Kinetic studies on the thermal cis-trans isomerization of 1, 3-diphenyltriazene in aqueous solution. Effects Of acids and bases

The thermal cis-to-trans isomerization of 1,3-diphenyltriazene (DPT) has been investigated in buffered aqueous solutions by means of laser-flash photolysis techniques. The cis-to-trans isomerization process is found to be catalyzed by general acids and general bases as a result of acid/base-promoted 1,3-prototropic rearrangements. Acid catalysis is attributed to rate-limiting proton transfer to the nitrogen-nitrogen double bond of cis-DPT, whereas base catalysis is attributed to rate-limiting base-promoted ionization of the amino nitrogen of cis-DPT leading to the isomerization. In addition, a process ascribed to the interconversion of cis rotamers through hindered rotation around the nitrogen-nitrogen single bond is also observed; at high pH this process becomes rate-limiting.     

Binap-gold(I) versus Binap-silver trifluoroacetate complexes as catalysts in 1,3-dipolar cycloadditions of azomethine ylides

The 1,3-dipolar cycloaddition between azomethine ylides and alkenes is efficiently catalysed by [{(S(a))-Binap-Au(tfa)}(2)] (Binap=2,2'-bis(diphenylphosphino)-1,1'-binaphthyl; tfa=trifluoroacetyl). Maleimides, 1,2-bis(phenylsulfonyl)ethylene, chalcone and nitrostyrene were suitable dipolarophiles even when using sterically hindered 1,3-dipole precursors. The results obtained in these transformations improve the analogous ones obtained in the same reactions catalysed by [Binap-Ag(tfa)]. In addition, computational studies have also been carried out to demonstrate both the high enantioselectivity exhibited by the chiral gold(I) complex, and the non-linear effect observed in this transformation.     

Sterically hindered 1,3-diketones in the Michael reaction

The base catalyzed addition of sterically hindered 1,3-diketones to the activated multiple bond of ethyl acrylate and 4-methyl-4-methoxy-1-phenylpent-2-yne-1-one has been studied. The addition of methyl(2-propenyl)ketone is partially accompanied by intramolecular cyclization of the resulting adduct.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 1, pp. 147–149, January, 1996.     

Facile ketene-ketene and ketene-ketenimine rearrangements: a study of the 1,3-migration of alpha-substituents interconverting alpha-imidoylketenes and alpha-oxoketenimines, a pseudopericyclic reaction

Theoretical calculations (B3LYP/6-311+G(3df,2p)//B3LYP/6-31G) of the 1,3 migration of NR(2) transforming alpha-oxoketenimines 1 to alpha-imidoylketenes 3 and vice versa indicate that this process is a pseudo-pericyclic reaction with a low activation energy (NH(2) 97 kJ mol(-1), N(CH3)(2) 62 kJ mol(-1)). The oxoketenimines were found to be more stable (by 18-35 kJ mol(-1)) which is in line with experimental observations. The hindered amine rotation in the amide and amidine moieties adjacent to the cumulenes are important in the migration of the NR(2) group, as one of the rotation transition states is close to the 1,3 migration pathway. This gives an interesting potential energy surface with a valley-ridge inflection (VRI) between the orthogonal hindered amine rotation and 1,3 migration transition states. The imidoylketene may also undergo ring closure to an azetinone 5; however, this is metastable, and under the conditions that allow the 1,3-migration, the oxoketenimine 1 will be favored. The imine NH E/Z-interconversion of the ketenimine group takes place by inversion and has a low activation barrier ( approximately 40 kJ mol(-1)). In all the amidines examined the E/Z-interconversion of the imine function was predicted to be by rotation with a high barrier (>80 kJ mol(-1)), in contrast to all other reported imine E/Z-interconversions which are by inversion.     

Substituent effects on the thermal cis-to-trans isomerization of 1,3-diphenyltriazenes in aqueous solution

The thermal cis-to-trans isomerization of some symmetrically p,p'-disubstituted 1,3-diphenyltriazenes has been studied by means of laser-flash photolysis techniques. The geometric isomerization is catalyzed by general acids and general bases as a result of acid/base-promoted 1,3-prototropic rearrangements. Acid catalysis becomes more prominent as the electron-donating character of the para substituent increases, while base catalysis becomes more important as the electron-withdrawing character of the para substituent increases. In addition, the rate ascribed to the interconversion of neutral cis rotamers through hindered rotation around the nitrogen-nitrogen single bond is found to decrease as the electron-withdrawing character of the para substituent increases. Rates of interconversion of neutral cis rotamers are also found to decrease with decreasing solvent polarity, which is indicative of the involvement of a polar transition state. On the other hand, kinetic investigations of the acid-catalyzed decomposition of target triazenes are consistent with an A1 mechanism.     

