By the Wittig reaction

A good approach to 1,2-diols is hydroxylation of an olefin with reagents such as OSO4 or KMn04. The olefin can be made by the Wittig reaction so the discoimections arc ... 

Analysis The carbene synthon is easy it can be ethyl diazoacetate NiCHCOiEt. The diene can be made by the Wittig reaction from a familiar aUylic bromide (TM 31). 

The methyl enol ether 37 is oxidized to the a,/3-unsaturated aldehyde 39 via hemiacetal 38. Unsaturated aldehyde 39, elongated one carbon from the aldehyde 36, is prepared by the Wittig reaction of 36 to give 37, and application of this reaction[ 88]. 

Maleic anhydride is a convenient dienophile because of its rapid reaction with most dienes as well as its stability and ease in handling (although it is poisonous). The diene for this reaction, 1,4-diphenyl-1,3-butadiene, is readily prepared by the Wittig reaction with benzyltriphenylphosphonium chloride and cinnamaldehyde (Chapter 11, Section I). 

Aldehydes can be prepared by the Wittig reaction using (methoxymethylene)-triphenylphosphorane as the Wittig reagent and then hydrolyzing the product with acid. For example,... 

Monomer Synthesis. 4-Allyloxystyrene was prepared by the Wittig reaction of 4-allyloxybenzaldehyde and methyltriphenylphosphonium bromide, under basic conditions. The allyloxybenzaldehyde was prepared, in turn, by the alkylation of 4-hydroxybenzaldehyde with allyl bromide. This method, which provides high purity monomer in high overall yield, is outlined in Scheme 1 and has been previously described (2). Alternatively, the monomer may be prepared by the direct alkylation of p-vinylphenol with allyl bromide (8,9), although this method is less convenient due to the difficulties in synthesizing and storing the highly reactive vinyl phenol (10). 

Synthesis of (Z)-(lR)-trans-Norchrysanthemic Acid by the Wittig Reaction... 

Alternatively, bromo trienyne 66, prepared by the Wittig reaction of TMS-capped propargyl ylide with , -5-bromo-2,4-pentadienal, could be coupled with dienyl zinc reagent 67, as illustrated in equation 3657. Subsequent desilylation followed by treatment with trimethyl aluminum in the presence of catalytic Cp2ZrCl2 afforded the alane of tetraenyne 68 which, on exposure to chloroformate, gave essentially all- polyene ester 69. 

Improved synthesis by this method has been achieved in order to obtain solenopsin A (Id) more stereoselectively 388). A cis and trans mixture of pyridine derivative 158, obtained from 156 by the Wittig reaction, was reduced by Raney nickel catalyst in the presence of PtOj to yield the m-piperidine (Ic). The Af-nitroso derivative 159, obtained from Ic by treatment with isoamyl nitrite, was treated with potassium rert-butoxide and then subjected to hydrogenolysis over Raney nickel to give a mixture of ( )-solenopsin A (Id, 1 part) and its isomer (Ic, 1 part) (Scheme 3). 

The starting enitol was prepared by the Wittig reaction in 82% yield from 2,3-bis-... 

The ketone behaves in its normal fashion, first undergoing nucleophilic addition from the ylide to form a betaine (pronounced "bay -tuh-ene"). However, the betaine is unstable and quickly breaks down to a triphcnylphosphine oxide and the alkene. When possible, a mixture of both cis and trans isomers are formed by the Wittig reaction. 

Stereocontrolled ethynylation of methyl 2,3,4-tri-O-benzyl-a-D-g/Hco-hexodialdo-l,5-pyranoside (52) with a Grignard reagent formed from trimethylsilylacetylene, followed by a multistep procedure afforded the aminouronic acid 53, the a-amino acid on which miharamycin A is based.168 Uronic acid derivatives have also been produced by the Wittig reaction on the aldehydic side chain of dialdofuranose compounds.169... 

There are many other reactions that make C-C bonds using only one functional group. Among the most important involve alkynes by alkylation 73 (chapter 16), alkenes by the Wittig reaction 74 (chapter 15) and nitro compounds by alkylation 75 (chapter 22). Disconnections of alkenes outside the double bond 76 and especially disconnections of dienes between the double bonds 77 use palladium chemistry and are discussed extensively in Strategy and Control. 

In chapter 15 we saw that dienes could be made by the Wittig reaction and also by the addition of vinyl lithiums or Grignard reagents to ketones followed by dehydration of the allylic alcohol product. Derivatives of acetylenes can do the same job. The first disconnection is the same but a reagent for the synthon 40 replaces the vinyl metal derivative. 

We have expanded our collection of stereoselective reactions even more in the making of alkenes by the Wittig reaction (chapter 15), from acetylenes (chapter 16), by thermodynamic control in enone synthesis (chapters 18 and 19) and in sigmatropic rearrangements (chapter 35). We have seen that such E- or Z-alkenes can be transformed into three-dimensional stereochemistry by the Diels-Alder reaction (chapter 17), by electrophilic addition (chapters 23 and 30), by carbene insertion (chapter 30) and by cycloadditions to make four-membered rings (chapters 32 and 33). 

The dye-sensitized (eosin) photooxygenation at —50 °C of alkylidenecyclopropanes 85, easily available by the Wittig reaction of 3-bromopropyltriphenylphosphonium ylide44 and suitable ketones, gave the hydroperoxides 86, which were reduced in situ by an equivalent of triphenylphosphine 45 to 1-alkenylcyclopropanols 87 in good yields. When PPh3 was replaced by pyridine (5 %) 86 rearranged exclusively... 

Among insect pheromones a great number of mono- and polyolefinic compounds are found a lot of them can be obtained by the Wittig reaction. Especially the syntheses of sex attractants of female butterflies and moths, which are mostly mono- and bisunsaturated alcohols, acetates or aldehydes 168), offer a broad field for the application of the Wittig reaction and have stimulated the development of many new stereoselective variants. Thus, the methods of salt-free Wittig reactions (Chapter 2) like the sodium amide method11 31 32, the silazide technique33, potassium in HMPA 34,35 or the use of dipolar aprotic solvents like dimethyl formamide 169>, dimethyl sulfoxide 51,170) or hexamethylphosphoric triamide 51 170) were often used. 

Scheme 95 describes in principle the same synthesis technique using a bisphospho-nium salt 562 as the central molecular part of the molecules 563 and 565. Olefination of the ylide generated from 562 with two equivalents of the ketoaldehyde 561 yields ketocarotenoid 563211). Unsymmetrical ketocarotenoid 565 has been synthesized by the Wittig reaction of 562 with a mixture of aldehydes 564 and 511 and subsequent hydrolysis of the acetal protective group 271) (Scheme 95). 

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