Kinetics of the cis,cis to trans,trans isomerization of 1,1,2,2,5,5,6,6-octamethyl-1,2,5,6-tetrasilacycloocta-3,7-diene

The kinetics of the ruthenium-promoted cis,cis to trans,trans isomerization of 1,1,2,2,5,5,6,6-octamethyl-1,2,5,6-tetrasilacycloocta-3,7-diene were investigated. Incubation of a ruthenium alkylidene complex, (Cy(3)P)RuCl(2)(==CHPh)Ru(p-cymene)Cl(2), in CD(2)Cl(2) for 5 days at 40 degrees C afforded a catalytically active ruthenium species that was shown to be responsible for promoting the isomerization. The isomerization was observed to proceed in two steps: (1) conversion of the starting cis,cis isomer to a proposed cis,trans intermediate and (2) subsequent conversion of the intermediate to the product trans,trans isomer. Kinetic studies demonstrated that the two steps are first-order with respect to the concentrations of the cis,cis isomer, the intermediate, and the ruthenium alkylidene complex. The data were further consistent with a mechanism involving bimolecular hydride addition-elimination during the two isomerization steps.     

Counter-current chromatographic estimation of hydrophobicity of Z-(cis) and E-(trans) enalapril and kinetics of cis/trans isomerization

The kinetics of Z-(cis)/E-(trans) isomerization of enalapril was investigated by reversed phase high-performance liquid chromatography (RP-HPLC) using a monolith ODS column under a series of different temperature and pH conditions. At a neutral pH 7, the rate (k(obs)) of Z-(cis)/E-(trans) isomerization of enalapril at 4 degrees C (9.4 x 10(-3)min(-1)) is much lower than at 23 degrees C (1.8 x 10(-1)min(-1)), while the fractional concentration of Z-(cis) isomer is always higher than that of E-(trans) isomer in the pH range 2-7. The fractional concentration of the E-(trans) isomer becomes a maximum (about 40%) in the pH range 3-6, where enalapril exists as a zwitterion. The hydrophobicity (logP(O/W)) of both isomers was estimated by high-speed counter-current chromatography (HSCCC). Normal phase HSCCC separation using a tert-butyl methyl ether-acetonitrile-20mM potassium phosphate buffer (pH 5) two-phase solvent system (2:2:3, v/v/v) at 4 degrees C was effective in partially separating the isomers, and the partition coefficient (K) of each isomer was directly calculated from the retention volume (V(R)). The logP(O/W) values of Z-(cis) and E-(trans) isomers were -0.46 and -0.65, respectively.     

Stereochemistry of the [4 + 2] cycloadditions of trans,trans- and cis,trans-2,4-hexadiene to C(60)

The [4 + 2] cycloaddition of trans,trans-2,4-hexadiene with C(60) proceeds via a concerted mechanism with retention of stereochemistry in the cycloadduct 1a. However, when cis,trans-2,4-hexadiene reacts with C(60), isomerization of the cis,trans to the thermodynamically more stable trans,trans isomer occurs. Subsequently, the cis,trans diene isomerized to the trans,trans isomer and cycloadds to C(60), to form adduct 1a. When the reaction is carried out at higher temperatures, the formation of cycloadduct 1b is also obtained. This result is consistent with a concerted cycloaddition of cis,trans-2,4-hexadiene with C(60), which is more reactive at elevated temperatures and leads to the formation of the Diels-Alder adduct 1b.     

