Structural properties of five- and six-layered [3.3]metacyclophanes

We performed X-ray structural analyses of the five- and six-layered [3.3]metacyclophanes (MCPs) 1 and 2 and the six-layered [3.3]MCP tetraone 3. In the solid state, the MCP moieties of 1, 2, and 3 adopt different conformations from those of the free MCPs in solution. In the five-layered [3.3]MCP 1, all the [3.3]MCP moieties adopt anti (chair/boat) conformations. In the six-layered [3.3]MCP 2, two three-layered [3.3]MCPs are connected by a [3.3]MCP in the anti conformation with completely parallel benzene rings. In the six-layered [3.3]MCP tetraone 3, the outer [3.3]MCP moieties and diones adopt general syn and anti geometries, respectively. However, the inner [3.3]MCP moiety adopts an anti geometry. Based on density functional theory (DFT) calculations, the most stable conformers of 1, 2, and 3 are syn (chair/chair) in the [3.3]MCP moieties and anti (twist boat/twist boat) in the dione moieties.     

Marked difference in singlet-chemiexcitation efficiency between syn-anti isomers of spiro[1,2-dioxetane-3,1′-dihydroisobenzofuran] for intramolecular charge-transfer-induced decomposition

Spiro[1,2-dioxetane-3,1′-dihydroisobenzofuran] syn-3 bearing a hydroxy group at the 6-position (as a model syn-rotamer of parent dioxetane 4 bearing a 3-hydroxyphenyl group) and its isomer anti-3 (as a model anti-rotamer of 4) were synthesized. When these spiro-dioxetanes were treated with tetrabutylammonium fluoride (TBAF) in DMSO, anti-3 emitted light with high efficiency (Φ^CL = 0.41), while the respective value for syn-3 was only 1/10 for anti-3. This significant difference in Φ^CL between syn-3 and anti-3 was attributed to the difference in their singlet-chemiexcitation efficiencies.     

Synthesis of conformationally constrained spirodihydrofuropyridine analogues of epibatidine

Conformationally constrained spirofuropyridine analogues of epibatidine, syn-2 and anti-2, in which the 7-azabicyclo[2.2.1]heptane system and the 2-chloropyridine ring are held rigidly with the shorter and longer N-N distances, respectively, were synthesized from N-Boc-7-azabicyclo[2.2.1]heptan-2-one. The preliminary binding studies suggested that syn-2 has stronger binding affinity for nAChRs than anti-2.     

Rhodium(III) and palladium(II) complexes of some P-heterocycles; synthesis and X-ray structures

Deoxygenation of the syn-3-phosphabicyclo[3.1.0]hexane 3-oxides bearing a 3-phenyl or a 3-(4-methylphenyl) substituent (1a,b) by trichlorosilane took place already at mild condition and resulted in the corresponding phosphines (2a,b) with retention of configuration at phosphorus, while in the case of 3-(2-methylphenyl)-3-phosphabicyclo[3.1.0]hexane (2c), the inversion of the phosphorus atom was observed in solution under ambient conditions that was evaluated by quantum chemical calculations. A further phosphine ligand (5) was obtained by the reduction of 4-dichloromethylene-1,4-dihydrophosphinine oxide (4). The phosphine ligands (2 and 5) were used in the preparation of Rh(III) complexes (3 and 6). A Pd(II) complex of type PdCl₂(5)₂ (7) was also prepared. The stereostructures of a series of Rh(III) complexes of 3-aryl-3-phosphabicyclo[3.1.0]hexanes (3b-syn, 3c-syn and 3c-anti) were elucidated by single crystal X-ray analysis confirming the relative position of the dichlorocyclopropane and the P-substituent.     

Rotamer-dependent chemiluminescence in the intramolecular charge-transfer-induced decomposition of bicyclic dioxetanes bearing a hydroxyaryl group

Base-induced chemiluminescent decomposition of acylamino-substituted dioxetane 1b bearing a 3-hydroxyphenyl group proceeded according to dual phase kinetics due to syn-anti isomerism of the aryl group. For dioxetane 7 bearing a 6-hydroxynaphthalen-2-yl group, syn- and anti-rotamers were each isolated and their structures were determined by X-ray single crystallographic analysis. Both rotamers underwent base-induced decomposition accompanied by the emission of red light to exclusively give the same keto imide 8. However, a marked difference in chemiluminescence efficiency was observed between anti-7 and syn-7.     

Total synthesis of phytoprostane F1 and its 16 epimer

The first synthesis of the two enantiomers of phytoprostane F₁ methyl ester 1 and 2 is described using the syn-anti-syn alcoxy ester 3 as starting material.     

