No abstract

A highly selective Negishi coupling of zinc-metallated ferrocenyl p-tolyl sulfoxide with aryl bromides was developed. With Pd(PPh 3 ) 4 as catalyst, a well-matched system in terms of reactivity of organometallic compound, aryl bromide, and catalyst, was obtained. The scope of the reaction was studied by the use of aryl bromides 7a−g, which afforded high yields of coupling products. The reaction conditions for the preparation of ferrocenyl p-tolyl sulfoxide, according to the Andersen method, were optimised to give a yield of 80% and an enantio-

No abstract

A number of pentasubstituted acylferrocenes were selectively prepared from ferrous chloride, sodium acylcyclopentadienides, and the corresponding pentasubstituted lithium cyclopentadienides in good yields. The selectivity is governed by the different steric and electronic properties of the acylcyclopentadienides vs the pentasubstituted cyclopentadienides.

The acetate/acetate-d 3 exchange reaction of the ring-bonded acetate of bis(4-acetoxy-[η 3-(1,2,3)-cyclohexenyl])palladium acetate-d 3 complexes 1a−c was studied in acetic acid solutions using 1H NMR spectroscopy. The reactions followed first-order kinetics in palladium, and the rates were highly affected by the presence of methanesulfonic acid or lithium acetate. The nature of the substituent in the 2-position of the complex was found to have a large impact on the reaction rate. Complexes 1a−c are observed intermediates in the benzoquinone-assisted palladium(II)-catalyzed 1,4-diacetoxylation reaction of 1,3-dienes. Complex 1b was treated with stoichiometric amounts of the enantiomerically pure ligand (S)-(+)-2-(4‘-fluorophenylsulfinyl)-1,4-benzoquinone 4 under conditions where no exchange reaction occurs. Kinetic resolution was observed, implying that the two enantiomers of 1b reacted to trans-1,4-diacetoxy-2-phenyl-2-cyclohexene with different rates. Attempts to demonstrate dynamic kinetic resolution in stoichiometric reactions between 1b and 4 were unsuccessful. The major reason for this is presumably that with lithium acetate the equilibrium reaction between the two enantiomers of 1b is too slow compared to the chiral benzoquinone-induced attack of acetate to give the products. Under very acidic conditions the decomposition of the (π-allyl)palladium complex is faster than benzoquinone-induced product formation. This scenario is in full agreement with our observed rates.

Melflufen is a novel cytostatic currently in phase III clinical trials for treatment of multiple myeloma. Development of a process suitable for production is described. The two key features of the novel method are late introduction of the alkylating pharmacophore and an improved method for formation of the bis-chloroethyl group.

(−)-3-(2-Benzothienyl)-8-H-8-azabicyclo[3,2,1]oct-2-ene acetate, NS9544 acetate, is a candidate drug intended to treat pain and other CNS disorders. In the synthetic route tropinone was enantioselective deprotonated with a chiral lithium amide derived from [R-(R*,R*)]-bis(α-methylbenzyl)amine hydrochloride. The formed enolate was trapped as triflate and coupled with benzo[b]thiophene-2-boronic acid under Suzuki conditions. To further enhance the enantiomeric purity crystallisation with l-(+)-tartaric acid was performed. Finally N-demethylation with trichloroethylchloroformate followed by treatment with acetic acid afforded NS9544 as the acetate salt with high enantiomeric purity.

For Abstract see ChemInform Abstract in Full Text.