Phosphonium Wittig synthesis with

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 synthesis of poly-dibenzylidene-l,3-dithietane 201 is based on the Wittig reaction of/ -xylcnc-bis(triphcnyl-phosphonium) chloride 199 with carbon disulfide <2001MM346, 2002MM3806>. The phosphonium salt 199 was converted to the ylide 200, which reacted with carbon disulfide, yielding, after methanolysis, a thioketene. The latter was stirred at room temperature for 12 h to provide the polymeric compound 201, bearing 1,3-dithietane moieties in 54% yield (Scheme 25) <2001MM346, 2002MM3806>. 

In a synthesis of PGEt reported by Corey 89) for the preparation of the 0,S-acetal-protected dienol thioether aldehyde 122, the ylide generated from phosphonium salt 119 was used as an electrophile in the alkylation of 118. The following Wittig reaction of the resulting phosphonium salt 120 with the thioenolether aldehyde 121 in the presence of phenyllithium as the base gave intermediate 122 in 35% yield. 

The C10-dialdehyde 539 serves as the central olefination synthon in the preparation of the symmetrical carotenoid zeaxanthin 560 270). In this synthesis the phospho-nium salt 559 which can easily be prepared from the vinyl hydroxyionol 558 and triphenylphosphine hydrobromide, 504, is reacted with 539 in 1,2-epoxybutane, a solvent which seems to be especially suitable for Wittig reactions with polyene dialdehydes 270). The same phosphonium salt 559 was used in the synthesis of P-eryptoxanthin and zeinoxanthin. 

An industrial synthesis for p-carotene (1), the orange-red colorant of carrots and the important provitamin A, is based on the linking of two C15 phosphonium salts (13) with a C10 dialdehyde (22), in a double Wittig reaction 40) ... 

The same year, Gerlach described a synthesis of optically active 1 from (/ )- ,3-butanediol (7) (Scheme 1.2). The diastereomeric esters produced from (-) camphorsulfonyl chloride and racemic 1,3-butanediol were fractionally recrystallized and then hydrolized to afford enantiomerically pure 7. Tosylation of the primary alcohol, displacement with sodium iodide, and conversion to the phosphonium salt 8 proceeded in 58% yield. Methyl-8-oxo-octanoate (10), the ozonolysis product of the enol ether of cyclooctanone (9), was subjected to Wittig condensation with the dilithio anion of 8 to give 11 as a mixture of olefin isomers in 32% yield. The ratio, initially 68 32 (E-.Z), was easily enriched further to 83 17 (E Z) by photolysis in the presence of diphenyl disulfide. The synthesis was then completed by hydrolysis of the ester to the seco acid, conversion to the 2-thiopyridyl ester, and silver-mediated ring closure to afford 1 (70%). Gerlach s synthesis, while producing the optically active natural product, still did not address the problem posed by the olefin geometry. 

The Julia olefin synthesis is rather like the Wittig reaction with a sulfone instead of a phosphonium salt but with one other important difference the elimination step is stereoselective and both dia-stereoisomers of the intermediate can give the same isomer of the alkene. Treatment of the sulfone 147 with a strong base gives the anion 148 (or a metal derivative) that combines with an aldehyde to give a diastereomeric mixture of adducts 149. Elimination by various methods gives, in open chain compounds, mostly -150 but, in cyclic compounds, mostly the Z-alkene.29... 

For the synthesis of the naturally occurring (6 R)-p,G-carotene (127), (R)-a-ionone [(R)-78] was reacted with vinylmagnesium chloride (80) to give the Cis-alcohol 128 which was converted into the phosphonium salt 129. The subsequent Wittig reaction with 12 -apo-p-caroten-12 -al (130) and NaOMe as base gave 127 in 45% yield referred to (R)-78 (Scheme 29). 

The first synthesis of lycopene (1) was reported by the school of Karrer [82] in 1950. By analogy with his pioneering synthesis of p,p-carotene (2) the Ci6 + C8 + Ci6 = C4o route was used. The first synthesis of lycopene (1) via the Wittig reaction used the strategy Cio + C2o + Cio = C4o [83]. Linalool (148) was converted, with phosphorus tribromide and triphenylphosphine, into the phosphonium salt 149. The Wittig reaction with crocetindialdehyde (27) and BuLi as base gave lycopene (1) in an overall yield of 36% referred to 148 Scheme 33). 

