Dioxa-twistanes

Treatment of endo-2-hydroxy-exo-6-iodo-9-oxabicyclo[3.3.1]nonane 210) in metha-nolic KOH-solution at reflux temperature yielded a mixture of 68% of the dehydro-halogenated compound 119 and 8% of 2,7-dioxa-twistane 212f the product of intramolecular substitution. The ratio of elimination to substitution could lean strongly in favor of the latter by refluxing 210 in pyridine 47% of the twistane 212 and only 28% of the unsaturated bicyclic alcohol 119 were formed °  

By the same pathway reaction of endo-2-hydroxy-exo-6-tosyloxy-endo-7-methyl-9 oxabicyclo[3.3.1]nonane 211) in methanolic NaOH-solution, 4° -methyl-2,7-dioxa-twistand 213) could be obtained in high yield  

On the basis of the results described in 2.2.2.3., namely, the easy intramolecular ketal formation of 131 to 133, the question arose whether endo-6-hydroxy-9-oxa-bicyclo[3.3.1]nonan-2-one 214) might analogously be converted to the corresponding l-methoxy-2,7-dioxa-twistane 219). The experiments, even under drastic acidic conditions in methanol (5.5N HCl in CH3OH, 2 days at 80°), showed that no ring closure 214 219 occurred. Introduction of an endo-methyl group at C(7), however, 

The synthesis of the twistane-ketal 279 using endo-6-hydroxy-9-oxabicyclo[3.3.1]-nonan-2-one (274) or its acetate 227, resp., was nevertheless successful by applying the following route according to a procedure by Inhoffen etal. the keto-acetate 221 was treated with trimethyl orthoformate. From the reaction mixture which contained the dimethoxy-ketals 222 and 223 as well as the enolethers 224 and 225, the acetates 222 (63%) and 224 (5%) were isolated by chromatography. On base-hydrolysis they gave the alcohols 223 and 225. Pyrolysis of the ketal 222 and simultaneous distillation yielded 67% of the enolether 224. Finally by treating the dime- 

219 was also already formed during the reaction of the hydroxy-ketone 214 with trimethyl orthoformate and acid. However, it is difficult to isolate 219 from this reaction mixture. 

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The subsequently applied synthetic scheme was analogous to the one for the corresponding racemic compounds (see 2.2.2.I., 3.2.3. and 3.2.4.). Treatment of the (—)-alcohol 379 with iodine in chloroform yielded the (-)-10° -iodide 383 as sole product. Its reaction with silver tosylate in acetonitrile led to a mixture of 10°(7).tosyloxy-isotwistane 384 and -twistane 386, which was directly treated with LiAlH4 in refluxing dioxane to give a mixture, easily separable by vpc., of (—)-2,7-dioxa-isotwistane 385 [oc]d = —23.3 0.7°) and (-)-2,7-dioxa-twistane 387, see Table 8). The absolute configuration of 387 [(—)-( R, 3R, 6R, 8R), right-handed helix (P)] and of all other compounds involved in its synthesis was determined by chemical correlation with (—)-(2S)-malic acid (559). As relais compounds served the endo-2-hydroxy-9-oxabicyclo[3.3.1]nonanes +)-390 and (—)-J97, (-t)-5-hydroxy-cyclooct-l-ene [ +)-392] and the 4-methoxy-suberic acid dimethylester —) 393 and +)-394. 

Catalytic hydrogenation (Ha/Pd, C) of the dienes -)-401 and (+)-402 gave t ie corresponding saturated 2,7-dioxa-twistanes (—)-387 (see Table 8) and (+)-J55 (see Table 8), resp. These correlations on the one hand allowed the unequivocal assignments of the absolute configuration to the dienes -)-401 and (+)-402 and on thd other hand give the information about their optical purity, which again is > 99%. 

On the basis of chemical correlations Tichy was able to deduce the absolute configuration of carbocyclic (+)-twistane (403) as (IR, 3R, 6R, 8R), left-handed helix (M). Comparison of this result with the ones described in 4.6.1. and 4.6.2. demonstrate, that carbocyclic twistane and 2,7-dioxa-twistane having the same sign of the optical rotation, possess the same helicity (see Table 8). 

Between approx. 1200 and 800 cm all dihetero-tricyclodecanes show marked sharp absorption bands. Comparing, e.g. the spectra of unsubstituted skeletal isomers, already gives good hints for the assignment of a certain structure type because compounds of higher symmetry exhibit less absorption bands than those of lower syih-metry [e.g. 2,7-dioxa-twistane 212) and 2,7-dioxa-isotwistane 128), resp.]. 

In 1970 a paper appeared by Dittmann and Sunder-Plassmann ). These authors are supposed to have obtained 2,7-dioxa-twistane (212) by an independent route. However, from the experiments they described it seems very unlikely to be the case. 

Compare also the coupling constants of the C(10)-substituted 2,7-dioxa-twistanes 247,... 

The dioxa analogues 37-40 of the twistanes 3a, b and of 2,7-twistadienes 34, 35 show lower rotation strengths compared to the corresponding carbocyclic skeletons. 

Base-hydrolysis of the. lO -acetoxy-isotwistane 246 (3.2.3.) yielded the corresponding alcohol 137, which was also characterized as its tosylate 267 (3.2.3.). The azide 287 (3.2.3.) was catalytically reduced (H2/raney-nickel) to the 10° -amino-iso-twistane 330. Oxidation of the isotwistanol 137 with Jones-reagent gave the ketone 331, which was transformed via desulfuration with raney-nickel of the corresponding thioketal 332 to unsubstituted 2,7-dioxa-isotwistane 128, see also 2.2.2.1.). 

Dioxa-twista-4,9-diene (363), which still represents the first heterocyclic twistadiene prepared thus far (meanwhile also pure carbocyclic twistadiene has been synthesized ) was easily accessible using the diacetate 243 (3.2.2.2.) as starting. material. LiAlH4-reduction yielded the diol 361 (90%), which was transformed to, its dimesylate 362 (85%). Treatment of the latter for 3 days at room temperature with t-BuOK in dimethyl sulfoxide gave 70% of 2,7-dioxa-twista-4,9-diene (363), which was catalytically reduced (Ha/Pd, C) to the twistane 212 (85%). 

Optically Active 2,7-dioxa-isotwistane, -twistane and -twista-4,9-diene ... 

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