7-Functionalized phosphonium salts, synthesis

Heterocycles.—The phosphonium salt (59) is an effective three-carbon synthon, as demonstrated by its reaction with enolates of /9-keto-esters (Scheme 20) to give cyclopentenyl sulphides via an intramolecular Wittig reaction.63 Ylides are also intermediates in the synthesis of dihydrofurans (60) from the cyclopropylphos-phonium salt (61) and sodium carboxylates (Scheme 21).64 Cumulated ylides are very useful for the synthesis of heterocyclic compounds, e.g. (62), from molecules which contain both an acidic Y—H bond and a carbonyl or nitroso-function, as shown in Scheme 22.65... 

Other Degraded Carotenoids. A new synthesis of the fungal sex hormone ( )-(7 , 9 )-trisporic acid B methyl ester (114) utilized as the key step a Michael-aldol sequence on the /3-keto-ester (115) to yield the highly functionalized cyclo-hexenone (116). The latter underwent Wittig reaction with the phosphonium salt (117) to give (114). After basic alumina-catalysed hydrogen exchange in tritiated... 

The alkylation of tertiary phosphines is, in general, compatible with elaborate structures bearing various functions or chiralities, as illustrated by the preparation of a phosphonium salt (18), intermediate in the synthesis of pseudomonic acid248 (reaction 17). For the preparation of dialkylphosphonium salts, diphenylphosphine can be directly alkylated, but it is more advantageous to use triphenylphosphine as the starting material,... 

Phosphonium salts, when functionalized (with e.g. keto, hydroxy, halo groups), are able to give characteristic reactions of such specific functions. This has been used in the synthesis of modified species nevertheless, the absence of any strong basic agent is the required condition (see 3A-C). 

Vinylpolystyrene, a useful intermediate for the preparation of various functionalized supports for solid-phase synthesis [7,57-59], has been prepared by the polymerization of divinylbenzene [7], by Wittig reaction of a Merrifield resin derived phosphonium salt with formaldehyde [59-62], or, most conveniently, by treatment of Merrifield resin with trimethylsulfonium iodide and a base [63] (Figure 5.7). 

Very likely the ammonium fluorides are the proton sources and therefore the reason for incomplete conversions, since potassium fluoride in acetonitrile gives high yields in a very elegant [3 + 2]-annuIation process 87). It combines a Michael addition to a vinyl phosphonium salt with an intramolecular Wittig reaction and proceeds only in the presence of 18-crown-6 with satisfying yield. This cyclopentene synthesis has been executed in a repetitive manner to prepare linear triquinanes as illustrated in Scheme 6. Unfortunately, the sequence is non-stereoselective with regard to the ethoxycarbonyl functions. 

A stereospecific total synthesis of prostaglandins E3 and F3, containing an additional double bond in this side chain, starts from the optically active phosphonium salt 161. In this synthesis the ( )-13-double bond and the 15-hydroxy function are generated simultaneously by condensation of the chiral bicyclic aldehyde 163 with the P-oxido ylide 162 obtained by treatment of 161 with methyllithium. The corresponding phosphonium salt S) +)-161, already possessing the (Z)-configurated A17-double bond of prostaglandins, was prepared from (S)(—)-tartaric acid 1351 (Scheme 29). 

The Merck Frosst solution employed L-arabinose as a starting material, which was converted to the protected differentiated dialdehyde synthon 60 which functionally serves as a masked (7 )-2-OH-succinaldehyde. The protected hydroxyl is the future 12(/ )-hydroxyl in LTB4. Scheme 2.20 describes the synthesis of 63, the left part of LTB4, This intermediate is elaborated in several steps to phosphonium salt 64, which is then coupled to chiral aldehyde 68b, which comes from 2-deoxy-D-ribose following the route shown in the same scheme. Aldehyde synthon 68 contains the (5S)-protected hydroxyl necessary for LTB4. The asterisks indicated in the scheme for L-arabinose and 2-deoxy-D-ribose correspond to the stereocenters retained in intermediates 63 and 68, respectively. 

The Merck Frosst group has prepared LTB (107) by a novel route where the key synthon, methyl (6 ,8Z)-10-bromo-6-r-butyldimethylsilyloxydecadieneoate (125), previously used in the synthesis of 5-HETE, was converted to the phosphonium salt 126 and reacted with the LTB4 synthon (27 )-r-butyldimethyl-silyloxy-(4 )-decen-l-al (127) to provide a 3 1 mixture of the (10 )- and (10 -adducts 128 and 129. The unusual preponderance of the rrons-isomer was attributed to steric hindrance in the normal kinetically favored erythro betaine caused by the bulky a-siloxy function (Scheme 5.36). 

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