Functionalizations and bridgehead reactivity of 4-homoisotwistane (tricyclo[5,3,1,0^3,8]undecane). Synthesis of 3-substituted derivatives

Abstract

Bromination and hydride transfer-carboxyla-mantane rearrangement of tricycloundecane precursors. Our recent discovery of a convenient synthesis of (I)4 enabled us to study its functionalizations.Reaction of (I) with excess of bromine at room temperature for 10 min gave in 85% yield the 3-bromo-derivative (II),? m.p. 5 9 ~5 " ~ an/e (re1 intensity) 230 (0.2%, M+), 228 IT has been foundlsB that 4-homoisotwistane (tricycle-(0-3%, M+), and 149 (loo%), lH n.m.r. 6 (CCI,) 1-0-2-6 [5,3,1,03~*]undecane) (I)3 is the key intermediate in ada-(complex m), 13C n.m.r.1 (CDCl,) 20.2 (t, l ) , 24.7 (t, 2), 26.3 tion of 4-homoisotwistane (tricyclo[5,3,1 ,03~8]undecane) (I) to give the 3-substituted derivatives (11) and (111) as well as ready hydrolysis of the 3-bromide (11) shows the high reactivity of the 3-bridgehead in the hydrocarbon (I). 7 Satisfactory elemental analyses were obtained for all the new compounds, $ P.p.m. downfield from Me,Si as internal standard. Fine structure on off-resonance proton decoupling and relative intensity of the signals are shown in parentheses.

Biologically active polycycloalkanes. 2. Antiviral 4-homoisotwistane derivatives

“…Anal. (CnHisO) C, H. 4-Homoisotwistane-3-carboxylic Acid (12). A solution of 30 g (0.41 mol) of tert-butyl alcohol in 55 g (1,20 mol) of 99% formic acid was dropped in a period of 2.5 h to an efficiently stirred mixture of 15 g (0.10 mol) of 4-homoisotwistane (3), 100 ml of cyclohexane, and 450 g of 95% sulfuric acid kept at 10-15°with external cooling.…”

“…Collection of the fraction boiling at 135-140°(0.9 mm) gave 12.5 g (63% yield) of crude 12, which solidified on standing at ambient temperature overnight. Purification by sublimation in vacuo gave a pure sample: mp 95-96°(sealed tube); ir (neat) 2940, 2920, 2860, 2700-2500,1680,1450,1400,1280,1110, 960, 900, 830 cm*1; NMR (CDCls) 0.8-2.6 (complex m, 17 H), 10.20 (s, 1 H, vanished on treatment with D2O); mass spectrum m/e (rel intensity) 194 (12, M+), 150 (13), 149 (100), 92 (12), 80 (19), 78 (15), 66 (27), 57 (12), 41 (17). Anal.…”

“…(C12H20O) C, H. 4-Homoisotwist-3-ylcarbonyl Chloride (15). To a solution of 5.5 g (0.028 mol) of 4-homoisotwistane-3-carboxylic acid (12) in 20 ml of benzene was dropped at ambient temperature with stirring 12 ml of thionyl chloride and the mixture was stirred under reflux for 1 h. After most of the benzene and the excess thionyl chloride had been distilled off, the residue was fractionated to give 5.4 g (90% yield) of 15: colorless liquid; bp 96-97°(0.9 mm); n22D 1.5238; ir (neat) 2930, 2860,1790,1470,1450, 990, 920, 880, 750, 650 cm*1; NMR (CCU) 1.2-2.4 (complex m); mass spectrum m/e (rel intensity) 194 ( 23), 150 (12), 149 (100), 93 (14), 91 (15), 81 (22), 79 (21), 67 (36), 41 (21), 39 (14), 28 (15). Anal.…”

“…Bromination of 3 with liquid bromine at room temperature gave exclusively the 3-bromo derivative 4 in 85% yield. 12 The structure of the bromide 4 Of the three different kinds of bridgeheads in 3, the C-3 was shown to be much more reactive than the two others in bromination. This would be readily explained based on the difference in the stabilities of the corresponding carbocations.…”

“…and exo-trimethylenenorborn-2-exo-yl (18b)], amide (16), and /V-alkylamides [methyl (19a), n-butyl (19b), cyclohexyl (19c), and 1-adamantyl (19d)] of 12 were prepared through the acyl chloride (15). Thionyl chloride dehydration of the amide 16 gave the corresponding nitrile (20), while lithium aluminum hydride reduction of 16 led to 3-aminomethyl-4-homoisotwistane (17) which was neutralized in ether to give the hydrochloride 21.…”