In situ generated rhodium‐based catalyst for addition of phenylboronic acid to aldehydes

New 1,3‐dialkylperhydrobenzimidazolinium and 1,3‐dialkylimidazolinium salts ( 2,4 ) as NHC precursors have been synthesized and characterized. These salts in combination with [RhCl(COD)]₂ provided active catalysts for the addition of phenylboronic acid to aldehydes under mild conditions. The in situ prepared three‐component system [RhCl(COD)]₂/imidazolinium salts ( 2,4 ) and KOBu^t catalyse the addition of phenylboronic acid to sterically hindered aldehydes affording the corresponding arylated secondary alcohols in good yields. © 2005 Wiley Periodicals, Inc. Heteroatom Chem 16:461–465, 2005; Published online in Wiley InterScience ( www.interscience.wiley.com ). DOI 10.1002/hc.20132     

Domino reaction of 1,3-bis(trimethylsilyloxy)-1,3-dienes with oxalyl chloride: general and stereoselective synthesis of gamma-alkylidenebutenolides

The Lewis acid catalyzed cyclization of oxalyl chloride with 1,3-bis(trimethylsilyloxy)-1,3-dienes 3, derived from 1,3-dicarbonyl compounds 1, provides a new and general approach for the synthesis of gamma-alkylidenebutenolides 4, a pharmacologically and synthetically important class of substances. A variety of butenolides were efficiently prepared in good yields and with very good regio- and stereoselectivities. An up-scaling of the reaction was possible. The use of the Lewis acid trimethylsilyl-trifluoromethanesulfonate (TMSOTf) proved to be superior to other activation conditions. Sterically undemanding gamma-alkylidenebutenolides could be prepared alternatively by reaction of the corresponding 1,3-dicarbonyl dianions with N,N'-dimethoxy-N,N'-dimethylethanediamide (2d). In contrast to the dianion method, the Lewis acid catalyzed reaction also facilitated the cyclization of sterically hindered, base-labile, cyclic and functionalized substrates. From a methodology viewpoint, the dianion reaction represents the first cyclization of a bis-Weinreb amide and the first cyclization of an oxalic acid-synthon with an ambident dianion. The TMSOTf-catalyzed reactions are both the first cyclizations of 1,3bis(trimethylsilyloxy)-1,3-dienes with a C2 dielectrophile and the first cyclizations of 1,3-bis(trimethylsilyloxy)-1,3-dienes with a carboxylic acid dichloride or a related dielectrophile.     

Improved synthesis of tertiary alcohols from reactions of organoboranes with 2-lithio-1,3-benzodithioles

Treatment of trialkylboranes with 2-lithio-1,3-benzodithioles and then mercuric chloride (or methyl fluorosulhonate) followed by oxidation gives tertiary alcohols in high yields. The method is applicable to reactions of hindered organoboranes that fail using 1-lithio-1,1-bis(phenylthio)alkanes.     

Revisiting [3 + 3] route to 1,3-cyclohexanedione frameworks: hidden aspect of thermodynamically controlled enolates.

We have revisited the traditional consecutive Michael-Claisen [3 + 3] process (MC-[3 + 3]) promising the synthesis of a cyclohexane-1,3-dione derivatives from nonactivated simple ketones and enoates and evaluated its potential in modern organic synthesis. Twenty to thirty examples were demonstrated to be effective. The reactions exhibited remarkable regioselectivity with the Michael addition proceeding through nucleophilic attack by the more hindered site of the ketones without exception. The subsequent Claisen condensation resulted in the formation of carbon-carbon bonds between less hindered site of the ketones and acyl carbon of the enoates. The MC-[3 + 3] process described is useful for the synthesis of Taxol A-ring synthons in multigram quantities and for the synthesis of other six-membered carbocyclic compounds. A number of control experiments have been conducted to provide strong support for the mechanism of this MC-[3 + 3].     

A new route to hindered tertiary amines

The Rh(2)(OAc)(4)-stabilized carbenoid derived from dimethyl diazomalonate has been found to insert into the N-H bond of sterically hindered secondary aliphatic amines to afford hindered tertiary aliphatic amines in quite satisfactory yields. For example dimethyl 2-(dicyclohexylamino)propanedioate was formed in 85% yield from dicyclohexylamine, and the severely hindered dimethyl 2-(2,2,6,6-tetramethyl-1-piperidinyl)propanedioate was formed in 38% yield from 2,2,6,6-tetramethylpiperidine. The Rh(2)(OAc)(4) - dimethyl diazomalonate reaction was found to work also for arylalkylamines and diarylamines. In these cases, small amounts of products resulting from formal insertion of the carbenoid into an aromatic C-H bond were detected. Substitution at ortho positions caused the yield of C-H insertion products to increase. Other diazo compounds, viz. ethyl diazoacetoacetate, 2-diazocyclohexane-1,3-dione, and 2-diazo-5,5-dimethylcyclohexane-1,3-dione, performed satisfactorily in Rh(2)(OAc)(4)-catalyzed reactions with arylalkylamines and diarylamines, but led to complicated reaction mixtures with dialkylamines.     

