Use of the electrophilic c-arylation by aryllead triacetates in the construction of synthons for aizoaceae and amaryllidaceae alkaloid synthesis

The vinylogous β-keto esters, ethyl 2-methyl-4-oxocyclohex-2-ene-carboxylate (Hagemann's Ester) (4), ethyl 4-oxocyclohex-1-ene-carboxylate (7a) and its double bond isomer (7b), undergo regiospecific arylation with aryllead triacetates at C1; reaction of the mixture of isomers (7a) and (7b) with aryllead compounds (5a), (5c) and (5d) provides intermediates for the synthesis of (±)-o-methyl-joubertiamine (1), (±)-mesembrine (2) and (±)?lycoramine (3) respectively.     

Diazonamide support studies: stereoselective formation of the C10 chiral center in both the CDEFG and AEFG fragments

The synthesis of both the AEFG macrolactam and the CDEFG bis-indole/tyrosine units found in the marine natural product diazonamide A is presented. Key to the success of the synthesis is the highly stereoselective direct C-arylation of an oxindole by an aryllead(IV) reagent derived from tyrosine.     

The α-arylation of derivatives of malonic acid with aryllead triacetates. New syntheses of ibuprofen and phenobarbital.

Derivatives of Meldrum's acid and the sodium salts of substituted malonic esters undergo rapid arylation in high yield when treated with aryllead triacetates. These reactions have been applied to the synthesis of ibuprofen, an analgesic, and in a closely related reaction 5-ethylbarbituric acid has been reacted with phenyllead triacetate to give phenobarbital.     

The arylation of nitroalkanes and nitronate salts with aryllead triacetates

Nitroalkanes and their nitronate salts undergo α-arylation in good yield when treated with an aryllead triacetate in dimethyl sulfoxide.     

Reactions of diborane with organic derivatives of tin and lead

Diborane reacts with aryltin and aryllead compounds to give intermediates which on hydrolysis give arylboronic and arylborinic acids, and on oxidation give phenols.     

Asymmetric carbon-carbon coupling of phenols or anilines with aryllead triacetates

The asymmetric coupling of various phenol or aniline derivatives with bulky aryllead triacetates was thoroughly investigated using optically active amines, including strychnine and brucine. We found that conformationally restricted tertiary amines, as well as lithium aryloxides and molecular sieves, are essential for accelerating the rate of phenol coupling. Consequently, the reaction can be carried out at a low temperature (-40 to -20 degrees C) and gives a high degree of diastereo- and enantioselectivity. In contrast to the effectiveness of lithiation in phenol coupling, magnesation of anilines was a critical technique for aniline coupling with aryllead triacetates. Using these coupling methods, a diverse set of di-, tri, and polyaryl compounds with axial chirality can be easily obtained, and these should be useful for the construction of a variety of aryl-aryl frameworks involved in metal ligands, natural products, and artificial helical polymers.     

Reductive coupling of polyfunctionalized organobismuth and organolead arylating reagents in the synthesis of benzopyran derivatives

Benzopyran derivatives were synthesized in good yields by the reactions of tris[2-(chloromethyl)phenyl]bismuth diacetate and 2-(halomethyl)aryllead triacetates with phenols and naturally occurring 4-hydroxycoumarins in the presence of bases according to a three-step one-pot procedure. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 11, pp. 2520–2529, November, 2005.     

First total synthesis of the 7,3'-linked naphthylisoquinoline alkaloid ancistrocladidine

[structure: see text] The first total synthesis of the rare 7,3'-linked naphthylisoquinoline alkaloid, ancistrocladidine, has been completed. The key feature of the synthesis is the formation of the extremely hindered biaryl linkage by Pinhey-Barton ortho-arylation of a naphthol with an aryllead triacetate. The biaryl aldehyde formed is elaborated in 10 steps to form a 1:1 mixture of ancistrocladidine and its atropisomer. Recrystallization of the mixture afforded ancistrocladidine, which was identical in all respects to the reported data.     