An efficient and practical procedure for Strecker reaction: a highly diastereoselective synthesis of a key intermediate for (+)-biotin

Treatment of α-amino aldehyde 2, which was prepared through Moffatt oxidation of the corresponding β-amino alcohol 5, with aqueous sodium bisulfite allowed clean conversion to a water-soluble bisulfite adduct 6 [>99% conversion, 89% yield (two steps)]. The aqueous solution of 6 was treated with benzylamine followed by easy-handling NaCN to effect the Strecker reaction to afford α-amino nitrile 3 with high diastereoselectivity and in high yield (syn/anti = 11:1, 95% assay yield). Both the compounds syn-3 and anti-3 were converted to a key intermediate 4 for (+)-biotin through S,N-carbonyl migration in high yields.     

Synthesis and conformational analysis of 3-hydroxypipecolic acid analogs via CSI-mediated stereoselective amination

A short and efficient stereoselective synthetic approach toward substituted piperidines, involving (2S,3S)-3-hydroxypipecolic acid 1, (2R,3S)-3-hydroxypipecolic acid 3, and their acid-reduced analogs 2 and 4, has been developed. The requisite anti- and syn-1,2-amino alcohols 11 and 12 for the preparation of title four piperidine analogs 1-4 were synthesized via the regioselective and diastereoselective amination of anti- and syn-1,2-dibenzyl ethers 13 and 14 using chlorosulfonyl isocyanate (CSI). As a result, reaction of anti-1,2-dibenzyl ether 13 with CSI afforded exclusively the anti-1,2-amino alcohol 11 with the diastereoselectivity of 49:1 in toluene at −78 °C and syn-isomer 14 gave the syn-1,2-amino alcohol 12 as the major product with the diastereoselectivity of 12:1 in hexane at −78 °C. The result of these reactions could be explained by the neighboring group effect leading to retention of stereochemistry. In addition, conformational changes of trans-piperidine intermediate 9 in terms of the nature of N-protecting groups are described. The conformations of 9 and 24-28 were confirmed by ¹H NMR analysis and NOE correlation. Furthermore, the conformations of piperidines 18 and 23 with hydroxyl methyl substituent at C-2 were investigated by NMR spectroscopy.     

Synthesis, crystal structure, and magnetic properties of two-dimensional divalent metal glutarate/dipyridylamine coordination polymers, with a single crystal-to-single crystal transformation in the copper derivative

Hydrothermal reaction of divalent metal chlorides with glutaric acid and 4,4′-dipyridylamine (dpa) has afforded an isostructural family of coordination polymers with formulation [M(glu)(dpa)]_n (M=Co (1), Ni (2), Cu (3); glu=glutarate). Square pyramidal coordination is seen in 1-3, with semi-ligation of a sixth donor to produce a “5+1” extended coordination sphere. Neighboring metal atoms are linked into 1D [M(glu)]_n neutral chains through chelating/monodentate bridging glutarate moieties with a syn-anti binding mode, and semi-chelation of the pendant carboxylate oxygen. These chains further connect into 2D layers through dipodal dpa ligands. Neighboring layers stack into the pseudo 3D crystal structure of 1-3 through supramolecular hydrogen bonding between dpa amine units and the semi-chelated glutarate oxygen atoms. The variable temperature magnetic behavior of 1-3 was explored and modeled as infinite 1D Heisenberg chains. Notably, complex 3 undergoes a thermally induced single crystal-to-single crystal transformation between centric and acentric space groups, with a conformationally disordered unilayer structure at 293 K and an ordered bilayer structure at 173 K. All materials were further characterized via infrared spectroscopy and elemental and thermogravimetric analyses.     

Intramolecular rearrangement of 1,3-bistriflate ester of thiacalix[4]arene to 1,2-counterpart: an efficient di-O-protection method for the stereoselective synthesis of anti-1,2-diethers

A net anti-selective dialkylation of the proximal hydroxy groups of thiacalix[4]arene 2 is achieved for the first time via the initial protection of the two proximal hydroxy groups of compound 2 with Tf moieties by intramolecular rearrangement of easily preparable 1,3-bistriflate ester 3 to 1,2-counterpart 4, followed by anti-selective dialkylation of the remaining hydroxy groups with alkyl halides or under the Mitsunobu conditions and subsequent removal of the Tf moieties.     

