Volume 75, Issue 1

In connection with the de elopment of a practical synthesis of the right half, and its analog E7389, of halichondrin B, an efficient and scalable synthesis of the two major building blocks is reported. In addition, a new synthesis of the C20–C26 segment via a regiospecific and stereoselecti e S N 2' process is presented. A sulfonamide class of ligands is shown to be effective for asymmetric Ni/Cr-mediated reactions under both stoichiometric and catalytic conditions, and the X-ray structure reveals this class of ligands to be tridentate. On the basis of three X-ray structures, a possible mechanism is suggested for this process. Stable and crystalline Cr(III)/sulfonamide complexes are shown to be effective for catalytic Cr-mediated coupling reactions of allyl, alkenyl, and alkyl halides with aldehydes, and some examples for application of the stoichiometric and catalytic asymmetric processes are presented.

Electrophilic amination of Grignard reagents has been accomplished by using O -sulfonyloximes as amination reagents. Benzophenone O -sulfonyloxime derivatives react with Grignard reagents on sp 2 nitrogen, yielding primary amines by successive hydrolysis of the resulting N -alkylimines. Various cyclic imines are synthesized by Pd-catalyzed reaction from olefinic oxime derivatives. That is, treatment of O -pentafluorobenzoyloximes of olefinic ketones with a catalytic amount of Pd(PPh 3 ) 4 and triethylamine affords nitrogen-containing heterocycles, such as pyrroles, pyridines, isoquinolines, spiro-imines, and aza-azulenes. This reaction proceeds via the initial formation of alkylideneaminopalladium(II) species generated by oxidative addition of the oximes to the Pd(0) complex, and the following intramolecular amination on the olefinic moiety. Cyclic imines are prepared from γ,δ-unsaturated O -acetyloximes by treatment with acetic acid and 1,4-cyclohexadiene in the presence of a catalytic amount of 1,5-naphthalene-diol. γ,δ-Unsaturated ketone O -methoxycarbonyloximes are transformed to 2-bromomethyl-3,4 dihydro- 2H -pyrroles by the action of a catalytic amount of Cu(I) bromide dimethyl sulfide complex and lithium bromide.

Stereocontrolled total synthesis of (+)-vinblastine ( 1 ) has been achieved using a novel radical-mediated indole synthesis developed in our laboratories. The isothiocyanate 18 , prepared readily from quinoline 17 , underwent a facile addition of the malonate anion to give 19 . The o -alkenylthioanilide 19 was then converted to indole 20 by radical cyclization and protection. (−)-Vindoline ( 2 ) was prepared from this key intermediate 20 in a highly efficient manner. The indole core of the 11-membered intermediate 3 was constructed similarly from quinoline. The critical coupling reaction between 2 and the chloroindolenine derived from 3 proceeded with complete control of stereochemistry to give the desired product 66 in 97 % yield, which could be successfully converted to (+)-vinblastine ( 1 ).

tert -Butanesulfinamide is prepared using catalytic enantioselective methods in two steps from the extremely inexpensive oil waste by-product, tert -butyl disulfide. Direct condensation of tert -butanesulfinamide with aldehydes and ketones provides tert -butanesulfinyl imines in uniformly high yields. The tert -butanesulfinyl group activates the imines for the addition of many different classes of nucleophiles, serves as a powerful chiral directing group, and after nucleophilic addition is readily cleaved by treatment with acid. A wide range of highly enantioenriched amines, including α-branched and α,α-dibranched amines, α- and β-amino acids, 1,2 and 1,3-amino alcohols and α-trifluoromethyl amines are efficiently synthesized using this methodology.

The reactions of N -acyliminium ions with tethered π-bonds are among the most important methods for preparing complex nitrogen-containing heterocycles. Pummerer-based cyclizations are also finding widespread application in both carbo- and heterocyclic syntheses. As part of a program concerned with new methods for alkaloid synthesis, we became interested in using a linked Pummerer/ N -acyliminium ion cyclization sequence since we felt that this combination offers unique opportunities for the assemblage of complex target molecules. A synthetic method that combines transformations of different reaction types significantly broadens the scope of such procedures in synthetic chemistry. α-Thiocarbocations generated from the Pummerer reaction of β-phenylsulfinylmethyl-α,β-unsaturated amides can be intercepted by the adjacent amido group to produce transient amino- substituted furans, which undergo subsequent Diels-Alder cycloadditions. Using this domino amido-Pummerer/Diels-Alder cascade , we were able to assemble novel polycyclic systems in a single operation. The key step in the process involves the generation of a reactive N -acyliminium ion by fragmentation of an amino-substituted [4+2] cycloadduct. The successful synthesis of a number of alkaloids by this sequence of reactions reveals the usefulness and importance of this unique domino cascade.

A unified approach for the synthesis of the four major groups of C -aryl glycosides has been developed. The strategy incorporates two integrated approaches, the first of which features the [4+2] cycloaddition of a glycosyl furan with a substituted benzyne followed by the acid-catalyzed opening of the resultant adduct. The second route involves the sequential palladium-catalyzed opening of a benzyne-furan cycloadduct with an iodo glycal followed by oxidation of the resultant dihydronaphthol ring and reduction of the glycal moiety. The utility of this strategy has been established by a concise formal synthesis of the C -aryl glycoside antibiotic galtamycinone.

Stability constants and thermodynamic functions of metal complexes of crown ethers in various solvents published between 1971 and the beginning of 2000 have been critically evaluated. The most studied crown ethers have been selected: 1,4,7,10 tetraoxacyclododecane (12C4), 1,4,7,10,13 pentaoxacyclopentadecane (15C5), and 1,4,7,10,13,16 hexaoxacyclooctadecane (18C6). The metal ions chosen are: alkali and alkaline earth metal ions, Ag + , Tl + , Cd 2+ , and Pb 2+ . The solvents considered are: water, methanol, ethanol, and their mixtures, as well as acetonitrile, N , N' -dimethylformamide, dimethylsulfoxide, and propylene carbonate. The published data have been examined and grouped into two categories, “accepted” and “rejected”. The “accepted” values were considered as: (i) recommended ( R ), when the standard deviations (s.d.) on the constant K or on Δ r H were inferior to 0.05 lg unit or inferior to 1 kJ mol −1 , respectively; (ii) provisional ( P ), when s.d. is superior to 0.05 and inferior to 0.2 for lg K or s.d. is superior to 1 and inferior to 2 kJ mol −1 for Δ r H ; (iii) recommended 1 ( R1 ), if the values were obtained by a single research group, but were considered reliable in comparison with related systems, and considering that the research team usually presents R-level values for other similar systems.

In this paper, the chemical properties of the transactinide elements rutherfordium, Rf (element 104); dubnium, Db (element 105); and seaborgium, Sg (element 106) are critically reviewed. The experimental methods for performing rapid chemical separations on a time scale of seconds are reviewed, and comments are given on the special situation with the transactinides for which the chemistry has to be studied with single atoms. There follows a systematic description of theoretical predictions and experimental results on the chemistry of Rf, Db, and Sg - their mutual comparison and evaluation. The literature cited has the cutoff date of March 1999. The more recent chemical identification of bohrium, Bh (element 107), and of hassium, Hs (element 108), should be evaluated in a future Part II of this report.