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Stereoselektive Totalsynthese von natürlichem Phytol und Phytolderivaten und deren Verwendung zur Herstellung von natürlichem Vitamin K 1
Author(s) -
Schmid Max,
Gerber Fernand,
Hirth Georges
Publication year - 1982
Publication title -
helvetica chimica acta
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.74
H-Index - 82
eISSN - 1522-2675
pISSN - 0018-019X
DOI - 10.1002/hlca.19820650307
Subject(s) - chemistry , stereochemistry , bromide , total synthesis , stereoselectivity , phytol , allylic rearrangement , medicinal chemistry , organic chemistry , catalysis , biochemistry
Steroselective Total Synthesis of Natural Phytol and Derivatives thereof; Use of these Compounds in the Synthesis of Natural Vitamin K 1 The Li 2 CuCl 4 ‐catalyzed couplings of the easily accessible bifunctional C 5 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 (2 E , 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 , 11 R )‐ 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 K 1 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 K 1 ((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 C 5 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 Li 2 CuCl 4 ‐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 S N 2′‐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 Li 2 CuCl 4 ‐catalyst concentration was increased from 0.2 to 25 mol‐% or upon substitution of Li 2 CuCl 4 by copper (I) chloride or iodide ( Table 4 ).