Iodine ( III )-Mediated Ring Contraction Reactions : Synthesis of Oxygen-and Nitrogen-Substituted Indanes

The synthesis of oxygenand nitrogen-substituted indanes was successfully performed by iodine(III)-mediated ring contraction of 1,2-dihydronaphthalenes. Acetoxy and benzoyloxy alkenes afforded indanes in 60-71% yield, irrespective of their position on aromatic ring. Similarly, the nitrogen containing substrates protected with 9-fluorenylmethyloxycarbonyl (Fmoc) and benzoyl (Bz) groups smoothly undergoes ring contraction giving indanes in 64-77% yield. The tosyl-protected substrate resulted only in addition products.

Iodine(III) is known to act as single-electron-transfer (SET) for methoxy-substituted aromatic compounds forming reactive cation radical intermediates. 41,42The generation of these cation radicals could be a possible reason of rearrangement failure in substrates like 1b, due to their susceptibility towards nucleophilic attack and other side reactions.Thus, we consider that the ring contraction could take place with an acetyl group instead of a methoxy making it useful in the synthesis of oxygen-substituted indanes.Several reaction conditions were tested for the  oxidation of alkene 9g with PhI(OH)OTs (HTIB) (Table 4).The desired ring contraction product 2g was successfully obtained in 47% yield using trifluoroethanol (TFE)/DCM (1:4) as solvent (entry 1).Using pure TFE, the yield of acetal 2g increased to 66% (entry 2).The deprotection of substrate 9g into phenol 1g was observed when MeOH was used as solvent (entry 3).With the optimized conditions, ring contraction was successfully carried out in other oxygenated substrates (Table 5).Benzoyl protected alkene 9gg gave acetal 2gg in 71% yield (entry 1).Acetyl protected alkene 9h smoothly afforded product 2h in 60% yield (entry 2).Acetyl alkene 9b gave acetal 2b in 65% yield (entry 3).
Oxidation with HTIB was also studied in amine protected alkenes (Table 6).Benzoyl protected alkene 1c experienced ring contraction giving acetal product 3c in 77% yield in MeOH/DCM (8:1) as solvent (entry 1).DCM was added to solubilize substrate 1c and to increase the rate of reaction.When the reaction was tried in pure MeOH, indane 3c was obtained in 51% yield and took 1 h to consume all starting material (entry 2).The protecting group tolerance was further investigated with Fmoc protected alkene 1e and the anticipated ring contraction product 3e was isolated in 64% yield (entry 3).The reaction of tosyl protected 7-amine alkene 1d with HTIB was also investigated under different reaction conditions (Table 7).Tosyl amide could have a facilitating effect on ring contraction by increasing electronic density on migrating carbon 4a. 13 However, only the formation of addition products trans-4d and cis-4d were observed in MeOH and in DCM/MeOH as solvents (entries 1 and 2).Fluorinated solvents like TFE and hexafluoroisopropanol (HFIP) proved to be ineffective under the conditions tested (entries 3 and 4).
Oxidation in acetyl protected 6-amine alkene 1f was explored.In this case, amide substituent meta to migrating carbon would decrease the electronic density by inductive effect of nitrogen atom and does not increase directly the electronic density at migrating carbon by mesomeric effect. 13Several conditions were tested for ring contraction of alkene 1f (Table 8).Slow reaction and complex mixtures were observed for substrate 1f using HTIB either in MeOH or in DCM/MeOH at different temperatures (entries 1-3).Fluorinated solvents, such as TFE and HFIP/DCM, also did not provide ring contraction product (entries 4 and 5).

Conclusions
In conclusion, the ring contraction of 1,2-dihydronaphthalenes using HTIB was expanded to substrates bearing oxygen and nitrogen substituents in the aromatic ring.Oxidative rearrangement was successfully carried out in oxygenated substrates independent on their position on aromatic ring.Acetoxy and benzoyloxy alkenes afforded indanes in 60-71% yield.The N-protecting groups Fmoc and Bz are stable under the reaction conditions giving indanes in 64-77% yield.The Ts-protected substrate gave only addition products.The results showed the tolerance of protecting groups in ring contraction reaction mediated by HTIB.

Experimental
All commercially available reagents were used without further purification unless otherwise noted.All solvents used for reactions and chromatography were dried and purified by standard methods. 43Thin-layer chromatography (TLC) analyses were performed using silica gel 60F 254 precoated plates, with detection by UV-absorption (254 nm) and by spraying with p-anisaldehyde and phosphomolybdic acid solutions followed by charring at ca. 150 °C for visualization.Flash column chromatography was performed using silica gel 200-400 Mesh.All nuclear magnetic resonance (NMR) analyses were recorded using CDCl 3 as solvent and tetramethylsilane (TMS) as internal standard.Chemical shifts are reported in ppm downfield from TMS with reference to internal solvent.

Table 6 .
Reaction of 7-amine alkenes with 1.2 equiv HTIB at 0 o C

Table 7 .
Reaction of tosylamide 1d with HTIB 7c (0.995 g, 3.75 mmol) in MeOH (40 mL).The mixture was stirred for 30 minutes at 0 o C. The temperature was raised to room temperature (rt) for another 1 h.The reaction was quenched by addition of distilled H 2 O (10 mL) and the mixture was extracted with EtOAc (3 × 30 mL).
The reaction was performed using ketone 7e (1.15 g, 3.00 mmol), MeOH (50 mL) and NaBH 4 (0.227 g, 6.00 mmol).After workup, solvent was removed under reduced pressure and crude alcohol (1.12 g, 2.91 mmol, 97.0%) was obtained as white solid and used in the next step without purification.