Experimental evidence in support of transannular interactions in diketones

The acid catalyzed condensation of polycyclic ketones 1 - 4 with thiadithiols was carried out. The reaction of ketone 1 with thiadithiols 5 and 6 afforded corresponding crown ethers 7 and 8 respectively. However all diketones 2 - 4 reacted with 5 or 6 to give corresponding ethylene dithioketals 9 - 13 . To the best of our knowledge, these results provide the first example of chemical evidence for the operation of transannular interactions in rigid polycarbocyclic systems.


Introduction
Since the electron delocalization through homoconjugation in terms of direct ("through-bond") and indirect ("through-space") interactions has been described by Hoffmann, 1 this phenomenon has been extensively investigated.Several papers have appeared that compare changes in 13 C nmr shift values of the sp 2 carbon atoms in difunctional systems with those of the corresponding monofunctional congeners. 2Transannular orbital interactions have been detected by photoelectron 3,4 and electron transmission spectroscopy. 5The origins of transannular interactions in diketones and methyleneketones also have been studied by ab initio MO 6 and semiempirical electron density analysis. 7erein we report remarkable difference between the reactions of thiadiethanethiols with monoketone 1 and with diketones 2, 3 and 4, and we present experimental evidence for transannular interactions in diketones 3 and 4.

Results and Discussion
Recently, it was shown that acid catalyzed condensation of 2,2'-thiadiethanethiol with carbonyl compounds or equivalents thereof could lead to thiacrown ethers that contain thioacetal units. 8rom our interest in the synthesis of adamantane-containing thiacrown ethers, 9 we have studied the acid catalyzed condensation of adamantanones 1-3 with 2,2'-thiadiethanethiol ( 5) and 3,6dithiaoctane-1,8-dithiol (6).The required starting compounds 1, 10 2, 11 3, 12 and 4, 13 could be prepared by using straightforward literature procedures.Acid catalyzed condensation of 1 with 5 or 6 gave spiro-adamantane thiacrown ethers 7 and 8, respectively, in a good yield (Scheme 1).However the same reactions performed with diketones 2 or 3, instead of corresponding crown ethers, afforded corresponding ethylene dithioketals 9-12 (Scheme 2).Ethylene dithioketals 9 and 10 as well as 11 and 12, were separated by preparative TLC.Structures of all new compounds were characterized via analysis of their respective IR, proton NMR, and carbon-13 NMR spectra (see the Experimental Section) and by elemental microanalysis.Structural assignments were confirmed by comparison with NMR spectra of authentic samples prepared by using standard methods via reaction of ethanedithiol with diketones 2 and 3.  When reaction was performed by using a 1:2 molar ratio of diketone and dithiol the corresponding bis(ethylene dithioketals) 9 and 11 were obtained (Table 1).The unusual course of the reactions observed when diketones 2 and 3 were employed as substrates could be explained in terms of electron delocalization through homoconjugation. 2,6Clearly, when two carbonyl groups are present (as in substrates 2 and 3), one C=O group exerts a profound influence upon the reactivity of the other toward nucleophilic reagents.b Small amount of starting diketone was isolated.
In order to obtain additional insight into the nature of transannular electronic effects that originate from localized carbonyl groups, the corresponding acid catalyzed condensation of diketone 4 with dithiol 5 was studied.Again, the bis(ethylene dithioketal) 13, was isolated in 89% of yield as a sole product (Table 1).It should be noted that both diketones, 3 and 4, possess D 2d symmetry.The C=O groups in diketone 3 and 4 are separated by four and five σ-bonds, respectively.It was calculated 6 that sp 2 carbon atoms in 3 are separated by a transannular distance of 3.463 Å; the corresponding distance in 4 is considerably greater (i.e., 5.265 Å).However, the calculations clearly indicated that electron density is greater around the carbonyl carbon atoms in 3 and 4 vis-à-vis that in the corresponding monoketone reference compounds. 6n the basis of the results shown in Scheme 1 and 2 and in Table 1, it is apparent that protonated ketone is the reacting electrophile when the reaction is performed under acidic conditions. 15Under these conditions two reaction mechanisms may operate (Scheme 3).With monoketone 1, path a appears to be more likely and tertiary carbocation is formed leading to the formation of crown ether 7.
However, when a second carbonyl group is present in the substrate (as, e.g., in 3), the transannular dipolar effect of this C=O group is expected to destabilize an incipient carbocationic center, 16 thereby favoring path b and formation of thionium ion, which decomposes to 12. Reaction of 12 with the second mole of dithiol 5 leads to the formation of 11.
To the best of our knowledge, the foregoing results provide the first example of chemical evidence for the operation of transannular interactions in rigid polycarbocyclic systems.

Experimental Section
General Procedures. 1 H and 13 C NMR spectra were obtained by using Varian Gemini 300 nuclear magnetic resonance spectrometer.The assignment of the NMR signals was done by a combination of 2D NMR techniques ( 1 H-1 H COSY and 1 H-13 C HETCOR).IR spectra were recorded on a Perkin-Elmer M-297 spectrophotometer and MS on Extrel FTMS 2001 spectrometer.The purity of adamantyl compounds was determined by GLC analysis carried out on a Varian 3300 gas chromatograph equipped with a DB-210 capillary column.Melting points were determined on Kofler apparatus and are uncorrected.Elemental analyses were performed at Central Analytical Laboratory, IRB, Zagreb.Unless stated otherwise, reagent grade solvents were employed.