Synthesis of 3-Ethoxy-2-Oxo-3-Phenyl-1,2-Oxaphosphorinane-3,5-Diene

Abstract

In view of the limited number of examples of 2-oxo-l,2-oxaphosphorinane3,5diene derivatives^1,2, we investigated the preparation of the title compound and derivatives of the same. Of additional interest were the spectroscopic propertits of this class of compounds, their stability, and the outcome of their reaction with nucleophilts. Prior work in our laboratory on the synthesis of simple phostones and their derivatives³, led us to use these as starting mataials. The presence of the phenyl substituent in la, (cis and trans isomers) permitted facile introduction of a bromo group through free radical bromination with NBS/AIBN to give 2a,b in 79% overall yield. The individual isomers of 2 were separated; tentative stereochemical assignments were made using NMR spectroscopy. Treatmnt of 2 with LiCl/DMF gave 3; the trans isomer (phenyl and OEt trans) 2b reacted much faster than the cis isomer. Treatmnt of 3 with NBS/AIBN gave 4a,b and 5 which were separated by flash chromatography. Dehydrobromination of 4 (71% yield) was achieved by heating with an excess of Et₃N in toluenc at 95°C to produce 6; likewise, dehydrobromination of 5 at 70°C gave 7.     

Probing highly efficient photoisomerization of a bridged azobenzene by a combination of CASPT2//CASSCF calculation with semiclassical dynamics simulation

Mechanism of phototriggered isomerization of azobenzene and its derivatives is of broad interest. In this paper, the S(0) and S(1) potential energy surfaces of the ethylene-bridged azobenzene (1) that was recently reported to have highly efficient photoisomerization were determined by ab initio electronic structure calculations at different levels and further investigated by a semiclassical dynamics simulation. Unlike azobenzene, the cis isomer of 1 was found to be more stable than the trans isomer, consistent with the experimental observation. The thermal isomerization between cis and trans isomers proceeds via an inversion mechanism with a high barrier. Interestingly, only one minimum-energy conical intersection was determined between the S(0) and S(1) states (CI) for both cis → trans and trans → cis photoisomerization processes and confirmed to act as the S(1) → S(0) decay funnel. The S(1) state lifetime is ～30 fs for the trans isomer, while that for the cis isomer is much longer, due to a redistribution of the initial excitation energies. The S(1) relaxation dynamics investigated here provides a good account for the higher efficiency observed experimentally for the trans → cis photoisomerization than the reverse process. Once the system decays to the S(0) state via CI, formation of the trans product occurs as the downhill motion on the S(0) surface, while formation of the cis isomer needs to overcome small barriers on the pathways of the azo-moiety isomerization and rotation of the phenyl ring. These features support the larger experimental quantum yield for the cis → trans photoisomerization than the trans → cis process.     

Light-driven molecular hinge: a new molecular machine showing a light-intensity-dependent photoresponse that utilizes the trans-cis isomerization of azobenzene

[reaction: see text] A new class of molecular machine exhibits a hingelike motion upon photoirradiation. The motion (close and open) can be operated by alternate irradiation with UV and visible light. The trans/trans and cis/cis isomers are thermally stable at 40 degrees C, and the photochemical closure reaction (from trans/trans to cis/cis isomer) is dependent on the intensity of the light used because of the short-lived intermediate (trans/cis isomer).     

Synthesis of 3,4-disubstituted piperidines by carbonyl ene and prins cyclizations: switching between kinetic and thermodynamic control with Brønsted and Lewis acid catalysts

A novel approach to cis and trans 3,4-disubstituted piperidines is described. Carbonyl ene cyclization of aldehydes 4a-e catalyzed by MeAlCl(2) in refluxing chloroform afforded the trans piperidines 7a-e with diastereomeric ratios of up to 93:7, while aldehyde 4f afforded solely the cis product 6f, which was resistant to isomerization to the trans isomer. It was demonstrated for 4a that the cyclization catalyzed by a variety of Lewis acids at low temperature proceeded under kinetic control to afford predominantly the cis piperidine 6a, and this isomerized to the thermodynamically more stable trans piperidine 7a on warming. In contrast, Prins cyclization of 4a-e catalyzed by concentrated hydrochloric acid in CH2Cl2 at low temperature afforded cis piperidines 6a-e with diastereomeric ratios of up to >98:2. The yield and diastereoselectivity of these cyclizations could be improved by using HCl-saturated CH2Cl2 to form the corresponding chloride, followed by elimination of HCl effected by ammonia. Aldehydes 4f and 4galso cyclized in good yield under the latter conditions. Mechanistic studies supported by DFT calculations (B3LYP/6-31G(d)) suggest that the cyclizations proceed via a mechanism with significant carbocationic character, with the cis carbocation being more stable than the trans carbocation. DFT calculations (B3LYP/6-31G(d)) of the transition state energies for concerted cyclization show that the cis piperidine is also the favored product from cyclization through a more concerted mechanism.     

