absorption, cyclic voltammetry, and DFT calculations. The quinoidal benzidine-linked cyclophanes show thermally populated paramagnetic activity with a relatively large singlet-triplet energy gap. Two enantiomers for the ortho-cyclophanes ( 1-NH and 1-N ) were isolated and their chiral figure-of-eight macrocyclic structures were identified. The cage-like cyclophanes 2-NH and 3-NH with concave surface can selectively encapsulate fullerene C₇₀.     

Formation and reactivity of the addition products of alkoxides and thiolate anions to vinyl selenones

Vinyl selenones react with sodium methanethiolate in methanol to give the product of conjugate addition and subsequent displacement of the selenonyl group. On the contrary, the same reaction carried out with alkoxide anions affords the conjugate addition products in excellent yields. These β-alkoxy alkyl phenyl selenones are stable compounds which can react in several ways with loss of the selenonyl group. Their reactions with MeONa or MeSNa have been investigated both in MeOH and in DMF. The products observed derive from substitution and elimination processes as well as from retro Michael reactions followed by nucleophilic substitution of the vinyl selenone thus generated. These results indicate that the ArSeO₂ is a strong electron attracting group with peculiar properties. Beside making acidic the α-hydrogen atoms it activates the carbon-carbon double bond towards the addition of anionic reagents and it acts as a good leaving group in nucleophilic substitution, both aliphatic and vinylic, and in elimination reactions. The appropriate choice of the reagent and of the solvent allows to direct the reaction towards the desired products. Useful synthetic applications of these reactions are presented.     

Exploring structural and conformational behaviour of cyclophanes incorporating imidazole-2-thiones

New cyclophanes containing two imidazole-2-thione moieties linked by two xylylene groups have been synthesized by the reaction of imidazolium-linked cyclophanes with sulfur in the presence of K₂CO₃. The conformational behaviour of the new cyclophanes was explored by NMR spectroscopy and X-ray diffraction studies. In cyclophanes containing o-xylylene or 2,4,6-trimethyl-m-xylylene linking groups, the imidazole-2-thione groups were mutually syn in both the solid state and in solution, the cyclophanes adopting a conformation reminiscent of the cone conformation of calix[4]arenes. Cyclophanes containing p-xylylene or m-xylylene linking groups exhibited two conformations in solution, one in which the imidazole-2-thione groups are mutually syn, the other in which they are mutually anti, and these conformations did not interconvert on the NMR timescale. Both conformations co-crystallised in the m-xylylene linked cyclophane, while for the p-xylylene-linked cyclophane the anti conformation crystallised separately.     

Palladium(II)-catalyzed cycloisomerization of substituted 1,5-hexadienes: a combined experimental and computational study on an open and an interrupted hydropalladation/carbopalladation/β-hydride elimination (HCHe) catalytic cycle

The Pd(II)-catalyzed cycloisomerization of 3-alkoxycarbonyl-3-hydroxy-substituted 1,5-hexadienes has been studied experimentally and computationally. Experimentally, the reaction is characterized by a rapid room temperature formation of monomeric as well as dimeric cycloisomerization products using the commercially available precatalyst [(CH(3)CN)(4)Pd](BF(4))(2). In situ NMR measurements indicate the initial kinetic advantage of the desired cycloisomerization pathway to methylene cyclopentanes; however, double bond isomerization, elimination, and dimer formation are competitive undesired pathways. Evaluation of the obtained product structures by NMR spectroscopy and X-ray crystallography indicates that the sole determinant for the monomer/dimer ratio is the regioselectivity of the initial hydropalladation in favor of the allylic (monomer formation) or the homoallylic double bond (dimer formation). In order to account for the experimental results, we propose the coexistence of two product-forming catalytic cycles, an open, monomer generating, as well as an interrupted and redirected, dimer generating, hydropalladation/carbopalladation/β-hydride elimination (HCHe) process. Results from computational studies of the proposed competing catalytic cycles are supportive to our mechanistic hypothesis and pinpoint the pivotal importance of Pd(II)-hydroxo-chelate complexes for the reactivity-stability interplay of on- and off-pathway intermediates.     

New building blocks for fluorinated bioimidazole derivatives II: preparation of beta-fluorourocanic acids

Replacement of vinyl hydrogen with fluorine is based on addition of an FBr equivalent to a double bond followed by HBr elimination. This sequence has been adapted to prepare 3-fluoro-3-imidazolyl-propenoic acids (beta-fluorourocanic acids), and the related fluorinated imidazolyl propenals and prop-2-en-1-ols, from urocanic acid. Tritylation of the imidazole nitrogen was necessary for successful addition of "FBr" to the double bond, and prior reduction of the carboxyl group to the alcohol was required to provide the desired chemoselectivity in the elimination of HX. Reoxidation and deprotection produced the fluorinated urocanic acids.     

Synthesis and palladium-catalyzed coupling reactions of enantiopure p-bromophenyl methyl sulfoximine

[reaction: see text] The asymmetric synthesis and chemical modification of p-bromophenyl methyl sulfoximine (2) is described. Starting from p-bromophenyl menthyl sulfinate (5), enantiopure 2 can be obtained in a short reaction sequence involving a well-established substitution reaction followed by stereospecific imination with O-mesitylenesulfonylhydroxylamine (MSH). Palladium-catalyzed Buchwald/Hartwig, Suzuki, and Stille coupling reactions allow a broad variation of the sulfoximine aryl group, which is otherwise difficult to achieve. The incorporation of a p-morpholino-substituted derivative into a pseudotripeptide demonstrates the applicability of the novel sulfoximine derivatives.