1,3-dithiolanes from cycloadditions of alicyclic and aliphatic thiocarbonyl ylides with thiones: regioselectivity

The regiochemistry of 1,3-dithiolanes obtained from thiocarbonyl ylides 9 and thiones 10 shows a striking dependence on substituents. Previously and newly performed experiments indicate that sterically hindered cycloalkanethione S-methylides and dialkylthioketone S-methylides react with alicyclic and aliphatic thiones to give the 2,2,4,4-tetrasubstituted 1,3-dithiolanes 11 exclusively. Aryl groups in one or both reactants lead to a preference for, or even complete formation of, 4,4,5,5-tetrasubstituted 1,3-dithiolanes 12. Several mechanisms appear to be involved, but the paucity of experimental criteria is troubling. Quantum-chemical calculations (see preceding paper) on the cycloaddition between thioacetone S-methylide and thioacetone furnish lower activation energies for the concerted process than for the two-step pathways via C,S- or C,C-biradicals; the favoring of the 2,4-substituted 1,3-dithiolanes over the 4,5-substituted type would be expected to increase with growing bulk of substituents. Aryl groups stabilize intermediate biradicals. Experimental criteria for the differentiation of regioisomeric dithiolanes are discussed. Thiocarbonyl ylides 9 are prepared by 1,3-cycloadditions between diazomethane and thioketones and subsequent N(2) elimination from the usually isolable 2,5-dihydro-1,3,4-thiadiazoles 17; different ratios of the two rate constants lead to divergent product formation scenarios.     

An ortho‐lithiated derivative of protected phenylboronic acid: an approach to ortho‐functionalized arylboronic acids and 1,3‐dihydro‐1‐hydroxybenzo[c][2,1]oxaboroles

2‐(2′‐Bromophenyl)‐6‐butyl‐[1,3,6,2]dioxazaborocan, prepared readily by the esterification of 2‐bromophenylboronic acid with N‐butyldiethanolamine (BDEA), undergoes Br/Li exchange using BuLi/THF at ? 78 °C. A resulting intermediate proved useful in synthesis of various ortho‐functionalized arylboronic acids. Specifically, reactions with benzaldehydes provide a convenient access to 1,3‐dihydro‐1‐hydroxy‐3‐arylbenzo[c][2,1]oxaboroles that exhibit a remarkably high rotational barrier around the C? aryl bond. In addition, the molecular structure of sterically hindered 1,3‐dihydro‐1‐hydroxy‐3‐(2′, 6′‐dimethoxyphenyl)benzo[c][2,1]oxaborole is reported. Copyright © 2007 John Wiley & Sons, Ltd.     

Functionalizations of Mixtures of Regioisomeric Aryllithium Compounds by Selective Trapping with Dichlorozirconocene

The reaction of mixtures of aryllithium regioisomers obtained either by directed lithiation or by Br/Li exchange with substoichiometric amounts of Cp₂ZrCl₂ proceeds with high regioselectivity. The least sterically hindered regioisomeric aryllithium is selectively transmetalated to the corresponding arylzirconium species leaving the more hindered aryllithium ready for various reactions with electrophiles. As an application, these regioselective transmetalations from Li to Zr were used to prepare all three lithiated regioisomers of 1,3‐bis(trifluoromethyl)benzene.     

Stereoselective Diels–Alder reactions of 3-phosphonopropenoyl derivatives of 1,3-oxazolidin-2-ones

Dienophiles of the general structure (EtO)₂P(O)CHCHCOX have been prepared, where X represents an oxazolidinone chiral auxiliary. Use of the (S)-4-isopropyl-5,5-diphenyl-1,3-oxazolidin-2-one auxiliary gave Diels–Alder adducts with several cyclic and acyclic dienes. The crystal structures of the main cyclohexa-1,3-diene and 2,3-dimethylbutadiene adducts formed during reactions in the presence of dialkylaluminium halides are consistent with a reaction, which is stereoselectively endo with respect to the carbonyl group and occurs on the less hindered face of the dienophile when aluminium is chelated between the two carbonyl groups.     

E stereoregular 1,1 and 1,3 constitutional units from 1,3-butadiene in copolymerizations catalyzed by a highly hindered c(2) symmetric metallocene

Unprecedented 1,1 and 1,3 constitutional units from 1,3-butadiene, both presenting only the E configuration of the double bond, have been achieved by copolymerization with ethene, conducted at high temperature and low ethene concentration, when catalyzed by a highly hindered C(2) symmetric metallocene. Ethene/butadiene copolymerizations by this catalyst generally lead to prevailing methylene-1,2-cyclopropane units from butadiene. Polymer microstructures obtained for different comonomer concentrations clearly indicate that the rate-determining step leading to cyclopropanation involves ethene, while that leading to 1,1 and 1,3 constitutional units does not. A general copolymerization scheme and a molecular modeling study of the cyclopropanation reaction are presented. Molecular modeling also indicates that the E stereoselectivity for 1,1 and 1,3 constitutional units can be rationalized, in the assumption that an allyl isomerization of the terminal of the growing chain would occur.     

