Wittig synthesis compounds

Planning a Wittig Synthesis The Wittig reaction is a valuable synthetic tool that converts a carbonyl group to a carbon-carbon double bond. A wide variety of alkenes may be synthesized by the Wittig reaction. To determine the necessary reagents, mentally divide the target molecule at the double bond and decide which of the two components should come from the carbonyl compound and which should come from the ylide. 

Triphenylphosphinelethylene oxide Ethylene derivatives from halides and 0x0 compounds Shortened Wittig synthesis... 

Wittig synthesis. Tritium compounds. Abs. ethanol-O-t and tri-cyclohexylbenzylphosphonium chloride added under Ng to Na-ethoxide, allowed to stand 1 hr. for T-ex-change, benzaldehyde added, and refluxed 1.5 hrs. frans-l,2-diphe-nylelhylene-l-t. 

The four-membered oxyphosphorane ring system is involved as an (usually unstable) intermediate when a phosphorane reacts with a carbonyl compound in the Wittig synthesis (6.415). Some of these intermediates have, however, been isolated and their ring structures confirmed by x-ray analysis (Figure 6.27). From the reaction of hexafluor acetone with hexaphenylcarbodiphosphorane in the presence of 1,2 diethoxyethane (diglyme), colourless crystalline 4,4 bis (trifiuoromethyl)-2,2,2 triphenyl-3-(triphenylphosphoranylidene)-l,2 oxa phosphetane, mp=115 C, can be obtained. 

T ri phenylphos phine/po tassi umtert- hutoxid e Wittig synthesis of dihalogenomethylene compounds... 

Wittig synthesis via (a-halogeiialkylidene)phosphines a-Halogen-a, -ethylenecarboxylic acids and a,j -acetylenecarboxylic acids from 0X0 compounds... 

Dilithium tetrachlorocuprate is recommended as an additive for cross coupling of Grignard compounds with tosylates even allylic and benzylic acetates give good yields . a-Methylene-ketones, -carboxylic acids and -lactones have been prepared via sulfides and sulfoxides. A convenient and general synthesis of acetylene derivatives from boranes via the reaction of iodine with lithium 1-alkynyltriorganoborates has been published ar-Nitrostyrenes can be easily obtained by a Wittig synthesis with formaldehyde in an aqueous medium . A new synthesis of unsym. ketones by reaction of dialkyldiloroboranes with lithium aldimines has recently been published . Metallo aldimines have also served for the synthesis of a variety of other compound classes such as a-hydroxyketones, a-keto acids, nitriles, and for the asym. synthesis of a-amino acids . Polycondensations of malononitriles with benzylic chlorides have been carried out quantitatively under mild conditions in dimethyl sulfoxide with triethylamine as acid acceptor . Carbonyl compounds can react with dibromoacetonitrile to yield a-bromo esters with additional carbon atom . ... 

A unique feature of Inhoffen s synthesis of vitamin D3 is the wide use of the Wittig reaction to introduce the Cg, C7, C o, and C23—C27 atoms of the steroid skeleton. At the same time, the lack of stereodirectivity and the low yields in a number of stages deprive this synthesis of preparative importance. The synthesis of vitamin D3 under consideration is only formally a total synthesis, since in the appropriate stages of the synthesis compounds (79), (87), and (94) were replaced by products identical with them obtained by the degradation of natural vitamin D [899, 902]. 

In view of the synthetic importance of dicarbonvl compounds surprisingly little has been done, apart from carotene synthesis, on dialkenylation with Wittig reagents. However, from the few examples reported one may conclude, that no special problems are involved. Benzocyclobutanedione was converted by two equivalents of methoxycarbonylmethylidenetri-phenylphosphorane to the corresponding diene in 85% yield (M. P. Cava, 1960). 

Out first example is 2-hydroxy-2-methyl-3-octanone. 3-Octanone can be purchased, but it would be difficult to differentiate the two activated methylene groups in alkylation and oxidation reactions. Usual syntheses of acyloins are based upon addition of terminal alkynes to ketones (disconnection 1 see p. 52). For syntheses of unsymmetrical 1,2-difunctional compounds it is often advisable to look also for reactive starting materials, which do already contain the right substitution pattern. In the present case it turns out that 3-hydroxy-3-methyl-2-butanone is an inexpensive commercial product. This molecule dictates disconnection 3. Another practical synthesis starts with acetone cyanohydrin and pentylmagnesium bromide (disconnection 2). Many 1,2-difunctional compounds are accessible via oxidation of C—C multiple bonds. In this case the target molecule may be obtained by simple permanganate oxidation of 2-methyl-2-octene, which may be synthesized by Wittig reaction (disconnection 1). 

H. C. Brown (Purdue) and G. Wittig (Heidelberg) for their development of boron and phosphorus compounds, respectively, into important reagents in organic synthesis. 

The discovery of junipal focused the attention of Sorensen, who had been investigating the occurrence of polyacetylenes in Com-positae, on the possibility that these acetylenes were accompanied by thiophenes. From Coreopsis grandiflora Hogg ex sweet, 2-phenyl 5-(1-propynyl) thiophene (240) was isolated and its structure confirmed by synthesis of the tetrahydro compound, 2-phenyl-5-n-propyl-thiophene. From the root of tansy, the cis and trans isomers of methyl 5-(l-propynyl)-2-thienylacrylate (241) have been isolated. The total synthesis of trans (241) was achieved by reacting junipal with methylcarbethoxy triphenylphosphonium bromide (Wittig reaction) Several monosubstituted thiophenes, (242), (243), and... 

With respect to the carbonyl substrate, a variety of additional functional groups is tolerated, e.g. ester, ether, halogen. With compounds that contain an ester as well as a keto or aldehyde function, the latter usually reacts preferentially. Due to its mild reaction conditions the Wittig reaction is an important method for the synthesis of sensitive alkenes, as for example highly unsaturated compounds like the carotinoid 17 shown above. 

Herbert C. Brown and Georg Wittig development of boron (H. C. B.) and phosphorus (G. W.) compounds into important reagents in organic synthesis... 

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