Methylenation, Wittig olefination

Fluonnated ylides have also been prepared in such a way that fluonne is incorporated at the carhon P to the carbamonic carbon Vanous fluoroalkyl iodides were heated with tnphenylphosphine in the absence of solvent to form the necessary phosphonium salts Direct deprotonation with butyUithium or hthium dusopropy-lamide did not lead to yhde formation, rather, deprotonation was accomparued by loss of fluonde ion Flowever deprotonation with hydrated potassium carbonate in thoxane was successful and resulted in fluoroolefin yields of45-S0% [59] (equation 54) P-Fluorinated ylides may also be prepared by the reaction of an isopropyli-denetnphenylphosphine yhde with a perfluoroalkanoyl anhydnde The intermediate acyl phosphonium salt can undergo further reaction with methylene tnphenylphosphorane and phenyUithium to form a new yhde, which can then be used in a Wittig olefination procedure [60] (equation 55) or can react with a nucleophile [6/j such as an acetyhde to form a fluonnated enyne [62] (equation 56)... 

Examples have also been reported in which glyconolactones are olelinated generating exoenitols (Fig. 10) for example by methylenation (Tebbe reaction),20 difluoromethylenation,21 and dichloromethylenation,22 the Wittig olefination.23... 

The Wittig olefination of the tricyclic y-oxo ester 231f affords the 6-methylene tricycle 244. Treatment of the latter with diluted hydrochloric acid results in the formation of the 6-methyl-2-oxobicyclo[3.2.1]oct-6-ene derivative 240f in 94% yield (Scheme 70) [106,108]. This transformation maybe realized also in a one-pot procedure giving compound 240n in 70% yield (Scheme 70) [104b]. The overall yield in the step-by-step preparation of this compound, as shown in Schemes 65 and 68, was only 55% starting from the chloro ester 1-Me. 

Rauter and coworkers demonstrated that C-5-aIkylidene derivatives 112 of D-hexofuranurono-6,3-lactone can be obtained by Wittig olefination of the a-ketolactone 111 (Scheme 32) [160]. The related a-methylene lactone 114 was prepared in three steps from 3,6-anhydro-l,2-0-isopropylidene-a-D-j y/ )-5-hexulo-furanose 113 via Wittig reaction and aUylic oxidation. 

A Michael-type addition of secondary amines or thiols to 3-methylene-2-oxetanones (33) and subsequent pyrolysis of the adduct (34, X = NR22 or SR2) to yield allylic amines (35, X = NR22) or sulphides (35, X = SR2) has been proposed as a useful alternative to the Wittig olefination procedure (95JOC578). 

The Wittig olefination of 1,5-oxazocine 416 with [(methoxy)methylene]triphenylphosphorane led to the formation of the enol ether 431a (88% yield) as an inseparable mixture of E and Z isomers (2.5 1 ratio). Instead, when the reaction was carried out using methyltriphenylphosphorane as Wittig reagent, the as 3,5-disubstituted diastereoisomer 431b was exclusively formed in 85% yield (Scheme 84) <1998JOC3492>. 

A number of more complex structures, useful in total syntheses, are accessible from olefins formed by Wittig olefinations of keto-sugars. A fmitful reaction is the dihydroxylation of double bonds. Obviously, methylene derivatives will give the hydroxymethyl branched-chain derivatives. 

Wittig olefination of aldehydes and ketones with triphenylcyclopropylidenephos-phorane (Route c) leads to a wide range of (organylmethylene)- or (diorganyl-methylene)-cyclopropanes in satisfactory to good yields120) (Eq. 60). 

Our next objective was to methylenate the hemiacetal 40a,so as to obtain diene 39 (Scheme 14). Standard Wittig olefination procedures on 40 with methyl triphenylphosphoranylidene, generated in situ from methyl triphenylphosphonium bromide and w-BuLi, or with KOBu-t in THF (Entries 1 and 2, Scheme 14) simply furnished unreacted starting material. Tebbe olefinations were also unsuccessful a complex mixture of products arising under the conditions investigated in Entry 3 (Scheme... 

The formation of ylides by use of the carbenes from chloroform249 or methylene dichloride109,250 and a base require only a mention here since such ylides are always used for Wittig olefinations without isolation. 

Alkene positional isomerism is a problem that arises from time to time. It is conceptually related to regiochemistry and is presented here. Careful synthetic planning is usually required to solve this problem, as illustrated by the Burk-Soffer synthesis of e-cadinene (53) and V2-cadinene (54). 9 Conversion of 52 first to the ketone, then to the tertiary alcohol, and finally to the tertiary chloride allows E2 elimination to give 53. Conversely, Wittig olefination (sec. 8.8.A) of the ketone gave the exo methylene derivative, 54. It is important to note that formation of the C2-C3 C=C unit is favored for trans decalin derivatives over the C3-C4 unit. 

Syntheses of 4,5-Unsaturated Cyclic Compounds - Swem oxidation of methyl 2,3,4-tri-C>-acetyl-a-D-glucopyranoside followed by base-induced elimination of acetic acid afforded unsaturated aldehyde 33. Further transformation of the aldehyde group into a methylene unit by way of a Wittig olefination and replacement of the acyl groups with benzyls or methyls yielded 34 which underwent a Diels-Alder reaction (the acyl protected variant of 34 was unreac-tive) with 2-methoxycarbonyl-p-benzoquinone, followed by acid-catalysed double... 

Oxoisophorone 68 can be converted into trimethylcyclohexanone (74), in a series of reduction and elimination steps [82], opening up a new route to p,p-carotene (3) and vitamin A [85,86]. The Cio-epoxide 75 can be obtained by Wittig olefination of 73 with methylene-triphenylphosphorane, isomerization and reaction with peracids. Lewis acid-catalysed rearrangement to give the five-membered ring yields the capsorubin synthon 76 [9]. 

The Peterson reaction has two more advantages over the Wittig reaction 1. it is sometimes less vulnerable to sterical hindrance, and 2. groups, which are susceptible to nucleophilic substitution, are not attacked by silylated carbanions. The introduction of a methylene group into a sterically hindered ketone (R.K. Boeckman, Jr., 1973) and the syntheses of olefins with sulfur, selenium, silicon, or tin substituents (D. Seebach, 1973 B.T. Grdbel, 1974, 1977) illustrate useful applications. The reaction is, however, more limited and time consuming than the Wittig reaction, since metallated silicon derivatives are difficult to synthesize and their reactions are rarely stereoselective (T.H. Chan, 1974 ... 

The Wittig reaction consists in the replacement of carbonyl oxygen of aldehydes and ketones by a methylene group with the aid of phosphine-methylenes resulting in the formation of cis or trans olefines. The reaction proceeds through the nucleophilic addition of Wittig reagent (phosphine methylene) across the > C = O bond and formation of an intermediate cyclic. 

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