Carbanion stabilization by distal silyloxy groups. Origin of the high diastereoselectivity in the formation of quaternary centers with aryllead(IV) triacetate reagents

Derivatives of methyl 5-hydroxy-2-oxo-1-cyclohexanecarboxylate react with aryllead(IV) reagents in high yield and with wide variation in diastereoselectivity. Ab initio calculations are consistent with a heretofore unrecognized attraction between the carbanionic center of the beta-ketoester intermediate and the distal OSiR(3) group. This attractive interaction stabilizes the silyl group in the axial conformation and leads to the excellent trans diastereoselection in the formation of quaternary centers. [reaction: see text]     

Cascade synthesis of polyoxygenated 6H,11H-[2]benzopyrano-[4,3-c][1]benzopyran-11-ones

2-(methoxymethoxymethyl)aryllead triacetates, obtained in situ from the corresponding arylboronic acids, reacted with 4-hydroxycoumarins, leading to 3-(2-methoxymethoxymethyl)aryl-4-hydroxycoumarin derivatives in good to high yields. These compounds underwent a cascade sequence of reactions, deprotection-halogenation-annulation, to afford polyoxygenated tetracyclic 6H,11H-[2]benzopyrano-[4,3-c] [1]benzopyran-11-ones in good yields. Some compounds showed a moderate cytotoxicity against human epithelial mammary HBL100 cells.     

Total synthesis of the 7,3'-linked naphthylisoquinoline alkaloid ancistrocladidine

The first total synthesis of ancistrocladidine, a rare 7,3'-linked naphthylisoquinoline alkaloid, has been completed, with the key feature of the synthesis being the formation of the extremely hindered biaryl linkage by ortho-arylation of a naphthol with an aryllead triacetate. Initial efforts were focused on the generation of a heteroaryl lead species, which would have allowed a convergent synthesis to be developed. However, it was not possible to generate such a lead species. A simpler aryl lead triacetate was prepared and reacted. The resulting biaryl aldehyde was elaborated in 10 steps to form a 1:1 mixture of ancistrocladidine and its atropisomer. Recrystallization of the mixture afforded ancistrocladidine, which was identical in all respects to the reported data.     

Complete N-1 regiocontrol in the formation of N-arylimidazoles. Synthesis of the active site His-Tyr side chain coupled dipeptide of cytochrome c oxidase

Under catalysis by copper(II) acetate, complete regiocontrol (N-1 versus N-3) was obtained in the arylation of substituted imidazoles with aryllead(IV) reagents. The mildness of the reaction conditions (rt, no added base) allows for the first synthesis of the histidine-tyrosine side chain coupled dipeptide found in the active site of cytochrome c oxidase.     

Welwistatin support studies: expansion and limitation of aryllead(IV) coupling reactions

Recent support studies on the total synthesis of the welwistatin system are described. The target step involves lead-mediated arylation of sterically demanding aryl groups and carbon acid coupling partners in order to establish the highly congested tetracyclic core structure. Type 7 beta-ketoesters and beta-ketonitriles were successfully arylated with a variety of ortho- and meta-substituted aryllead compounds generated by a halogen-boron-lead exchange sequence. The enolates of compounds 15, 19, and 25, each bearing all-carbon quaternary centers adjacent to the arylation site, failed to couple.     

Stereoselective synthesis of 3a,7a-dihydro-3H,4H-furo[3,4-c]pyran-1-ones via intramolecular hetero-Diels-Alder reaction

The synthesis of 3a,7a-dihydro-3H,4H-furo[3,4-c]pyran-1-ones via an intramolecular hetero-Diels-Alder reaction of easily accessible α,β-unsaturated γ-ketoesters was investigated. The reaction was found to proceed in a highly stereoselective way leading to single, cis-configured product isomers. The same diastereomer is formed, independently of the configuration of the enone double bond of the precursor. The respective E- and Z-isomers react either through an endo-E-syn or an exo-Z-syn transition state.     

A generalised friction model for the evaluation of angular momentum auto correlation functions

A theory of brownian motion where the friction coefficient is a finite correlation function of molecular torque is used to derive an expression for the angular velocity autocorrelation function, ψ(r). This is related to the orientational a.c.f., φ(t), using an analysis of bandshapes due to Kubo and extended by Shimizu. Both functions φ(t) and ψ(t) contain inherent weaknesses since ψ(t) has a MacLaurin expansion even up to t⁴ only, and π(t) does not reduce to the Kummer function for an ensemble of free rotors in the so-called limit of vanishing friction. Reasons for this behaviour are discussed.     