Research on Au(I)-catalyzed ene-yne cycloisomerization for construction of quassinoid scaffold

Compounds that undergo Au(I)-catalyzed cycloisomerizations affording tetracyclic products that can be converted into compounds with the skeleton of bruceantin are described. The Au(I)-catalyzed cycloisomerizations reported herein are hindered by a 1,3-diaxial interaction between the substituent and the methyl group in the transition state. The use of small substituents was found to increase the yield of the desired product, while the reaction of substrates with large substituents afford undesired constitutional isomers.     

Unusual Facial Selectivity in the Cycloaddition of Singlet Oxygen to a Simple Cyclic Diene(1)

Syntheses of 5-isopropyl-1,3-cyclohexadiene and syn-5-isopropyl-2,3-dioxabicyclo[2.2.2]octane, by routes that would allow completely diastereoselective introduction of deuterium labels, are described. The reaction of the isopropyl cyclohexadiene with singlet oxygen is shown to give an endoperoxide that is derived by preferential attack on the more sterically hindered face of the diene. A possible mechanistic explanation of this result is that the attack from the less hindered face leads to "ene" reaction rather than endoperoxide formation. However, this mechanism would require that the "ene" reaction and cycloaddition proceed via a common intermediate-presumably a perepoxide.     

3-Neopentylallyllithium II. Reactions in hydrocarbon media

Product distributions are reported for several reactions in hydrocarbon solvent of 3-neopentylallyllithium, the 1,4-addition product of tert-butyllithium and 1,3-butadiene. Protolysis with several agents yields predominately the “normal” products [(Ia) and (Ib)] with less than 6% of the terminal olefin observed. The ratio of the cis/trans isomers [(Ia) and (Ib)] parallels the ratio of the lithiated forms before protolysis. Reaction with chlorotrimethylsilane also shows no “rearranged” product. Carboxylation and ketone addition reactions, however, proceed with marked rearrangement unless the ketone is very hindered. Di-tert-butyl ketone and benzophenone give no rearranged product. Addition of a second mole of butadiene also results in predominant (60%) rearrangement of the neopentylallyl group. Bromination with molecular bromine and 1,2-dibromoethane yields a mixture of dibromo-derivatives in the former case and C₁₆-diolefin coupling products in the later case. Tentative mechanisms for protolysis and addition reactions are discussed.     

Synthesis of the western half of breviones C, D, F and G

The enantioselective synthesis of the diterpenic moiety in the abeo-breviano skeleton is reported. The synthesis is carried out starting from 2-methyl-1,3-cyclohexanedione and EVK in eleven steps following a ring-expansion strategy once the tricyclic perhydrophenantrene skeleton has been obtained. A new Tiffeneau-Demjanov rearrangement under dark conditions is reported in which the insertion of the new methylene group is directed towards the most hindered side of the carbonyl group. This result is new and opposite to those reported in the literature under light (filtered or un-filtered wavelengths) conditions where insertion in the less hindered side is usually preferred.     

[2 + 3]‐Cycloadditions of Phosphonodithioformate S‐Methanides with CS,NN,and CC Dipolarophiles

The reaction of the methyl (dialkoxyphosphinyl)‐dithioformates (= methyl dialkoxyphosphinecarbodithioate 1‐oxides) 10 with CH₂N₂ at − 65° in THF yielded cycloadducts which eliminated N₂ between − 40 and − 35° to give the corresponding phosphonodithioformate S‐methanides ( =methylenesulfonium (dialkoxyoxidophosphino)(methylthio)methylides) 11 (Scheme 3). These reactive 1,3‐dipoles were intercepted by aromatic thioketones to yield 1,3‐dithiolanes. Whereas the reaction with thiobenzophenone ( 12b ) led to the sterically more congested isomers 15 regioselectively, a mixture of both regioisomers was obtained with 9H‐fluorene‐9‐thione ( 12a ). Trapping of 11 with phosphono‐ and sulfonodithioformates led exclusively to the sterically less hindered 1,3‐dithiolanes 16 and 18 , respectively (Scheme 4). In addition, reactive CC dipolarophiles such as ethenetetracarbonitrile, maleic anhydride, and N‐phenylmaleimide as well as the NN dipolarophile dimethyl diazenedicarboxylate were shown to be efficient interceptors of 11 (Scheme 5).