Synthesis of mono- and trinuclear palladium(II) complexes via oxidative addition of a bulky hexathioether containing a disulfide bond to palladium(0)

The oxidative addition reactions of a bulky hexathioether containing a disulfide bond, TbtS(o-phen)S(o-phen)SS(o-phen)S(o-phen)STbt (1) (Tbt = 2,4,6-tris[bis(trimethylsilyl)methyl]phenyl, o-phen = o-phenylene), to a palladium(0) complex were studied. In the reaction of 1 with 3 molar amounts of [Pd(PPh₃)₄], a trinuclear palladium(II) complex, [Pd₃{S(o-phen)S}₂{(o-phen)STbt}₂(PPh₃)₂] (2), was formed via three-step palladium insertion reaction including unusual C(aryl)-S bond cleavages. On the other hand, the reaction of 1 with an equimolar amount of [Pd(PPh₃)₄] afforded mononuclear palladium(II) complex having a pseudo-octahedral structure, [Pd{S(o-phen)S(o-phen)STbt}₂] (3). The hexa-coordinated geometry for the palladium center in 3 was confirmed by the atoms in molecule (AIM) analysis, which revealed the presence of the bond critical points between the central Pd atom and the S atoms at the axial positions. In contrast to the bulky system, the reaction of Ph-substituted hexathioether, PhS(o-phen)S(o-phen)SS(o-phen)S(o-phen)SPh (4), with an equimolar amount of [Pd(PPh₃)₄] gave a palladium(II) complex having square-planar structure, [Pd{S(o-phen)S(o-phen)SPh}₂] (5). Theoretical calculations revealed that there is no remarkable difference among the energies of isomers of [Pd{S(o-phen)SPh}₂], 6a-syn, 6a-anti, 6b-syn, and 6b-anti. This result suggests that a reason for the preference of the trans-anti-conformation in 3 is the steric repulsion between the bulky Tbt groups, and that of the cis-syn-conformations in 5 and 6 is the intermolecular interactions.     

Stereospecific mono- and difluorination of the C7-bridge of norbornenes

Fluorinated norbornenes are very desirable monomers in the semiconductor and high-temperature polyimide industries. We describe herein a synthetic strategy for the stereospecific mono- or difluorination of the C₇-carbon in norbornene systems beginning with 7-ketonadic anhydride 1. In particular, anti-7-fluoro methyl diester 4 and its 7,7-difluoronadic analog 7 can be prepared from 1 in 3 or 4 steps: saponification, reduction (for 4), esterification, fluorination with DAST. In addition, anti-7-fluoro-syn-7-fluoromethylnadic diester 16 is obtained from epoxide 14, and dimethyl 7,7-difluorobicyclo[2.2.2]oct-5-ene-2,3-dicarboxylate (17) from ketone 15. Anchimeric assistance of the norbornene double bond guides the introduction of attacking fluoride anions stereospecifically anti to the olefinic linkage.     

Steric course of some cyclopropanation reactions of L-threo-hex-4-enopyranosides

Completely protected 4-deoxy-α-L-threo-hex-4-enopyranosides 1c,d undergo the dichlorocarbene addition affording exclusively diastereomeric adducts 5c,d with the cyclopropane ring anti to the C-3 alkyloxy substituent, while the reaction with 3-unprotected derivatives 1a,b affords a mixture of syn and anti derivatives. Under the Simmons-Smith cyclopropanation adducts 2a-d with a syn stereochemistry are obtained. Starting from 5b, the cyclopropanated sugar 3b is obtained by reduction with LiAlH₄, thus the two diastereomers 2b and 3b can be stereoselectively obtained through the two different pathways. For a useful comparison, 4-deoxy-β-L-threo-hex-4-enopyranoside 1e was also subjected to the above two cyclopropanation methods affording the expected cycloadduct 2e and a diastereomeric mixture of dichlorocycloadducts 4e and 5e (4e/5e=2.8:1).     

Concise route to defined stereoisomers of the hydroxy acid of the chondramides

The use of Kobayashi vinylogous aldol reaction in the reaction with acetaldehyde led to anti-aldol product 11. After reductive removal of the chiral auxiliary, the primary alcohol was converted to the allyliodide 14. This compound could be engaged in an Evans alkylation reaction, leading eventually to hydroxy acid 19. Inclusion of a Mitsunobu inversion reaction on the sequence starting with ent-11 led to hydroxy ester 30, featuring a 6,7-syn-configuration. These hydroxy acids should help to elucidate the correct stereostructure of the chondramide depsipeptides.     

