Convenient Synthesis of 2-(1-Adamantyl)furans †

: A simple method of obtaining 2-(1-adamantyl)furans using a smaller amount of catalyst, providing a higher yield of the target products, as well as the possibility of varying the substituents in the furan ring was developed. The result wasachieved by the adamantylation of furans with 1-adamantanol in a nitromethane medium in the presence of a Lewis acid, for which aluminum or bismuth triflate was used in an amount of 10 mol%.

The method for 1-adamantylation of furans ring-substituted with electron-withdrawing groups (2-acetylfuran XIV, furan-3-carboxaldehyde XVII) using 1-iodoadamantane XV in the presence of 10 mol% tetrakis(triphenylphosphine)palladium(0), 14 mol% 1,3-bis(diphenylphosphino)propane (dppp), and 200 mol% cesium carbonate in trifluorotoluene is known [4] (Figure 4).Adamantylation using 1-bromoadamantane in the presence of Lewis acid was used in the patent application: methyl furan-2-carboxylate XIX was treated with 1-bromoadamantane XX in ortho-dichlorobenzene in the presence of 200 mol% aluminum chloride.The yield of the target product XXI was 49% [5] (Figure 5).Adamantylation of 2-furancarboxylic acid XXII in dichloromethane in the presence of 200 mol% aluminum chloride proceeds similarly.The yield of the target product XIV was 65% [6] (Figure 6).The above-mentioned methods for the synthesis of 1-adamantylated furans have drawbacks, which includethe many steps in the synthesis scheme, the necessity for expensive palladium catalysts and specific reaction media, andthe formation of mixed reaction products.In addition, none of the methods given above was realized for a wide spectrum of furan substrates, which would allow one to talk about its versatility.

Materials and Methods
1 H and 13 C NMR spectra were recorded on an ECA 400 (JEOL) instrument in CDCl3 or (CD3)2SO (Cambridge Isotop Laboratories Inc., Tewksbury, MA, USA) using residual solvent signals as the internal standard.IR spectra were recorded on an IR Prestige instrument (Shimadzu, Kyoto, Japan) in KBr pellets.The course of the reactions was monitored by gas chromatography-mass spectrometry (GC/MS) using a GC-2010 instrument (Shimadzu) with QP-2010 Plus mass selective detector (Shimadzu): the column was a Supelko SLB-5ms, 30 m, withprogrammed heating from 60 to 265 °C at a rate of 30 °C/min.Melting points were measured in open-end capillaries on a Stuart SMP30 instrument.The reagents used were commercially available from Aldrich, Acros, or ABCR.

Results and Discussion
We propose performingadamantylation of furans with 1-adamantanol in nitromethane in the presence of Lewis acid, which could be aluminum or bismuth triflate in the amount of 10 mol%, according to Figure 7. Optimum conditions for the preparation of adamantylated furans were selected on the model reaction of 2-tert-butylfuran with 1-adamantanol whose course was controlled by chromatography-mass spectrometry.
The degree of conversion of 1-adamantanol into 2-(1-adamantyl)-5-(tert-butyl)furan, depending on the Lewis acid used, is shown in the figure .As the figure shows, consumption of 1-adamantanol and accumulation of the adamantylation product occur most rapidly whenusing 10 mol% of bismuth triflate (97% conversion after 2.5 h at room temperature), while the same amount of aluminum triflate within the same time provides a conversion of 85%.Nevertheless, aluminum triflate gives a conversion of 97% upon mixing the reagents for 4 h.In the case of scandium triflate, the 82% conversion is achieved only after 22 h and, in the case of zinc triflate, the conversion within the same time was only 5%.
Depending on the nature of substituents at the furan ring, adamantylation was carried out at room temperature or upon heating to 50-80 °C.
This method can be extended to several alkyl-and arylfurans, as well as to furans containing functional groups, such as carbethoxy and β-nitrovinyl which are most promising to be used in the synthesis of bioactive substances.

Conclusions
A simple method of obtaining 2-(1-adamantyl)furans using aluminum or bismuth triflate in nitromethane an amount of 10 mol% was developed.This method can be extended to several alkyland arylfurans, as well as to furans containing functional groups, such as carbethoxy and β-nitrovinyl which are most promising to be used in the synthesis of bioactive substances.