A short synthesis of dimethyl tricyclo[3.3.0.0^3,7]octane‐1,5‐dicarboxylate and its 3,7‐dimethyl derivative. A new route to the tricyclo[3.3.0.0^3,7]octane skeleton

Abstract

Five-step syntheses of dimethyl tricycl0[3.3.0.d~~]wtane-1,5-dicarboxylate (13) and its 3,7-dimethyl derivative 14 from the readily available cis-bicyclo[3.3.0]octane-3,7-diones 1 and 2, respectively, are described. The key-step implies the iodine oxidation of the bisenolate derived from the corresponding dimethyl cis-bicyclo-[3.3.0]octane-3,7-dicarboxylates 11 and 12, thus being developed a new synthetic entry into the tricycl0[3.3.0.0~~~]octane skeleton. Also, some attempts to synthesize diester 13 by using known methodology for the synthesis of compounds containing this tricyclic skeleton are described.Some time ago we published ' ) several attempts to develop a new synthetic entry into the tricyclo[3.3.0.03~7]~ctane skeleton in order to synthesize dimethyl tricyclo-[3.3.0.03~7]octane-1,5-dicarboxylate (13) and reviewed the described routes to obtain compounds containing this strained carbocyclic skeleton. Since then no other new synthetic entry to this type of carbocyclic derivatives has been described". We describe herein the synthesis of diester 13 and dimethyl 3,7-dimethyltricyclo[3.3.O.O3~7]octane-1,5-dicarboxylate (14) in a straightforward manner from the readily available cisbicyclo[3.3.0]octane-3,7-dione (l)3J and cis-1,5-dimethylbicyclo[3.3.0]octane-3,7-dione (2)3J, respectively.Reaction of diketone 1 with excess sodium cyanide in water gave a mixture of stereoisomeric bis-cyanohydrins that was dehydrated as such by reaction with phosphoryl chloride in boiling pyridine to give a mixture of cis-bicyclo-[3.3.0]octa-2,6-diene-3,7-dicarbonitrile (3) and -2,7-diene-3,7-dicarbonitrile (4) in 54% yield. This mixture, in which 3 was slightly predominant (GLC), was separated by semipreparative HPLC. The 200-MHz 'H NMR spectra of 3 and 4 could be fully assigned by double-resonance experiments (Table 1).Only four kinds of protons were observed for dinitrile 3 according to its Cz symmetry. For dinitrile 4, however, five kinds of protons were observed in accord to its C , symmetry. Assignment of the exo-4(8)-H and endo-4(8)-H absorptions of 3 was made on the basis of their coupling constants and chemical ~h i f t s~.~) .As expected from the Karplus equation, the coupling constant value l-H,exo-8-H (6.6 Hz) is greater than that for l-H,endo-8-H (2.2 Hz). The assignment of dinitrile 4 was carried out in a similar manner. The 50-MHz 13C NMR spectra of dinitriles 3 and 4 (Table 2) were also in accord with their symmetry. The assignment was based mainly on the multiplicity and intensity of the absorptions. To assign the absorptions of C-I and C-5 in 4, the values predicted by using the data of Bremser et a1.6) were conclusive.Hydrogenation of the mixture of dinitriles 3 and 4 was easily achieved. The product consisted essentially of one of the three possible stereoisomers, that was obtained in pure state by crystallization from ether. On the basis of its Czl symmetry and the expected preferred hydrogenation of the carbon-carbon double bonds of 3 and 4 by their less hind-

Total Synergistic Effect between Triflic Acid and Bismuth(III) or Antimony(III) Chlorides in Catalysis of the Methanesulfonylation of Arenes

“…Mesitylene (5) is a strong π donor arene capable of generating Menschutkin complexes, which are most probably involved in deactivation of the catalyst. [15] When 10% mol of pure SbCl 2 OTf [12] was used in the methanesulfonylation of 5, a 9% yield of methyl 2Ј,4Ј,6Ј-trimethylphenyl sulfone (18) was isolated (same conditions than for Entry 5), indicating that the deactivation of the system B arises from the inhibition of the reaction between 1 and 3 through its complexation with 5 (step a). In the case of 9, the difference between the two systems stems from the solubility of 3 in aromatics (a consequence of the respective ionic and covalent natures of 2 and 3).…”

“…[c] Products are: mixture of methyl methylphenyl sulfones 17, methyl 2,4,6-trimethylphenyl sulfone (18), mixture of dimethylphenyl methyl sulfones 19Ϫ21, mixture of fluorophenyl methyl sulfones 22, methyl phenyl sulfone (23), mixture of chlorophenyl methyl sulfones 24, mixture of dichlorophenyl methyl sulfones 25, mixture of difluorophenyl methyl sulfones 26, mixture of fluoromethylphenyl methyl sulfones 27Ϫ29.…”

Synthesis of Several Halobisnoradamantane Derivatives and Their Reactivity through the SRN1 Mechanism

“…Synthesis. The synthesis of iodo esters 5 and 7 was carried out from the known diester 1 by following standard procedures (Scheme 1). Hydrogenation of 7 at a pressure of 35 atm, using 10% Pd on charcoal as catalyst, was shown to be a very slow process, providing a mixture of starting 7 and tert -butyl ester 8 in a ratio of about 1:1 after 1 week of reaction.…”

Multigram Synthesis of Dimethyl Stellane‐1,5‐Dicarboxylate as a Key Precursor for ortho‐Benzene Mimics**

“…At first glance, Camps' group described a promising approach over 40 years ago for the synthesis of compound 1 based on lithiation/I 2 -mediated oxidation of dimethyl octahydropentalene-2,5-dicarboxylate 2 (Figure 1). [15] However, the problematic scale-up and challenging purification hampers further study of stellanes. In light of the unreliable reproducibility of the literature synthetic protocol for stellane core assembly and the growing interest in benzene mimics research, we aimed to conduct a detailed study targeting largescale preparation of 1 as starting material in various medicinal chemistry programs.…”