Diastereocontrol by a hydroxyl auxiliary in the synthesis of pyrrolidines via radical cyclization

[reaction: see text] Organoselenium precursors of 3-aza-5-hexenyl radicals carrying a 1-hydroxyalkyl group in the 2-position were prepared by addition of organometallic reagents to N-allyl-2-aziridinecarbonitrile, reduction of the resulting aziridine ketone, and regioselective benzeneselenol ring opening of the aziridine. Reductive radical cyclization was highly selective, affording the corresponding trans-2,4-disubstituted pyrrolidine (cis/trans ca. 1/10) as the major diastereomer. Recrystallization afforded material that was substantially more enriched in the trans isomer (cis/trans < 1/25).     

Synthesis of 7-azabicyclo[2.2.1]heptane and 2-oxa-4-azabicyclo[3.3.1]non-3-ene derivatives by base-promoted heterocyclization of alkyl N-(cis(trans)-3,trans(cis)-4-dibromocyclohex-1-yl)carbamates and N-(cis(trans)-3,trans(cis)-4-dibromocyclohex-1-yl)-2,2,2-trifluoroacetamides

We have studied the base-promoted heterocyclization of alkyl N-(cis(trans)-3,trans(cis)-4-dibromocyclohex-1-yl)carbamates and N-(cis(trans)-3,trans(cis)-4-dibromocyclohex-1-yl)-2,2,2-trifluoroacetamides, investigating the effect of the nitrogen protecting group and the relative configuration of the leaving group at C3 and C4 on the outcome of this reaction. We have observed that the sodium hydride-promoted heterocyclization of alkyl N-(cis-3,trans-4-dibromocyclohex-1-yl)carbamates (10, 12, 14, 16, 18) is a convenient method for the synthesis of 7-azabicyclo[2.2.1]heptane derivatives. For instance, the reaction of tert-butyl N-(cis-3,trans-4-dibromocyclohex-1-yl)carbamate (10) with sodium hydride in DMF at room temperature provides 2-bromo-7-[(tert-butoxy)carbonyl]-7-azabicyclo[2.2.1]heptane (2) (52% yield), whose t-BuOK-promoted hydrogen bromide elimination affords 7-[(tert-butoxy)carbonyl]-7-azabicyclo[2.2.1]hept-2-ene (31) in 78% yield, an intermediate in the total synthesis of epibatidine (1). However, the NaH/DMF-mediated heterocyclization of alkyl N-(trans-3,cis-4-dibromocyclohex-1-yl)carbamates (11, 13) is a more structure dependent reaction, where the nucleophilic attack of the oxygen atom of the protecting group controls the outcome of the reaction, giving rise to benzooxazolone and 2-oxa-4-azabicyclo[3.3.1]non-3-ene derivatives, respectively, from low to moderate yields, in complex reaction mixtures. Conversely, the NaH/DMF heterocyclizations of N-(cis-3,trans-4-dibromocyclohex-1-yl)-2,2,2-trifluoroacetamide (40) or N-(trans-3,cis-4-dibromocyclohex-1-yl)-2,2,2-trifluoroacetamide (42) are very clean reactions giving 7-azabicyclo[2.2.1]heptane or 2-oxa-4-azabicyclo[3.3.1]non-3-ene derivatives, respectively, in good yields. Finally, a mechanistic investigation, based on DFT calculations, has been carried out to rationalize the formation of the different adducts.     

