Phosphonium salts 1,3-dienes

The phosphonium salt method works best with nucleophilic olefins [//, 12, 16, 17, 18, 19] (Table 1 and equations 1-3) and has been used m mechanistically important studies of difluorocarbene additions to norbornadienes [20 21, 22, 23] that provided the first example of a concerted homo-l,4-addition (equation 4) A recent modification uses catalytic 1,4,7,10,13,16 hexaoxacyclooctadecane (18-crown-6) to shorten reaction times and increase yields with less nucleophilic olefins [12] (Table 1) Neither procedure, however, compares with the use of phenyl(tri-f1uoromethyl)mercury or (trifluoromethyl)trimethyltin reagents [efficient reactions with less nucleophilic olefins (equations 3 and 5) and cyclic dienes [24, 25] (equations 6 and 7)... 

The crystal structure of the phosphonium salt (118) confirms that the compound is a diene and not a delocalized structure. 

Before examining the reaction of deactivated alkenes, the phosphonium salt synthesis was applied to 1,3-dienes.21 When ( )-6-phenyl-l,3-hexadiene was treated with equimolar amounts of PPh3 and CF3S03H in the presence of RhH(PPh3)4 (2.5 mol%) in THF at 0 °C for 3 h, ( )-(6-phenyl-3-hexenyl)triphenylphosphonium salt was obtained in 89% yield after anion exchange with LiPF6 and recrystallization (Scheme 16). The addition of phosphine and hydrogen occurred at the 1- and 2-carbon atoms of the 1,3-diene, respectively. The reaction of (7)-1,3-dienes was then performed for comparison. 

Dienes reacted considerably faster than the (Z)-isomers, and this feature was utilized to separate the (Z)-isomer from the stereoisomeric mixture. When 6-phenyl-1,3-hexadiene (EIZ = 50/50) was treated with 0.6 molar amounts of PPh3 and CF3S03H at 0 °C for 6 h, the ( )-phosphonium salt (53%) was formed. The unreacted (2)-1,3-diene could be separated by ether extraction in 41% yield. This procedure provides easy access to (Z)-1,3-dienes.22... 

A series of conjugated polyenes capped with chromophores and containing an androstane spacer were synthesized by Wittig or Wittig-type olefinations from epi-androsterone 5150. For example, vinyl carboxaldehyde 52, prepared from 51 in 60% yield as shown in equation 32, was treated with 9-anthrylmethylphosphonium bromide and n-butyllithium to give diene 53. Exocyclic diene 53 was subsequently oxidized to vinyl carboxaldehyde 54. The androsterone vinyl aldehyde intermediate could either be treated with a tetraphenylporphyrinpolyenyl phosphonium ylide, or, as shown below, the phosphonium salt of the androsterone (55) could be reacted with TPP polyeneal 56. The desired all-(E) isomer, 57, was obtained from the ( )/(Z)-isomeric mixture by chromatographic purification. 

The second synthesis of 654 and 655 makes use350,351 of the Wittig reaction. The (methylthio)methyl ether 656 is converted into the chloromethyl ether 657, which reacts with triphenylphosphine to yield a crystalline phosphonium salt (658). Reaction of 658 with phenyllithium gives a phosphorane, treatment of which with acryl-aldehyde leads to ethers 654 and 655 in —50% yield. Pure trtms-diene 654 was obtained352 in a reversed way consisting in preparation of a sugar ether acrylaldehyde (660) by replacement of the p-tolylsulfonyl group in 659, followed by reaction of 660 with methylenetriphenyl-phosphorane. 

Ferrocenyl ligands, via zinc reagents, 9, 120 Ferrocenylmethyl phosphonium salts, with gold(I), 2, 274 Ferrocenylmonophosphine, in styrene asymmetric hydrosilylation, 10, 817 Ferrocenyl oxazolines, synthesis, 6, 202 Ferrocenylphosphines with chromium carbonyls, 5, 219 in 1,3-diene asymmetric hydrosilylation, 10, 824-826 preparation, 6, 197 various complexes, 6, 201 Ferrocenylselenolates, preparation, 6, 188 Ferrocenyl-substituted anthracenes, preparation, 6, 189 Ferrocenyl terpyridyl compounds, phenyl-spaced, preparation 6, 188 Ferrocifens... 

