Stereoselektive Totalsynthese von natürlichem Phytol und Phytolderivaten und deren Verwendung zur Herstellung von natürlichem Vitamin K1

Steroselective Total Synthesis of Natural Phytol and Derivatives thereof; Use of these Compounds in the Synthesis of Natural Vitamin K1 The Li2CuCl4‐catalyzed couplings of the easily accessible bifunctional C5 allylic acetates (E)‐18a and (E)‐18b with racemic hexahydrofarnesylmagnesium bromide ((3 RS/RS, 7 RS/SR)‐19a) proceed with high chemo‐ and stereoselectivity (≥98% (E)‐retention) to give the (2E, 7 RS/RS, 11 RS/SR)‐phytol derivatives 1a and 1b, respectively, in yields of 72–80% (Scheme 5). The same couplings performed with optically active hexahydrofarnesylmagnesium bromide (3 R, 7 R)‐19a yielded the (E)‐phytol derivatives of the natural series (7 R, 11R)‐1a and (7 R, 11 R)‐1b. Acid‐catalyzed hydrolysis of(2 E, 7 R, 11 R)‐1b gave natural phytol((2 E, 7 R, 11 R)‐1c) Friedel‐Crafts alkylation of ‘menadiol monobenzoate’ 11b with (2 E, 7 R, 11 R)‐1a or (2 E, 7 R, 11 R)‐1b gave the dihydrovitamine K1 derivative (2 E/Z, 7′ R, 11′R)‐12b ((E/Z)≈︁ 9:l). Conversion of configurationally pure (2 E, 7′ R, 11′ R)‐12b (yield 73%; obtained after chromatographic removal of the (Z)‐isomer) into natural vitamine K1 ((2 E,7′ R, 11′ R)‐2) was achieved in the usual way by saponification and oxidation with air. Some further investigations of the coupling reactions of bifunctional C5 allylic synthons with hexahydrofarnesylmagnesium bromide (3 RS/RS, 7 RS/SR)‐19a showed the outcome of these reactions to be critically dependent on the nature of the leaving group, the double‐bond geometry and the nature and concentration of the catalyst. Thus, the Li2CuCl4‐catalyzed couplings of (3 RS/RS,7 RS/SR)‐19a with the allylic halides 29a and 29c as well as with p‐toluenesulfonate 29b yielded besides the phytol derivatives 1a and 1b ‐ also the SN2′‐type products 30a and 30b (Scheme 8, Table 2); the same result was found for the coupling with the cis‐configurated allylic acetates (Z)‐18a and (Z)‐18b (Table 3). A similar loss of chemo selectivity as well as the loss of stereoselectivity in the coupling reactions of 19 with the bifunctional (E)‐olefins of type 18 was observed when the Li2CuCl4‐catalyst concentration was increased from 0.2 to 25 mol‐% or upon substitution of Li2CuCl4 by copper (I) chloride or iodide (Table 4).