Bicyclo hexane-3-methanols

Special interest has been paid to the synthesis of bridged four-membered rings. The smallest system of this type, the bicyclo[1. l.l]pentane skeleton 6, could be prepared by photolysis of 3-diazobicyclo[2.1.1]hexan-2-one in methanol,43 however, the yield was very low ( 2%). 

Disilyl ethers of bicyclo[2.2.0]hexane-l,4-diols were transformed to cyclohexane-1,4-diones by oxidation after hydrolysis in methanol to the diols, which can be isolated.100 Sodium periodate101-103 and molecular oxygen100,101,104 were used as oxidants. 

To a solution of 5-methoxymethoxy-7-oxa-bicyclo[4.1.0]hept-3-ene-3-carboxylic acid methyl ester (4.9 g, 22.9 mmol) in 8/l-Me0H/H20 (175 ml, v/v) was added sodium azide (7.44 g, 114.5 mmol) and ammonium chloride (2.69 g, 50.4 mmol) and the mixture was refluxed for 15 h. The reaction was diluted with water (75 ml) to dissolve precipitated salts and the solution was concentrated to remove methanol. The resulting aqueous phase containing a precipitated oily residue was diluted to a volume of 200 ml with water and was extracted with ethyl acetate (3 times 100 ml). The combined organic extracts were washed with saturated NaCI (100 ml), dried (MgS04), filtered and evaporated. The crude was purified on silica gel (1/1-hexane/ethyl acetate) to afford 5-azido-4-hydroxy-3-methoxymethoxy-cyclohex-l-ene-l-carboxylic acid methyl ester (5.09 g, 86%) as a pale yellow oil. Subsequent preparations of 5-azido-4-hydroxy-3-methoxymethoxy-cyclohex-l-ene-l-carboxylic acid methyl ester provided material which was of sufficient purity to use in the next step without further purification. 

The reaction of bicyclo[4.1.0]heptane with diborane and subsequent treatment with hydrogen peroxide produced predominantly cyclohexylmethanol (5b) in high yield.Under modified experimental conditions small amounts of isomeric methylcyclohexanol (6b) and cycloheptanol (7b) were isolated. In contrast to the hydroboration of alkenes, the cyclopropane cleavage reaction is inhibited by ethereal solvents such as diethyl ether, tetrahydrofuran or 2-methoxy-ethyl ether. Bicyclo[3.1.0]hexane reacted with diborane in a similar fashion to give mainly cyclopentylmethanol (5a).The reaction of l-methylbicyclo[4.1.0]heptane gave a mixture of cis- and tram-(2-methylcyclohexyl)methanol (5c) in an initial ratio of 60 40. Spiro[2.5]octane reacted with diborane to yield only products derived from scission at the spiro carbon. The main product was 2-cyclohexylethanol (8). ... 

Alkyl-2-(2-oxopropyl)cyclopentane-l,3-diones 33 were smoothly converted into 2-acetyl-3-alkylcyclohexane-l,4-diones 34 by treatment with sodium hydroxide in water or sodium methoxide in methanol. Ring expansion results from intramolecular aldol reaction followed by ring opening of the bicyclo[3.1.0]hexane system. ... 

Die in anti-Stcllung halogenierten Benzo-bicyclo[2.2.1]heptadiene photoisomerisieren sich in Methanol oder Hexan zu den syw-Formen3 ... 

Cerium(III) chloride as well as some other lanthanide salts invert the stereoselectivity of the reduction of bicyclo[3.1.0]hexane-2,4-diones and bicyclo[3.1.0]hexane-2-ones compared to sodium borohydride in methanol alone. This reversal leads to the more favored attack of the hydride from the most hindered, concave face of these molecules to give exo-4-hydrobicyclo[3.1.0]hexan-2-ones and exo-bicyclo[3.1.0]hexan-1 -ols, respectively, in excellent yields37 If Luche conditions are used on 30 at low temperatures, complete stereoselectivity is induced in the production of 31. 

To a 2 mL THF solution of 0.120 g n(i6>-2-deuterio-2-hydroxy-lR,5R-bicyclo[3.3.0]oct-3-ene (0.96 mmol) at 0°C, were added 0.30 g triphenylphosphine (1.14 mmol, 1.2 eq.), 0.20 gram DEAD (1.15 mmol, 1.2 eq.), and 0.14 g benzoic acid (1.14 mmol, 1.2 eq.). The resultant solution was stirred for 1 h at this temperature, and then the solvent was removed under reduced pressure, followed by the addition of 10 mL hexane/EtOAc (2 1). The solution was filtered, the solvent was removed under reduced pressure, and the crude product was purified by silica gel chromatography (petroleum ether). The purified benzoate mixture was then hydrolyzed by addition of 5 mL 5% NaOMe/methanol, and the resulting mixture was stirred for 3 h. The solvent was removed under reduced pressure, and the crude mixture was dissolved in 10 mL ether, washed once with 5 mL water and 5 mL brine, dried over Na2S04, filtered, and concentrated to provide 80% of alcohols, with 79% of inversion. 

In cyclopropanes a C—C bond can be cleaved by way of anodic oxidation. The electrochemical oxidation of bicyclo[4.1.0]heptane (31) and bicyclo[3.1.0]hexane gave products in which the cyclopropane ring was opened. Anodic oxidation was conducted at a carbon rod anode in methanol/TEATos. The products obtained from 31 are given in equation 22. The products found are completely different from those of the acidic hydrolysis of the cyclopropanes. Whilst in the methanolysis of 31 in methanol/toluene-sulfonic acid the selectivity of external/internal bond cleavage is 88/12, that of anodic oxidation is 0/100. Also, in the cleavage with Pb(OAc)4 or Tl(OAc)3 the external bond... 

Interratingly, irradiation for 6 h of the 1 1 complex 61 compc d of 8 a and 58 which had been prepared by keeping a solution of 8a and an equimolar amount of 58 in benzene-hexane at room temperature for 12 h (colorless needles of mp 133 to 136 °C) gave the optically active photocyclization product (—)-bk yclo[4.2.0]oct-7-en-2-one (62) Qa]p —60.6 (c 0.18, CHCI3)] in quantitative yield The photocyclization reaction is in contrast to the photodimerization of 58 in 59. In the case of 61, the photodimerization of 58 is probably prevented by steric hindrance. It is almost certain that one optical conformer of 58 is included in 61, but a real proof of this fact requires an X-ray structural study in the future. However, the formation of the optically active 62 is valuable, because photoreaction of 58 in solution does not give any intramolecular photocyclization product It has been reported that irradiation of bicyclo[5.1.0]octa-3,5-dien-2-one (63) in methanol leads to a mixture of racemic tricyclo[4.2.0.0 ]oct-7-en-2-one (65), 37, and cyclohepta-l,3,5-triene Control of the reaction was also tried in expectation... 

H202 added with stirring at 0° to a soln. of exo-6-(l -heptenyl)bicyclo[3.1.0]-hexan-3-one in ice-cold 97-98%-formic acid buffered with Na-carbonate, brought to room temp, and stirred 30-40 min. under N2, the formic acid removed in vacuo, the residue dissolved in methanol, aq. Na-carbonate added with stirring, which is continued 3 hrs. at room temp., and acidified with 3 N HCl exo-6-(l, 2 -dihydroxyheptyl) bicyclo[3.1.0]hexan-3-one. Y 85%. F. e. s. E. S. Ferdinandi and G. Just, Can. J. Chem. 49, 1070 (1971). 

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