The trimethylsilylated ylides (1), easily generated from trimethyl chlorosilane and ylides, react with aldehydes 2 to form vi-nylsilanes 3 (2,3). The vinylphosphonium silanolates 4 are also formed. Compounds 3 are versatile reagents for further reactions (4). The ylide J (with R1 =H) reacts with aldehydes 2 to give the dienes j). The oxidation of with the adduct 6, from triphenyl-phosphite and ozone, gives access to a generaT synthesis of acyl-silanes (trimethylsilylketones) (2). The silylated ylides react to form phosphonium salts 7 with halogen compounds. The salts 7.can be desilylated by fluorine ions. The disubstituted ylides JO Tormed can be converted in statu nascendi with aldehydes V[ into the tris-substituted olefin J2 (2,3). In the case of R3-I, vinyl... 

Phosphonate (80) is deprotonated by u-butyllithium and the resulting anion has been reacted with the aldehyde (81), giving the diene derivative (82). Aldehyde (81) can be prepared from the phosphonium salt (83) and glyoxal <91JCS(P 1)2873). 

Difluorocarbene can be conveniently generated at room temperamre by the addition of fluoride ion to bromodifluorophosphonium bromide and, provided that the solvents are scrupulously dry, can be trapped by alkenes [60], dienes [61] and cycloalkenes [62] (Figure 6.42). The phosphonium salt may be generated in situ, allowing cyclopropanation to be carried out in a one-pot process [60] (Figure 6.43). Addition of 18-crown-6 to the reaction medium enhances the solubility of the metal fluoride and allows cyclopropanation of less nucleophilic alkenes and alkynes to be performed [63] (Figure 6.44). 

Similar types of alkylation have been applied in syntheses of other steroidal side-chains, including that of 22-trans-26,27-dinorergosta-5,22-dien-3j8-ol (387), a novel marine sterol. In addition, the Wittig reaction has been used to prepare various possible polyene intermediates in phytosterol biosynthesis. The aldehydes (389) and (390) were prepared (Scheme 26) from stigmasterol acetate (388b) by modification of a known procedure. These aldehydes were then alkylated with a variety of ylides derived from phosphonium salts, leading to a series of polyenes (391) and (392). ... 

N-acylaziridines occurs on treatment with triphenylphosphine with the formation of the ylides (67), thereby providing a route to a-substituted primary allylic amines via their in situ reactions with aldehydes.The reactions of triphenylphosphine with epoxides in phenolic media provide a new access to the vinyl-phosphonium salts (68). A route to 1-hydroxyalkylphosphonium salts is provided by the reactions of trimethyl- or triethyl-phosphine with aldehydes or ketones in the presence of anhydrous acids. The related 1-trimethylsiloxyalkylphosphonium salts can be isolated in the presence of trimethylsilyl chloride.Further Wittig-products have been isolated from the reaction of 1,2,3-indanetrione with triphenylphosphine, and, in related work, it has been shown that furoin is deoxygenated on heating with triphenylphosphine to form 2-furfuryl(2-furyl)ketone and triphenylphosphine oxide.The structure of the blue product from the reaction of triphenylphosphine with 2,3,5,6-tetracyano-7-oxabicyclo(2,2,1]hepta-2,5-diene has now been shown by X-ray techniques to be the stable ylide (69). ... 

Phosphenium ions (142) with isocyanides gave the new 1,3-azaphospheten cations (143) with t-butyl isocyanide and larger substituents on the amino groups elimination of isobutene occurred to give cyanophosphines, e.g. (144). The reaction of chlorophosphenium ions (145) with silylated amidines gave the new 1,3,2-diaza-phospheten cations (146). Several new phosphonium salts have been obtained from phosphenium ions and 1,3-dienes or o-quinones, e.g. (147). ... 

Axelrod et alP have describe the synthesis of 1,5-dienes by alkylation of an allylic phosphonium ylide with an allylic bromide. The method was used to synthesize pure all-( )-squalene from ( , )-fame-syl bromide and its tributylphosphonium salt. No isomerization occurred during the reaction and reduction of the resulting phosphonium salt with lithium in ethylamine gave squalene in 65% yield. 

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