The synthesis of symmetrical i -carotene (152), which has 7,8 and 7, 8 single bonds, was carried out efficiently according to the C15 + C10 + C15 = C40 strategy by use of the Wittig reaction to couple the building blocks [84]. frans-Nerolidol (154) was converted, with phosphorus tribromide and triphenylphosphine, into the Ci5-phosphonium salt 155. The Wittig reaction with the Cio-dialdehyde 45 and BuLi gave -carotene (152) in an overall yield of 45% referred to 154 (Scheme 34). 

The Ci5-phosphonium salt 284, a key intermediate also in the industrial synthesis of vitamin A (29), is reacted in a double Wittig olefination with the Cio-dial (45) to give p,p-carotene (2) in an overall yield of ca. 80% [111,112], Alternatively also the Wittig reaction of retinal (33) with retinyltriphenylphosphonium salt (285) gives 2 in yields up to 85% [113,114],... 

Complex phosphonates and phosphonium ylides have been used in a variety of syntheses. For example an olefination reaction of the phosphonate (244) has been used to construct the carbon skeleton in a convergent synthesis of the structural fragment (245) of the marine metabolite halichondramide 27 and Wittig reactions with the ylide (246) have been used to prepare the polycyclic cervinomycin A -trimethyl ether and A2-methyl ether. 2 Both complex phosphonates (247) and phosphonium ylides (248) have been investigated for use in the synthesis of calyculin A. Use of the phosphonate (247) was not successful due to a competing elimination reaction and the ylide (248) was used in the actual synthesis. 29... 

In the first route (Scheme 101) [20], a Wittig reaction of 590 with 1-hexylidene-triphenylphosphorane gives the Z-olefin 699 in satisfactory yield. Conversion to phosphonium iodide 700 and Wittig reaction with aldehyde 701 affords methyl 12( S)-HETE (702). In this synthesis the upper aldehyde fragment and lower phosphorane fragment are joined at the -olefin. 

The Wittig reaction has been used widely in organic synthesis. For example, a number of steps in a synthesis of the neurotoxin brevetoxin B make use of the Wittig reaction with both stabilized and non-stabilized phosphonium ylides, two of which are shown in Scheme 2.74. This synthesis also uses a Wittig reaction in a later, key step to combine two large fragments using a non-stabilized phosphonium ylide to prepare a Z-alkene. 

Reuse of the phosphine resins for Wittig reactions has been reported without details several times. In the only detailed results 92% conversion of phosphine oxide to phosphine with trichlorosilane was attained with a 2% cross-linked polymer, and repeated synthesis of stilbene by quatemization with benzyl bromide and Wittig reaction with benzaldehyde gave 97% gc yields in both the second and the third cycles based on the amount of phosphonium bromide used (H). Identical recycling of a 20% cross-linked macroporous polymer gave 75% gc yield of stilbene compared with 80% from the first use (131. 

The most effective method for the synthesis of symmetrical carotenoids has proved to be the double Wittig condensation of a Cis-phosphonium salt 48 with the symmetrical Cio-di aldehyde 34. 

For the synthesis of 36, 6-methylhept-5-en-2-one (49) was selected as starting material. Hydrogenation of 49 in the presence of palladium gave the ketone 50 which, in a Horner-Emmons reaction, was condensed with ethyl diethylphosphonoacetate (51) to give the a,P-unsaturated ester 52. Reduction with LiAlHa and treatment of the resultant alcohol 53 with triphenylphosphine hydrobromide gave the phosphonium salt 54. Wittig reaction with crocetindialdehyde (536) and BuLi resulted in 1,2, r,2 -tetrahydrolycopene (36) in an overall yield of 10% referred to 49 and the C3o-aldehyde 55 as a byproduct [10,11] (Scheme 14). 

In another synthesis of spirilloxanthin (166) [13] the ketone 62 was ethynylated with sodium acetylide (68) to give 69 which was partly hydrogenated to 70. Treatment with triphenylphosphine hydrobromide led to the Cio-phosphonium salt 77. The Wittig reaction with crocetindialdehyde (536) and PhLi gave l,r-dimethoxy-l,2,r,2 -tetrahydrolycopene (170)... 

By analogy with the synthesis of rhodopin (93), chloroxanthin (100) was synthesized by the Wittig reaction of the phosphonium salt 79 with apo-8 -neurosporenal (74) and sodium methoxide (Scheme 24) [16]. 

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