Proton-induced cis-trans conversion of a platinum(II) center coordinated by L-cysteinatocobalt(III) metalloligands

Treatment of LambdaL-[Co(L-cys-N,S)(en)2]+ (l-H2cys = L-cysteine) with [PtCl4]2- in water, followed by the addition of acid, gave an S-bridged CoIII2PtII trinuclear complex ([1]4+), which was reversibly converted to its deprotonated complex ([2]2+) in an aqueous solution. While [1]4+ formed only a trans isomer, [2]2+ existed as a mixture of trans and cis isomers. The selective formation of a cis isomer was achieved by treatment of [1]4+ or [2]2+ with phthalic acid in water, which afforded a unique CoIII4PtII2 hexanuclear complex ([3]4+). Complex [3]4+ was reverted back to [1]4+ by treatment with aqueous HCl, accompanied by the complete cis-to-trans conversion.     

Highly selective intra- and intermolecular coupling reactions of diazo compounds to form cis-alkenes using a ruthenium porphyrin catalyst

[Ru(2,6-Cl(2)TPP)(CO)] catalyzed intramolecular coupling reactions of bisdiazoacetates and intermolecular coupling reactions of monodiazoacetates to afford the coupling products in up to 76% and 93% yields, respectively. Only the cis isomers were obtained from the reactions. Employing such a ruthenium-catalyzed coupling reaction of a diazo compound as a key step allowed the synthesis of Patulolide B in 67% yield with a ratio of >40:1 against its trans isomer.     

Pseudo-rotation mechanism for fast olefin exchange and substitution processes at orthometalated C,N-complexes of platinum(II)

Bridge splitting in chloroform of the orthometalated chloro-bridged complex [Pt(micro-Cl)(2-Me(2)NCH(2)C(6)H(4))](2)(1), with ethene, cyclooctene, allyl alcohol and phosphine according to 1+ 2L --> 2[PtCl(2-Me(2)NCH(2)C(6)H(4))(L)], where L = C(2)H(4)(3a), C(8)H(14), (3b), CH(2)CHCH(2)OH (3c), and PPh(3)(4a and 4b) gives monomeric species with L coordinated trans or cis to aryl. With olefins the thermodynamically stable isomer with L coordinated cis to aryl is formed directly without an observable intermediate. With phosphine and pyridine, the kinetically controlled trans-product isomerizes slowly to the more stable cis-isomer. Bridge splitting by olefins is slow and first-order in 1 and L, with largely negative DeltaS(++). Substitution of ethene cis to aryl by cyclooctene and allyl alcohol to form 3b and 3c, and substitution of cot from 3b by allyl alcohol to form 3c are first order in olefin and complex, ca. six orders of magnitude faster than bridge cleavage due to a large decrease in DeltaH(++), and with largely negative DeltaS(++). Cyclooctene exchange at 3b is first-order with respect to free cyclooctene and platinum complex. All experimental data for olefin substitution and exchange are compatible with a concerted substitution/isomerization process via a turnstile twist pseudo-rotation in a short-lived labile five-coordinated intermediate, involving initial attack on the labile coordination position trans to the sigma-bonded aryl. Bridge-cleavage reactions of the analogous bridged complexes occur similarly, but are much slower because of their ground-state stabilization and steric hindrance.     

d-生物素的不对称全合成研究(Ⅱ)

1,3－二苄基咪唑啉－2－酮－顺－4,5－二羟酸经脱水、单酯化,折分成分（4S,5R）－顺1,3－二苄基－5－甲氧基羧基－2－氧代咪唑啉－4－羧酸,再经还原环合,硫代成(3aS,6aR)-1,3－二苄基－四氢－4H－噻吩并[3,4-d)咪唑－2,4（1H)-二酮（7）,后者经格氏反应、脱水、还原、裂解环合一锅合成（3aR,8aS,8bS)－1,3－二苄基－2－氧代十氢咪唑[3,4-d]噻吩并[1,2-a]锍翁溴化物（11）,继而经缩合、开环、水解、脱羧、脱苄而得d－生物素（1）,总收率为14．5％。     

Oligometallic template strategy for ring-closing olefin metathesis: highly cis- and trans-selective synthesis of a 32-membered macrocyclic tetraoxime

An oligometallic template effect was observed on the cis/trans selectivity of a 32-membered macrocyclic tetraoxime in ring-closing olefin metathesis of an acyclic diallyl derivative H4L; the metathesis of heterotrinuclear complex LZn2M (M=Ca2+, La3+) afforded the cis isomer, whereas uncomplexed H4L gave the trans isomer.     

