Racemic chromanes

Racemic substrates have been employed in Mn(salen)-catalysed epoxidation reactions. Reasonable to good kinetic resolution of racemic chromanes (selectivity factor, S = 2.7-9.3) and racemic allenes have been achieved using enantiomer-ically pure manganese(salen) complexes to catalyse epoxidation. 

A more promising approach to 4-deoxo derivatives of eucomol appeared to be reduction of a suitable thioketal derivative. Eucomol (10) itself did not react with ethanedithiol and boron-trifluoridediethyl ether complex as catalyst. The negative result is probably due to chelate formation. 5,7-Di-O-methyleucomol (24), however, was smoothly transformed to the thioketal (70) which gave 4-deoxo-5,7-di-0-methyleucomol (71) and the racemic chromane (73) on treatment with Raney nickel in ethanol. An attempt to interrelate these compounds via an elimination of water from (71) in boiling acetic anhydride yielded only the 3-O-acetyl derivative (72) (64). 

Batista JM, Lopez SN, da Silva Mota J, Vanzolini KL, Cass QB, Rinaldo D, Vilegas W, da Silva Bolzani V, Kato MJ, Furlan M. Resolution and absolute configuration assignment of a natural racemic chromane from Peperomia ohtusifolia (Piperaceae). Chirality 2009 21(9) 799-801. 

The asymmetric intramolecular crossed benzoin reaction catalysed by a chiral triazolium salt has been used to synthesise 3-hydroxychroman-4-ones 34 in good to high yields and ee. The absolute configuration at the quaternary stereocentre C-3 has been shown to be S by X-ray analysis of the camphanyl ester <06SL2431>. Both enantiomers of 2-(2-phenylethyl)chroman-4-one, flindersiachromanone, have been obtained from racemic l-phenylhex-5-en-3-ol after resolution via lipase-catalysed acetylation <06H(68)483>. 

Developments in the chemistry of the smenochromenes, marine macrolides with a chromene core, include a four-step synthesis of racemic smenochromene D 16 from hydroxyfamesyl acetate and 4-hydroxy-3-methoxyphenyl formate and its conversion into racemic smenochromene B by way of a macroring contraction and bond isomerisation <07T6529>. Several [/>,c]-fuscd chromans, e.g. 17, related to rhododaurichromanic acid and... 

For example, a four stage Inversion sequence provides a route for transforming 41c into the ( )-enantiomer required for synthesis of" (42). Similarly, the homologous, unwanted (R)-chroman-2-ace c acid 42c can be utilized by means of a racemization-recycling process (43). While these approaches still rely on classical resolutions, the modifications incorporated substantially improve the overall efficiency in terms of obtaining optically pure intermediates. 

The enzymic preparation of intermediates for the formation of the chroman ring in tocopherols has been investigated, notably the resolution of a racemic dioxolane derivative (ref. 116) by selective hydrolysis with a carboxyesterase (ref. 127). 

Further uses of Novozyme 435 have been described in recent patent applications filed by the Mitsubishi Gas Chemical Company and comprise processes for the production of optically active secondary alcohols (Scheme 33) [98] and the manufacture of optically active chroman-2-carboxylic acids (Scheme 34) [99]. In the first case the resolution of racemic 4-isopropyloxy-2-butanol (rac-108) by Novo 435 was an important step toward (R)-(+)-4-(isopropyloxy)-2-bu-tanol ((R)-108) via acetate 109. Compound R)-10S can be used for the synthesis of liquid crystal materials. 

The kinetic resolution of racemic compounds enzymatically has been successively achieved for 2-hydroxymethyl-2,5,7,8-tetramethylchroman-6-ol, valuable for the synthesis of tocols <97TA523>, and chroman-4-ols <97TA3059>. 

In their successful synthesis of racemic y-rubromycin 58 [170], highly functionalized chroman 333 and naphthoquinone 332 underwent oxidative [3+2]-cycloaddition (Scheme 81). The o- and p-quinone spiroacetals 334 and 335 were obtained as a 1 2 mixture in 58 % yield. Fortuitously, the demethylation conditions also catalyzed isomerization of 334, converting the mixture of quinones to ( )-y-rubromycin 58 in moderate yield. 

Recently, the stereoselective synthesis of bicyclic primary or secondary alcohols was reported by Brenna et al. [52]. Again, the combination of an ER with an ADH was used to catalyze reactions on substrates based on tetralin or chroman backbones, which led to precursors of important active pharmaceutical ingredients (rotigotine, robalzotan, and ebalzotan) with optical purities up to >99% (Figure 18.5b) [52]. In this case, the addition of an ADH allowed for a minimization of the spontaneous chemical racemization of the imstable saturated aldehyde intermediate. 

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