Synthesis of an O-acyl isopeptide by using native chemical ligation to efficiently construct a hydrophobic polypeptide

By using dimethylformamide to suppress the O-to-N acyl migration, we efficiently synthesized an O-acyl isopeptide by native chemical ligation of a peptide-thioester and a Cys-O-acyl isopeptide. The reaction mixture was then loaded onto an octadecylsilane reverse-phase HPLC column, and the isopeptide was purified by using a linear gradient of CH₃CN in 0.1% aqueous trifluoroacetic acid. The recovery rate of the O-acyl isopeptide was considerably higher than that of the corresponding native polypeptide. Synthesis of O-acyl isopeptides via native chemical ligation, with O-to-N acyl migration as the final step to give the native form, has potential as an efficient method of constructing hydrophobic polypeptides.     

Asymmetric synthesis of β-substituted Baylis-Hillman products via lithium amide conjugate addition

A three-step protocol for the asymmetric synthesis of a range of β-substituted Baylis-Hillman products has been developed. This procedure involves the diastereoselective conjugate addition of lithium (R)-N-methyl-N-(α-methylbenzyl)amide to an α,β-unsaturated ester to generate an N-protected β-amino ester in high de. Subsequent asymmetric aldol reaction via deprotonation with LDA, transmetallation with B(OMe)₃ and addition of an aldehyde gives a range of syn-aldol products in moderate to high de. Purification of the syn-aldol products to homogeneity followed by tandem N-oxidation and Cope elimination gives the desired β-substituted Baylis-Hillman products in good yield and high de and ee.     

H-Phosphonate oligonucleotides from phosphoramidite chemistry

A novel phosphoramidite methodology allowing the formation of H-phosphonate oligonucleotides was employed to introduce backbone modifications into oligonucleotides. Novel N,N-diisopropylamino-para-methoxybenzylphosphoramidites were prepared and used in a two-step synthesis cycle during the elongation process. The coupling step was directly followed by an acidic treatment performing concomitant deprotection and phosphite deprotection through an Arbuzov reaction to yield an H-phosphonate linkage.     

Time-dependent perturbation: a recursive generation of the transition amplitudes between bound states

We present a new expansion of the solution to the time-dependent Schrödinger equation it ∂U/∂t = {H₀ + V(t)}U. A complete set of eigenvectors of H₀ spanning the Hilbert space in which H₀ and V operate is partitioned in two subsets. Transition amplitudes from the first subspace to the second one are calculated by building an adequate series of intermediate representations with respect to the couplings which produce the transition from the model space into its orthogonal complement. These expansions yield a coupling matrix series V⁽ⁿ⁾ for which an iterative solution V⁽ⁿ⁾ → V⁽ⁿ⁺¹⁾ is derived. This solution leads to a recursive numerical treatment of the calculation of transition amplitudes. A simple example, concerning a harmonic oscillator under an intense laser field, is considered using a Fourier analysis of the perturbation.     

Electrochemically driven stereoselective approach to syn-1,2-diol derivatives from vinylarenes and DMF

We have developed an electrochemically driven strategy for the stereoselective synthesis of protected syn-1,2-diols from vinylarenes with N,N-dimethylformamide (DMF). The newly developed system obviates the need for transition metal catalysts or external oxidizing agents, thus providing an operationally simple and efficient route to an array of protected syn-1,2-diols in a single step. This reaction proceeds via an electrooxidation of olefin, followed by a nucleophilic attack of DMF. Subsequent oxidation and nucleophilic capture of the generated carbocation with a trifluoroacetate ion is proposed, which gives rise predominantly to a syn-diastereoselectivity upon the second nucleophilic attack of DMF.

An electrochemical method that provides an operationally simple synthesis of masked syn-1,2-diols from styrenes and DMF has reported. The TFA ion is engaged in the formation of a key intermediate, which gives rise predominantly to syn-selectivity.