ISSN:
0018-019X
Keywords:
Chemistry
;
Organic Chemistry
Source:
Wiley InterScience Backfile Collection 1832-2000
Topics:
Chemistry and Pharmacology
Notes:
Steroselective Total Synthesis of Natural Phytol and Derivatives thereof; Use of these Compounds in the Synthesis of Natural Vitamin K1The 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).
Additional Material:
4 Tab.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1002/hlca.19820650307
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