Aspects of stereocontrol in the L-Selectride reduction of 4-acyl-1,3-dioxolane derivatives

The application of L-Selectride, either alone or in combination with ZnCl₂, to aryl ketones 1, 8 and 11 resulted in highly anti-stereoselective reduction. In contrast, lactols 22 and 23 gave a moderate syn-preference using L-Selectride alone and a high syn-preference in the presence of ZnCl₂. Uniquely, high anti- stereoselectivity was observed in the reduction of o-anisyl lactol 37 with L-Selectride alone, which was switched to a high syn-preference when ZnCl₂ was present.     

Calix[4]quinones. Part 4: The ClO2 oxidation of calix[4]arene dialkyl ethers

Except for the special case of calix[4]arene diethyl ether 1, the chlorine dioxide oxidation of dialkyl ethers 2-5 yielded only the corresponding calix[4]diquinone dialkyl ethers 8-11. Chlorine dioxide oxidation of calix[4]arene diethyl ether 1 produced two isomeric products 6 and 7, which were stable enough to be isolated by column chromatography. However, a slow conformational interconversion between isomeric pair 6 and 7 was observed at room temperature, and the equilibrium was reached after 400 h at 18 °C with an amount of 5:3 in favor of syn-isomer.     

Bu3SnH-mediated 5-exo selective radical cyclization of N-vinyl-α,β-unsaturated amides leading to γ-lactams

Treatment of N-vinyl-α,β-unsaturated amides 1a-h with Bu₃SnH and a catalytic amount of AIBN in boiling benzene caused 5-exo cyclization of allylic O-stannyl ketyl radicals generated by addition of Bu₃Sn· on the amide-oxygen atoms to provide γ-lactams 2a-h after acidic workup. When enamide 1d was treated with Bu₃SnH in the presence of AIBN followed by aldehydes 3a-d, sequential radical cyclization and aldol reactions occurred to afford anti-adducts 4a-d and syn-adducts 5a,b.     

Lewis acid-catalyzed synthesis of dodecamethoxycalix[4]arene from 1,3,5-trimethoxybenzene and its conformational behavior and host-guest property

Lewis acid-catalyzed condensation of 1,2- and 1,3-dimethoxybenzenes with paraformaldehyde afforded an ortho-bridged cyclic trimer (1) and a meta-bridged cyclic tetramer (2), respectively. Furthermore, condensation of 1,3,5-trimethoxybenzene with paraformaldehyde in the presence of Lewis acid catalyst successfully rendered the first dodecamethoxy-substituted calix[4]arene (3) with high yield. From X-ray crystallography, it was found that 3 formed the partial cone conformation. The conformational behavior of 3 in the solution was investigated by variable temperature ¹H NMR measurements. The partial cone structure observed in the solid state was retained in the solution at low temperatures. Furthermore, because of the slow conformational exchanges of 3 on the NMR time scale, bimodal conformational exchanges were found. The host-guest property of 3 with the electron accepting guest, tetracyanoethylene (TCNE) was examined by UV-Vis measurements, and the ability to associate with the 3-TCNE complex was three times higher than that of the 2-TCNE complex. The observation is due to the superior electron donating property and slow conformational exchanges of 3 compared with those of analogous 2.     

Synthesis and characterization of tetramethylene-syn-sesterbicyclo[2.2.2]octene

The synthesis of syn-sesterbicyclo[2.2.2]octene (7) bilaterally grafted by an exocyclic s-cis-butadiene moiety is achieved from 1,8,9,10-tetrachloro-11,11-dimethoxy-endo-tricyclo[6.2.1.0^2,7]undeca-3,5,9-triene (8) employing repetitive Diels-Alder cycloadditions between 1,3-cyclohexadiene, generated from p-benzoquinone, and diethyl fumarate or maleic anhydride as the exocyclic butadienyl equivalent, followed by subsequent transformation to the conjugated diene moieties. In comparison with the corresponding sesquibicyclo[2.2.2]octene 6, the ¹H NMR demonstrates the anisotropic shielding effect operating within the three parallel laticyclic double bonds. However, the UV absorption of 7 shows less effect by the increase of laticyclic conjugated ethylene units.     

Short-step syntheses and complexation properties of Z,Z-tribenzodidehydro- and all-Z-tribenzo[12]annulenes

Syntheses of all-Z-tribenzo[12]annulenes (1a-c) and Z,Z-tribenzodidehydro[12]annulenes (2a-c) by the reduction of the corresponding tribenzohexadehydro[12]annulenes 3a-c were carried out using a low valent titanium complex generated from Ti(O-i-Pr)₄ and i-PrMgCl. The unique structure of the first reduction products 2a-c as well as 1a-c was fully characterized. Complexation of these annulenes with silver(I) ions produces the corresponding silver complexes. Among them, the silver complexes of 2a-c exhibit interesting monomer-dimer equilibrium.