Racemic compounds alcohols, 2-methoxy-2-

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. 

Certain classes of compounds are too reactive for the present method. Ethyl mandelate produced a racemic, protected phenyl glycine derivative. Benzylic alcohols with two methoxy groups (directly conjugating in the 2 and 4 positions) gave azide of 50% e.e. 

However, a source of the non-natural 9S isomer (2) was first required. The ready availability of natural crinitol made a racemization/resolution route, as illustrated in Scheme 1, attractive. Racemization was accomplished by Collins oxidation (16,25) to the dicarbonyl compound (14), followed by lithium aluminum hydride (LAH) reduction to give the racemic mixture (1 + 2). Resolution via diastereomeric derivatives seemed plausible. Esterification with enantiomerically pure a-methoxy-a-(trifluoromethyl) phenylacetic acid (MTPA) (17), followed by separation of diastereomers by recycle-HPLC (R-HPLC), had earlier been used to purify enantiomers of ipsenol and ipsdienol (26). A model system, the resolution of -3-nonen-2-ol, a secondary allylic alcohol naturally occurring in Rooibos tea (16,27), also worked satisfactorily. Therefore, the route using the bis-(MTPA) esters was selected for crinitol. 

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