Selection of the cis and trans phosph(III)azane macrocycles [{P(mu-NtBu)}2(1-Y-2-NH-C6H4)]2(Y=O, S)

The 1 : 1 reactions of [ClP(mu-NtBu)]2 with the difunctional aromatic amines 1,2-1-YH-2-NH2-C6H4 in the presence of Et3N give the dimeric phosph(III)azane macrocycles [{P(mu-NtBu)2(1-Y-2-HN-C6H4)]2, predominantly as the cis isomer in the case of Y=O (1.cis) and as the trans isomer for Y=S (2.trans). Model M.O. calculations suggest that the selection of the cis and trans isomers is not thermodynamically controlled. The alternative isomers 1.trans and 2.cis are generated exclusively by the deprotonation of the model intermediates [(1-Y-2-NH2-C6H4)P(mu-NtBu)]2[Y=O (3), S (4)] with nBuLi followed by cyclisation with [ClP(mu-NtBu)]2. The solid-state structures of 1.cis/trans(50 : 50), 2.cis, 3 and 4 are reported.     

PHOTOREGULATION OF α-CHYMOTRYPSIN ACTIVITY BY ISOMERIZABLE INHIBITORS. STUDY OF THE ACTION MECHANISM*

Abstract— The N- p -phenylazophenyl-N-phenylcarbamyl chloride (PAPC) in its cis form is five times more active as inhibitor of α-chymotrypsin than in the trans form. In the present work, derivatives of PAPC have been synthesized. Each of these new compounds is photoisomerizable and is an inhibitor (in the cis and in the trans form) of α-chymotrypsin. The cis isomer is always more active than the trans. The m -methyl derivative is 17.5 times more active in the cis form than in the trans , whereas, for the para -substituted compound, this ratio is only 3.5.
Several hypotheses can explain this difference of activity between the cis and trans isomers: (1) steric hindrance towards the trans isomer, (2) lower affinity of the enzyme for the trans isomer, (3) higher reactivity of the complex formed between the enzyme and the cis form of the inhibitor. These hypotheses are discussed.     

The Structure of 2,4-Diorganyl-2,4-Dithioxo-1,3,2λ5,4λ5-Dithiadiphosphetanes in Solution

Abstract

Compounds of the overall composition RPS₂, so called perthiophosphonic acid anhydrides, prefer a dimeric structure in szlution, as it has already been known for the solid compounds. Following compounds [RP(S)S]₂ with R=methyl, ethyl, propyl, isopropyl, butyl, tert-butyl, cyclohexyl, phenyl, 4-methoxy-phenyl and 3,5-dimethyl-piienyl were prepared and characterized by iJJR spectroscopy. The 3,5-ditert-butyl-4-hydroxy-phenyl-compound [1] was also investigated. NHR investigations give evidence for the existence of conligurational isomers of the 2,4-Diorganyl-2,4-dithi-oxo-1,3,2λ⁵,4λ⁵-dithiadiphosphetanes. In solutions an equllibrium between cis and trans isomers is established. The concentration of the two isomers depends on the kind of P and the solvent used. In general the trans isomer has a nigher concentration than the cis isomer. The easy preparation of unsymmetrical compounds by mixing solutions of compounds with different R shows a continous dissociation and association process of the PSPS-ring. This result underlines the existence of a monomeric compound of low concentration as intermediate. An interesting result is obtained for the isopropyl compound. After dissolving e.g. in CDC1₃ almost 90% of the compound is transformed into the other isomer. The progress of the transformation can be followed by NXR spectroscopy. In all other cases the equilibrium state is immediately achieved after preparation of the solution.     

Transition-state effects in acid-catalyzed aryl epoxide hydrolyses

The hydronium ion-catalyzed hydrolyses of 5-methoxyindene 1,2-oxide and of 6-methoxy-1,2,3,4-tetrohydronaphthalene-1,2-epoxide were each found to yield 75-80% of cis diol and only 20-25% of trans diol as hydrolysis products. The relative stabilities of the cis and trans diols in each system were determined by treating either cis or trans diols with perchloric acid in water solutions and following the approach to an equilibrium cis/trans mixture as a function of time. These studies establish that the trans diol in each system is more stable than the corresponding cis diol. Thus, acid-catalyzed hydrolysis of each epoxide, which proceeds via a carbocation intermediate, yields the less stable cis diol as the major product. Transition-state effects, presumably of a hydrogen-bonding nature, selectively stabilize the transition state for attack of water on the intermediate 2-hydroxy-1-indanyl carbocation leading to the less stable cis diol in this system. Transition-state effects must also be responsible for formation of the less stable cis diol as the major product in the acid-catalyzed hydrolysis of 5-methoxy-1,2,3,4-tetrahydronaphthalene 1,2-epoxide. However, in this system steric effects at the transition state may be more important than hydrogen bonding in determining the cis/trans diol product ratio. The synthesis of 5-methoxyindene 1,2-oxide and a study of its rate of reaction as a function of pH in water and dioxane-water solutions are reported. Both an acid-catalyzed reaction leading to only diol products and a pH-independent reaction yielding 71% of 5-methoxy-2-indanone and 29% of diols are observed; the half-life of its pH-independent reaction in water is only 2.4 s.     

New trans/cis tetrahydroisoquinolines. 2. trans‐ and cis‐3‐(1‐methyl‐1h‐pyrrol‐2‐yl)‐1‐(2H)‐oxo‐2‐phenethyl‐1,2,3,4‐tetrahydroisoquino‐lin‐4‐carboxylic acids and subsequent transformations

Stereochemical course of the reaction of homophthalic anhydride and N‐(1‐methyl‐1H‐pyrrol‐2‐yl‐methylidene)‐phenethylamine was studied. Mixtures of the expected trans‐ and cis‐1,2,3,4‐tetrahydroiso‐quinoline‐4‐carboxylic acids trans‐ 4 and cis‐ 4 were obtained along with by‐products 5 and 6 . The ratios of all products and the diastereomers, obtained under different reaction conditions, were established by pmr. THF as a solvent and ultrasonic treatment are applied for the first time in the reaction of this type. The reaction was made diastereoselective towards any isomer. The carboxylic group of trans‐ 4 was transformed in four steps into various cyclic amino‐methyl groups yielding numerous new tetrahydroisoquinolinones trans‐ 10a‐i incorporating a given fragment of pharmacological interest. Reduction of 10a‐i was studied.     

Theoretical study of the mechanism of NO2 production from NO + ClO

The reaction of NO with ClO has been studied theoretically using density-functional and wave function methods (B3LYP and CCSD(T)). Although a barrier for cis and trans additions could be located at the RCCSD(T) and UCCSD(T) levels, no barrier exists at the B3LYP/6-311+G(d) level. Variational transition state theory on a CASPT2(12,12)/ANO-L//B3LYP/6-311+G(d) surface was used to calculate the rate constants for addition. The rate constant for cis addition was faster than that for trans addition (cis:trans 1:0.76 at 298 K). The rate constant data summed for cis and trans addition in the range 200-1000 K were fit to a temperature-dependent rate in the form kdi) = 3.30 x 10(-13)T(0.558) exp(305/T) cm3.molecule(-1).s(-1), which is in good agreement with experiment. When the data are fit to an Arrhenius plot in the range 200-400 K, an activation barrier of -0.35 kcal/mol is obtained. The formation of ClNO2 from ONOCl has a much higher activation enthalpy from the trans isomer compared to the cis isomer. In fact, the preferred decomposition pathway from trans-ONOCl to NO2 + Cl is predicted to go through the cis-ONOCl intermediate. The trans --> cis isomerization rate constant is kiso = 1.92 x 10(13) exp(-4730/T) s(-1) using transition state theory.